B/27. General properties of NSAIDs. Acetylsalicylic acid.

Question 1

Drugs need to know in this topic

Answer 1

acetylsalicylsav

colchicin

allopurinol

rasburicase

Question 2

acetylsalicylic acid

Answer 2

1. Irreversible inhibition of COX enzymes (acetylation of
   serine hydroxyl group)
2. Oral
3. Low doses → first order elimination, T1/2 3-5 h’
4. High doses → zero-order elimination, T1/2 up to 15 h’
5. Renal elimination

• *Dose-dependent effects:**
  1. Low dose (< 300 mg/d):
  1. anti-platelet aggregation effect (post MI prophylaxis, reduce the risk of CV events)
  2. Medium dose (300-2400 mg/d): analgesic and anti-pyretic effects
  3. High dose (2400-5000 mg/d): anti-inflammatory effects

Side effects

∙Gastric bowel ulcers :↓PG level+local destroying effect
∙Decreased renal function, water retention :↓RBF, accumulation of NSAIDs
∙Cartilage damage: ↓PG level ->higher ROS level
∙Ductus Botallo closure : COX1 inh are CI in the 3rd trimester
∙Decrease of uterus contractility: prolonged delivery, increased bleeding
∙Pseudoallergic reaction: rash, bronchoconstriction
∙Cardiotoxicity: proarrythmic effects

Question 3

Colchicine

Answer 3

Microtubule assembly inhibitors

Bind to tubulin → altered microtubular polymerization, LTB4 ↓, altered leukocyte and granulocyte migration

Oral, parentera

1. Acute gout – high doses required (use is limited due to severe diarrhea)
2. Chronic gout – low doses
3. Familial Mediterranean fever
4. Potential role in the management of pericardial diseases (pericarditis, pericardial effusion)

Side effects:

1. Acute: severe diarrhea, GI pain
2. Longer use: hematuria, alopecia, myelosuppression, gastritis, peripheral neuropathy

Question 4

Allopurinol

Answer 4

Xanthine oxidase inhibitors

Inhibit xanthine oxidase → decreased purine metabolism → serum uric acid ↓

1. Oral
2. Prodrug, activated by xanthine oxidase
3. At high doses, active metabolite acts as a ‘suicide inhibitor’
   (irreversible inhibition)
4. Drug interaction → inhibit metabolism of 6-MP
5. Chronic gout
6. Adjunct to cancer chemotherapy and radiotherapy (‘tumor-lysis
   syndrome’ – may precipitate gout attack)
   Side effects:
7. GI irritation
8. Hypersensitivity reaction, Stevens-Johnson syndrome
9. Bone marrow suppression

Question 5

Rasburicase

Answer 5

Recombinant urate oxidase

Urate oxidase enzyme catalyzes the metabolism of uric acid to allantoin (water-soluble) → serum uric acid ↓, uric acid precipitation ↓

1. IV
2. T1/2 up to 18 h’