Analgesics - antipyretics

Question 1

Classification of the Anti-pyretics?

Answer 1

1. Salicylic acid derived - Aspirin.
2. Pyrazolone derived - Metamizole.
3. Aniline derived - Paracetamol.
4. “Combined preparations” ( Containing paracetamol, a mix of codeine/paracetamol and a metamizole preparation.

Question 2

Pharmacokinetics of the anti-pyretics?

Answer 2

1. Aspirin - Has good oral absorption, is able to penetrate BBB and BPB. Metabolism in liver and urine excretion.
2. Metamizole - Good oral absorption, available as tablets, solution for IM injections. Liver metabolism and excretion in urine and feces.
3. Paracetamol - Good oral absorption, available as tablets, powders and solutions for IV injection. Liver metabolism and urinary excretion. Paracetamol overdose generates toxic metabolis NAPQI. N-Acetylcysteine is the antidote for paracetamol poisoning (NAC).

Question 3

Aspirin pharmacodynamics?

Answer 3

COX enzymes are responsible for production of prostaglandins. Aspirin causes Irreversible acetylation of the Cycloxygenase enzyme (COX) which inactivates the enzyme. Inactivating the COX-1 has an effect on the functions of PGE2/PGF to produce a protective mucus layer in stomach –> Stomach ulcers and GI bleedings. The inhibition of COX also reduces the production of prostaglandins, hence regulating the parts of the inflammatory process regulated by the prostaglandins. PGE2 also sensitises nerve endings to the effects of bradykinin, without it the sensation of pain is reduced. Thermo regulation is also disturbed without PGE2, as changes to the set point in the thermoregulatory centre are mediated by prostaglandins.

Question 4

Pharmacodynamics of Metamizole and Paracetamol?

Answer 4

1. Paracetamol - Nitric oxide anti inflammatory activity and inhibition of COX-3 –> reduced prostaglandins (anti-pyretic and analgesic).
2. Metamizole - Nitric oxide anti - inflammatory activity and anti - pyretic and spasmolytic activity, unlike paracetamol.

Question 5

Therapeutic uses for Aspirin?

Answer 5

1. Relief of fever in adults and children (anti-pyretic).
2. At low dose is analgesic and at high dose is anti-inflammatory.
3. Reduces risk of stroke/MI and prevents platelet aggregation (thrombolytic).
4. Treatment of acne/warts.

Question 6

Therapeutic uses of Metamizole and Paracetamole?

Answer 6

Metamizole - Headache, toothache, myalgia and arthralgia. 500mg-1g per day/ every 6 hours.

Paracetamol - Tooth ache, lower back pain, joint pain and muscular pain and other mild to moderate pains. Not to be used more than 1g every 6 hours.

Question 7

Contraindications of the anti-pyretics?

Answer 7

1. Aspirin - 3rd trimester of pregnancy, Patients under 20 with flu/chicken pox, ulcers and bleeding disorders (Aspirin inhibits COX enzyme).
2. Metamizole - 3rd trimester of pregnancy, chemotherapy patients and patients with impaired hematopoesis.
3. Paracetamol - Hepatic and renal failure.

Question 8

ADR’s of the anti-pyretics?

Answer 8

1. Aspirin - GI bleedings and ulcers due to irreversible COX acetylation causing its inactivation. Also “Oedema” is another complication as PGE is required for maintaining renal blood flow, without it there is sodium and water retention.
2. Metamizole - Allergic reaction on IM injection administration, which does not occur in parenteral or IV administration !. Another ADR is agranulocytosis (severely reduced WBC count) and red urine.
3. Paracetamol - Hepatotoxicity, only with overdose of the drug. In therapeutic doses there are no noticable ADR’s.