Poisoning, overdose, antidotes

Causes of toxicity

1     Drug toxicity.

2       Accidental ingestion and suicide attempts:

a       drugs: sedative hypnotics, antidepressants, paracetamol, salicylates.

b     non-drugs: detergents / solvents, herbicides, insecticides.

3.       Industrial toxicity.

4.       Environmental & ecotoxicology:

a.       air/water/soil pollution.

b.    food addictives/preservatives.

c.       ozone depletion, nuclear wastes, etc.

Assessment of patient

1.    Fast or irregular pulse:

a.       salbutamol.

b.       antimuscarinics.

c.       TCAs.

d.       quinine.

e.       phenothiazines.

2.    Slow respirations: opiate toxicity.

3.       Hypothermia:

a.       phenothiazines.

b.       barbiturates.

c.       TCAs.

4.       Hyperthermia:

a.       amphetamines.

b.       MAOIs.

c.       cocaine.

d.       antimuscarinics.

5.       Coma:

a.       benzodiazepines.

b.       alcohol.

c.       opiates.

d.       TCAs.

e.       barbiturates.

6.       Seizures:

a.       recreational drug use.

b.       hypoglycaemic agents.

c.       TCAs.

d.       phenothiazines.

e.       theophyllines.

7.       Constricted pupils:

a.       opiates.

b.       organophosphates.

8.       Dilated pupils:

a.       amphetamines.

b.       cocaine.

c.       quinine.

d.       sympathomimetics.

Prevention of absorption

1.       When a poison has been inhaled or absorbed through the skin, the patient should be taken from the toxic environment, contaminated clothing removed and the skin cleansed.

2.    Oral adsorbents:

a.       activated charcoal reduces drug absorption, is easiest to administer and has fewest side effects; it should be given as soon as possible after the poison is ingested.

b.       substances not adsorbed by charcoal: iron, lithium, cyanide, strong acids and alkalis, and organic solvents and corrosive agents.

c.       activated charcoal also accelerates elimination of poison that has been adsorbed.

d.       Fuller’s earth and bentonite: bind and inactivate the herbicides, paraquat and diquat.

e.       cholestyramine and colestipol adsorb warfarin.

3.       Gastric lavage:

a.    best confined to the hospitalized adult who is believed to have taken a significant amount of a toxic substance within 4-6h.

b.       worth undertaking in any unconscious patient, provided the airways are protected by a cuffed endotracheal tube.

4.       Emesis:

a.    in fully conscious patients only, may be used for children and also for adults who refuse activated charcoal or gastric lavage.

b.       emesis is induced by ipecacuanha.

c.    it can cause prolonged vomiting, diarrhoea and drowsiness that may be confused with effects of the ingested poison.

5.    Both emesis and lavage are contraindicated for corrosive poisons, because there is a risk of perforation of the gut, and for petroleum distillates due to the danger of causing inhalational chemical pneumonia.

6.       Cathartics:

a.       whole-bowel irrigation used for removal of sustained-release formulations: theophylline, iron, aspirin.

b.       activated charcoal in repeated dose is preferred.

Specific antidotes

1.       Categories:

a.       receptors, which may be activated, blocked or bypassed.

b.       enzymes, which may be inhibited or reactivated.

c.       displacement from tissue binding sites.

d.       exchanging with the poison.

e.       replenishment of an essential substance.

f.       binding to the poison.

2.       Dimercaprol:

a.       provides –SH groups which combine with the metal ions to form harmless ring compounds which are excreted, mainly in the urine.

b.       repeated administration is necessary to ensure that an excess is available until all the metal has been eliminated.

c.    used for poisoning by antimony, arsenic, bismuth, gold and mercury.

d.       adverse effects: nausea and vomiting, lachrymation and salivation, paraesthesiae, muscular aches and pains, urticarial rashes, tachycardia and a raised blood pressure.

e.       gross overdose: overbreathing, muscular tremors, convulsions and coma.

3.       Sodium calciumedetate:

a.       effective in lead poisoning because of its capacity to exchange calcium for lead.

b.       adverse effects: hypotension, lachrymation, nasal stuffiness, sneezing, muscle pains and chills.

4.       Dicobalt edetate:

a.       forms stable, nontoxic complexes with cyanide.

b.       toxic, causing hypertension, tachycardia and hcest pain.

Acceleration of elimination of poison

1.       Techniques for eliminating poisons depends directly or indirectly, on removing drug from the circulation and successful use requires that:

a.    the poison should be present in high concentration in the plasma relative to that in the rest of the body.

b.    the poison should dissociate readily from any plasma protein binding sites.

c.    the effects of the poison should relate to its plasma concentration.

