NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide

NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide

NSG 6005 Advanced Pharmacology Midterm—Study Guide

There will be 75 questions on the Midterm.  Most will be multiple choice.  There are a couple True/False and 5 matching questions.  I suggest you review your PowerPoints and Textbook Assignments.  I hope this study guide is helpful.

Make sure you know the following topics very well. 

  • When a medication is listed below, make sure you know all about it and how to apply it to different patient situations: What disease process it is used for?,  how does it work?, when should it not be used?, adverse effects, pros/cons, interactions, patient education factors (should it be taken w/ food? At bedtime?), tapering, preliminary and post treatment labs, black box warnings/CI, etc. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  • If a disease process is mentioned below—know how to diagnose and recommended treatment guidelines.
  • General principles of pharmacokinetics and dynamics?

PHARMACOKINETICS-  What the body does to the drug”

Struggling to meet your deadline ?

Get assistance on

NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide

done on time by medical experts. Don’t wait – ORDER NOW!

Absorption –Entry of drug to the blood stream. Usually depends on passive diffusion of drug through cell membranes.

  • Absorption depends on: blood flow at site, drugs lipid soluability (> lipic, > soluabililty that directly penetrate the memebrane), local PH and drug ionization (non-ionized absorb better), pharmaceutical processing (coatings and additives.
  • Blood brain barrier: allow lipid soluable only. May pump out any drug that it sees as foreign, hard to treat CNS infections.
  • Placenta: allows lipid drugs so does not protect from lipid soluable drugs, which is why pregnant women are limited to drugs. Know gestation age. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

: fat ratio changes may alter distribution, especially a people age.

  • Fat soluable drugs may be accumulated: weight loss will release these drugs.
  • Water soluable drugs are affected by dehydration

Biotransformation (Metabolism) : Drugs become more hydrophilic (water soluable) for excretion.

  • Also referred to as the P450 system or cytochrome P450 system. (a group of enzymes in the liver identified for their ability to breakdown drugs.)
  • Hepatic “First Pass Effect” (parenteral (IV or IM) meds bypass this enzymatic effect)
  • breaks PO meds down to some degree, some are protected with coating but they don’t always work
  • Metabolites
    Usually less active, less toxic, easier
  • to excrete
  • Prodrugs – inactive in form given but metabolized to active drug (ex: enalapril)
  • Liver function determined by liver enzymes. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  • Failing liver produces fewer enzymes, drugs available longer: caution
  • Excretion: Process by which medications are eliminated from the body unchanged or as metabolites
  • Kidneys are main organ of excretion
  • If poor renal function, drug may accumulate, may
    wish to prescribe less of drug
  • Also eliminated via respiration, breast milk, defecation. Tears, sweat, saliva not as significant.

PHARMOCODYNAMICS- “effect of drug on the body”

Receptors: Drugs must bind to for effect o Help a process happen: agonist

o Block a process from happening: antagonist o Know that:

  • All drugs have an effect
  • A drug’s ability to cause a response is 
called its efficacy
  • If you give a bigger dose you will get a bigger effect up to a point, most drugs have a ceiling.

NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide


  • Effectiveness: elicits responses for which it is given – most important
  • Safety: Cannot produce harmful effects even at very high dosages and for long time
    oNo such thing as completely safe drug
  • Selectivity: Only elicits response for which it is given, no side effects
  • No such thing as a selective drug, all have ADRs
  • Reversible action: most drugs should be reversible. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  • Predictability: Know with certainty exactly how individual patient will respond – impossible, must individualize
  • Ease of administration: simple, convenient route – enhances compliance and decreases errors
  • Freedom from drug interactions: few drugs are without drug interaction
  • Low cost: easy to afford; significant factor in adherence, esp. with elderly
  • Chemical stability: drugs ability to be stored for long time without loss of effectiveness – variable between drugs
  • Possession of simple generic name: easier to remember and less confusion amongst drugs

3) SYNERGISTIC EFFECT: When two or more drugs are given

together they can react with each other: An effect arising between two or more agents, entities, factors, or substances that produces an effect greater than the sum of their individual effects. It is opposite of antagonism.

Can be positive (synergistic) • Morphine and Motrin

Can be negative (compete with each other) • Asa and Coumadin

4) Therapeutic drug levels: (not sure if this is correct)

Minimal Effective Concentration (MEC) – plasma drug level below which therapeutic effects will not occur.

Therapeutic Index or Range– margin of safety

  • The wider or bigger it is, the safer the drug. o Example 1: Drug A: normal dose is 1 mg, toxic dose is 10 mg
  • Acetaminophen’s therapeutic range is 30 times the MEC
    o Example 2: Drug B: normal dose is 9 mg, toxic dose is 10 mg o Lithium’s therapeutic range is 3 times the MEC.


Metabolism is the process of changing one chemical into another.  The liver is a major organ for drug metabolism because it contains high amounts of drug-metabolizing enzymes and because it is the first organ encountered by drugs once they are absorbed from the GI tract. Metabolism by the liver following oral administration is called FIRST-PASS METABOLISM and is important in determining whether a drug can be orally administered. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


  • Half-life- amount of time it takes to reduce the plasma concentration by 50%.
  • In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is fairly in dynamic equilibrium with its elimination. In practice, it is generally considered that steady state is reached when a time of 4 to 5 the half-life for a drug after regular dosing has started.


            AGONISTS:  Drugs that produces a physiological response when combined with a receptor.

ANTAGONISTS:  a substance or drug that interferes with or inhibits the physiological action of another.

8) SUSTAINED RELEASE MEDICATION CONSIDERATIONS- implies slow release over time. It is defined as the type of dosage in which a portion of the drug is released immediately, and then the remaining/maintenance dose) is then released slowly by achieving a therapeutic level which is prolonged. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.



  • Sublingual medication administration (under the tongue) and buccal (between the cheek and gum) allow drugs to have a more rapid onset of action and to avoid liver metabolism as they enter the blood stream.
  • Nitroglycerin given under the tongue can act within minutes to treat an angina attack.


  • The first step in the prescribing process is an accurate diagnosis and a determination of a therapeutic objective. (page 29)









            Before deciding what medication to prescribe, it is important to clarify the therapeutic objective.

  • Is this goal to cure the disease
  • Relieve symptoms of the disease
  • Long term prevention
  • Is the goal treating the combination of 2 outcomes (pain and inflammation)
  • Palliative therapy
  • The provider should clarify whether the treatment goals are curative, symptom relieving or preventative.
  • Include patient in this stage as a partner of treatment. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

12.) Patients at risk for adverse drug reactions. (page 55)

  • Genetic abnormalities
  • Age
  • Sex
  • Polypharmacy
  • Concomitant medical conditons
  • Children- are at higher risk primarily because medication dosages must be tailored to their body weight, immature organ function.
  • Elderly- polypharmacy, decreased renal and hepatic function


  • Highest risk is those patients with asymptomatic condition, chronic conditions. Cognitive impairment, psychiatric illness or disorders with significant lifestyle changes (smoker), and those with complex multiple daily dosing.
  • Adherance implies a voluntary act of negotiation and joint acceptance of a treatment regimen.
  • Patients harbor strong concerns about the need for their medication and the risk for taking it. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  • Limited access to health care
  • Restricted formularies
  • High drug costs and co-payments


  1. a) the presence of food in the GI tract can influence the rate and extent of absorption
  2. b) alteration of PH- food tends to increase stomach PH by acting as a buffer.
  3. c) gastric emptying –fats and some drugs tend to reduce gastric emptying and delay onset of action of drugs.
  4. d) stimulation of GI secretions- GI secretions produced in response to food may result in degredation of drugs that are susceptible to enzymatic metabolism, reducing bioavailablity. Secretions may also increase bioavailability. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  5. e) fats stimulate bile secretion- bile salts dissolute poorly soluable drugs.
  6. f) food induced changes in blood flow- blood flow to the GIT and liver increases blood flow after a meal. The faster the rate of drug presentation to the liver: the larger the fraction of the drug that escapes first-pass metabolism.

g)competition of food components and drugs: possibility of competitive inhibition of drug absorption, especially with drugs who have similar chemical structure of nutrients.


  1. A) Dietary fiber may lower cholesterol
  2. b) provide feeling of fullness, thus causing weight loss.
  3. c) increased soluable fiber intake has been associated with better glucose and improve blood lipid panels.


  1. a) vitamin A- can effect embryonic development


18.Warfarin – This  is used to treat  (such as in – or pulmonary embolus-PE) and/or to prevent new clots from forming in your body. Preventing harmful  helps to reduce the risk of a  or . Conditions that increase your risk of developing  clots include a certain type of irregular  rhythm (), valve replacement, recent , and certain surgeries (such as hip/).

 is commonly called a “,” but the more correct term is “anticoagulant.” It helps to keep  flowing smoothly in your body by decreasing the amount of certain substances (clotting proteins) in your blood. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.




  • Well-absorbed when taken orally
  • Metabolized by CYP 1A2 and 2C9
  • Half-life of 3 to 4 days
  • Precautions and contraindications§

Pregnancy category X

  • Use cautiously in patients with fall risk, dementia, or

uncontrolled hypertension.

  • Avoid in hypermetabolic state.
  • Adverse drug reactions
  • Bleeding
  • Antidote is vitamin K
  • Allergic reactions
  • Many drug-drug interactions
  • Antiplatelet drugs
  • Thrombolytic drugs
  • Anticoagulant effect may be decreased by
  • Oral contraceptives, carbamazepine, etc.
  • Vitamin K-containing foods

Clinical use and dosing

  • Drug of choice for deep vein thrombosis (DVT) and pulmonary embolism (PE)
  • Start at 5 mg per day (7.5 mg/d if weight greater than 80 kg).
  • Consider lower dose if
  • Older than 75 years
  • NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Multiple comorbid conditions

  • Elevated liver enzymes
  • Changing thyroid status
  • Dose to maintain international normalized ratio (INR) between 2 and 3.


  • INR daily until in therapeutic range for 2

consecutive days

  • Then two or three times weekly for 1 to 2 weeks
  • Then less frequently but at least every 6 week


Vitamin K, is a critical component of blood clotting, is found in many foods and is synthesized by intestinal bacteria. Newborns are at risk for early vitamin K–deficiency bleeding

American Academy of Pediatrics(AAP) recommends that all newborns receive

vitamin K within the first 2 weeks of life .

The dose of vitamin K (phytonadione) recommended  0.5 mg to 1.0 mg IM, ideally given within the first hour of life (AAP Committee on Fetus and Newborn, 2003).

Oral vitamin K is used by some countries and by some providers in the United States. The AAP notes that vitamin K–deficiency bleeding in newborns who received oral vitamin K. The AAP recommends IM administration until further study of oral administration is conducted. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Warfarin interferes with the vitamin K–dependent clotting factors (II, VII, IX, and X), leading to decreased formation of clots.

Vitamin K(phytonadione) is prescribed for patients who develop critically high INRs while on warfarin. Patients with an INR greater than 10 with no evidence of bleeding can be administered oral vitamin K (5–10 mg): if high INR with bleeding occurs, vitamin K (5–10 mg IV) is administered along with prothrombin complex (Guyatt et al, 2012).

Foods high in vitamin K compete with warfarin. Therefore, drug–nutrient interactions must be considered to utilize drugs effectively in the prevention and treatment of disease. Patient education must be provided about drug–food interactions, especially if there is a potential for adverse patient outcomes. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Patients who are taking warfarin should not ingest foods high in vitamin K, as the combination may lead to therapeutic failure.

 Vitamin K Content in Common Foods

Food Serving Size Daily Value (%)
Foods High in Vitamin K (more than or equal to 200% DV) Eat No More Than 1 Serving per Day
Kale, fresh, boiled 1/2 cup 660
Spinach, fresh, boiled 1/2 cup 560
Turnip greens, frozen, boiled 1/2 cup 530
Collards, fresh, boiled 1/2 cup 520
Swiss chard, fresh, boiled 1/2 cup 360
Parsley, raw 1/2 cup 300
Mustard greens, fresh, boiled 1/2 cup 260
Foods Moderately High in Vitamin K (60% to 199% DV) Eat No More Than 2 Servings per Day
Brussels sprouts, frozen, boiled 1/2 cup 190
Spinach, raw 1 cup 180
Turnip greens, raw, chopped 1 cup 170
Green leaf lettuce, chopped 1 cup 125
Broccoli, raw, chopped 1 cup 110
Endive lettuce, raw 1 cup 70
Romaine lettuce, raw 1 cup 70


Power point information (short and sweet..)

Vitamin K

A critical component of blood clotting

Found in many foods

Synthesized by intestinal bacteria

Newborns need 0.5 mg to 1.0 mg, ideally within the first hour of life, to prevent vitamin K-deficiency bleeding. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Vitamin K is used as an antidote to critically high international normalized ratio in patients                      taking warfarin


20.Vitamin C (ASCORBIC ACID)


Vitamin C, also known as ascorbic acid, is a water-soluble vitamin that humans do not have the ability to synthesize so they must get adequate amounts of it in their diet. Patients with inadequate vitamin C intake may develop scurvy, with symptoms of fatigue, malaise, and gum inflammation or bleeding. Smokers and persons who are heavily exposed to secondary smoke have decreased vitamin C levels; therefore, it is recommended they take 35 mg more vitamin C per day than nonsmokersOther groups at risk of vitamin C deficiency are infants fed evaporated milk or boiled milk without additional supplementation of vitamin C, patients with malabsorption disorders, and patients with end-stage renal disease who are on hemodialysis (ODS, 2013b).

Vitamin C therapy has been studied for its effects on health because of its antioxidant and immune function action. It has been touted as prevention or treatment of the common cold since the 1970s, when Linus Pauling published his landmark study. A Cochrane Review in 2007 of 30 trials did not find that vitamin C decreases the incidence of colds in the general population (Douglas, Hemiliä, Chalker, & Treacy, 2007). NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

The role of antioxidants in reducing the risk of cardiovascular disease . The Nurses’ Health Study found an inverse relationship between coronary heart disease and vitamin C intake (Myint et al, 2008). A meta-analysis of 16 studies examining vitamin C intake, circulating vitamin C levels, and risk of stroke suggests lower stroke risk with higher vitamin C intake and levels (Chen, Lu, Pang, & Liu, 2013).


Humans do not have the ability to synthesize vitamin C.

Inadequate vitamin C intake may cause scurvy.

Smokers have decreased vitamin C levels (+35 mg/day).

Vitamin C does not decrease incidence of URIs.

Mixed results in decreasing cardiovascular disease ,stroke and cancer


Vitamin C Children:1–3 yr

4–8 yr

Adolescents aged 9–13 yr

14–18 yr male

14–18 yr female

Adult males

Adult females


15 mg/d

25 mg/d

45 mg/d

75 mg/d

65 mg/d

90 mg/d

75 mg/d

85 mg/d

Citrus fruits, tomatoes, tomato juice, potatoes, Brussels sprouts, cauliflower, broccoli, strawberries, cabbage, and spinach




  1. IRON

Iron is an essential mineral required for the regulation of cell growth and differentiation, as well as a component of oxygen transport. Patients with irondeficiency will develop microcytic-hypochromic anemia and have red blood cells that are small in size, pale, and low in hemoglobin. Iron-deficiency anemia (IDA) reduces the oxygen-carrying capacity of the blood, leading to fatigue and decreased immunity. Too much iron can lead to iron toxicity; therefore, patients should be advised to take only the recommended amount for their age and condition.


Needed for oxygen transport

Patients with iron deficiency will develop microcytic-hypochromic anemia.

Adequate intake is determined by age.

All infants should be assessed for adequate iron in diet. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


0–6 mo    0.27 mg/d 

7–12 mo    11mg/d 

1–3 yr

4–8 yr

9–13 yr

14–18 yr male

14–18 yr female

19–50 yr male              8mg/d

19–50 yr female          18mg/d

19 to 50 yr pregnant    27mg/d

50+ yr                           8mg/d

Chicken liver, oysters, beef, clams, turkey dark meat. Legumes, dark green vegetables. Fortified breads and cereals. Iron-fortified infant formula.




