Toxicity Management

1. Various Drug Toxicity & their
Treatment
Dr. Rajib Karmakar
PG-Final Year
Dept of Pharmacology, RMCH, Bareilly

2. Digoxin
 Digitalis purpurea- digitoxin
 Digitalis lanata- digoxin &
digitoxin
 Usual Fatal Dose
■ Digitalis leaf: 2 gram
■ Digoxin: 10 mg
■ Digitoxin: 3 mg

5. Initial Treatment
 Gastric lavage
 Activated charcoal
 Forced diuresis
 All patients with a H/O cardiac glycoside ingestion should have a
baseline ECG & serial serum levels of electrolytes.
 Patients who remain asymptomatic with normal (or unchanged
from previous) baseline & follow-up ECG, declining & normal
serum electrolytes, may be discharged after 6 hours of
observation.
Treatment of Digoxin toxicity

8. Treatment of Digoxin toxicity
Advanced Treatment
 Antidote: Digoxin-specifc antibody fragments
(Fab)
 Fab fragments are administered i/v.
 Indication-life-threatening arrhythmia,severe
hyperkalaemia, Plasma digoxin ˃ 10 nmol/L.
 For tachyarrhythmias- KCl 20 m.mol/hour i.v. or
orally in milder cases
 For ventricular arrhythmias- Lidocaine i.v.
 For supraventricular arrhythmias-
Propranolol may be given i.v. or orally
 For A-V block and bradycardia- Atropine
0.6–1.2 mg i.m.
 External or transvenous pacemaker
 Percutaneous cardiopulmonary bypass

9.  Paraaminophenol derivative
 Acute paracetamol poisoning It occurs especially in small children who have low
hepatic glucuronide conjugating ability. If a large dose (> 150 mg/kg or > 10 g in an
adult) is taken, serious toxicity can occur.
 Early manifestations are just nausea, vomiting, abdominal pain and liver tenderness with
no impairment of consciousness.
 After 12–18 hours centrilobular hepatic necrosis occurs which may be accompanied by
renal tubular necrosis and hypoglycaemia that may progress to coma.
 Jaundice starts after 2 days.
Paracetamol Poisoning

10. Treatment of Paracetamol Poisoning
 General Measures
 Gastric lavage done.
 Activated charcoal is given orally or
through the tube to prevent further
absorption.
Specific
 N-acetylcysteine- 150 mg/kg should be
infused i.v. over 15 min, followed by
the same dose i.v. over the next 20
hours.
 It replenishes the glutathione stores of
liver and prevents binding of the toxic
metabolite to other cellular
constituents

11.  Nonselective COX inhibitors
 Antiinflammatory action is exerted at high doses (3–6 g/day or 100 mg/kg/ day)
 Analgesic,antipyretic doses 300-600mg,6-8hrly
 Antiplatelet dose 75-100mg/day
 Fatal dose in adults is estimated to be 15–30 g, but is considerably lower in children.
Serious toxicity is seen at serum salicylate levels > 50 mg/dl.
 Therapeutic serum salicylate levels should not exceed 30 mg/100 ml.
Aspirin

12. Clinical features of Aspirin Poisoning
 Acute Poisoning
 Early—Nausea, vomiting, sweating,
tinnitus, vertigo, hyperventilation,
Irritability, confusion, disorientation,
hallucinations, ataxia & restlessness
may be early fndings in patients with
severe toxicity.
 Late—Deafness, agitation, delirium,
convulsions, hallucinations
 Complications—Metabolic acidosis,
pulmonary oedema,rhabdomyolysis,
cardiac depression,
thrombocytopenic purpura.
Gastrointestinal bleeding, Reye’s
Syndrome
Chronic Poisoning (Salicylism)
 Characterised by slow onset of
confusion, agitation, lethargy,
disorientation, slurred speech,
hallucinations, convulsions &
coma.
 There may also be tinnitus,
hearing loss, nausea, dyspnoea,
tachycardia and fever.

14. Treatment of Aspirin Poisoning
General measures
Stomach wash may be
beneficial upto 12 hours
after ingestion
Activated charcoal (AC)-It
is said to be very
effcacious in the
treatment of salicylate
poisoning since each
gram of AC can adsorb
550 mg of the drug.
Urinary alkalinisation
Haemodialysis
Supportive measures
 Correction of fluid & electrolyte
imbalance
 Correct dehydration with NS
 Hypoprothrombinaemia- 2.5 to 5 mg of
vitamin K IV every day.
 Correction of metabolic acidosis with
NaHCO3.
 Treatment of convulsions with
benzodiazepines
 Give blood or blood products (fresh
frozen plasma) if bleeding is
excessive. Vitamin K may be beneficial
in the presence of a prolonged PT or
INR.

