Adverse Effects and Pharmacotherapeutics

Question 1

Clinical Manifestations of Type 1 Hypersensitivities (IgE)–[4]

Answer 1

1. GI allergy
2. Urticaria (hives)
3. asthma
4. anaphylactic shock

Question 2

Clinical Maneifestations of Type–II Hypersensitivities (IgM, IgG)
-cytotoxic; autoimmune [4]

Answer 2

1. Leukopenia
2. thrombocytopenia
3. hemolytic anemia
4. granulocytopenia

Question 3

Clinical Maneifestations of Type–III Hypersensitivities (Ag-Ab)
-Arthus; immune complex [4]

Answer 3

1. serum sickness
2. vasculitis
   * stevens-johnson syndrome–induced by sulfonamides
3. arthritis
4. glomerular nephritis

Question 4

Clinical Maneifestations of Type–IV Hypersensitivities (T-cells)
-cell-mediated [4]

Answer 4

1. contact dermatitis
2. tuberculosis
3. allergic encephalitis
4. contact nephritis

Question 5

Type II Hypersensitivities–Drug examples [5]

Answer 5

1. penicillin–hemolytic anemia
2. methyldopa–autoimmune hemolytic anemia
3. quinidine–thrombocytopenia
4. sulfonamide–granulocytopenia
5. clozapine–granulocytopenia

Question 6

Type III Hypersensitivities–Drug examples [5]

Answer 6

1. sulfonamides
2. penicillins
3. thiouracils
4. anticonvulsants (lamotrigine)
5. Iodides

Question 7

Drug Idiosyncrasies–1

Patients w/ abnormal SERUM CHOLINESTERASE develop apnea when given NORMAL doses of _____

Answer 7

succinylcholine

Question 8

Drug Idiosyncracies–2

“Fast” and “slow” acetylators is an important distinction for the following drug

Answer 8

Isoniazid

• Slow acetylators have low N-acetyltransferase (NAT) are are homozygous autosomal recessive
• slow acetylators are prone to isoniazid-induced vitamin B6 deficiency (presents as anemia and various neuropathies)

Question 9

Drug Idiosyncracies–3

Hemolytic anemia ellicited by ____ in patients deficient in G6PD (glucose-6-phosphate dehydrogenase)

Answer 9

Primiquine (also sulfonamides and nitrofurantoin

• 10% of black males in US develop acute hemolytic anemia
• normal RBC have mechanisms to protect against ROS (via primiquine metabolites)

Question 10

Drug Idiosyncracies–4

Barbituate-induced porphyria occurs in individuals w/ abnormal ___ ___

Answer 10

heme biosynthesis…

*barbituates bind ALA synthetase instead of heme–which heme is an INHIBITOR…thus causing excess porphyrin production

Question 11

Drug Interactions

-Cholestryamine

Answer 11

resin binds w drugs and prevents absorption

Question 12

Drug Interactions

-Antacids

Answer 12

metals chelate tetracyclines and fluoroquinolones–preventing their absorption

Question 13

Drug Interactions

-Anticholinergics (atropine)

Answer 13

decrease GI motility, slow absorption of many drugs

Question 14

Buzzwords for Phases of Clinical Trials–Human Testing

-Phase 1:

Answer 14

• 20-30 subjects
• Goals:
  
  • find maximum tolerated dose
  • characterize adverse effects
  • define pharmacokinetics
• NEVER DOUBLE-BLIND

Question 15

Buzzwords for Phases of Clinical Trials–Human Testing-Phase: 2:

Answer 15

• 100s of subjects
• determine clinical effectiveness
• measure biomarkers for efficacy
• single- or double-blind

Question 16

Buzzwords for Phases of Clinical Trials–Human Testing-Phase: 3:

Answer 16

• 10,000 subjects
• test efficacy and toxicity
• complete..file for new drug app (w/ nFDA)

Question 17

Buzzwords for Phases of Clinical Trials–Human Testing-Phase 4:

Answer 17

post-marketing surveillance

*chloramphenicol causes aplastic anemia 1/40,000