1. 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

2. Mechanism & management of
Paraceamol toxicity
Uses of paracetamolUses of paracetamol
• AnalgesicAnalgesic
• AntipyreticAntipyretic
• ArthritisArthritis
• HeadacheHeadache
• DysmenorrheaDysmenorrhea

3. 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

4. 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

5. • 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 toxicityMechanism of paracetamol toxicity

6. Mechanism of paracetamol toxicity

7. Management/treatment of Paracetamol toxicityManagement/treatment of Paracetamol toxicity
Adult 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.

8. Aspirin
(Acetylsalicylic acid)
Uses
• Antipyretic
• Analgetic
• Headache
• Myocardial infarction
• Rheumatic fever

9. • 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.

10. • 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

11. • 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