Vitamin A plays a critical role in vision, bone growth, reproduction, immune function, cell division and differentiation . There are two types of vitamin A: preformed vitamin A, which is derived from animal sources, and provitamin A carotenoid, which is derived from plant sources. Ahealthy diet should contain a variety of carotenoid-rich fruits and vegetables. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Vitamin A deficiency can lead to night blindness and decreased immune function. Vitamin A may reduce the severity and duration of diarrheal episodes in malnourished children in developing countries but not in well-nourished children (Imdad et al, 2011; ODS, 2013a). NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. Vitamin A supplementation has also been found to decrease bronchopulmonary dysplasia in extremely low-birth-weight infants with no increase in mortality or neurodevelopmental disorder. Chronic alcoholism may lower vitamin A levels, and patients with chronic alcoholism may require supplementation. Patients with cystic fibrosis (CF) are predisposed to malabsorption and fat-soluble vitamin deficiency, with 10% to 40% of CF patients being vitamin deficient and requiring supplementation .

Caution should be used to avoid excessive vitamin A supplementation, as toxicity may occur. Levels above recommended amounts may be teratogenic in pregnant women; vitamin A is labeled Pregnancy Category X if intake is greater than recommended amounts.



Critical role in vision, bone growth, reproduction, immune function, cell division and differentiation

Vitamin A Children:1–3 yr

4–8 yr

Adolescents aged 9–13 yr

Adult males

Adult females


300 mcg/d

400 mcg/d

600 mcg/d

900 mcg/d

700 mcg/d

770 mg/d

Liver, dairy products, fish, darkly colored fruits and leafy vegetables


  1. Vitamin B6

Vitamin B6, also known as pyridoxine, is a water-soluble vitamin needed for protein and red blood cell metabolism, as well as glucose regulation. Vitamin B deficiency may lead to microcytic anemia, dermatitis with mouth sores and cracked lips, and glossitis (ODS, 2011a). Vitamin B6 deficiency may be drug-induced by use of isoniazid (INH), cycloserine, or hydrazine, or caused by a diet that is deficient in vitamin B6–containing foods (fortified cereals, potatoes, bananas, meat). Pyridoxine (vitamin B6) 25 mg/day should be added to the regimen for pregnant patients to decrease the incidence of peripheral neuropathy associated with INH (American Thoracic Society, 2003). Pyridoxine (adults 100 to 200 mg/d in divided doses) may also be given prophylactically to patients on isoniazid, cycloserine, or hydrazine to prevent drug-induced neuritis. Vitamin B6 supplements may reduce the symptoms of premenstrual syndrome, and nausea and vomiting associated with pregnancy (10 to 25 mg TID). NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Vitamin B6 (pyridoxine)

Deficiency may be drug-induced

Pyridoxine given prophylactically to patients on isoniazid, cycloserine, or hydrazine to prevent peripheral neuropathy




Vitamin B12 is a water-soluble vitamin that is essential for red blood cell formation and neurological function. Older adults and patients with reduced stomach acid levels, gastric bypass surgery, or intestinal disorders (celiac disease or Crohn’s disease) may not absorb vitamin B12 well and are at risk for deficiency . Also, women who follow strict vegetarian diets without supplementation place their breastfed infant at risk for vitaminB12 deficiency. Acid suppression medications (proton pump inhibitors or H2 receptor antagonists) and metformin reduce the absorption of vitaminB12vitamin B12 deficiency will lead to megaloblastic anemia, fatigue, loss of appetite, and neurological changes (numbness and tingling in hands and feet). NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Deficiency will lead to megaloblastic anemia

PROTON PUMB INHIBITORS causes Risk for significant nutrient deficiencies: iron, vitamin B12, and calcium.

Antacid therapy or potassium therapy can reduce absorption of folic acid, iron, and vitamin B12.

Pregnant women need 600 mcg/day of folic acid, a multivitamin/mineral supplement, 27 mg/day of iron (60 mg/day if patient is anemic), and vitamin B12 if the patient is vegan or lacto-ovo-vegetarian.

Older adults over age 50 need 2.4 mcg/day of vitamin B12 and need to ensure adequate intake of vitamin D and calcium.



Folate is a water-soluble vitamin that is critical to the production and maintenance of new cells. Folate is found in foods such as green leafy vegetables, citrus fruits, and dried legumes. Folic acid, the synthetic form of folate, is added to breads, flours, pastas, rice, and other grain products (ODS, 2012a). Folate deficiency occurs in times of increased demand, such as occurs in pregnancy and lactation, or when loss increases (malabsorption, alcohol abuse, dialysis, liver disease). Medications may interfere with folate utilization, leading to deficit. Folic acid supplementation is recommended for all women of childbearing age (400 mcg/d), with extra given when a woman is pregnant (600 mcg/d) to prevent neural tube defects in the fetus . NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. Lactating women should take 500 mcg/day.


Antiepileptic drugs (phenytoin, primidone)









Oral contraceptives

Folate is necessary for the normal maturation and functioning of red blood cells. Folate deficiency produces a macrocytic-normochromic anemia. Patients with folic acid–deficiency anemia commonly complain of glossitis, stomatitis, nausea and anorexia, and diarrhea, and a systolic ejection murmur may be heard. Oral folic acid is well absorbed, and doses of 1 to 2 mg/day result in correction of the deficiency in 4 to 5 weeks. Hemoglobin (Hgb) levels begin to rise within the first week, and anemia is completely corrected in 1 to 2 months. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.



  • Critical to the production and maintenance of new cells
  • Found in foods such as green leafy vegetables, citrus fruits, and dried legumes
  • Folic acid is the synthetic form of folate.
  • Folate deficiency occurs during pregnancy and with increased losses.
  • Folic acid supplementation is recommended for

Childbearing age teens and women: 400 mcg/day

             Pregnant women: 600 mcg/day

            Lactating women: 500 mcg/day

Antacid therapy or potassium therapy can reduce absorption of folic acid, iron, and vitamin B12.Phenytoin reduces the level of folic acid.



Vitamin B1 (thiamine) is a water-soluble vitamin critical for many body functions and is widely available in fortified breads and cereals. Deficiency of thiamine can lead to beriberi or Wernicke’s encephalopathy. Alcoholic patients develop thiamine deficiency at 8 to 10 times the rate of the nonalcoholic population . Wernicke’s encephalopathy is a serious neurological illness in alcoholic patients and requires immediate high-dose levels of thiamine (500 mg IV TID for 2 days, then 500 mg/d IV or IM for 5 days). Patients should be given a daily 100 mg dose of oral thiamine until no longer considered at risk. Treatment for beriberi in children is IV thiamine 10 to 25 mg or 10 to 50 mg daily for 2 weeks, and in adults 50 mg IM/IV for several days or 5 to 30 mg/day for a month. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.



Vitamin B1 (thiamine)

Deficiency can lead to beriberi or Wernicke’s encephalopathy

Alcoholics at high risk

26.Symptoms of Folate and Vitamin B12 Deficiency.


vitamin B12 deficiency will lead to megaloblastic anemia, fatigue, loss of appetite, and neurological changes (numbness and tingling in hands and feet). Deficiency will lead to megaloblastic anemia

Folate is necessary for the normal maturation and functioning of red blood cells. Folate deficiency produces a macrocytic-normochromic anemia. Patients with folic acid–deficiency anemia commonly complain of glossitis, stomatitis, nausea and anorexia, and diarrhea, and a systolic ejection murmur may be heard. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. Oral folic acid is well absorbed, and doses of 1 to 2 mg/day result in correction of the deficiency in 4 to 5 weeks. Hemoglobin (Hgb) levels begin to rise within the first week, and anemia is completely corrected in 1 to 2 months.

27.Characterstics of each Anemia and treatment

ANEMIA: Decreased iron-carrying capacity of the blood

  • Iron deficiency anemia
    • Caused by poor intake or blood loss (acute or chronic)
    • Treated with iron replacement
  • Folic acid deficiency anemia
    • Seen in alcoholics, chronic malnutrition, fad diets, and diets low in vegetables
    • Drugs: dilantin, sulfamethoxazole/trimethoprim, oral contraceptives, methotrexate
  • Pernicious anemia
    • Vitamin B12 deficiency leads to macrocytic-normochromic anemia.
    • Vegetarians, vegans, genetic predisposition, autoimmune disease
  • GOAL:Restore hemoglobin (Hgb) and red blood count to normal levels to maintain oxygen-carrying capacity of blood.
  • Prevention
  • Adequate intake via iron-rich diet
  • Monitor in periods of rapid growth (infancy, adolescence, pregnancy).
  • Replacement in infants 1 mg/kg/day starting at 4 months (2 mg/kg/day in preterm infants)
  • Treatment
  • Iron replacement based on age
  • Divide dose in three doses per day.
  • Monitoring
  • Reticulocyte count 5 to 10 days after starting therapy
  • Hgb, hematocrit (Hct), ferritin at 4 weeks, then at 3 months and annually
  • Outcome evaluation
  • Return to normal Hgb, Hct, and ferritin levels
  • If Hgb, Hct, and ferritin do not return to normal levels the patient should be evaluated for a source of blood loss of other pathology.
  • Patient education NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  • Importance of prevention with adequate iron intake in diet
  • Administration
  • Empty stomach if tolerated
  • Three times per day is best
  • Constipation (may need a stool softener)
  • Risk groups
  • Infants fed goat’s milk or powdered milk formula
  • Vegetarians and vegans
  • Pregnancy increases daily requirement need.
  • Patients with sprue, Crohn’s disease, giardial infections, and short bowel syndrome
  • Patients taking drugs that affect folic acid absorption
  • Prevention
  • Adequate dietary intake
  • Folic acid supplementation in pregnancy
  • Drug therapy for deficiency
  • Oral folic acid 1 to 2 mg/day for 4 to 5 weeks
  • Hgb levels start to rise in a week
  • Women of childbearing age and pregnant women should consume 0.4 to 0.8 mg/day.
  • Monitoring
  • Follow Hgb/Hct in 4 weeks and then regularly
  • Education
  • Need for folic acid
  • Administration
  • Pernicious anemia is caused by inadequate vitamin B12.
  • Defective secretion of gastric intrinsic factor, which is necessary for vitamin B12 absorption
  • Vitamin B12 malabsorption occurs in 10% to 30% of adults over age 50 due to reduced pepsin activity and gastric acid secretion.
  • Prevention
  • Eat foods high vitamin B12, such as mollusks (e.g., clams), fortified breakfast cereals, liver, trout, salmon, milk, and eggs.
  • Drug therapy
  • Oral, intramuscular (IM), and intranasal vitamin B12 replacement
  • Nutritional deficit: 1,000 mcg/day of cobalamin is given until normal B12 levels
  • Pernicious anemia: vitamin B12 therapy 1,000 mcg IM daily for 1 week followed by 100 to 1,000 mcg IM weekly for a month
  • Parental, nasal, or oral therapy may be used once a patient’s B12 levels return to normal. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  • Parenteral: 1,000 mcg of vitamin B12 IM monthly
  • Nasal: 500 mcg of cyanocobalamin weekly
  • Oral: 1,000 mcg daily (least expensive)
  • Monitoring
  • Reticulocyte counts, Hgb and Hct, iron, folic acid, and vitamin B12 serum levels prior to treatment, at 5 to 7 days of therapy, then frequently until the Hgb and Hct are normal. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  • Monitor potassium levels.
  • Liver function tests every 2 to 4 weeks to monitor for hepatotoxicity
  • Patient education
  • Disease process and need for lifelong therapy
  • Vitamin B12 therapy regimen
  • Monitoring
  • Anemia of chronic disease
  • Occurs due to a disease process
  • Older adults
  • Patients with renal failure, osteomyelitis, tuberculosis, rheumatoid diseases, hepatitis, carcinoma, myeloma, lymphoma, and leukemia at risk

28.Powerpoint: Children with autism or attention deficit hyperactivity disorder may respond to omega-3 supplements.

Omega-3 fatty acids have received attention as a possible treatment for autism and attention deficit-hyperactivity disorder (ADHD). The theory is that either deficiency in omega-3 or an imbalance in the omega-3 to omega-6 fatty acid ratio is affecting neurocognitive development in children. It is clear that sufficient amounts of the essential fatty acids are crucial in central nervous development, with deficiency or imbalance found in multiple observational studies of children with neurocognitive issues . NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. This has led to the addition of DHA and ARA to commercial infant formulas (Enfamil LIPIL) to meet the need in the key developmental period of infancy.

In an extensive review of new and novel treatments for autism spectrum disorder, autistic children administered 1 g of omega-3 fatty acids daily demonstrated a 33% improvement on the AutismTreatment .

ensuring a diet that is rich in essential fatty acids throughout infancy and childhood is critical, with the trial of supplemental omega-3 fatty acids in children with autism or ADHD warranted.

Recommended amounts of omega-3 fatty acids can be ingested in the diet by eating fatty fish or by taking fish oil capsules. The American Heart Association (2014b) recommends two servings a week of fatty fish such as salmon, mackerel, herring, lake trout, sardines, and albacore tuna for heart health. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. The recommended amount of omega-3 fatty acid from fish per day is 500 mg/day if there is no history of coronary heart disease (CHD), 1 g per day if there is a documented history of CHD, and 2 to 4 g/day to lower triglycerides (American Heart Association, 2014; Covington, 2004; Lee, O’Keefe, Lavie, Marchioli, & Harris, 2008). It may take 2 to 3 weeks for the effects of omega-3 to be seen. The National Heart Lung and Blood Institute (NHLBI) guidelines for reducing cardiovascular risk in children and adolescents recommend increasing dietary fish intake to increase omega-3 fatty acid intake (NHLBI, 2012). The studies of omega-3 for the treatment of ADHD and autism used 500 mg to 1 g/day.


  1. Antacids and kidney stones .


carbonic anhydrase inhibitors may increase the risk of kidney stones.  Calcium supplements can also increase the incidence of kidney stones. In addition, there is concern that excess serum calcium deposits into soft, vascular plaque, which makes the plaque less able to regress in the face of statin therapy. These adverse issues should be tempered with the knowledge that taking calcium cuts overall mortality in women compared with women who do not take the supplements (Langsetmo et al, 2013). NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. 

Antacids consist of a metallic cation and basic ion (calcium carbonate, magnesium hydroxide, etc.), which neutralize acidity in the stomach by raising the pH. The basic property of these drugs causes them to interact with most medications, by either binding with the drug molecule or altering pH and thus the absorption of drugs that need an acidic environment for optimal absorption. Most interactions can be avoided by separating the dosing of antacids by at least 2 hours from the dosing of the other oral medications. Intraluminal interactions occur in the stomach when an antacid chelates another drug or adsorbs another drug onto its surface.

The best-known antacid interaction is with tetracycline. Aluminum hydroxide and magnesium hydroxide have a strong affinity for tetracycline and form an insoluble and inactive chelate. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. This interaction can reduce the bioavailability of tetracycline by 90% and result in clinical failures. This chelation occurs with all other forms of tetracycline, including doxycycline and minocycline. Patients should not take any antacid until at least 2 hours after tetracycline administration. A similar interaction exists with the quinolone antibiotics, such as ciprofloxacin and ofloxacin. Antacids are discussed in 

Topiramate othe  medicine that can cause kidney stones



  • GERD is a common problem in primary care and is listed as the primary diagnosis for 6,859,000 ambulatory care visits annually, a rate of 2,332 per 100,000.
  • Pathophysiology
    • Lower esophageal sphincter tone
    • Gastric content regurgitation into the esophagus
    • Complaints of burning substernal pain that radiates upward
    • Persistent acid reflux that occurs more than twice a week is considered GERD.

                            DRUGS USED FOR GERD

               Histamine(H2) receptor antagonists

  • Proton pump inhibitors (PPIs)
  • Antacids
  • Prokinetics
  • Dyspepsia or mild GERD
  • Antacids and lifestyle modification
  • H2 receptor agonists for 4 to 8 weeks
  • If better, continue for 12 weeks then wean off.
  • Moderate to severe GERD
  • PPIs for 8 weeks
  • If better, wean off PPIs.
  • If symptoms not improved, refer.
  • Moderate to severe GERD (cont’d)
  • Symptoms not relieved: Increase PPI to twice daily for 4 to 8 weeks.
  • If symptom free for 4 weeks, step down to once a day PPI and reassess in 6 to 12 months.
  • If symptoms not relieved after 8 weeks, refer.


