Adverse reaction, mechanism & management of following drugs:

• Paraceamol• Acetylsalicylate• Pyrazolone derivatives• Mefenamic acid• Iron• Water soluble & fat soluble vitamins• CNS stimulants and depressants• Tubercular drugs• Cardiovascular drugs• Cytotoxic drugs• Anesthetic drugs

By fagoson

Mechanism & management of Paraceamol toxicity

Uses of paracetamolUses of paracetamol

• AnalgesicAnalgesic

• AntipyreticAntipyretic

• ArthritisArthritis

• HeadacheHeadache

• DysmenorrheaDysmenorrhea

Absorption: Paracetamol is well absorbed from the GI

tract

Half life: 2-3 hours

Excreion: 5% excreted unchanged in the urine,

remainder metabolized in the liver by the

cytochrome p-450 system.

Toxicokinetics of ParacetamolToxicokinetics of Paracetamol

Paracetamol can produce fatal hepatotoxicity in untreated patients through the generation of a toxic metabolite

Adverse Effects (overdose >10 gram)

• Phase I (12-24 hours post ingestion): nausea, vomiting,

anorexia and diaphoresis (sweating).

• Phase II (1-4 days post ingestion): asymptomatic.

• Phase III (2-3 days in untreated patients): nausea, abdominal

pain, progressive evidence of hepatic failure, coma and death.

Adeverse Effect of Paraceamol

• Acetaminophen is rapidly absorbed from the stomach and small

intestine and metabolized by conjugation in the liver to nontoxic

agents, which then are eliminated in the urine.

• In acute overdose or when maximum daily dose is exceeded over a

prolonged period, the normal pathways of metabolism become

saturated.

• Excess acetaminophen is then metabolized in the liver via the

oxidase P450 system to a toxic metabolite.

• Under conditions of excessive metabolite formation or reduced

glutathione stores, the reactive metabolite is free to covalently

bind to vital proteins and the lipid bilayer of hepatocytes; this

results in hepatocellular death and subsequent liver necrosis.

Mechanism of paracetamol toxicity Mechanism of paracetamol toxicity

Mechanism of paracetamol toxicity

Management/treatment of Paracetamol toxicityManagement/treatment of Paracetamol toxicityAdult patients who have ingested >7 gram or children who have ingested >100 mg/kg require treatment.

• The recommended treatment is gastrointestinal decontamination with

syrup of ipecac (induce vomiting) or gastric lavage (wash out) for patients

presenting within 2 hours of ingestion.

• Antidote therapy with N-acetyl cysteine (NAC) is indicated for patients

with toxic blood levels of paracetamol.

Dose: 140 mg/kg as a loading dose followed by 70 mg/kg every 4 hours for

a total of 17 doses.

Patients with severe nausea secondary to NAC may be prevented with IV

metoclopramide (antiemetic and increase the rate of absorption of NAC)

10 mg 6 hours.

• Supportive care with IV electrolyte and Vitamin-K if bleeding is

occurred.

• In severe case hemoperfusion is necessary for quick elemination of the

toxic intermediate.

Aspirin(Acetylsalicylic acid)

Uses

• Antipyretic

• Analgetic

• Headache

• Myocardial infarction

• Rheumatic fever

• Initially, hyperventilation develops (loss of CO2) secondary to

direct stimulation of the respiratory centers. This may be the only

consequence of mild salicylism. Disturbance in acid-base occurs.

• A severe metabolic (ketolactic) acidosis may develop with severe

salicylate intoxication.

• Excretion of hydrogen ions produces acidic urine.

• Overdose produces: Tinnitus, tachycardia, CNS depression,

seizures, nausea & vomiting, GI hemorrhage, prolonged bleeding

time, dehydration. Death may occur from acidosis.

Adverse Effect (>15-20g)

Prolong administration of large doses (3.6 gram daily) produces

adverse effects. At a dose >150, >250 & >500 mg/kg produce mild,

moderate & severe poisoning respectively.

• Salicylates cause oxidative phosphorylation.

• Thus catabolism occurs with the following results:

- increase oxygen consumption,

- increase carbon dioxide production,

- accelerate activity of the glycolytic and lipolytic

pathways,

- depletion of hepatic glycogen, hyperpyrexia.

Mechanism of Action

• Gastric lavage may be beneficial, up to 60 minutes after

salicylate ingestion.

• Fluid losses from vomiting and sweating are replaced by IV

fluid.

• Hemodialysis is effective method for enhanced elimination of

salicylate and correcting acid-base and fluid balance

abnormalities.

• Sodium bicarbonate is given to alkalinize the urine & increase

salicylate excretion.

• Use of multiple doses of activated charcoal is currently

recommended.

• Monitored glucose levels closely.

Management/Treatment