2.       Repeated doses of activated charcoal:

a.       activated charcoal by mouth adsorbs drug that diffuses from the blood into the gut lumen and drugs that are secreted into the bile.

b.       repeated-dose activated charcoal is increasingly preferred to alkalinization of urine for phenobarbitone and salicylate poisoning.

3.       Alteration of urine pH and diuresis: by manipulation of the pH of the glomerular filtrate, a drug can be made to ionize, become less lipid-soluble, remains in the renal tubular fluid, and so be eliminated in the urine.

4.       Alkalinzation:

a.    used for salicylate (> 500 mg/l + metabolic acidosis or in any case > 750 mg/l), phenobarbitone or phenoxy herbicides.

b.    the objective is to maintain a urine pH of 7.5-8.5 by an i.v. infusion of sodium bicarbonate.

5.       Acidification:

a.    used for severe, acute amphetamine, dexfenfluramine or phencyclidine poisoning.

b.    the objective is to maintain a urine pH of 5.5-6.5 by giving i.v. infusion of arginine hydrochloride (10g) or lysine hydrochloride (10g) over 30 min, followed by ammonium chloride (4g) 2-hourly by mouth.

6.       Peritoneal dialysis:

a.       involves instilling appropriate fluid into the peritoneal cavity.

b.       poison in the blood diffuses into the dialysis fluid down the concentration gradient.

c.    the fluid is then drained and replaced.

d.    the technique requires little equipment but is one-half to one-third as effective as haemodialysis.

e.    used for lithium and methanol poisoning.

7.       Haemodialysis and haemoperfusion:

a.    a temporary extracorporeal circulation is established, usually from an artery to a vein in the arm.

b.    in haemodialysis, a semipermeable membrane separates blood from dialysis fluid and the poison passes passively from the blood, where it is present in high concentration.

c.    the principal of haemoperfusion is that blood flows over activated charcoal or an appropriate ion-exchange resin which adsorbs the poison.

d.    their use should be confined to cases of severe, prolonged or progressive clinical intoxication, when high plasma concentration indicates a dangerous degree of poisoning.

e.       haemodialysis is effective for: salicylate, isopropanol, lithium and methanol.

f.       haemoperfusion is effective for: phenobarbitone and other barbiturates, theophylline.

Common poisonings

1.       Antimuscarinic syndromes:

a.       consist of tachycardia, dilated pupils, dry, flushed skin, urinary retention, decreased bowel sounds, confusion, cardiac dysrhythmias and seizures.

b.       commonly caused by antipsychotics, TCAs, antihistamines, antispasmodics.

2.       Cholinergic syndromes:

a.       comprises salivation, lachrymation, abdominal cramps, urinary faecal incontinence, vomiting, sweating, miosis, muscle fasciculation and weakness, bradycardia, pulmonary edema, confusion, CNS depression and fits.

b.       common causes are organophosphates and carbamate insecticides.

3.       Sympathomimetic syndromes:

a.       these include: tachycardia, hypertension, hyperthermia, sweating, mydriasis, hyperreflexia, agitation, delusions, paranoia, seizures and cardiac dysrhythmias.

b.       common causes are amphetamine, cocaine, ephedrine, and theophylline.

4.       Sedatives, opioids and ethanol cause respiratory depression, miosis, hyporeflexia, coma, hypotension and hypothermia.

5.       Cyanide:

a.       causes tissue anoxia by chelating the ferric part of the intracellular respiratory enzyme, cytochrome oxidase.

b.       poisoning may occur as a result of self-administration of hydrocyanic acid, by accidental exposure in industry through inhaling smoke from burning polyurethane foams in furniture or from excessive use of sodium nitroprusside.

c.       acute poisoning: dizziness, palpitations, a feeling of chest constriction and anxiety.

d.       inhaled hydrogen cyanide may lead to death within minutes but when it is ingested as a salt several hours may elapse before the patient is seriously ill.

e.       chronic exposure damages the nervous system causing peripheral neuropathy, optic atrophy and nerve deafness.

f.       dicobalt edetate is the treatment of choice when the diagnosis is certain; dose is 300 – 600 mg given i.v. over one minute.

6.       Carbon monoxide:

a.       formed when substances containing carbon and hydrogen are incompletely combusted; poisoning results from inhalation.

b.       oxygen transport to cells is impaired and myocardial and neurological injury result; delayed neurological sequelae include parkinsonism and cerebellar signs.

c.       treated with hyperbaric oxygen.

