A.19

Question 1

Acetylsalicylic acid and drugs treating gout

Answer 1

1. Acetylsalicylic acid
2. treatment of Gout: Colchicin, Allopurinol, Rasburicase

Question 2

Acetylsalicylic acid

Answer 2

MOA: irreversible COX inhibitor (COX1>COX2);
Effect: irreversible inhibition of the enzyme in platelets→ ↓TXA2→ ↓effect of platelet aggregation;
IND: dose dependent effects:
1. 100mg/day → inhibition of platelet aggregation (post-MI prophylaxis).
2. 500mg/occasion→ analgestic and anti-pyretic.
3. 4-5g/day→ anti-inflammatory;
Contra-IND: in children based on the risk to develop Reye syndrome;
SEs: ↑bleeding time, ↑body T, GI bleeding, peptic ulcers, renal damage, hepatotoxicity, hypersensitivity reaction, NSAIDs-induced asthma, respiratory alkalosis(early)→ metabolic acidosis → respiratory acidosis, tinnitus, vertigo, hearing loss;
Extra: Good oral absorption, high plasma protein binding, hepatic metabolism;
ROA: p.o;
DOA: T1/2- less than 6 hours

Question 3

Colchicin

Answer 3

MOA: microtubule assembly inhibitor;
Effect: Binds to tubulin→ prevents polymerization, inhibits migration of leukocytes + phagocytosis, inhibits release of lysosomal enzymes. Mitosis inhibitor;
IND: acute gout attacks (high dose required→SEs), chronic gout (low doses), Familial mediterranian fever; SEs: Diarrhea, GI pain, hepatotoxic, neurotoxic, nephrotoxic;
ROA: p.o

Question 4

Allopurinol

Answer 4

MOA: uric acid synthesis inhibitor (Inhibits xanthine oxidase enzyme →↓uric acid concentration);
IND: chronic gout, adjunct to cancer chemotherapy; SEs: GI disturbances, BM depression, hepatotoxicity; Extra: increased toxicity if co-administered with Azathioprin (Azathioprin is metabolized to 6-MP→metabolized to thio-MP→ inactivated by xanthine oxidase), when they are co-adm. the azathioprin toxicity increases since less of it is inactivated by the enzyme;
ROA: p.o

Question 5

Rasburicase

Answer 5

MOA: recombinant urate oxidase;
Effect: urate oxidase enzyme catalyzes the metabolism of uric acid to allantoin→ ↓serum uric acid, ↓uric acid preparation;
IND: chronic gout (therapy resistant);
SEs: anaphylactic reaction, methemoglobinemia;
ROA: p.o

Question 6

Reye syndrome

Answer 6

children treated with aspirin for viral infection → acute liver failure, encephalopathy

Question 7

NSAID

Answer 7

non steroidal anti inflammatory drugs

Question 8

COX enzymes

Answer 8

COX1- constitutive enzyme→found in most tissues; COX2- Inducible enzyme→ expressed in inflammed tissue, induced by cytokins, endotoxins

Question 9

General effects of NASIDs

Answer 9

1. Anti-inflammatory effects
2. Analgestic effects
3. Anti-pyretic effects
4. Anti-platelet effects
5. Other effects

Question 10

Contra-IND of NSAIDs

Answer 10

Nursing and pregnancy
Serious bleeding
Allergy / Asthma / Angioedema
Impaired renal function
Drugs (anti-coagulant)