Drugs to Improve Lower Esophageal Sphincter Tone

Metoclopramide and bethanechol improve LES tone and have a prokinetic function but are not considered for monotherapy in the treatment of GERD. They are most useful in combination with acid suppression for patients with gastroparesis. Metoclopramide and bethanechol have not demonstrated significant healing of esophageal lesions. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Antacids also serve a dual purpose: they improve LES tone and increase gastric pH. They are usually patient-initiated drug therapy, along with lifestyle modifications.

Drugs to Reduce the Amount of Acid

Two main classes of drugs are used to reduce acid secretion: histamine2 receptor antagonists (H2RAs) and PPIs. H2RAs act on the parietal cells to decrease the amount of acid produced. Because most of these drugs are available OTC, many patients may have used these drugs as self-initiated therapy before seeking care. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. Providers need to determine self-medication for GERD in the initial history. H2RAs may be used as maintenance acid suppression or heartburn therapy in patients who do not have erosive GERD (Katz et al, 2013). The ACG guidelines recommend a trial of nighttime H2RAs for patients taking daytime PPIs to treat nighttime reflux (Katz et al, 2013).

Figure 34–1. Sites of action of drugs used to treat GERD and PUD (textbook).

PPIs are standard first-line therapy for GERD and decrease acid secretion by almost 100%. PPIs improve esophageal healing to about 80%.

Drugs to Improve Peristalsis

A few patients continue to report symptoms despite reduced acid secretion. These patients may benefit from prokinetics, which improve both LES tone and peristalsis. Metoclopramide may provide some benefit but has limited usefulness because of adverse drug reactions.

Drugs to Decrease Mucosal Exposure

Two cytoprotective agents are available to decrease the exposure of the gastric mucosa to acid: sucralfate (Carafate) and misoprostol (Cytotec). Sucralfate acts largely as a Band-Aid to cover sites having erosive damage but is more often used with ulcers. Misoprostol acts by increasing the production of cytoprotective mucus. Older adults or those taking multiple drugs may benefit from sucralfate. Misoprostol is reserved largely for use when NSAIDs are a contributing factor to the increased acid load. These drugs are not mentioned in GERD guidelines, although discontinuance of NSAIDs is mentioned.

The pharmacokinetics and pharmacodynamics of each of the categories of drugs are discussed in more detail in .

Goals of Treatment

Therapy for patients with GERD has four goals: (1) reduce or eliminate the symptoms; (2) heal any esophageal lesions; (3) manage or prevent complications such as stricture, Barrett’s esophagus, or esophageal carcinoma; and (4) prevent relapse. Meeting these goals requires a combination of lifestyle modification and drug therapy. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Rational Drug Selection


For most patients, GERD is treated with PPI therapy.  presents an algorithm for GERD treatment.

Lifestyle Modifications

Antireflux maneuvers, dietary changes, and cessation of smoking are central to the management of GERD regardless of the step. Antireflux maneuvers reduce back pressure on the LES from intra-abdominal contents. Dietary changes reduce the total volume and acid content of the stomach. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. Smoking reduces LES tone and increases gastric acid secretion.  lists appropriate lifestyle modifications.

Drug Therapy

Lifestyle modifications and OTC antacids are a logical first step for treatment of heartburn, dyspepsia, or mild nonerosive GERD. Most patients have tried an OTC antacid before they seek health care. This step alone may be sufficient. H2RAs may be sufficient if symptoms are mild and no erosive disease is evident. Tachyphylaxis may occur with H2RAs.

PPIs are first-line therapy for patients with moderate or severe GERD or erosive disease. PPI therapy continues for 8 weeks and 70% to 80% of patients should have complete relief with PPIs (Katz et al, 2013). NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. There are no major differences in response between the PPIs (Katz et al, 2013). Maintenance PPI therapy should be prescribed for patients who have symptoms that recur after PPI therapy is discontinued or patients with complications such as erosive esophagitis or Barrett’s esophagitis (Katz, et al). The patient should be reassessed in 6 to 12 months to determine if he or she can be weaned off therapy. Patients who do not respond to PPIs need to be referred to a gastroenterology specialist.


Drug 1 Drug 2 Drug 3 Drug 4 Comments
Triple therapy Proton pump inhibitor bid Clarithromycin 500 mg bid or metronidazole 500 mg bid Amoxicillin 1 g bid Treat for 10–14 dUsual first-line therapy
Triple therapy Proton pump inhibitor bid Clarithromycin 500 mg bid Metronidazole 500 mg bid Treat for 7–14 dUse as first-line therapy in penicillin-allergic patients
Quadruple therapy Proton pump inhibitor bid orRanitidine 150 mg bid Metronidazole 250 mg qid Tetracycline 500 mg qid Bismuth subsalicylate 525 mg qid Treat for 10–14 dUsually used as second-line therapy in patients who fail first-line therapy
Levofloxacin-based triple therapy Proton pump inhibitor bid Levofloxacin 250–500 mg bid Amoxicillin 1 gm bid Treat for 10–14 dSecond-line or rescue therapy

Drug Treatment Protocols for Helicobacter pylori Eradication

*Children <8 yr should not take tetracycline. Other treatment regimens with dosage adjustments for children are acceptable. Some come with drugs grouped in packets.

Proton pump inhibitors include esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, rabeprazole 20 mg.

Source: Crowe, 2013b; Lew, 2009. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Duodenal and gastric ulcers recur in up to 80% of patients treated with drugs to reduce gastric acid but not treated for eradication of H. pyloriinfection. By comparison, 6% to 15% of patients have recurrent ulcers when their H. pylori infection is cured.

Maintenance therapy with an antisecretory agent is not generally required after eradication of H. pylori. However, it is prudent to prescribe maintenance therapy for certain high-risk groups: smokers; patients older than 60 years; patients with chronic obstructive pulmonary disease, coronary artery disease, or renal failure; patients with a history of bleeding or perforated ulcer; patients with persistent symptoms; and those who must take NSAIDs or other ulcerogenic drugs.

Patients with gastric or duodenal ulcers who fail to become symptom-free or who develop complications such as GI bleeding while on antisecretory therapy require a referral to a gastroenterologist. Surgery is contemplated for gastric ulcer patients.

Lifestyle Modifications

Evidence is lacking that dietary modifications affect the course of PUD. Frequent small meals and decreased consumption of spices, alcohol, caffeine, and fruit juices have never been demonstrated to affect healing. Dietary changes should be directed at those substances that cause symptoms in each particular patient. An important lifestyle modification is smoking cessation. Smoking both increases the risk for gastric and duodenal ulcers and delays their healing (Soll & Vakil, 2012).

Aspirin and NSAIDs are known to be ulcerogenic. Their use should be discouraged and a high index of suspicion for NSAID and aspirin use is required because patients do not always report OTC use (Soll & Vakil, 2012).

Drug Therapy

Currently, the FDA approves eight treatment regimens; however, several other combinations have been used successfully. Regimens include triple or quadruple drug therapy with a variety of drugs. The treatment regimens that have the highest rate of success in eradication, the best likelihood of adherence related to number of drugs taken, and adverse effects are presented in Table 34-6. All include a twice-daily dose of a PPI. The most popular antibiotics are clarithromycin (Biaxin) and amoxicillin. Because all these drugs can be taken twice daily, the regimen is simple and has a limited number of drugs.

Selection among the protocols is based on cost, convenience, ability to tolerate the adverse drug reactions of the total regimen, antimicrobial resistance, patient variables, and eradication rates. For each patient, assess the likelihood of adherence and use the most cost-effective but simplest drug regimen that will get the job done.

Adverse Drug Reactions for the Total Regimen

Adverse drug reactions have been reported in up to 70% of patients taking bismuth-based four-drug regimens. Metronidazole-based regimens have increased adverse reactions. Overall, the best regimen for tolerability appears to be a PPI-based three-drug regimen. Happily, these regimens also are highly efficacious.

Antimicrobial Resistance

Concern about antimicrobial resistance has increased, regardless of the disease process for which these drugs are being used.  discusses resistance to the various antimicrobials. Resistance associated with H. pylori eradication has been linked to the length and complexity of the treatment regimen and the tolerability of adverse reactions. Resistance to metronidazole is most common and higher in women (Crowe, 2013b). Resistance to clarithromycin is low (10%), as is resistance to amoxicillin and tetracycline. Acquired resistance occurs in up to two-thirds of treatment failures. Changing drugs and trying a different treatment regimen may be useful in these instances. First- and second-line therapy options are presented in .

Patient Variables

Several patient variables need to be considered. Patients with allergies to any of the drugs in a treatment regimen require a different regimen. Women of childbearing age should use a regimen that does not include tetracycline because of the risk for fetal harm. The same is true for children younger than 8 years because of problems related to discoloration of teeth. Each of the drugs in these regimens has potential drug interactions. Other drugs the patient may be taking must be taken into account.

Given all these parameters, the treatment regimen with good to excellent eradication rates, a low to medium adverse reactions profile, likelihood of adherence based on complexity of the regimen and moderate cost, and limited antimicrobial resistance appears to be clarithromycin plus amoxicillin plus a PPI, all taken twice a day for 10 to 14 days.


Monitoring parameters for each of the drugs in these treatment regimens are presented in  and . Documentation of ulcer healing by endoscopy 12 weeks after the end of therapy is the gold standard. Cost considerations suggest reserving it for patients who are at high risk for complications, patients with recurrence, and those who will be on long-term therapy. The urea breath test or stool antigen testing can be used to screen symptomatic patients who are suspected of having recurrent ulcers associated with H. pylori infection. Note that serological testing for H. pylori may be falsely negative if the patient is on PPIs or recently on antibiotics. Documentation by endoscopy is optional for low-risk patients.

Outcome Evaluation

 shows the treatment algorithm for PUD. Outcome evaluation targets eradication of H. pylori and relief of symptoms. Evaluation also includes the other goals for therapy: healing of lesions, prevention of complications, and prevention of relapse. Relapse rates are high for patients with PUD but can be significantly reduced with appropriate maintenance therapy or eradication of H. pylori infection.

Patients with PUD who remain symptom-free without drugs or on maintenance therapy require no more frequent follow-up than their annual physical examination.

  1. Anti- diarrheal -PEPTO BISMOL

ACTION: Bismuth subsalicylate: antisecretory and antimicrobial effects

Bismuth subsalicylate dissociates into salicylate that is absorbed (similar to aspirin), metabolized in the liver, and excreted in the urine with the bismuth that is not absorbed NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide

Bismuth subsalicylate appears to have antisecretory and antimicrobial effects in vitro and may have some anti-inflammatory effects. The salicylate moiety provides the antisecretory effect, and the bismuth moiety may exert direct antimicrobial effects against bacterial and viral enteropathogens. Because of these effects, it is also used as part of a multidrug regimen for the eradication of H. pylori.

  • EDUCATE about Bismuth turning tongue and stool black

CONTRAINDICATION Bismuth subsalicylate is contraindicated in children with viral or flu-like illness.

Avoid bismuth subsalicylate in pediatric patients with influenza or chicken pox because of the risk of Reye syndrome.

  • Acute diarrhea
    • Treat the source of diarrhea.
    • Absorbents (kaolin-pectin or bismuth subsalicylate) used after each loose stool
    • Maintain hydration.
      • Electrolyte solution in infants and young children
      • Flat soda or water in adults
    • Opioids dosed 3 or 4 times/day or after each stool
  • Chronic infantile diarrhea
    • Bismuth subsalicylate
  • Traveler’s diarrhea
  • Bismuth subsalicylate and loperamide are used for traveler’s diarrhea

Bismuth subsalicylate with each meal and at bedtime to prevent traveler’s diarrhea

If diarrhea develops

  • Bismuth subsalicylate every 30 minutes (maximum 8 doses) for up to 48 hours
  • Loperamide 4 mg then 2 mg after every stool (maximum 8 mg/day)

3.FOR PUD Bismuth subsalicylate: 525 mg four times/day. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. 


Bismuth subsalicylate undergoes chemical dissociation in the GI tract; the salicylate moiety is absorbed, with plasma levels similar to those of aspirin. There is only negligible absorption of the bismuth moiety.

The salicylate portion of bismuth subsalicylate is metabolized in the liver and more than 90% is excreted in urine.

The salicylate component of bismuth subsalicylate contraindicates its use in children or teenagers during or after recovery from chickenpox or flu-like illness. It is also contraindicated for patients with aspirin hypersensitivity. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

All antidiarrheals (except crofelemer) require cautious use in older adults and others in whom impaction is a high risk. Older adults are especially sensitive to diphenoxylate or difenoxin because of the atropine content and anticholinergic properties.

There are no contraindications for the use of crofelemer in patients with HIV/AIDS–associated diarrhea.

Pregnancy categories vary among the antidiarrheal drugs. Kaolin and pectin are Pregnancy Category B. All others are Pregnancy Category C except loperamide, which is Pregnancy Category B. Crofelemer is Pregnancy Category C. However, there are no adequate and well-controlled studies in pregnant women for any of these drugs, and safety during pregnancy has not been established. Some of the drugs are excreted in breast milk, and the safety of any of the antidiarrheals has not been established in lactating women. They should be avoided or used with caution.

None of the antidiarrheals has established safety for children younger than age 2 years. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. All except crofelemer have published children’s doses. It is important to keep in mind that dehydration may influence younger children’s response to these drugs. Antidiarrheals are contraindicated in the treatment of diarrhea in most children; the standard of care is oral rehydration therapy (ORT) to treat the electrolyte and fluid loss of diarrhea. The safety and effectiveness of crofelemer in children with or without HIV/AIDS have not been established.

Adverse Drug Reactions

The main adverse drug reaction for all traditional antidiarrheals is rebound constipation. For bismuth subsalicylate, additional reactions that all patients should be warned about are gray/black stools and black tongue, the results of the bismuth. Patients should be told to expect this reaction and that it does not indicate GI bleeding.

Drug Interactions

Bismuth subsalicylate may potentiate the risk for toxicity if taken with aspirin, and the risk for hypoglycemia if given in large doses with insulin or oral hypoglycemic

Avoid bismuth subsalicylate in pediatric patients with influenza or chicken pox because of the risk of Reye syndrome.


Patients concurrently taking aspirin and bismuth subsalicylate are at risk for salicylate poisoning.

Clinical Use and Dosing

Simple, Acute Diarrhea

After the cause of the diarrhea has been determined and, if possible, eliminated, absorbent preparations are commonly used for relief of symptoms in adults. Kaolin-pectin or bismuth subsalicylate taken after each loose stool may be effective.