7.       Methanol:

a.       widely available as a solvent and in paints and antifreezes.

b.    as little as 10ml may cause permanent blindness and 30ml may kill.

c.       acidosis is due to formic acid, which itself enhances pH-dependent hepatic lactate production, so that lactic acidosis is added.

d.       clinical features: severe malaise, vomiting, abdominal pain and tachypnoea, loss of visual acuity and scotomata.

e.       therapy is aimed at correcting the acidosis, inhibiting methanol metabolism with use of ethanol and eliminating methanol and its metabolites by dialysis.

8.       Ethylene glycol:

a.    a constituent of antifreeze for car radiators.

b.       metabolism to glycolate and oxalate causes acidosis and renal damage.

c.    first 12 hours after ingestion: increasing acidosis, pulmonary edema and cardiac failure.

d.    2 –3 days: renal pain and tubulr necrosis.

e.       acidosis is corrected with i.v. sodium bicarbonate, ethanol is given to inhibit metabolism of ethylene glycol and haemodialysis is used to eliminate the poison.

9.       Hydrocarbons:

a.       chiefly cause CNS depression and pulmonary damage from inhalation.

b.    vital to avoid aspiration into the lungs during attempts to remove the poison or in spontaneous vomiting.

c.       gastric aspiration should be performed only if a cuffed endotracheal tube is in place.

10.       Dinitro-compounds:

a.    used selectively as weed killers and insecticides.

b.    they are absorbed through the skin and the hands, face or hair are usually stained yellow.

c.       symptoms: copious sweating and thirst proceed to dehydration and vomiting, weakness, restlessness, tachycardia and deep, rapid breathing, convulsions and coma.

d.       treatment is urgent and consists of cooling the patient and attention to fluid and electrolyte balance.

e.       phenoxy herbicides cause nausea, vomiting, pyrexia, hyper-ventilation, hypoxia and coma; their elimination is enhanced by urine alkalinization.

11.       Paraquat:

a.    a widely used herbicide which is extremely toxic if it is ingested.

b.       ulceration and sloughing of the oral and esophageal mucosa are followed 5 – 10 days later by renal tubular necrosis.

c.       subsequently there is pulmonary edema followed by pulmonary fibrosis.

d.       treatment is urgent and includes gastric lavage, activated charcoal or aluminium silicate by mouth as adsorbents, and osmotic purgation.

Paracetamol poisoning

1.       Severe hepatic and renal damage can result from taking 150 mg/kg (about 10g or 20 tablets) in one dose.

2.       Patients specially at risk are:

a.       those whose enzymes are induced as a result of taking drugs or alcohol for their livers and kidneys form more NABQI.

b.       those who are malnourished to the extent that their livers and kidneys are depleted of glutathione.

3.    The INR and plasma creatinine are used to monitor hepatic and renal impairment respectively.

4.       Clinical signs:

a.    do not become apparent for 24-48h and liver failure, when it occurs, does so between 2 and 7 days after the overdose.

b.       there may be vomiting and right upper quadrant pain.

c.    later there is jaundice and encephalopathy from liver damage and renal failure.

5.    Do an emergency blood level when 4h have elapsed since ingestion.

6.       Empty the stomach if > 7.5g has been taken.

7.    Give N-acetylcysteine by IVI, 150 mg/kg in 200 ml of 5% dextrose over 15 min.

8.    If the INR exceeds 2 there is risk of infection and gastric bleeding, and an antimicrobial plus either sucralfate or histamine antagonist should be given prophylactically.

Salicylate overdose

1.       Moderate overdose (500 – 750 mg/l):

a.       nausea and vomiting.

b.       epigastric discomfort.

c.       tinnitus and deafness.

d.       headache, sweating and pyrexia.

e.       hyperpnoea.

f.       hypokalaemia.

g.       restlessness.

2.       Severe overdose (> 750 mg/l):

a.       pulmonary edema.

b.       convulsions.

c.       coma with severe dehydration and ketosis.

3.       Mixed acid-base disturbance:

a.       respiratory alkalosis due to direct stimulation of the respiratory center.

b.       metabolic acidosis due to accumulation of lactic and pyruvic acids.

4.       Gastric lavage:

a.       worth undertaking at least up to 12 hr after overdose for tablets may lie as an insoluble mass in the stomach.

b.       activated charcoal is worth giving as it adsorbs salicylate.

5.       Correction of dehydration (< 4.3 mg/l): dextrose 5% given i.v. with added potassium.

6.       Acid-base disturbances (> 4.3 mg/l): sodium bicarbonate is used to correct metabolic acidosis (blood pH < 7.2) and to alkalinize the urine to remove salicylate.

7.       Removal of salicylate from the body: activated charcoal given in repeated doses or haemodialysis when plasma salicylate exceeds 750 mg/l and there is renal failure, or in any event exceeds 900 mg/l.