398 Section 11/ Chelating Agents & Treatment of Poisoning PRALIDOXIME It causes reactivation of the phosphorylated acetylcholinesterase enzyme After administration, it is metabolised in liver Adverse effects include blurred vision, dizziness, diplopia, headache, tachycardia, mild weakness and nausea In high dose it can cause neuromuscular blockage It is indicated as antidote for organophosphorus poisoning like malathion, TEPP, parathion etc NICOTINE Nicotine is a tertiary amine compound composed of a pyridine and a pyrrolidine ring It binds selectively to acetylcholine receptors at the autonomic ganglia in the adrenal medulla at neuro-muscular junction and in the brain It exerts a stimulating effect in the cortex and a ‘reward’ effect via the ‘pleasure system’ in the limbic system Adverse effects include erythema, pruritus or burning at the site of application, headache, somnolence, dizziness, arthralgia, myalgia, dyspepsia, dry mouth, diarrhoea, sweating, BP changes, angioneurotic edema, urticaria and dyspnea It is used in the treatment of nicotine dependence and as an aid to stop smoking BUPROPION The mechanism by which bupropion acts as an aid in smoking cessation is unknown Bupropion weakly inhibits neuronal reuptake of noradrenaline and serotonin and inhibits the reuptake of dopamine In tissues from rat brain, bupropion produced greater inhibition of dopamine reuptake than noradrenaline reuptake; however in, in vivo models, bupropion is a stronger inhibitor of noradrenaline than dopamine reuptake The metabolites hydroxybupropion and threohydrobupropion are pharmacologically active in vitro and in animal models of depression and are expected to contribute to the therapeutic effects of bupropion Adverse effects include abdominal pain, chest pain, facial edema, nausea, dry mouth, constipation, diarrhoea, anorexia, mouth ulcer, thirst, myalgia, arthralgia, anxiety, disturbed concentration, dizziness, nervousness, tremor, dysphoria, rhinitis, increased cough, pharyngitis, sinusitis, dyspnea, epistaxis, agitation, insomnia and headache It is indicated in smoking cessation in the dose of 150 to 300 mg twice daily TREATMENT OF POISONING The treatment of different drug poisoning is discussed in individual chapters In this section, general treatment is discussed The general principles of treatment are: Support ventilation Maintain cardiovascular function Reverse hypothermia if present Treat convulsions Correct fluid, acid-base and electrolyte imbalance Relieve pain Good nursing care Chelating Agents & Treatment of Poisoning Prevention of Poison Absorption The aim is to reduce the absorption of poison Gastric lavage may be useful for six hours after ingestion of poison The lavage should be done as early as possible but only if vital functions are adequate It is inappropriate to employ gastric lavage unless the lungs can be protected, either by virtue of patient having an adequate cough reflex or by means of a cuffed endotracheal tube Gastric lavage is contraindicated if corrosive or caustic substances have been taken, because oesophageal and gastric erosion and perforation may occur Activated charcoal is probably more effective than either emesis or lavage Accelerating Poison Elimination Alkalinisation of urine (alkaline diuresis) is effective for salicylates and phenoxyacetate herbicides Repeated dose of activated charcoal administered by oral route have been shown to enhance the non-renal elimination of carbamazepine, salicylates, phenobarbitone, phenytoin, digoxin, theophylline and meprobamate In severe cases activated charcoal is to be administered via a nasogastric tube Haemoperfusion, using a cartridge containing charcoal or an uncharged resin is effective in enhancing drug excretion in few selected cases of poisoning e.g theophylline, barbiturates, non-barbiturate hypnotics, etc (Also see Section I for the management of poisoning) 399 Frequent administration of activated charcoal is effective for the following substances: Substances which form masses: Aspirin, iron, lithium, enteric-coated tablets, meprobamate Substance which remain in the stomach for a long time: Barbital, aspirin, iron, alcohol, cholinergic blockers, narcotic