Drug Interacting Drug Possible Effect Implications
Bismuth subsalicylate Aspirin May potentiate salicylate toxicity Avoid concurrent use
Tetracycline May decrease GL absorption Separate administration by 2 h
Thrombolytics, warfarin, heparin Large doses may increase risk for bleeding Avoid concurrent use or use small doses; monitor clotting studies closely
Insulin, oral hypoglycemics Large doses increase risk of hypoglycemia Avoid concurrent use or use small doses

Dosage Schedule: Selected Antidiarrheals

Drug Indication Dosage Form Initial Dose Additional Doses
Bismuth subsalicylatePepto-Bismol


Acute diarrhea Tablets/chewable: 262 mgLiquid: 262 mg/15 mL

Liquid: 524 mg/15 mL

Adults: 524 mg every 30 min or 1,048–1,200 mg every 60 min as neededChildren 9–12 yr: 262– 300 mg every 30–60 min as needed

Children 6–9 yr: 176 mg every 30–60 min as needed

Children 3–6 yr: 88 mg every 30–60 min as needed

Children <3 yr weighing >13 kg: 88 mg

Children <3 yr weighing 6.4–8 kg: 44 mg

May repeat q4h; not to exceed 6 doses/24 h

Not to exceed 4.2 g/24 hNot to exceed 2.4 g/24 h

Not to exceed 1.4 g/24 h

Not to exceed 704 mg/24 h

May repeat q4h; not to exceed 6 doses/24 h

NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide

Chronic Infantile Diarrhea

Bismuth subsalicylate has been used to treat chronic infantile diarrhea. The dose is 2.5 mL every 4 hours for children 2 to 24 months; 5 mL for children 24 to 48 months; and 10 mL for children 48 to 70 months (Taketomo, Hodding, & Kraus, 2009). NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


Traveler’s Diarrhea

Bismuth subsalicylate appears to have antibacterial and antisecretory properties and is used to treat traveler’s diarrhea in doses of two tablets or 2 fluid oz before each meal and at bedtime (4 times/d) for up to 3 weeks during brief periods of high risk (Centers for Disease Control and Prevention [CDC], 2014). NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. The management of traveler’s diarrhea can be divided into prevention and treatment. The most important risk factor for acquiring this disorder is the patient’s destination. High-risk areas include Central and South America, Africa, the Middle East, Mexico, and Asia. Intermittent-risk areas include Eastern Europe, South Africa, and a number of the Caribbean islands. Enterotoxigenic E. coli is the most common causative organism found in traveler’s diarrhea, followed by Campylobacter, Shigella, and Salmonella. Oral antimicrobials are also used for both prevention and treatment of this disorder; the provider should refer to the CDC Travel Web site () for current antimicrobial recommendations.  provides adults’ and children’s doses of selected antidiarrheals. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Rational Drug Selection


For acute diarrhea, any of the antidiarrheals is appropriate. The more severe the diarrhea is, the less likely it will be that absorbent agents will help. Bismuth subsalicylate and loperamide are the only drugs indicated for traveler’s diarrhea. Loperamide is the only drug with an indication for use with inflammatory bowel disease.

Adverse Reactions

All antidiarrheals have the potential for rebound constipation. As soon as symptoms of diarrhea are reduced, the dosage of the antidiarrheal drug should be reduced; it should be stopped as soon as symptoms resolve.

Bismuth subsalicylate can turn the tongue and stools gray/black. Patients should be told that this reaction can be expected and that it does not indicate GI bleeding. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

32.Long term use of PPI

There is evidence for significant nutrient deficiencies in patients taking PPIs long-term. Iron, vitamin B12, and calcium all need an acid environment for optimal absorption.

The PPIs are so effective in reducing acid production that patients are at risk for iron deficiency anemia, vitamin B12 deficiency, and calcium deficiency (Ali et al, 2009; Lodato et al, 2010). Patients on long-term PPIs may be at risk for osteoporosis and increased hip fractures, especially when combined with other risk factors for fracture such as age and female gender

Stomach acid provides a natural defense against microbial pathogens. Patients on long-term PPI therapy have an increased risk of Clostridium difficile, salmonella, and camphylobacter infections (Ali et al, 2009). Short-term use of PPIs increases the risk of pneumonia.

There are cellular level changes that occur with long-term PPI therapy, including hyperplasia of enterochromaffin-like cells, leading to a concern about the development of gastric cancers (Ali et al, 2009; Lodato et al, 2010; Vandenplas et al, 2009). Atrophic gastritis has been noted in patients taking omeprazole long-term, and chronic atrophic gastritis is a risk factor for developing gastric carcinoid tumors (Lodato et al, 2010). In spite ofthese cellular changes, at this time there is not strong evidence for the development of gastric cancers from long-term PPI use (). NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


Pre-, Pro-, and Symbiotics(POWERPOINT)

  • Probiotics are nonpathogenic bacteria normally found in the intestinal microflora.
    • Most common: Lactobacillus acidophilus and the Bifidobacterium species
    • Cochrane Review of probiotic use in rotavirus-associated acute diarrhea in children found it reduced diarrhea severity and duration by 1 to 3 days.
    • Reduced antibiotic-associated diarrhea
    • May improve inflammatory bowel disease and necrotizing enterocolitis


Probiotics are nonpathogenic bacteria normally found in the intestinal microflora, the most common of which are Lactobacillus acidophilus and the Bifidobacterium species. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. Prebiotics are nondigestible food ingredients that stimulate growth of probiotic organisms, and symbiotics are a mixture of probiotics and prebiotics. Probiotics are used to restore the normal balance of gut flora that is disturbed with antibiotics, immunosuppressive medications, and other conditions (Weichert et al, 2012; Williams, 2010).

Probiotics have been used for many years and have been studied extensively for their health benefits and their effects on diarrhea. A Cochrane Review of the use of probiotics in rotavirus-associated acute diarrhea in children found probiotics reduced diarrhea severity and duration by 1 to 3 days (Allen, Okoko, Martinez, Gregorio, & Dans, 2004). Probiotics also reduce antibiotic-associated diarrhea in adults (D’Souza, Rajkumar, Cooke, & Bulpitt, 2002; Safdar, Barigala, Said, & McKinley, 2008; Tong, Ran, Shen, Zhang, & Xiao, 2006) and in children (Johnston, Supina, Ospina, & Vohra, 2007). It is reasonable to prescribe probiotics for patients with infectious or antibiotic-associated diarrhea. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Probiotics may also improve inflammatory bowel disorders and necrotizing enterocolitis (NEC). Premature infants have sterile guts when they are born and are at risk for bowel problems, including NEC. Multiple studies and reviews have found probiotics beneficial in preventing NEC and death in preterm infants (AlFaleh & Bassler, 2008; Bosante, Iacobelli, & Gouyon, 2013; Deshpande, Rao, Patole, & Bulsara, 2010; Fernández-Carrocera et al, 2013; Lin et al, 2008). Probiotics improved colic symptoms in a multicenter, double-blind, placebo-controlled trial of infants started on probiotics soon after birth (Indrio et al, 2014). Use of probiotics improved Symptom Severity Scores in patients with irritable bowel syndrome (Williams et al, 2008). Probiotics have also been found to improve eradication rates in patients being treated for Helicobacter pylori (Tong et al, 2006).



OTC MEDICATION(in class she told Know what your patients take ,Dextromethorphan abuse has got alchol in it ,pseudoephenephrin has got methamphetamine can increase heart rate.)

  • 42% of adults take an OTC medication.
  • 49% report dietary supplement use.
  • Assume all patients have tried an OTC treatment.
  • OTC drugs are approved and labeled by the FDA.
  • OTC must go through the New Drug Application process just as prescription drugs.

There are 80 therapeutic categories of OTC drugs

Otc medication sale

  • Cough and cold medications: $4 billion
  • OTC analgesics: $3.99 billion
  • Heartburn: $2.28 billion
  • Laxatives: $1.3 billion
  • Acne: $617 million
  • Diarrhea: $225 million
  • Nicotine replacement: $855 million


 An OTC drug has the following characteristics:

  1. It must be safe.
  2. It has low potential for misuse or abuse.
  3. It can be labeled.
  4. The patient must be able to self-diagnose the condition.
  5. The condition must be able to be managed by the patient.


  • The patient must accurately diagnose and appropriately treat
  • Concerns

Treating serious illness that worsens due to lack of appropriate treatment

Example: treating bacterial pneumonia with OTC cough medication

Adverse effects of medications

Drug interactions

Herbal supplementation and regulations


35.BETA BLOCKERS Refer pharm in a flash also (refer text book lots of info)

  • Stage II HF : SBP greater than or equal to 160/DBP greater than or equal to 100
    • Two-drug combination: thiazide-type and ACEI, ARB, beta blocker (BB), or CCB
  • Class II: beta blockers
    • Reduce adrenergic activity in the heart
II. Beta blockers ANTIARRYTHMIC Propranolol, metoprolol, sotalolol, and others
  • Sotalol: considered a class II and III drug
  • Beta adregenic blockers :Various types include nonspecific beta antagonists, selective beta-antagonists, and those with and without intrinsic sympathomimetic activity (ISA)
    • In post-MI patients, cardioselective agents are preferred without ISA.
    • Some are used as antiarrhythmics. Used for angina
    • Drugs with ISA may help avoid a decrease in CO and HR. May be preferred for patients who experience bradycardia with other beta blockers.
  • More effective in African-American and older patients
  • BB USED FOR STAGE B and STAGE C Heart failure
  • BB AVOIDED FOR Diabetic patients
  • Changes definitions of control for elders to allow higher values to avoid orthostatic falls and increase adherence
  • Beta blockers no longer first-line drugs
  • Pregnancy may have increased risks to mother and fetus.
  • Methyldopa, beta blockers, and vasodilators are drugs of choice.
  • African Americans have a higher and earlier HTN incidence.
  • Reduced response to monotherapy, beta blockers, ACEIs, and ARBs
  • Equal response if mixed with diuretic
  • BiDil is the first drug suggested for African-American patients specifically.
  • BBs may NOT be abruptly withdrawn, increases beta receptor sensitivity

No longer first-line HTN drug choice

  • ACTION WHEN USED FOR ANGINA :Beta blockers (BBs) decrease the force of myocardial contractility and decrease heart rate and conduction velocity.
  • BBs decrease systemic vascular resistance and BP (afterload).
  • Decreased myocardial oxygen demand = decreased anginal pain



  • Pharmacodynamics
    • Inhibition of angiotensin-converting enzyme (ACE) activity results in decreased production of both angiotensin II (AT II) and aldosterone.
    • Can lower vascular resistance without decreasing cardiac output (CO) or glomerular filtration rate (GFR).
    • Does not produce reflex tachycardia.
  • Strong evidence for CV and cerebrovascular risk reduction, HF, and slowing renal disease
    • Improves oxygenation to heart muscle, decreases inappropriate remodeling of heart muscle after myocardial infarction (MI) or with heart failure, reduces affects of diabetes on the kidneys. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  • Improves insulin sensitivity, does not affect glucose metabolism or raise serum lipid levels


  • Use with
    • Young Caucasian patients
    • Patients with angina: prevents formation of AT II and decreases pulmonary vascular resistance by decreasing retention of sodium and water and reducing extracellular fluid and preload
    • Diabetic patients: prevents or slows nephropathy
    • HF patients
  • Not as effective for African-American patients
    • When combined with a diuretic, race no longer an issue

However, African Americans and Asians have three to four times greater risk of developing angioedema

  • Adverse drug reactions (ADRs): dry cough (bradykinin- mediated), hypotension, loss of taste, angioedema, blood dyscrasias, teratogenicity, hyperkalemia, acute renal failure, cholestatic jaundice, pancreatitis, rash
  • Monitoring
    • Possible orthostasis within 1 hour of dose when starting and with each dosage change
  • Patient education
    • Do not double dose if one is missed.
    • Hypotension most common ADR
    • Cough common with older agents


  Angitensin receptor blockers (refer pharm in a flash)

  • Prevent binding of AT II to receptors in kidney, brain, heart, and arterial walls
  • Inhibit the renin-angiotensin-aldosterone system (RAAS) and cause fall in peripheral resistance
  • Evidence supports use in kidney disease until late stage and heart failure, but not renal protective like ACEI
  • No bradykinin-mediated cough like ACEI. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  • Angiotensin II receptor blockers (ARBs) are considered in ACEI-intolerant patients, but more expensive.
    • Avoid ACEIs, ARBs, and direct renin inhibitors in pregnancy and sextually active woman .
  • If you hear an abdominal bruit in a patient known to have vascular disease, give captopril, a short-acting ACEI, and measure serum creatinine prior to the dose and within 1 or 2 days after the dose. A rapid rise in the creatinine level suggests renal artery stenosis. A slower rise probably indicates a problem with poor hydration that can be corrected by rehydrating the patient and discontinuing or lowering the dose of any diureticsthe patient is taking. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  • Cost of generic ACE inhibitors provides significant advantage over branded ARBs (generics now available for some).
  • Considered alternatives for patients who cannot tolerate ACE or become resistant
  • Many combined with hydrochlorothiazide (HCTZ)


When patients receiving digoxin, a cardiac glycoside used to slow and strengthen the heart, have clinical signs of toxicity and high blood levels, they can be given antibody fragments to digoxin (Digibind). The antibody fragments remain in the central circulation and bind to digoxin in the bloodstream, essentially pulling digoxin back into the bloodstream from its sites of action throughout the body. But since digoxin is binding to its antibody in the bloodstream, the blood concentration of digoxin rises even though there is much less free digoxin to produce pharmacological effects and toxicity. This illustrates how plasma protein binding holds drugs in the circulation and prevents their distribution to other sites in the body. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Verapamil, diltiazem, and some dihydropyridines have an additive bradycardic effect with BBs or digoxin. Serum digoxin levels may be increased with risk of toxicity when it is concurrently used with verapamil, diltiazem, or nifedipine.

All ARBs Antacids Decreased absorption of ACEI; increased risk for digoxin or lithium toxicitY Avoid use or separate doses by at least 1 h.



Toxicity typically occurs with serum levels greater than 2 ng/mL. Toxicity is commonly caused by excessive administration of a CG, too much diuresis resulting in hypokalemia, concurrent development of renal insufficiency, or by administration of drugs that interfere with excretion of digoxin (see the section “Drug Interactions”). This is especially common in older adults who have polypharmacy changes. Each of these common etiologies and the patient’s calcium and magnesium levels should be considered in the differential diagnosis.

Diagnosis of toxicity is based on both clinical and laboratory data. Serum levels alone are insufficient to diagnose toxicity. Patient tolerance plus cardiac output and vital sign outcomes are important considerations to determine if individuals actually need levels above or below common ranges. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. Providers are cautioned that a faster heart rate in a patient previously controlled on a CG may be a sign of toxicity, not the need for increasing the dose! Incorrect timing of lab draws can be a factor (see the Monitoring section for times to draw serum levels). Toxicity is an important differential diagnosis of arrhythmias and neurological and GI symptoms for patients taking CGs.


A full neutralizing dose of Digibind is expensive (up to 20 vials at $750 per vial). This cost should be considered in deciding to treat patients with suspected or non–life-threatening toxicity. It should also be remembered that Digibind has a half-life of 2 to 6 hours, and during that time the rhythm disturbance for which the CG was given may recur and cannot be treated with a CG.

Treatment of toxicity depends on the problem. AV junctional and first-degree block rhythms, ventricular ectopic beats, or an excessively slow ventricular response to atrial fibrillation often requires CG dosage adjustment and careful monitoring. Potassium administration should be considered to reduce automaticity, even when serum potassium is in the normal range, unless a high-grade AV block is also present. Lidocaine has minimum effects on the AV node and may be used to treat ventricular ectopic beats that threaten hemodynamics. Bradycardia and second- or third-degree AV block usually respond to atropine. When toxicity is severe or life-threatening, the antidote for CG toxicity is antidigoxin immunotherapy, digoxinimmune fab (Digibind). Patients who require this medication are hospitalized so that cardiopulmonary resuscitation equipment and medications are available when it is administered. A short holding of the next dose or two may be sufficient to return to normal values without using Digibind. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Any patient who becomes toxic on a CG should have the indications for that drug carefully reviewed. In some cases, it is possible to stop the drug altogether. There is new recognition that women fare worse on CG, so as a group they should be evaluated for treatment with other meds. Several studies, however, have shown negative consequences for withdrawal of digoxin, so the decision should be carefully made in consultation with cardiology.


38. Furosemide

Loop diuretics: potential for cross-sensitivity with sulfa

Example:Furosemide, bumetanide, torsemide

hyperuricemia from furosemide

Donepezil does not interact with furosemide, digoxin, and warfarin, drugs often prescribed for older adults who are also likely candidates for donepezil.

The liver is the primary site of metabolism for most diuretics. Furosemide (Lasix) has nonhepatic and hepatic metabolism. Amiloride is not metabolized by the liver. All diuretics are excreted mostly unchanged in the urine. Metolazone, amiloride, bumetanide (Bumex), and spironolactone have some excretion in feces and bile. Plasma half-lives vary from 30 to 60 minutes for furosemide to 35 to 50 hours for chlorthalidone. Impaired renal or hepatic function increases the half-life of furosemide.