15.  Long acting BZDs
 Hypnotic, Anxiolytic & Anticonvulsant
 Hypnotic dose- 5-10mg
 Usual Fatal Dose- Uncertain
Diazepam

16. Clinical features of Diazepam Poisoning
Acute Poisoning
Mild—Drowsiness,
ataxia, weakness.
Moderate to Severe—
Vertigo, slurred speech,
nystagmus, partial
ptosis, lethargy, coma.
Chronic Poisoning
 Long-term use- associated with
the development of tolerance.
 Abrupt cessation provokes a mild
withdrawal reaction
characterised by anxiety,
insomnia, headache, tremor &
paraesthesia.
 Restlessness, encephalopathy,
and hallucinations may occur
after abrupt withdrawal from
high daily doses.

17. Treatment of Diazepam Poisoning
General measures
Stomach wash may be helpful if the patient is
seen within 6 to 12 hours after the ingestion
Activated charcoal
Establishment of clear airway. Oxygen and
assisted ventilation are often necessary.
IV fluids- Ringer’s lactate
Correction of hypotension: Begin by infusing 10
to 20 ml/kg of isotonic fluid. If hypotension
persists, administer dopamine or noradrenaline.
Antidote- Flumazenil is effective in reversing the
coma induced by benzodiazepines

18.  Antiepileptic & Preanesthetic medication
 Poisoning is mostly Suicidal rarely accidental
 Usual Fatal Dose
■ Phenobarbitone: 6 - 10 g.
■ Amobarbitone, pentobarbitone, secobarbitone: 2 - 3 g.
Barbiturates

19.  Slurred speech, ataxia, lethargy, confusion, headache, nystagmus.
 CNS depression, coma, shock.
 Pupils are at first constricted, but later dilate because of hypoxia.
 Hypothermia.
 Cutaneous bullae-These are clear, erythematous or haemorrhagic blisters,
and occur in various areas of the body, most typically on the hands, buttocks,
and between the ankles and knees, usually over pressure points.
 Death may occur from respiratory arrest or cardiovascular
collapse.
Clinical features of Barbiturate Poisoning

21.  Monitor CBC, serum electrolytes, glucose, blood urea nitrogen, creatinine, and urine
myoglobin in patients with signifcant intoxication.
 Gastric lavage can be done with beneft upto 12 to 24 hours postingestion.
 Activated charcoal
 Forced alkaline diuresis
 Haemodialysis or haemoperfusion: Barbiturate elimination can be increased by
haemodialysis or charcoal haemoperfusion.
 For hypotension: First administer 10 to 20 ml/kg of isotonic IVF, If the patient is
unresponsive to isotonic fluid therapy administer a vasopressor-Dopamine or
noradrenaline
 Supportive measures: supplemental oxygen, intubation, assisted ventilation
Treatment of Barbiturate Poisoning

24. Treatment of allergic reactions and allergic disorders.
■ Symptomatic relief of common cold.
■ Treatment of vertigo, travel sickness.
■ Anti-emetic.
■ Sleeping aid.
Antihistaminics

25. The toxicity of antihistamines is related to their anticholinergic
(antimuscarinic) activity
The action of acetylcholine at muscarinic receptors is blocked
Main symptoms include somnolence, lethargy, mydriasis, blurred
vision, convulsions, hallucinations, extra-pyramidal movement
disorders & psychosis.
Dryness of skin and mucous membranes, cutaneous flushing,
anhydrosis, hyperthermia, urinary retention,
Skin is usually flushed, warm and dry after overdose.
Hypertension is more commonly reported than hypotension.
Tachycardia is also very common.
Clinical features of Antihistaminic Poisoning

26. Treatment of Antihistaminic Poisoning
 Stomach wash
 Activated charcoal
 Diazepam IV for agitation/psychosis, or convulsions
 Cooling measures for hyperthermia. Sponge patient
with water, and use fans to maximise evaporative
heat loss.
 For hypertensive emergencies- Nitroprusside is
preferred.
 Dysrhythmias can be corrected with IV magnesium
sulfate or lignocaine
 Physostigmine- 2 mg (adults); 0.5 mg (children), by
slow IV. It can be repeated at 5–10 minute intervals if
there is no signifcant improvement.