drugs, phenytoin, antidepressants Substances which have a long half-life when present in large amounts: Theophylline, aspirin, alcohol, phenytoin, chloral hydrate, acetaminophen Substances which have active metabolites: Benzodiazepines, chloral hydrate, acetaminophen, antidepressants, procainamide Substances whose poisonous metabolites are eliminated slowly: Ethylene glycol, methanol, primidone, isopropyl alcohol, carbon tetrachloride, levothyroxine Substances which are reabsorbed from the urinary tubules in a pH dependent manner: Phenobarbital, aspirin, amphetamine Substances with persistent tissue accumulation: Iron, lithium Substances which enter the enterohepatic circulation: Carbamazepine, digoxin, phenobarbital The specific antidotes for various poisons are listed in table 11.1.1 ORGANOPHOSPHORUS POISONING These compounds are mainly used as agricultural and household insecticides The poisoning may be occupational (for those who are involved professionally with these agents), accidental (accidental consumption) or suicidal due to intentional ingestion of these compounds Section 11/ Chelating Agents & Treatment of Poisoning 400 Table 11.1.1 List of specific antidotes for various poisons Poison Antidote 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 Dimercaprol, BAL, D-penicillamine Oxygen (100%), dicobalt edetate, Amyl nitrite, sod nitrite Ethanol Naloxone Atropine and pralidoxime mesylate Desferrioxamine Atropine for bradycardia, glucagon Digoxin specific antibody fragments (DIGIBIND) Oxygen (100%) Vitamin K (phytomenadione) Protamine sulfate Sodium calcium edetate, D-penicillamine Dimercaprol, D-penicillamine, BAL Ethanol N-acetylcysteine Flumazenil Physostigmine Pyridoxine Folinic acid N-acetylcysteine BAL, EDTA D-penicillamine Folic acid, Leucovorin Antisnake venom polyvalent Pyridoxine Esmolol Neostigmine Glucose Arsenic Cyanide Ethylene glycol, methanol Opioids Organophosphorus insecticides Iron Beta-blockers Digoxin Carbon monoxide Oral anticoagulants Heparin Lead (inorganic) Mercury (inorganic) Methanol Paracetamol, gold Benzodiazepines Atropine Isoniazid Folic acid antagonists Acetaminophen (Paracetamol) Copper Methotrexate Snake bite Hydroxzines Theophylline Curare compounds Insulin a Local exposure produces miosis, spasm of accommodation, headache, irritation of eye, lacrimation and blurring of vision b On ingestion fall in blood pressure, tachycardia, cardiac arrhythmias, ataxia, convulsion, respiratory paralysis and vasomotor collapse occurs The death is generally due to respiratory failure Treatment Gastric lavage, fresh air for termination of further exposure to compound Maintenance of a patent airway Use oropharyngeal or nasopharyngeal airway or endotracheal intubation if airway obstruction persists Washing of skin, mucous membrane and eye Supportive therapy: Maintenance of blood pressure, artificial respiration, rehydration (fluid/electrolyte therapy) and control of convulsions Antidote/Reactivators a Atropine is highly effective in counteracting the muscarinic Chelating Agents & Treatment of Poisoning symptoms It is given in a dose of mg IV every 10 till muscarinic effects are controlled b The cholinesterase reactivators are used to restore neuromuscular transmission Pralidoxime (pyridine-2-aldoxime methiodide; 2-PAM) is an antidote and cholinesterase reactivator It breaks the bond between the organophosphate poison and the molecular surface of acetylcholinesterase and the enzyme is freed and reactivated to hydrolyse the excess of acetylcholine at the receptor sites It is to be given in the dose of 1-2 g IV infusion along with 100-200 mg of atropine Other cholinesterase reactivators are diacetylmonoxime (DAM) which combines with free organophosphate molecule in the body fluids It is administered 1-2 g IV slowly CHRONIC ALCOHOLISM It is associated with development of psychic dependence, tolerance and physical dependence and sudden withdrawal of alcohol may lead to withdrawal syndrome In addition, the alcohol addicts are liable to other neuropsychiatric syndrome (Korsakoff’s psychosis) which is associated with hallucination, suicidal tendencies and encephalopathy They may also suffer from hyperlipidemia, hyperuricemia, pancreatitis