Hydantoins Reduces diuretic effect of furosemide Monitor diuretic effect and adjust dose prn
Cimetidine, furosemide Increases plasma levels of metformin without concurrent increase in renal excretion Dosage adjustments of metformin may be needed


Furosemide (Lasix) (G) Refractory edema of CHF, hepatic and renal disease Solution: 40 mg/5 mL; 10 mg/mLTablets: 20, 40, 80 mg 20–80 mg daily or 2 doses daily Titrate in increments of 20–40 mg q6–8h until desired diuresis; give 2 doses daily 8 a.m. and 2 p.m.Max: 600 mg/d in divided doses
HTN 40 mg 2 doses daily Titrate up or down to controlHTN
Edema in infants and children Children: 2 mg/kg/d Titrate in increments of 1 mg/kg q6–8h until desired diuresisMax: 6 mg/kg/d


For mild to moderate disease, start therapy with furosemide 40 mg twice daily. Loop diuretics can cause marked diuresis. Before starting them, discontinue any thiazide diuretic currently being used. For loop diuretics, divide the daily dose to prevent great diuresis at one time. If the patient does not respond adequately to the divided dose, try giving the entire daily dose in the morning before increasing the dose. The goal with diuretics is to give the lowest possible dose that achieves the desired effect. Doses should be titrated to increased urine output and promote weight loss of 0.5 to 1 kg daily. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. Single daily doses are effective, but during times of increased pathology, oral absorption may be compromised, and the IV route or high doses of oral formulations may be needed. Dosing schedules are given in . Monitor weight gain, changes in exercise tolerance, and electrolytes. Diuretic resistance may occur in the presence of decreased renal perfusion or renal stenotic or obstructive pathologies, or with the concurrent administration of NSAIDs. If symptoms seem resistant to the standard doses of the diuretic, check creatinine clearance. Thiazide diuretics cannot be used with creatinine clearances that are lower than 25 mL/min. Loop diuretics can be used with these low creatinine clearances. Patients may also benefit from the addition of metolazone (Zaroxolyn) for its synergistic action on diuresis, but it is not recommended for chronic daily use because of potential for severe electrolyte shifts.

Although initiation of diuretic therapy is important for patients who have HF with volume overload, it is also important to avoid excessive diuresis, especially for patients who are also on sodium restrictions. Volume depletion can lead to hypotension and prerenal azotemia. For patients concurrently taking ACE inhibitors, renal insufficiency can be induced. Diuretics may be stopped, if necessary, to allow rehydration before restarting an ACE inhibitor. They can be reintroduced after the dose of the ACE inhibitor has been stabilized. ACE inhibitors augment the effectiveness of thiazide and loop diuretics because they decrease glomerular filtration fractions and increase the delivery of solute and water to the distal nephron segments that are responsive to the action of these diuretics.

Long-term use of diuretics can stimulate increased R-A-A activity and sodium retention, which are both counterproductive in treating heart failure. This result is less likely with low doses. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. In addition to the potential for fluid volume changes, thiazide and loop diuretics present risks for acid–base and electrolyte disturbances that can be proarrhythmic. Monitoring for these problems is discussed in .

The most common electrolyte problem is hypokalemia. Any potassium supplementation must be based on serum levels because not all patients become hypokalemic or require supplementation beyond dietary changes. Potassium supplements must be used cautiously, if at all, for patients concurrently taking ACE inhibitors, which cause elevated potassium. Oral potassium supplements should provide chloride as well to prevent diuretic-induced hypokalemic alkalosis. Hypomagnesemia is also common and may impair potassium repletion. Diuretics also contribute to abnormal glucose and lipid metabolism. Care must be taken and diagnostic tests frequently monitored when diuretics must be used for patients with diabetes or lipid abnormalities.


        All antiarrhythmics are metabolized by the liver. Half-lives of these drugs vary from 3 to 4 hours for procainamide to 26 or more days for amiodarone. As the only short-acting antiarrhythmic, procainamide requires frequent dosing administration, with steady state achieved in 2 to 3 days. Other antiarrhythmics have longer half-lives and require more time to achieve steady state. Hepatic impairment increases half-life in those drugs eliminated totally or partially in feces. Renal impairment significantly increases half-life in those drugs eliminated all or largely in the urine. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. Reduced dosages of procainamide and quinidine are required for patients with CHF or renal impairment that decreases volumes of distribution of these drugs. Many cardiac patients who need antiarrythmics have either decreased systolic function or renal impairment. Because of these concerns, quinidine and procainamide are infrequently used for such patients. Approximately 10% of patients are slow metabolizers of propafenone, resulting in an increase in half-life from 7 hours to 10 to 32 hours. Because this drug has been associated with proarrhythmia and increased mortality post-MI, the trend is away from its use.

Licorice interacts with many medications: antihypertensives, diuretics, corticosteroids, digoxin, loratadine, procainamide, quinidine, and spironolactone.

Procainamide can be used in a hemodynamically stable patient for the acute treatment of focal atrial tachycardia and the acute management of stable atrial flutter. It can also be used in the long-term management of recurrent, well-tolerated atrial flutter if combined with an AV node-blocking agent and if no significant structural cardiac disease is present.

Generic procainamide requires dosing every 6 to 8 hours; its cost is increased when switched to the sustained-release form, but adherence is improved.

        For disopyramide, mexiletine, procainamide sustained-release, propafenone, and tocainide, a dose that is missed should be taken as soon as it is remembered, unless the next dose is due in 4 hours or less. For flecainide, the missed dose should be taken unless the next dose is due in 6 hours, and for sotalol, 8 hours. For quinidine and standard formulations of procainamide, the separation is 2 hours.

Procainamide occasionally is associated with a lupus-like syndrome. Joint swelling and rashes should be reported.

There are many drug interactions with metformin (Table 21-12). Carbonic anhydrase inhibitors may increase the risk for lactic acidosis and should be used cautiously. Cationic drugs that are eliminated by renal secretion (e.g., amiloride, digoxin, morphine, procainamide, quinidine, ranitidine, triamterene, trimethoprim, and vancomycin) may compete with metformin for its elimination pathway. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


This  is used to treat a certain serious, life-threatening irregular heartbeat (ventricular ). It is used to restore normal  rhythm and to keep a regular, steady heartbeat.  is known as an anti-arrhythmic drug. It works by blocking certain electrical signals in the  that can cause an irregular heartbeat.


Antiarrhythmic Agents:

Membranes stabilizing agents (sodium channel blockers): procainimide

40.Primary and Secondary HTN

        The level of BP is strongly familial, and studies of rare genetic disorders affecting BP have led to the identification of genetic abnormalities associated with several rare forms of HTN. Genetic polymorphisms have also been discovered that may harbor genes contributing to primary HTN. To date, none of these genetic abnormalities has been shown, either alone or in combination, to be responsible for a clinically significant portion of HTN in the general population.

Although 90% to 95% of all cases of HTN are primary in nature with no identifiable cause, there are identifiable causes of HTN in which a cure may be effected by appropriate diagnosis and treatment.



  • Primary or “essential” (95%) HTN
    • Atherosclerosis
  • Secondary (5%) HTN
    • Adrenal, renal
  • BP relies on balance between CO and PVR




Calcium is a vital component in the excitation-contraction process in muscles, in electrical excitation, and in facilitating myocardial relaxation. Calcium enters cells via three types of voltage-dependent calcium channels (L-type, N-type, and T-type). The L-type, or long-lasting, channels are predominant in cardiac and smooth muscle and are the ones blocked by most calcium channel blockers (CCBs). CCBs have multiple indications, including angina, HTN, and selected tachyarrhythmias. Unlabeled indications include migraine headache prophylaxis, Raynaud’s syndrome, cardiomyopathy, and esophageal spasm. Laboratory evidence indicates that CCBs may interfere with platelet aggregation and reduce the development of atherosclerotic lesions. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


As shown in Figure 16-2, contraction of smooth muscles is triggered by an influx of calcium through transmembrane calcium channels. CCBs directly block the influx of calcium at the onset of the cycle, like the sodium channel blockade in local anesthetics. The drugs act from the inner side of the membrane and bind to channels in depolarized membranes, converting the mode of operation of the channel from frequent openings to rare openings. The result is a marked decrease in transmembrane calcium content and prolonged vascular smooth muscle relaxation.

The blocking action of CCBs occurs via three different receptors: diphenylalkylamine-based and benzothiazepine-based (both type 1 receptors) and dihydropyridine-based (type 2 receptors). The physiological response in the calcium channel is different for these two receptor types, and these differences are important in the clinical choice of CCB. All CCBs relax arterial smooth muscle but have little effect on venous beds. This results in significant reduction in afterload but limited effect on cardiac preload. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. In cardiac muscle, reduction in contractility (negative inotropism) and decreases in sinoatrial (SA) and atrioventricular (AV) nodal conduction velocity also occur. Although this is true of all classes of CCBs, the greater degree of vasodilation seen in the dihydropyridines causes sufficient reflex increase in sympathetic tone to overcome the negative inotropic effects.

All CCBs are extensively metabolized by the liver via the CYP 3A4 channel. Inducers and inhibitors of that isoenzyme system can affect CCB metabolism. This is more of a problem for type 1 CCBs than for dihydropyridines. Many CCBs have elimination routes in both the urine and the feces (see Table 16-5). Dosage reduction based on renal impairment is recommended only for nicardipine.

Most CCBs have short-acting forms with half-lives between 2 and 8 hours and sustained-release forms with half-lives of 12 to 24 hours. Amlodipine is the exception, with a half-life of 30 to 50 hours. Reduced adverse reactions are seen with the use of sustained-release forms.

Verapamil has the strongest negative inotropic effect and should be avoided in HF, in which this effect can worsen the disorder. It also has the strongest effect on nodal conduction and can significantly worsen bradycardia. Diltiazem also affects nodal conduction and can worsen or cause bradycardia, although less than verapamil. None of the CCBs are drugs of choice immediately after MI, but diltiazem has shown some benefit in reducing mortality in non–Q-wave MI for a selected group of patients whose ejection fractions are above 40%. For those with ejection fractions below 40% and for all other patients early after MI, type 1 CCBs are contraindicated because of their negative inotropic and bradycardic effects. Patients with ventricular dysfunction, SA or AV nodal conduction disturbances, and SBPs below 90 mm Hg should not be treated with type 1 CCBs because of the high risk for induction of HF and significant hypotension.

The more common adverse reactions of CCBs are extensions of their actions. Reduction in BP secondary to vasodilation may result in dizziness, headache, hypotension, and syncope. These lead to HF with congestion, shortness of breath, cough, and palpitations; though a potential class effect, HF is worse with verapamil, diltiazem, and nifedipine. Gastrointestinal (GI) symptoms can include dry mouth, nausea, vomiting, reflux, and constipation.

Additive hypotensive effects are major concerns with all CCBs given concurrently with other antihypertensives, nitrates, quinidine, or alcohol. Antihypertensive effects may be decreased with concurrent use of NSAIDs. Verapamil, diltiazem, and some dihydropyridines have an additive bradycardic effect with BBs or digoxin.

Calcium Channel Blockers (headaches)

Verapamil (Rx: Calan, Isoptin)

Adults: Start with 40 mg bid and slowly increase

Children: Not recommended

Adults: 480 mg/d

Tablets: 40, 80, 120, mg

– Contraindicated in pregnancy (Category C), Parkinson’s disease, and depression.

– May be first-line choice in patients with hypertension who cannot take beta blockers.

Calcium channel blockers are also commonly used for migraine preventive therapy, although their effectiveness has had mixed results and they should not be a first-line choice. Calcium channel blockers are thought to prevent migraine by inhibiting vasospasm of the cerebral arteries and by preventing cerebral hypoxia during migraine attacks.                Verapamil (Calan, Isoptin) is the most commonly used for migraine prevention. Nifedipine and diltiazem are not as effective in controlling migraines and probably should not be prescribed for this use. Calcium channel blockers may be the first-line choice for patients with hypertension who cannot take beta blockers. Dosing of verapamil is shown in Table 35-2. Adverse effects include sedation, weight gain, depression, and extrapyramidal symptoms. Calcium channel blockers are contraindicated in pregnancy, Parkinson’s disease, and depression.

While the pathology of HF is associated with altered contractility in part associated with calcium movement within the cell, calcium channel blockers (CCBs) are used with considerable caution (Yancy et al, 2013). The NICE (2010) guidelines state that patients should not be routinely treated with calcium channel blockers for HF.

Calcium channel blockers act as vasodilators to reduce pressure by relaxing vascular smooth muscle, the

reby dilating resistance vessels and increasing the area over which blood must flow, and through their negative inotropic activity to reduce cardiac output. Direct vasodilators produce the same effect as the calcium channel blockers on vascular smooth muscle.

In African Americans, calcium channel blockers are suggested as first line BP therapy in lieu of the ACE family due to a common lower renin response in this ethnic group. ACE medications are added to the regimen to cover all pertinent indications. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Powerpoint: (Week 3)

  • Calcium channel blockers (CCBs) cause arterial smooth muscle relaxation, which leads to peripheral vasodilation and decreased afterload.
  • CCBs may cause coronary vasodilation.
    • Atherosclerotic vessels do not dilate.
  • Functionally act as vasodilators, lowering calcium (Ca++) influx into smooth muscles
  • Two major classes
    • Type I – Non-dihydropyridines: affect conduction through the atrioventricular (AV) node and have negative chronotropic effects
      • Why it is used in treating supraventricular tachycardia
      • Diltiazem (Cardizem), verapamil (Calan)
    • Type II – Dihydropyridines: do not affect conduction through the AV node
      • Nifedipine (Procardia), amlopidine (Norvasc), felodipine (Plendil)
    • Pharmacokinetics: All CCBs are metabolized by the liver, CYP 450 3A4.
    • ADRs: All are very constipating and can cause dizziness, headache, edema, rash, and gingival hyperplasia.
    • Monitoring
      • Verapamil has strongest negative inotropic effect and should be avoided in patients with HF.
      • Using CCB/ACE combination decreases peripheral edema by 50% vs. those on CCB high dose alone.
    • Patient education: pregnancy category C
      • Avoid NSAIDs, alcohol, being in jacuzzi alone. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
      • Gastroesophageal reflux disease symptoms get worse due to decrease in esophageal tone.

  • Class IV: calcium channel blockers
    • Block the influx of calcium, reduction in contractility (negative inotropism), decrease SA and AV node conduction
    • Significantly reduce afterload but little effect on preload
    • Verapamil, diltiazem, bepridil
  • CCBs (stable angina)
    • Initial drugs of choice for coronary artery vasospasm associated angina
  • Combinations of BBs and CCBs have been shown to be more effective than the individual drugs used alone.
  • CCBs and ACEIs are the most expensive.
    • Generics less expensive


Constipation is especially common with verapamil, with almost 100% of patients experiencing significant issues. Patients taking this drug should be encouraged to increase the fiber in their diet and may need to use a stool softener.

42.Heart Failure

        Heart failure is a complex clinical syndrome that can result from any structural or functional cardiac disorder that results in a cardiac output that is inadequate to satisfy the oxygen demands of the body. In HF, several abnormalities occur. Coronary artery disease (CAD) causing myocardial ischemia is the underlying cause in about two-thirds of patients with left ventricular dysfunction.

Four main categories of drugs are used to treat HF, whether it is systolic or diastolic in nature. The four categories of drugs: diuretics, angiotensin-converting enzyme (ACE) inhibitors, cardiac glycosides, and the beta blockers. (Loop diuretics, Dig, ACEI, BB- pharm in flash)

          Diuretics reduce preload by decreasing extracellular fluid volume and can be used to decrease hypertension that increases afterload. ACE inhibitors act on the R-A-A system to decrease preload and afterload. They also affect heart tissue remodeling so that fewer abnormal myocardial cells are generated. Digoxin, a cardiac glycoside, improves myocardial contractility and cardiac output. Beta-adrenergic blockers affect the SNS counterregulatory mechanism of HF. Aldosterone antagonists augment the actions of ACE inhibitors on the R-A-A system. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

The drugs used to treat HF vary in cost from minimal to quite expensive. Diuretics are among the least expensive, but they vary from indapamide (Lozol) ($25 per month) to generic HCTZ ($1.04 per month). HCTZ is the drug of choice for a variety of reasons, and cost certainly also makes it desirable. The ACE inhibitors have become less expensive because several of them are now available as a generic formulation. Because digitalis has been used for so long, it is among the least expensive.

