Adverse Effects and Pharmacotherapeutics

Question 1

Know cited examples of organ-directed toxicities

Answer 1

Organ-directed toxicities : toxicity associated with particular organ or organ system:

• Aspirin-induced gastrointestinal toxicity
• Aminoglycoside-induced renal toxicity
• Acetaminophen-induced hepatotoxicity
• Doxorubicin-induced cardiac toxicity

Question 2

Recognize overextension of pharmacological actions of drugs

Answer 2

Overextension of the pharmacological response : Responsible for mild, annoying adverse effects as well as severe adverse effects:

• Atropine-induced dry mouth
• Propranolol-induced heart block
• Diazepam-induced drowsiness

Question 3

Know cited examples of fetal toxicities

Answer 3

• Sulfonamide -induced kernicterus
• Chloramphenicol -induced Gray baby syndrome
• Tetracycline -induced retardation of bone growth

Question 4

Understand the 4 types of drug-induced hypersensitivities (know cited examples).

Question 5

What are drug idiosyncrasies?What are the classic 4 examples of it?

Answer 5

Drug Idiosyncrasies - Abnormal response not immunologically mediated; often caused by genetic abnormalities in enzymes or receptors ; often referred to as pharmacogenetic disorders.

• Patients with abnormal serum cholinesterase develop apnea when given normal doses of succinylcholine “Fast” and “slow” acetylation of isoniazid :
• Genetic studies identify individuals as “fast” or “slow” acetylators with bimodal distribution in general population
• “Slow” acetylators have low hepatic N-acetyltransferase (NAT) activity and are homozygous for autosomal recessive gene
• “Slow” acetylators: more prone to isoniazid-induced vitamin B 6 deficiency (may produce anemia and various neuropathies) Hemolytic anemia due to G6PDH deficiency, this is due to drugs
• Primaquine
• Sulfonamide
• Nitrofurantoin
• Dapsone
• Barbiturate induce porphyria

Question 6

Understand the importance of the placebo response

Answer 6

Placebo Response:Most patients perceive any therapeutic intervention by caring, interested and enthusiastic health care professionals as a positive measure; a factor in alternative medicines and therapies

Question 7

Know the cited drug-drug interactions in terms of pharmacokinetic interactions.

Answer 7

Rate and extent of drug absorption can be altered:
* Cholestyramine : – resin binds with drugs and prevents absorption
* Antacids : – metals chelate tetracyclines and fluoroquinolones preventing their absorption
* Anticholinergics (e.g., atropine ): – decrease gastrointestinal motility and slow absorption of many drugs
* There can also be displacement of drugs from plasma proteins for example digoxin is displaced by quinidine.
* Finally, drug excertion in the urine is effected by other drugs that can acidify or alkalanize urine

Question 8

Know the cited drug-drug interactions in terms of pharmacodynamic interactions.

Answer 8

• Synergistic effect observed with some drugs - valium and alcohol
• Combined use of 2 drugs can enhance toxicity - aminoglycosides with vancomycin can enhance oto and renal toxicty Drugs can oppose pharmalogical effects:
• propnaolol and isoproterenol
• naloxone and morphine

Question 9

Understand the 4 phases of human drug testing

Question 10

Understand the requirements for human testing

Answer 10

Informed Consent

• Required for Phase 1, 2, and 3 subjects
• Must be in writing for Phase 1 and 2
• Peer review (Institutional Review Board, HSC) protects the interest of subjects, investigators, & institutions