and hepatitis 401 and available in 200 mg tablet The treatment is initiated with 800 mg single dose which is gradually reduced over days to a maintenance dose of 100 to 200 mg daily and treatment may be continued up to one year After a week’s therapy, if a small quantity of alcohol is consumed by the patient, it produced unpleasant toxic reactions such as flushing, palpitation, nausea, vomiting throbbing headache, uneasiness, dizziness, visual disturbances, fall in blood pressure and even collapse The patient thus realizes that during the treatment he can not tolerate even a small amount of alcohol and would abstain from alcohol drinking The drug disulfiram interferes with the oxidation of acetaldehyde formed during the metabolism of alcohol This increases the blood level of acetaldehyde which acts directly on cardiovascular system and produce these toxic reactions Disulfiram also inhibits dopamine beta oxidase and thus interferes with the synthesis of noradrenaline, which causes depletion of catecholamines Disulfiram is slowly absorbed incompletely from the gut and is metabolised slowly METHYL ALCOHOL (METHANOL) DISULFIRAM Methyl alcohol is only used to denature ethyl alcohol in percent concentration It is metabolised to formaldehyde and formic acid by alcohol and aldehyde dehydrogenases Its absorption and distribution are similar to ethyl alcohol Chemically it is tetraethyl thiuram disulphide, commonly known as antabuse Ingestion of methyl alcohol produces the following signs and symptoms: Drug Treatment of Chronic Alcoholism (Aldehyde Dehydrogenase Inhibitors) Section 11/ Chelating Agents & Treatment of Poisoning 402 • Nausea and vomiting • Blurring of vision, hyperemia of optic disc and blindness • Pancreatitis • Albuminuria • Coma followed by death Treatment of Methanol Poisoning • Gastric lavage, activated charcoal • Hospitalization: Correction of acidosis • IV/oral ethyl alcohol • Maintenance of nutrition • Administration of folinic acid (1 mg/ kg, IV) together with folic acid (1 mg/ kg IV) to accelerate the metabolic degradation of formate • Administration of 4-methylpyrazole (inhibitor of alcohol dehydrogenase) • In severe case: Haemodialysis TREATMENT OF SNAKE BITE Vipers, Cobras and Kraits are the common poisonous snakes and in India 40,000 to 50,000 deaths recorded per year due to snake bite Local Signs & Symptoms in the Bitten Part • Fang marks • Local pain & bleeding • Bruising • Lymphangitis • Inflammation (swelling, redness, heat) • Blistering • Lymph node enlargement • Local infection, abscess formation & necrosis Generalised (Systemic) Symptoms & Signs • Nausea, vomiting, malaise, abdominal pain weakness • Visual disturbances, faintness, collapse, shock, hypotension, pulmonary edema & conjunctival edema • Bleeding & clotting disorders • Skeletal muscle breakdown • Acute pituitary/adrenal insufficiency First-aid Treatment • First aid treatment is carried out immediately before hospitalisation • Immobilise the bitten limb with a splint or sling • Consider pressure-immobilisation for some elapid bites • Avoid any interference with the bite wound as this may introduce infection, increase absorption of the venom and increase local bleeding • Tight (arterial) tourniquets are not recommended Treatment in hospital • Rapid clinical assessment and resuscitation • History (especially the snake identification) • Physical examination • Investigation/laboratory tests: – 20 minute whole blood clotting test (20 WBCT) – Haemoglobin concentration/ haematocrit – Platelet count – WBC count – Biochemical abnormalities – Urine examination etc ... etc (Also see Section I for the management of poisoning) 399 Frequent administration of activated charcoal is effective for the following substances: Substances which form masses: Aspirin, iron,... and perforation may occur Activated charcoal is probably more effective than either emesis or lavage Accelerating Poison Elimination Alkalinisation of urine (alkaline diuresis) is effective for. .. antidotes for various poisons are listed in table 11.1.1 ORGANOPHOSPHORUS POISONING These compounds are mainly used as agricultural and household insecticides The poisoning may be occupational (for