Acetaminophen

Question 1

Pharmacokinetics

Answer 1

Oral absorption is complete and fast in GIT with peak level within 30 min

Distribution is well

Metabolism : by liver conjugation , at high doses : its converted to toxic metabolites ( n-acetyl benzoquinone ) that causes hepatotoxicity
Excretion : mainly by renal

Question 2

Mechanism

Answer 2

Selective inhibitor of cox 3 that synthesis PGS in brain only so its analgesic and antipyretic and it has no effect on enzymes responsible for PGs synthesis in periphery so its not anti inflammatory drug

It has no or little effect on cvs , respiration and platelt

Question 3

Therapeutic uses

Answer 3

When aspirin is contraindications

In pregnancy as its safe than aspirin

Question 4

Adverse effects

Answer 4

In therapeutic doses
There may be skin rash and fever drug ( as allergic reaction)
In long term it can cause renal failure

In toxic doses there is dose dependant hepatotoxicity ( centrilobular necrosis) 15g for adult and 4 gm for children

Question 5

Mechanism of hepatotoxicity

Answer 5

Its converted to toxic metabolites ( N-actyel benzoquinone) that needs detoxification by reduced glutathione
When glutathione store is depleted , the toxic metabolite covalently bond to liver proteins causing this hepatocellular damage
This toxicity clinical features eg vomiting starts within the first 24h from it but hepatic damage appear from 2-6 days after

Question 6

Treatment of toxicity

Answer 6

GSH

G. Gastric lavage with activated charcoal
S Sulfhydryl donors ( actyelcysteine) to restore
Hepatic glutathione but better be started with
With the first 8 h after toxicity
H Hemodialysis : better be within the first 12h
After toxicity

Question 7

How actyelcysteine is administered

Answer 7

Follow 20hrs iv protocol

150 mg/ kg for over 60 m
12.5 mg/kg for 4 hrs
6.25 mg/kg for 16 hrs

Question 8

Mechanism of nefopam and effects

Answer 8

1- central anlgesic that has no antipyretic or inflammatory effect
2- the mechanism is unclear
3- potent than NSAIDS
4- its also used in severe hiccups

Question 9

Adverse effects of nefopam

Answer 9

Epileptic convulsions with patients with epilepsy
Has weak atropine like actions

Question 10

Contraindications in nefopam

Answer 10

Epilepsy
Old men with BPH

Question 11

Mechanism and effects of dipyrone

Answer 11

1- central analgesic and antipyretic without anti inflammatory effect
2- potent than aspirin
3- it was restricted in many countries due to agranulocytosis which not dose dependant

Question 12

Adverse effects of dipyrone

Answer 12

3 A
Agranulocytosis: its reversible after 10 days stoppage but lethal in 10% cases

Allergic reaction and anaphylaxis

bronchoconstruction in Asthma