Hyperkalemia risk increases for patients with chronic heart failure (HF) because of the reduced blood flow to the kidneys. Patients should have their serum potassium level checked prior to initiating therapy and within one week to note trends.

Heart Failure:

CAD is the underlying cause in about two-thirds of patients with LV dysfunction, which begins with some injury to the myocardium and progresses even in the absence of additional myocardial insults. The principal mechanism relates to remodeling. ACEIs and ARBs are useful in treating heart failure related to CAD, primarily for their role in reducing remodeling. Another underlying cause for HF is chronic HTN. ACEIs and ARBs are also effective in treating this underlying cause. DRIs do not carry an indication for HF.

ACEIs are a cornerstone of therapy for HF and are recommended for patients with a history of atherosclerotic vascular disease, diabetes mellitus, or HTN. They have been shown to improve symptoms, decrease morbidity, and increase life expectancy. Because they are the only drugs that address all of the pathological mechanisms that produce HF, they are appropriate for all subsets of patients unless these patients have an absolute contraindication. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. They are also useful for preventing the development of HF in patients with ventricular dysfunction but no overt symptoms. ACEIs are superior to all other drugs and drug combinations used to treat HF. They should be started immediately without waiting for symptoms to become overt.

For symptomatic HF, the dose is about half that used for HTN. Start low and go slow also applies here. In patients with congestive heart failure (CHF) and low ejection fractions (less than 40%), the vasodilating effect of ACEIs provides adequate perfusion even with SBP below 90 mm Hg. For patients who cannot tolerate an ACEI, hydralazine, in combination with a long-acting nitrate (ISDN), BiDil has been shown to be equally effective in reducing morbidity and mortality from HF. This is especially noted in African Americans (see ).

Although no longer the first-line drug for treatment of HF, digoxin is still central to treatment for patients with severe systolic dysfunction (ejection fractions less than 40% and with an audible S3 heart sound).


Heart failure treatment

  1. CGs should not be used unless there is clear evidence of severe chronic systolic dysfunction or atrial fibrillation. In older adults, ankle edema is more often due to venous insufficiency than to heart failure. Even if it is related to heart failure, it is more often caused by diastolic dysfunction and better treated with diuretics or ACEIs.
  2. Digoxin should not be discontinued unless a reversible cause of the heart failure has been completely corrected or there was no basis for the drug in the first place.
  3. ST-T wave changes on the ECG do not correlate directly with serum drug levels and should not be used as an indication of toxicity. Serum drug levels are needed. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Powerpoint: (week 3 starting on slide 137)

HF Patho:

  • Complex syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricles to fill or eject blood (cardiac output – CO)
  • Determinants of ventricular function
    • Preload, afterload
    • Contractility, stroke volume, CO
    • Heart rate
  • Left ventricular dysfunction
    • Increase in end systolic volume
    • Increase in end diastolic volume
    • Pulmonary congestion
    • Decreased CO, hypoperfusion
  • Compensatory systems
    • Sympathetic activation
    • Renin-angiotensin-aldosterone system

Treatment of HF:

  • Stage A
    • ACEIs are drug of choice.
    • ARBs are considered but more expensive.
  • Stage B
    • ACEI in all patients, ARB for those who cannot tolerate an ACEI
    • BBs in most
  • Stage C
    • ACEI and BBs (nonselective) in all patients
    • Diuretics, digoxin
    • Spironolactone
  • Stage D
    • Stage C treatments
    • Inotropes: dobutamine
    • Ventricular assist device, transplantation, hospice

Patient Variables and Heart Failure

  • Left ventricular dysfunction
    • Increase in end systolic volume
    • Increase in end diastolic volume
    • Pulmonary congestion
    • Decreased CO, hypoperfusion
  • Compensatory systems
    • Sympathetic activation
    • Renin-angiotensin-aldosterone system
  • Hypertension
    • Use diuretics early to decrease preload.
    • ACEIs
  • Hyperlipidemia
    • Statins
  • Infants and children
    • Digoxin, thiazide, and loop diuretics all used
  • Pregnancy
    • ACEIs contraindicated in pregnancy
    • Diuretics may decrease placental perfusion.

Monitoring HF:

  • Functional capacity
  • Fluid status
    • Weight changes
    • Jugular venous distension
  • Cardiac rhythm
  • Labs
    • Electrolytes
    • Creatinine
    • Thyroid and liver function


43.Angina—treatment and grading

        ACEIs are recommended for all symptomatic patients with chronic stable angina to prevent MI or death and to reduce symptoms. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


Powerpoint: (CH 28)- WEEK 3

Treatment of Angina

  • Lifestyle changes
  • Surgical intervention
  • Pharmacological management
    • Aspirin
    • Nitrates
    • Beta blockers
    • Calcium channel blockers
    • Angiotensin-converting enzyme (ACE) inhibitors
    • Statins
  • Agents that serve to increase myocardial oxygen supply
    • Nitrates (nitroglycerin, isosorbide)
      • Prototype: nitroglycerine (NTG)
    • Calcium channel blockers

  • Acute angina attack: Use nitroglycerin (NTG).
    • Sublingual NTG, a short-acting form, is 0.4 to 0.6 mg every 5 minutes for up to three doses.
  • Predictable angina: Use isosorbide.
    • Isosorbide dinitrate: 10 to 40 mg orally 2 to 3 times daily; sustained-release form 40 to 80 mg daily
    • Isosorbide mononitrate: Dosing is 20 mg twice daily.
    • Eccentric scheduling to avoid development of tolerance
  • Take the drug exactly as prescribed.
    • Eccentric dosing schedule separated by 7 hours due to need to have nitrate-free period
    • Take at 7 to 8 a.m. and 2 to 3 p.m. rather than “usual” twice daily regimen.
    • Need nitrate-free interval of 10 to 12 hours. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  • If anginal symptoms occur at night, have a daytime nitrate-free interval.
  • Storage of NTG
    • Adhere to the expiration date on the bottle, usually 6 months.
    • Do not open the bottle frequently or keep bottles of tablets next to the body (in a shirt pocket).

Drugs for Stable Angina:

  • ACEIs
    • Recommended for all symptomatic patients with chronic stable angina to prevent MI)or death and to reduce symptoms.
  • Angiotensin II receptor blocker
    • For patients who are intolerant to ACE inhibitors
  • BBs
    • Recommended as initial therapy by all the guidelines for all patients
  • CCBs
    • Initial drugs of choice for coronary artery vasospasm associated angina


For oral doses of Nitro taken more than once daily, a nitrate-free interval of 10 to 12 hours is necessary to prevent nitrate tolerance. An eccentric dosing schedule separated by 7 hours (e.g., 7 a.m., 2 p.m.) must be explained to help adherence.

At the first sign of an angina attack, the patient should sit down and place one sublingual tablet under the tongue and allow it to dissolve. It should not be swallowed. If the pain is not relieved, repeat every 5 minutes for up to three doses.

The major adverse reactions are throbbing headaches, rapid heart rates, and decreased BP when arising from a sitting or lying position, with the potential for fainting. Headache may be severe; it is best treated with acetaminophen (Tylenol). NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

For all forms, doses should not be doubled and should not be discontinued abruptly, which may result in rebound angina.                     Concurrent use of alcohol should be avoided with these drugs. Because some OTC drugs interact with nitrates or contain alcohol, no new OTC drugs should be taken, including cold remedies, without first discussing this with the health-care provider.

In generic form, the cost of NTG is low.



  • Oral Nitro
    • Sublingual tablet
    • Extended-release buccal tablet
    • Extended-release capsule
    • Lingual aerosol
    • Chewable tablet
  • Ointment
  • Transdermal topical systems


  • Acute angina attack: Use nitroglycerin (NTG).
    • Sublingual NTG, a short-acting form, is 0.4 to 0.6 mg every 5 minutes for up to three doses.
  • Predictable angina: Use isosorbide.
    • Isosorbide dinitrate: 10 to 40 mg orally 2 to 3 times daily; sustained-release form 40 to 80 mg daily
    • Isosorbide mononitrate: Dosing is 20 mg twice daily.
    • Eccentric scheduling to avoid development of tolerance
  • Take the drug exactly as prescribed.
    • Eccentric dosing schedule separated by 7 hours due to need to have nitrate-free period
    • Take at 7 to 8 a.m. and 2 to 3 p.m. rather than “usual” twice daily regimen.
    • Need nitrate-free interval of 10 to 12 hours.
  • If anginal symptoms occur at night, have a daytime nitrate-free interval.
  • Storage of NTG
    • Adhere to the expiration date on the bottle, usually 6 months.
    • Do not open the bottle frequently or keep bottles of tablets next to the body (in a shirt pocket).


45.Short Acting and Long acting nitrates

        Sublingual NTG has rapid action, long-established efficacy, easy use, and low cost. A disadvantage is its short duration of action. It is also volatile and must be kept in a tightly capped, amber container and stored in a cool place. Once a bottle is opened, it is generally effective for only about 6 months. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. Onset and duration of action of a single metered dose of translingual spray is about the same as for sublingual NTG. Each canister contains 200 doses and retains efficacy for up to 3 years. Some skill is required to use it; however, patients with advanced arthritis may prefer it to opening tightly closed bottles. Cost per dose is substantially higher than for the sublingual form, but the prolonged shelf-life helps reduce total cost for those patients who rarely need a dose. It is also a good alternative for patients who wear dentures or have dry mucosa.

Transdermal delivery systems offer easy use and release NTG at a constant rate to maintain steady-state plasma levels. Bioavailability varies significantly from patient to patient. Physical exercise and ambient temperatures may increase absorption.

Oral NTG has questionable efficacy and is available only in sustained release, a form associated with increased incidence of tolerance. Among the oral nitrates, isosorbide dinitrate provides sustained nitrate activity and better anginal prophylaxis. Single doses significantly improve hemodynamic parameters and exercise tolerance for up to 4 hours. Its action is not as rapid as sublingual NTG but does occur in 15 to 30 minutes, which is appropriate for angina prevention but not emergency intervention.

For patients who respond well to sublingual or translingual nitroglycerin and who experience angina episodes more than “rarely,” and who are intolerant of beta blockers, long-acting oral or transdermal nitrates are generally indicated. Among the available drugs, the most cost-effective are isosorbide mononitrate (Imdur) given daily or nitroglycerin transdermal patches applied daily with a 10 to 12 hour nitrate-free interval to prevent nitrate tolerance. The timing of the nitrate-free interval should coincide with the time of fewest episodes of angina, which is typically at night. The administration schedule that seems most effective is 7 a.m. and 2 p.m. daily. Headache is the most common adverse reaction but resolves over time. Starting with low doses and slowly increasing the dose reduces the incidence of headache.

To prevent or reduce the development of tolerance, a nitrate-free interval of 10 to 12 hours/day is required. This is why nitro patches are applied and removed within a set period of time. Sustained-release preparations are more likely to lead to tolerance and should be avoided unless used daily. Short-acting products with two or three doses daily are less likely to lead to tolerance. For twice-daily dosing, use an eccentric dosing schedule separated by 7 hours (e.g., 7 a.m., 2 p.m.). Patients whose anginal symptoms occur at night may do best with a daytime nitrate-free interval, and the reverse holds for those whose symptoms occur during the daytime. If around-the-clock coverage is necessary for anginal symptoms, using a BB or CCB during the nitrate-free interval may be needed. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

46.Nitrates and medication interactions

Drug Interactions

-Additive hypotension is possible with other drug classes that have actions or adverse effects of hypotension (i.e., antihypertensives, BBs, CCBs, haloperidol, or phenothiazines).

-Drugs with anticholinergic effects may decrease absorption of sublingual or buccal NTG.

-Aspirin increases nitrate serum concentrations and may potentiate their action.

-Nitrates may decrease the pharmacological effects of heparin.                    -Specific drug interactions and the appropriate actions to prevent them are given in Table 16-17.

Precautions and Contraindications

Precautions and contraindications are largely related to the actions of these drugs. Vasodilation can result in increased intracranial pressure, so nitrates are contraindicated in head trauma or cerebral hemorrhage. Vasodilation can also result in postural hypotension. Patients with volume depletion and anemia should avoid using nitrates. Drug Facts and Comparisons (Wolters Kluwer Health, 2011) states that closed-angle glaucoma is also a contraindication because intraocular pressure (IOP) may be increased. Some individuals have hypersensitivity or idiosyncratic responses to nitrates and must avoid them. For the transdermal patches, allergy to their adhesive may limit their use.

Because the activity of these drugs may compromise maternal-to-fetal circulation, they are Pregnancy Category C. Amyl nitrite is Pregnancy Category X because it markedly reduces system BP and blood flow on the maternal side of the placenta. It is not known if nitrates are excreted in breast milk. The importance of the drug for the mother and possible risks to the infant should be taken into consideration when deciding on nitrate use in nursing mothers. Safety and efficacy in children have not been established.

Adverse Drug Reactions

The major adverse reactions are direct extensions of therapeutic vasodilation: orthostatic hypotension with potential for syncope, tachycardia, and throbbing headache. Hypotension may result in decreased diastolic filling pressure, and the tachycardia may result in decreased diastolic filling time, leading to myocardial ischemia, arrhythmias, and rebound HTN. Headache may be severe and persists in up to 50% of patients. For patients with severe, persistent headache, it may be necessary to use a different drug group to treat the disease process.

Less common adverse reactions include nausea, vomiting, incontinence of urine and feces, dysuria, impotence, and urinary frequency. Nonallergic rash and cutaneous vasodilation with flushing may occur with transdermal applications. This can be reduced by rotating sites. The vasodilating effect is linked with an increased risk of age-related macular degeneration (Klein et al, 2014).


Patients with migraine headaches are especially at risk for nitrate headaches. Start them first on a beta blocker for migraine prophylaxis, and then add the nitrate to prevent the problem with chronic use. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


  • Oral or patch (transdermal)
  • Used for patients intolerant to BBs
  • Isosorbide dinitrate (Isordil) given 2 or 3 times/day
    • With a 10 to 12 hour nitratefree interval to prevent nitrate tolerance
    • Timing of the nitratefree interval should coincide with the time of fewest episodes of angina.

SHORTACTING (***No specific slide for short)

  • Acute angina attack: Use nitroglycerin (NTG).
    • Sublingual NTG, a short-acting form, is 0.4 to 0.6 mg every 5 minutes for up to three doses.


47.Hyperlipidemia—factors to determine treatment

        Hyperlipidemia presents a problem in therapeutic management because patients are usually asymptomatic until damage to the cardiovascular system occurs. Central aspects of treatment are lifestyle modifications, especially dietary, which include the reduction of elements that are often perceived as “making food taste good.” Finally, patients often want a prescription for a drug that will “cure” the problem, which currently is not a realistic treatment option. The drugs that are prescribed for hyperlipidemia are added to the therapeutic plan after lifestyle management has failed because the medications available can potentially produce serious adverse events. For effective management of hyperlipidemia, the treatment protocol must be palatable and low cost and have the fewest possible side effects. The factors to consider before developing a treatment plan are the presence or the absence of CVD, any associated risk factors, specific patient variables and desires, patient interest, plus a realistic consideration of a cost–benefit ratio.

        Multiple patient variables based on risk profiles are considered in setting individual goals for lipoprotein levels. The guidelines highlighting a 7.5% risk level are not meant to be absolute standards for starting medications, but only a trigger point for consideration of personal risks. These risks fall into modifiable and nonmodifiable categories. The modifiable risk factors such as diet, smoking behavior, and exercise are targets of therapy through lifestyle modifications. Nonmodifiable risk factors include age, gender, race, and family history. Both categories of risk factors are part of the calculation of overall risk for CVD. Table 39-2 presents the major risk factors for CVD exclusive of the serum LDL. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Five factors are considered contributory to low risk and negative risk for CVD: not smoking, normal BP, normal weight, normal glucose metabolism, and low cholesterol levels.

