Npsc521P Lecture 10 Adverse Effects

Front 1

1. Define adverse drug reactions

Back 1

a. Any undesirable action. Could be toxicity, side effect or drug hypersensitivity

Front 2

2. Differentiate between a toxicity and a side effect of a drug

Back 2

a. Toxicity: cell damage and tissue damage. Usually intolerable (e.g. hepatic cell damage)
b. Side effect: undesired effect, many of which can be tolerated (e.g. dry mouth)

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3/4. Identify the categories required by FDA and drug monographs to list adverse drug effects. Identify some examples reactions within each category

Back 3

The FDA categorizes side affect according to a body system or organ system. The adverse effects are listed according to the frequency of the effect!!! (They are
a. Body as a whole: malaise (tiredness), body pain, back pain, headache, chest pain, lower extremity pain
b. Skeletal muscle: arthralgia, leg cramps, myalgia, myasthenia, myositis, tenosynovitis.
c. Cardiovascular System: palpitations, angina-like pain, hypotension, arrhythmias
d. Nervous system: dizziness, mental depression, hallucinations, depression, tremors, sleepiness
e. Respiratory System: shortness of breath, cough, pharyngitis, cold symptoms, sinusitis
f. Hematologic: Anemia, leucopenia, thrombocytopenia, neutropenia, thrombocytosis, Agranulocytosis.
g. Digestive System: Nausea, heartburn, gastric irritation, vomiting, constipation, anorexia.
h. Special Senses: blurry vision, increased ocular pressure, ringing in ears, metallic taste
i. Endocrine System: diabetes mellitus symptoms, thyroiditis
j. Hypersensitivities: skin rash, asthmatic syndrome, rhinitis and anaphylaxis
k. Reproductive System: reactions on ovaries, uterus or testes
l. Genitourinary tract: dysuria, impotence, urinary frequency, vaginitis, hematuria
m. Skin: drug induced itching and redness, acne, alopecia, herpes simplex, sweating , urticaria, skin ulcers.

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5. Define and describe drug hypersensitivity reactions

Back 4

Approximately 10% of population are allergic to penicillin
a. Type I mediated by IgE: anaphylaxis, asthma syndrome, rhinitis, dermatitis
b. Type II mediated by IgG, IgM: hemolysis of red blood cells
c. Type II mediated by IgG: arthralgia, fever, lymphadenopathy

Front 5

6. Complete the Lexicomp exercise for ibuprofen

Back 5

a. Significant adverse effect oral (1-10%): 6 categories (CV edema, CNS, Dermatologic, Endocrine, GI  appetite decreased , Otic  tinnitus)
b. What are the adverse effect with the highest over all incidence (up to 9%) for ibuprofen?
i. Dizziness, Rash, epigastric pain, heartburn, tinnitus

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7. Define a teratogenic effect

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a. Ability of drugs to cause defects in developing embryo. Teratos  teros = monster

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8. Briefly describe differences between pregnancy categories A, B, C, D, and X

Back 7

a. controlled studies failed to demonstrate a risk to fetus
b. animal reproduction have not demonstrated fetal risk
c. animal studies have revealed effects on fetus but no data in humans
d. positive evidence of human fetal risk, but benefits of use in pregnant women may be acceptable
e. X: Studies in animals or humans have demonstrated fetal abnormalities  contraindicated

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9. What impact did the drug thalidomide have in the 1960s

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a. 20% of abnormal offspring due to thalidomide in Europe
b. Caused: absent limbs and digits, cleft palate, malformed ears and failure of closure of spinal cord

Front 9

10. What is today’s use and pharmacologic category for thalidomide

Back 9

a. Use: Treatment for multiple myeloma; tx and maintenance of cutaneous manifestations of erythema nodosum leprosum (ENL)
i. Shows promise in curing painful mouth and throat ulcers from AIDS and reverse “wasting” in AIDS
b. Pharmacologic Category: Angiogenesis inhibitor, Immunomodulator, systemic tumor necrosis Factor (TNF), Blocking agent

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11. Describe the field of pharmacogenetics

Back 10

a. Pharmacogenetic screening: to prevent side effects

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12. Provide some examples of how “misspelled genes” affect drug actions

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a. Misspelled genes (aberrant) that encode differences in drug receptor or CYP metabolizing enzymes can create situations leading to drug adverse reactions or ineffectiveness
i. Albuterol: ineffective in dilating smooth muscle in bronchioles
ii. Prozac: metabolized so slowly that can be toxic
iii. Isoniazid: metabolized so rapidly it is ineffective

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13. What drug example will use genetic profiling to better predict a therapeutic effect?

Back 12

a. Genetic profile screens  Starting to be used in establishing gene types prior to use of certain medications: e.g. Identify gene types when asthma is diagnosed to ensure that receptors in bronchioles will respond to albuterol.