Look to figure: 39-2

Positive RISK (CHD):

Age: Male: ≥45; Female: ≥55

Family history: Premature CHD (MI or sudden death before 55 yr in father or other male first-degree relative or before 65 yr in mother or female first-degree relative) NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Cigarette smoking: Current smoking (any cigarette smoking in past month)

HypertensionBP ≥140/90 mm Hg or on antihypertensive medication

HDL cholesterol: HDL ≤40 mg/dL

Diabetes mellitus: Presence, especially if poorly controlled




Drug therapies for Hyperlipidemia:

  • HMG CoA reductase inhibitors
    • Lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, rosuvastatin
  • Fibrates: fibric acid derivatives
    • Gemfibrozil, micronized fenofibrate, clofibrate
  • Bile acid sequestrants
    • Cholestyramine, colestipol, colesevelam
  • Niacin (has lost its luster)
  • Ezetimibe (Zetia): most effective in combination with statin
  • Vitamins/antioxidants/herbs/natural products
    • Vitamin E, C, folic acid, garlic, fish oils, fiber, coenzyme Q10, flaxseed
    • *Active liver disease is a contraindication for all except the bile acid sequestrants.


48.Thiazide diuretics

        The thiazide-type diuretics act on the distal renal tubule to inhibit sodium reabsorption. Their effect is generally longer-lasting, and they cause less brisk diuresis.

        Diuretics are still considered first-line therapy for HTN with the JNC-8. Thiazide diuretics are the most commonly prescribed agents for HTN. Higher doses of these drugs can cause modest and often transient increases in serum LDL cholesterol and TG, with little or no adverse effects on HDL cholesterol.

Electrolyte imbalances are common in all diuretic classes. Thiazide and loop diuretics cause hypokalemia and may cause hypercalcemia, hyponatremia, and hypomagnesemia. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Several thiazide and loop diuretics are Pregnancy Category C and should be used only when benefits clearly outweigh risks.

Thiazide and loop diuretics decrease the renal excretion of lithium and may induce lithium toxicity. These two classes may decrease the action of sulfonylureas and insulin. Thiazide diuretics and spironolactone diminish the anticoagulant effects of warfarin.


  • Thiazide diuretics
    • HCTZ, chlorthalidone, indapamide, metolozone
    • High dose therapy (HCTZ greater than 50) has increased risk of hypokalemia, increase in uric acid levels, and serious CV outcomes;
    • Use in combination vs. pushing high doses
    • Watch with patients with hyperlipidemia.
    • May increase glucose levels in DM
    • Initial drug therapy for HTN

  • Stage I: systolic blood pressure (SBP) 140 to 159/diastolic blood pressure (DBP) 90 to 99
    • Diuretics: thiazide-type
    • May consider angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), calcium channel blocker (CCB), or combination
  • Stage II: SBP greater than or equal to 160/DBP greater than or equal to 100
    • Two-drug combination: thiazide-type and ACEI, ARB, beta blocker (BB), or CCB
  • With compelling indications: heart failure (HF), DM, stroke, chronic kidney failure, point of maximal impact
    • Diuretics, ACEI, ARB, BB, CCB as needed


49.  HTN treatment in African Americans/Diabetics


African American and HTN:

        The prevalence of hypertension in African Americans is among the highest in the world (Brown, 2006). An estimated 30% of all deaths in this population are attributable to HTN, which develops at younger ages than it does in whites.

        The underlying pathology associated with hypertension in African Americans is thought to be salt sensitivity (Brown, 2006). This increased sensitivity to salt, along with the high prevalence in this population of obesity, cigarette smoking, and type 2 diabetes mellitus, means that lifestyle modifications are especially efficacious. Salt intake should be reduced to less than 6 g per day, and weight should be reduced, if necessary, to approach ideal body weight. If these modifications do not result in achievement of the BP goal, diuretics have been proved in RCTs to reduce morbidity and mortality and are the first agents of choice unless there are compelling reasons to choose another drug class (Gerber et al, 2013). NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Calcium channel blockers are recommended as first-line therapy for African Americans (James et al, 2014). The Atherosclerosis Risk in Communities (ARIC ) study found, however, that ACE medications are the most commonly prescribed for this group (Miedema, 2014). Monotherapy with most beta-adrenergic blockers is less effective than in whites but should still be used for the post-MI mortality benefit.

Racial differences in adverse responses to antihypertensive drugs may occur even in monotherapy. African Americans and Asians, for example, have a 3- to 4-fold higher risk of angioedema (ALLHAT, 2002; Wright et al, 2009), and more cough has been attributed to ACE inhibitors than in whites.

Other concomitant diseases that may affect the choice of drugs are discussed later. In African Americans, calcium channel blockers are suggested as first line BP therapy in lieu of the ACE family due to a common lower renin response in this ethnic group. ACE medications are added to the regimen to cover all pertinent indications.

DM and HTN:

Angiotensin-converting enzyme (ACE) inhibitors, for example, are drugs of choice in diabetes mellitus, heart failure, and myocardial infarction (MI).

An ACE inhibitor and a non-dihydropyridine calcium channel blocker may reduce proteinuria in a patient with diabetes better than either drug alone. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

In the presence of diabetes mellitus, ACE inhibitors should be used for their renal protective properties.



  • African Americans:
    • have a higher and earlier HTN incidence.
    • Reduced response to monotherapy, beta blockers, ACEIs, and ARBs
    • Equal response if mixed with diuretic
    • BiDil is the first drug suggested for African-American patients specifically.
  • ACEI- Not as effective for African-American patients
    • When combined with a diuretic, race no longer an issue
  • However, African Americans and Asians have three to four times greater risk of developing angioedema.
  • Beta Adrenergic Blockers- More effective in African-American and older patients

  • Diabetes
    • ACEIs: are drug of choice in patients with diabetes.
    • Thiazides may increase glucose levels.
    • Avoid beta blockers.

50.Statins: HMG CoA Reductase Inhibitors


Statins: HMG CoA Reductase Inhibitors

  • HMG CoA reductase inhibitors:
    • Lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, rosuvastatin
  • Block synthesis of cholesterol in the liver by competitively inhibiting HMG CoA reductase activity.
  • Decrease levels of LDL by 25% to 65%.
  • Modest decreases in triglycerides (10% to 40%) and very modest increases in HDL (5% to 17%) may occur.
  • Pregnancy category X
  • All statins (except fluvastatin and rosuvastatin) are metabolized at least in part by CYP 3A.
  • CYP 3A inhibitors may increase statin concentrations. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
    • Verapamil, diltiazem, azole antifungals, erythromycin, fluoxetine, nefazodone, protease inhibitors
  • CYP 3A inducers may decrease statin concentrations.
    • Rifampin, phenytoin, phenobarbital
  • Statins may also interact with other CYP 3A substrates; for example, cyclosporine.

Statins: ADRs

  • Common: HA, myalgia, fatigue, GI intolerance, flu-like symptoms
  • Myopathy: occurs in 0.2% to 0.4% of patients, some agents more likely
    • Reduced by using lowest effective dose
    • Cautiously combining statins with fibrates
    • Avoiding drug interactions
  • Increase in liver enzymes not enough to warrant frequent labs
    • Active liver disease is a contraindication.
    • Occurs in 0.5% to 2.5% of cases and is dose-dependent
    • Serious liver problems are rare.
    • Manage by reducing dose or stopping until levels return to normal.
  • Start with lower dose and increase as needed according to LDL response; absolute levels of LDL not as closely monitored now.
  • Rosuvastatin most potent: 5 to 20 mg day
    • Atorvastatin next most potent (best ADR profile)
      • 10 mg/day initially, increase no fewer than 2 to 4 weeks
    • Simvastatin: 20 to 40 mg/day
    • Lovastatin (IR) 20 mg/day (XR) 40 to 60 mg
    • Pravastatin: 40 mg/day
      • Pediatric dosing for children 8 to 13 years: 20 mg/day
    • Doses often are given traditionally in the evening/bedtime.
    • May need to decrease dose occasionally.
      • When adding potentially interacting drug
      • Profound drop in LDL
    • Monitoring
      • Lipid levels in 4 to 6 weeks then every 3 to 4 months until control established
      • LDL levels most important in those with suspected liver issues and in persons with prior severe liver disease.
      • Liver function tests (LFTs) before starting therapy and 3 to 6 months later only
        • No longer frequent monitoring unless underlying hepatic issues
      • Patient education
        • Lifestyle changes
          • Diet
          • Exercise


51.COPD and Asthma Treatment—know guidelines, staging, treatment, exacerbations, meds, etc.


  • ASTHMA: Pathophysiology
    • Chronic inflammatory disorder of the airways
    • Recurrent episodes of wheezing, breathlessness, and chest tightness
    • Airflow obstruction is reversible.
  • National Asthma Education and Prevention Program Expert Panel 3 Guidelines (2007) are used for management of all types of asthma. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  • Classification of asthma
    • Mild intermittent
    • Mild persistent
    • Moderate persistent
    • Severe persistent
  • Adult and children definitions differ slightly.
  • Goals of therapy
    • Reduce impairment
      • Prevent chronic symptoms.
      • Reduce use of inhaled short-acting beta agonists.
      • Maintain normal or near-normal pulmonary function.
      • Maintain normal activity levels.
      • Meet patient/family expectations of asthma care.
    • Reduce risk
      • Prevent recurrent exacerbations and minimize emergency department (ED) visits and hospitalizations.
      • Prevent loss of lung function. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
      • Provide optimal therapy with minimal adverse drug reactions (ADRs).


  • First determine severity of asthma symptoms.
  • Go to Step Therapy Chart and start at recommended step.
  • The Expert Panel 3 Guidelines prefer an aggressive approach to gaining quick control.
  • Asthma control is “the degree to which the manisfestations of asthma are minimized by therapeutic intervention and the goals of therapy are met” (NAEPP, 2007). NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


  • Step 1 therapy
  • Use short-acting beta2agonists as needed                        for symptoms.
  • Patients have symptoms when exposed to triggers (upper respiratory infections, allergens, chemical inhalants).
  • Exercise can be mild intermittent.
  • Need an annual flu shot.


  • Step 2 therapy
  • Treat with one long-term control medication daily.
    • Low-dose inhaled corticosteriods are the mainstay for all age patients.
    • Cromolyn or a leukotriene modifier are alternatives.
    • See dosage charge for low-dose schedule of each inhaled corticosteroid.
  • Use beta agonists as needed; if using 2 days or more per week, then step up in therapy.


  • Step 3 therapy
  • Treat with medium-dose inhaled corticosteroids.
    • Or low-dose inhaled steroids plus long-acting beta agonists (adults)
    • Alternative: medium-dose inhaled steroid plus leukotriene receptor modifier
  • May use short-acting beta agonists.
  • Exacerbations may require oral corticosteroids.


  • Step 4 therapy
    • Medium-dose inhaled corticosteroids plus long-acting beta agonist
    • Or medium-dose inhaled corticosteroid and a leukotriene modifier or theophylline
  • Step 5 therapy
    • High-dose inhaled corticosteroids plus long-acting beta agonists
  • Step 6 therapy
    • High-dose inhaled corticosteroids plus long-acting beta agonists and oral corticosteroids
  • Severe persistent asthma requires consultation with         asthma specialist. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


  • Once control is achieved, the patient is seen every 1 to 6 months to determine if a step up or step down in therapy is indicated.
  • The Expert Panel 3 Guidelines recommend the dose of inhaled corticosteroids be reduced about 25% to 50% every 2 to 3 months to lowest possible dose to maintain control.


  • Treat with oral steroids to regain control.
  • Use a short burst
    • Adults: 40 to 60 mg/day for 5 to 10 days
    • Children: 1 to 2 mg/kg daily (maximum 60 mg/day) for 3 to 10 days
  • If not effective, then step up in therapy.


  • Assess severity
    • Patients at risk of fatal asthma attack include: previous severe exacerbations requiring intubation or intensive care unit admission, two or more hospitalizations or three ED visits in past year, use of more than two short-acting beta agonist inhalers per month, worsening asthma, low socioeconomic status
  • In-home treatment
    • Increase inhaled beta-agonist (2 to 6 puffs every 20 minutes)
    • Oral corticosteroids
    • Good response: stepped up therapy for several days


  • Monitor asthma symptoms at each prenatal visit.
  • Inhaled beta-agonists are drug of choice during pregnancy.
  • Inhaled corticosteroids are the long-term drug of choice. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


  • Three categories of wheezing in children younger than age 5 years
    • Transient early wheezing
    • Persistent early-onset wheezing
    • Late-onset wheezing/asthma
  • The Expert Panel 3 Guidelines have treatment categories for
    0 to 4 years and 5 to 11 years.
  • Stepwise approach is similar in adults and children, but not the same.
    • Some medications not approved or should not be used in children.
    • Long-acting beta agonists should not be prescribed singly, need to be combined with an inhaled corticosteroid.


  • Delivering medication to children
    • Use Aerochamber with mask for infants and young children.
    • Use spacer for all children.
    • Home nebulizer is an option.
  • School-age and adolescent children need to use inhalers at school.
    • Need education and observation of self-administration.
    • Will need note for school to use medication at school.
    • Provide asthma action plan for school nurse.


  • Determine if symptoms are reversible (asthma) or not (possibly COPD)
  • Medications
    • Increased ADRs
    • Interactions with medications taken for chronic medical conditions (beta blockers)


  • Seasonal allergies
    • Start long-term control medications more than 1 month before allergy season starts.
  • Cough variant asthma
    • Trial of bronchodilator
    • Same stepwise management
  • Exercise induced asthma (EIA)
    • Most asthmatics have EIA.
    • Treatment
      • Short-acting beta agonist 15 minutes before exercise (2 to 3 hours)
      • Salmeterol lasts 10 to 12 hours (cannot use if using as long-term care medication)
      • Mask or scarf over mouth if EIA is cold-induced
      • Leukotriene modifier may help


  • The Expert Panel 3 Guidelines recommend ongoing monitoring of the following six areas:
    • Signs and symptoms
    • Pulmonary function
    • Quality of life and functional status
    • History of asthma exacerbations, pharmacotherapy
    • Patient-provider communication
    • Patient satisfaction


  • Optimal outcome is being able to do activities of daily living with minimal asthma symptoms.
  • Refer to an asthma specialist
    • If difficulty achieving or maintaining control
    • If immunosuppressive therapy being considered
    • Any adult who requires step 4 therapy or child who requires step 3 therapy
    • NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide


  • Written asthma action plan
    • Overall treatment plan
    • Specific drug therapy
    • Drugs as part of treatment regimen
    • Adherence issues
  • Review asthma action plan routinely, at least every 6 months. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


52. SABAs

  • Short-acting beta agonists
    • Albuterol (ProAir, Ventolin, Proventil)
    • Metaproterenol (Alupent)
    • Terbutaline (Brethine, Brethaire)
    • Bitolterol (Tornalate)
    • Pirbuterol (Maxair )
    • Levalbuterol (Xopenex)
  • Albuterol: Selective beta2agonist with minor beta1 activity
  • Levalbuterol is where the (S)-isomer from racemic albuterol is removed.
  • Salmeterol is more selective for beta2receptors than albuterol and has minor beta1
    • Salmeterol: 12 hour half-life

Bronchodilators: SHORT Acting Beta Agonists (SABA)

(Chronic Bronchitis/Emphysema/Asthma)

  • Albuterol (Ventolin)
  • Pirbuterol (Maxair)
  • Levalbuterol (Xopenex)




Action of Bronchodilators: Short Acting Beta Agonists:

  • SABAs Stimulate beta 2 receptors in the lungs causing rapid bronchodilation
    • (Beta 2 receptors=Bronchodilation)**

Bronchodilators: Short Acting Beta Agonists: Comments:

  • Albuterol is the therapy of choice for relief of acute symptoms of bronchoconstriction
  • Albuterol: Use for rapid symptom relief
  • Albuteral: Can increase heart rate
  • AlbuterolCan increase Blood pressure
  • Albuterol: Can cause QT prolongation and ST segment depression
  • Albuterol: Tolerance develops with prolonged use. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

 NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide

  1. LABAs
  • Long-acting beta agonists
    • Salmeterol (Serevent)
    • Formoterol (Foradil)
    • Indacaterol (Arcapta Neohaler)
    • Arformoterol (Brovana)

Bronchodilators: LONG Acting Beta Agonists (LABA)

          (Chronic Bronchitis/Emphysema/Asthma)


  • Salmeterol (Serevent)
  • Formoterol (Foradil)

                             (Meterol and Moterol)**


Action of Bronchodilators (Long Acting Beta Agonists):

  • LABAs Stimulate beta 2 receptors in the lungs causing bronchodilation


Bronchodilators (Long Acting Beta Agonists): Comment:

  • Do not use long-acting agents for immediate relief of acute symptoms
  • These agents take 10-20 minutes to produce bronchodilation
  • Should only be used in combination with inhaled steroid for asthma

Beta2 Agonists (Saba/Laba)

  • Precautions and contraindications  
    • Cardiac arrhythmias
    • Diabetics: potential drug-induced hyperglycemia
    • Long-acting beta agonists
      • Black Box warning: The risks of salmeterol (Serevent) and formoterol (Foradil) outweighed the benefits and should not be used singly in asthma for all ages.
      • Two-fold increase in catastrophic events (asthma-related intubations and death)
    • Terbutaline pregnancy category B (others category C)
    • Children
      • Albuterol safe for all age children
      • Salmeterol should not be used in children less than age 4 years and never singly. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Beta Agonist ADRs :

  • Usually transient
  • Tachycardia and palpitations
  • Some central nervous system (CNS) excitation effects
    • Tremors, dizziness, shakiness, nervousness,           and restlessness
  • Headaches
  • Salmeterol has an increased risk of exacerbation of severe asthma symptoms if the patient is deteriorating.
  • Digitalis glycosides: increased risk of dysrhythmia
  • Beta adrenergic blocking agents: direct competition for beta sites resulting in mutual inhibition of therapeutic effects
    • Including beta blocker eye drops
  • Tricyclic antidepressants and monoamine oxidase inhibitors potentiate effects of beta agonist on vascular system. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

CLINCAL USE of Beta Agonists:

  • Bronchodilators are used primarily in the treatment of bronchospasm associated with asthma, bronchitis (acute or chronic), and chronic obstructive pulmonary disease (COPD).
  • Albuterol metered dose inhaler (MDI) dose is 2 puffs every 4 to 6 hours.
    • Via nebulizer dose is 2.5 mg/dose
    • Dose may be repeated twice after 5 to 10 minutes.
    • May combine with ipratropium
  • Levalbuterol via nebulizer every 6 to 8 hours
  • Salmeterol DISKUS: 1 puff twice a day
    • Do not use alone for persistent asthma, combine with an       inhaled corticosteroid.
  • Exercise-induced bronchospasm (EIB)
    • Albuterol: 2 puffs 15 minutes before exercise
    • Salmeterol: 2 puffs 30 to 60 minutes before exercise
      • Do not use if already on daily dose of salmeterol.
    • Leukotriene modifiers taken daily may decrease EIB symptoms in 50% of patients, but patient will still need to use albuterol before exercise. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Beta Agonist: Drug selection:

  • The Expert Panel 3 says any short-acting beta agonist can be used in adults.
  • Age
    • Only albuterol and metaproterenol are approved for use in children younger than 4 years.
    • Albuterol is the safest to use in infants.
  • Cost
    • Albuterol is the least expensive.

Beta Agonist: Education:

  • MDI use
    • Demonstrate and have patient do return demonstration.
    • Check correct inhaler use if patient says the inhaler isn’t working.
    • Use a spacer with all patients.
  • Breath-actuated inhalers require inspiratory drive to deliver medication to lungs. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


  1. Anticholinergics:

Inhaled Anticholinergics:

  • Ipratropium bromide (Atrovent)
    • Blocks the muscarinic cholinergic receptors
  • Tiotropium bromide (Spiriva)
    • Inhibits the muscarinic Mreceptors in the lungs
  • Both cause bronchial smooth muscle relaxation

Anticholinergic: Precautions and Contraindications:

  • Known hypersensitivity
  • Not used for acute bronchospasm
  • Ipratropium bromide is pregnancy category B and tiotropium is pregnancy category C.
  • Not approved for use in children
    • Expert Panel 3 guidelines state ipratropium may be used in children as an adjunct to beta agonist (albuterol) therapy in acute exacerbations of asthma. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


Anticholinergic: Adverse Drug Reactions:

  • Cough is most common
  • Dry mouth
  • Mild anticholinergic effects in a few patients
    • Constipation
    • Urinary retention (less than 2%)
  • Rare allergic reaction
    • Allergy to soybeans, legumes, or soy lecithin appears to be correlated with hypersensitivity to ipratropium bromide.

Inhaled Anticholinergic: Clinical Use and Dosing:

  • COPD
    • Ipratropium: 2 puffs (36 µg) 4 times/day (maximum
      12 puffs per day)
    • Ipratropium: 1 unit dose via nebulizer 3 to 4 times/day, may be mixed with albuterol
    • Ipratropium-albuterol combination (Combivent): 2 puffs
      4 times/day
    • Tiotropium (Spiriva): 2 puffs of a single capsule once/day
    • Aclidinium bromide (Tudorza Pressair): 1 puff twice/day
  • Asthma
    • Ipratropium for asthma maintenance is 2 to 3 puffs 4 times/day for adults.
      • Children under age 12 years: 1 or 2 puffs every 6 hours
    • Ipratropium-albuterol combination (Combivent) is a second-line quick relief medication in the treatment of asthma.
    • Tiotropium and aclidinium are not indicated for the treatment of asthma. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Inhaled Anticholinergics:

  • Cost
    • Combined albuterol-ipratropium products are cheaper than the two individual drugs.
      • Generic ipratropium/albuterol nebulizer solution is $13.97 for a month’s supply.
    • Tiotropium (Spiriva) costs $223 per month.
    • Aclidinium bromide (Tudorza Pressair) costs $234 per month.
  • Patient education
    • Use as prescribed.
    • Educate on use of inhaler or Handihaler.
    • Rinse mouth after inhaling medication.


  1. Leukotriene inhibitors:

        – Leukotriene-receptor agonists (LTRAs) and 5-lipoxygenase pathway inhibitors were developed under the theory that cysteinyl leukotrienes play a significant role in the chronic inflammation associated with asthma and allergy. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide. Leukotrienes are substances that induce numerous effects that contribute to the inflammatory process, including smooth muscle contractility; neutrophil aggregation, degranulation, and chemotaxis; vascular permeability; and on lymphocytes. There are two LTRAs available for use in asthma, zafirlukast (Accolate) and montelukast (Singulair), and one 5-lipoxygenase pathway inhibitor, zileuton (Zyflo). (There is evidence that the cysteinyl leukotrienes contribute to the pathophysiology of asthma and allergy, including airway edema, smooth muscle constriction, and cellular changes associated with the inflammatory process.)

– Zafirlukast is rapidly absorbed from the GI tract following oral administration. Peak plasma concentrations are reached in 3 hours. The bioavailability of zafirlukast may be decreased when taken with food, and it should be taken on an empty stomach.

– Montelukast is rapidly absorbed following oral administration, with peak plasma concentration achieved in 3 to 4 hours for the film-coated tablet and in 2 to 2.5 hours after administration of the chewable tablet. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

– The leukotriene modifiers are not to be used for primary treatment of an acute asthma attack.

– Zafirlukast should be used with caution in patients with hepatic dysfunction because it is extensively metabolized by the liver.

– Leukotriene modifiers should not be abruptly substituted for inhaled or oral steroids. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

– The most common adverse reaction reported with zafirLukast use is headache. GI upset, myalgias, and fever are reported in a small percentage of patients.

– Zafirlukast is indicated in the treatment of chronic asthma in children aged 5 years or older and adults. Montelukast is indicated for use in the treatment of persistent asthma for patients aged 12 months or older. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

          Leukotriene Blockers: (ASTHMA/Allergic RHINITIS)

  • ZafirLukast (Accolate)
  • MonteLukast (Singulair)

Action of Leukotriene Blockers:

– Leukotriene blockers INHIBIT (prevent) the action of leukotrienes which are released from MAST CELLS and EOSINOPHILS and are associated with AIRWAY EDEMAincreased INFLAMMATORY activity and SMOOTH MUSCLE CONTRACTION

Leukotriene Blockers: Comments:

  • Leukotriene Blockers- are NOT substitutes for Bronchodilators or inhaled steroids
  • Take Leukotriene Blockers DAILY
  • Monitor for DRUG INTERACTION with ZAFIRLUKAST (Accolate)


  1. Inhaled and Oral Corticosteroids:

        – The Expert Panel Report 3 states that corticosteroids are the “most potent and effective anti-inflammatory medication currently available” (NAEPP, 2007, p 213). Their anti-inflammatory effects lead to reduction in the severity of asthma symptoms, increased peak flow readings, and decreased airway hyperresponsiveness. In general, inhaled steroids are safe and well tolerated at recommended dosages and can be used by both children and adults. Corticosteroids are also used intranasally for the treatment of allergic rhinitis.

– The commonly prescribed inhaled corticosteroids for asthma are beclomethasone dipropionate (QVAR), triamcinolone acetonide (Azmacort), budesonide (Pulmicort), flunisolide (AeroBid), mometasone furoate (Asmanex Twisthaler), fluticasone (Flovent), and ciclesonide (Alvesco). NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

In the treatment of asthma and allergic rhinitis, the primary actions of orally inhaled corticosteroids are anti-inflammatory. The inhaled adrenocorticosteroids inhibit the immunoglobulin E (IgE) and mast cell–mediated migration of inflammatory cells into the bronchial tissue (late-phase allergic reaction)

– Absorption of inhaled corticosteroids occurs from the lungs and from the GI tract. Approximately 10% to 30% of the dose from an MDI is delivered to the lungs. If a spacer device is not used, approximately 80% of the dose from an MDI is swallowed, with the oral bioavailability differing from drug to drug.

– All of the inhaled corticosteroid preparations are contraindicated in acute status asthmaticus or when intensive, acute therapy is warranted. They should not be used for relief of acute bronchospasm.

– Care should be used when substituting any of the inhaled corticosteroids for oral corticosteroid therapy. There have been deaths due to adrenal insufficiency in asthmatic patients who were switched from oral to inhaled corticosteroids.

– All of the inhaled corticosteroids are Pregnancy Category C. There have been no well-controlled studies of the effects of inhaled corticosteroids during pregnancy.

– Local immunosuppression can lead to oral candidiasis with any of the inhaled corticosteroids.

– The inhaled corticosteroids are the preferred long-term control medications for managing the inflammatory process associated with asthma.

– Severe persistent asthma requires daily high-dose inhaled corticosteroids and long-acting beta agonists.

  • Step 6 therapy for SEVERE persistent asthma:
    • High-dose inhaled corticosteroids plus long-acting beta agonists and oral corticosteroids

Managing asthma exacerbations:

  • Treat with oral steroids to regain control.



Inhaled Corticosteroids (Chronic Bronchitis/Emphysema/Asthma)


  • Budesonide (Pulmicort)
  • Fluticasone (Flovent)
  • Mometasone (Asamanex)
  • Beclomethasone (Qvar)
  • Triamcinolone (Azmacort)

Action of Inhaled Corticosteroids (Chronic Bronchitis/Emphysema/Asthma)

  • Glucocorticoids decrease activity of inflammatory cells and mediators
  • Inhaled CS= Inflammation reduction in airway
  • Inhaled=Inflammation
  • Steroid activity is local (in the lungs) and is associated with minimal systemic absorption. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.


Inhaled Corticosteroids: (Chronic Bronchitis/Emphysema/Asthma)

  • Slowly wean patients who are on oral steroids to inhaled steroids
  • Abrupt withdrawal can cause symptoms of adrenal insufficiency (which are fatigue, weakness, and hypotension)
  • Monitor for symptoms of FUNGAL infection (Oral Candidias) in the mouth and pharynx. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.



Xanthine Derivatives:

  • Theophylline and caffeine pharmacodynamics
    • Bronchial smooth muscle relaxation
    • CNS stimulants
    • Cardiovascular effects
    • Increased gastric acid production
    • Stimulate skeletal muscle
    • Increased renal blood flow and glomerular
      filtration rate


  • Pharmacokinetics
    • Absorbed rapidly and completely from gastrointestinal (GI) tract
    • Distributed widely
      • Volume of distribution altered in: premature neonates, elderly patients, cirrhosis, pregnant women (third trimester), and critically ill patients, probably because of altered protein-binding
    • Metabolized extensively in liver via CYP 450 into caffeine
      • Disease states and CYP inducers can influence metabolism of theophylline. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
    • Eliminated renally


  • Precautions and contraindications
    • Monitor patients with hypertension, ischemic heart disease, coronary insufficiency, congestive heart failure, or a history of stroke and cardiac arrhythmias.
    • Monitor for theophylline toxicity.
    • Prolonged clearance and half-life in neonate and the elderly
    • Pregnancy category C

Theophylline: ADRs:

  • Toxicity occurs with levels greater than 20 mcg/mL.
  • Some patients have seizures at 15 to 20 mcg/mL.
  • CNS effects: irritability, restlessness, seizures, insomnia
  • GI effects: reflux, worsening heartburn
  • Cardiac effects: palpitations, tachycardia, hypotension, and
    life-threatening arrhythmias
  • Toxicity (greater than 20): nausea, vomiting, diarrhea, headache, insomnia, and irritability
  • Toxicity (greater than 35 mcg/mL): hyperglycemia, hypotension, cardiac arrhythmias, tachycardia, seizures, brain damage, and death. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.

Theophylline: Drug and food interactions:

  • Many drug interactions due to metabolism via CYP 450 isoenzyme CYP 1A2, CYP 2E1, and CYP 3A3/4
  • Smoking tobacco increases clearance.
  • Benzodiazepines are antagonized by theophylline.
  • Beta agonists may cause additive toxicity.
  • Reduced lithium levels
  • Low-carbohydrate/high-protein diet increases clearance.
  • Charcoal-broiled foods accelerate the hepatic metabolism of theophylline.

        Bronchodilators (Xanthines)

(Chronic Bronchitis/Emphysema/Asthma)



  • Theophylline (Slo-Phyllin, Theo-24, Theo-Dur)
  • Aminophylline (Phyllocontin)

Action of Bronchodilators (Xanthines):

  • Cause bronchodilation by relaxing smooth muscle of the bronchi and pulmonary blood vessels
  • The Xanthines are central respiratory STIMULANTS
  • The Xanthines reduce fatiguability in patients with COPD


Bronchodilators (Xanthines): Comment

  • Must monitor serum plasma levels (10-20 mcg/ml is desirable)
  • Elevated levels predispose patient to Ventricular Arrhythmias
  • Elevated levels predispose patient to SEIZURES
  • Monitor for Tremors
  • Monitor for Anxiety
  • Monitor for Jitteriness
  • Many food-drug interactions involving CYP 450 system (metabolism of the drug)
  • Not used for asthma unless other agents are ineffective. NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide.
  • ONLY use xanthines for ASTHMA if OTHER AGENTS are INEFFECTIVE


58.Antihistamines—H1 and H2 blockers


60.Treating URIs in children

61.Inotropic Effect

62.Chronotropic effect

63.ASA in CV patients

64.Preventative and Abortive therapy and migraines

65.Cluster Has/Tension Has/Migraines

66.SSRIs (know food interactions)

67.Diuretics and potassium supplementation

68.Pneumonia treatment—healthy and patients with co-morbidities

69.Nicotine replacement tx

70.Treatment of Sinusitis

71.Treatment of Otitis Media—adults and children


73.Parkinson’s Dz

NSG 6005 Advanced Pharmacology Midterm & Final Exam Study Guide

Open chat
WhatsApp chat +1 908-954-5454
We are online
Our papers are plagiarism-free, and our service is private and confidential. Do you need any writing help?