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Toxico Overdose Lec07.

Toxico Overdose Lec07.



Drug poisoning.

Drug poisoning.



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Toxico Overdose Lec07. Toxico Overdose Lec07. Presentation Transcript

  • Poisons & Drug Poisoning Dr Mohamad shaikhani.
  • Accidental?
  • Poisoning classifiation: • Accidental: most common in children < 5 years, less common in adults as occupational exposure. • Deliberate self poisoning: common in adults > 15 ys ( parasuicide). • Non accidental: deliberate poisoning of a child by one of parents( manchausen by proxy). • Misadventure: By medical staff or nurse, usually error in dose or admintration. • Homicide: rare.
  • Incidence: • Relatively a common problem in the our ER. • Young persons specially females. • In UK: • 15-20% of all emergency medical admissions. • ~6,300 suicides /year – 20% of deaths in young people – Important way of committing suicide. • ~140,000 attempted suicides (parasuicides) – Most common 15-19 year old females – Most common method is poisoning • 50% paracetamol
  • Incidence: • 30% involve > 1 drug. • Involve alcohol in addition of the ingested drug in 60% males & 40% females. • 60% ingest drugs prescribed for themselves or a relative. • The mortality from drug poisoning is < 1% & should be < 2% in severely ill patient by effective ICU.
  • • Drugs play an important role in suicidal &accidental poisoning • Common drugs used in poisoning include: • Analgesics (salicylates) > sedatives & hypnotics (barbiturates) > psychotherapeutics (tranquilizers) > CNS stimulants &depressants (amphetamines) • Narcotics - Lomotilt, an antidiarrhetic with a similar lethal dose as morphine; due to CNS depression. – Propoxyphene , similar effect as methadone – Overdose treated with Naloxone.
  • Major drugs involved in poisoning: • Paracetamol. • Aspirin. • Benzodiazepines. • SSRIs. • TADs. • Antionvulsants. • Other analgesics inculding NSAIDs.
  • Poisoing by substanes other than drugs: • Petrolium distilates. • Nature toxines as mushrooms. • Industrial chemicals. • Toiletries. • Household products. • Agrochemicals. • Others.
  • General Comments • Try &get as much history as possible including witnesses • People truly wanting to commit suicide often lie • Remember the ABCs: – Airway Clear mouth & throat, gag reflex – Breathing O2 saturation, ABGs – Circulation Venous access, IV fluids if shocked • Assess GCS • Examination
  • History • When, what, how much ? • Why? • Circumstances • PMHx, Drug history • Psychiatric history • Assess mental status & capacity
  • Care with names: Generic vs Chemical name! • Dolostop: paracetamol+dextropropoxiphen. • Valium: diazepan. • Fluout: paraetamol + diphenhydramine.
  • Investigations • Always check blood glucose. • Send blood & urine for toxicology screening. • ALWAYS measure paracetamol & salicylate levels – Failure to diagnose & treat is negligent. • CBP, LFTs, glucose, ABG, clotting, bicarbonate • ECG, CXR • Specific blood levels
  • Toxins for which emegency blood levels measurements needed: • Paracetamol. • Aspirin. • Iron. • Lthium. • Theophylin. • Methanol. • Ethylene glycol.
  • Management • Supportive – Correct hypoxia, hypotension, dehydration, hypo- hyperthermia, and acidosis – Control seizures • Monitor – PR, BP, ECG, Oxygenation, GCS • General ↓ Absorption ↑ Elimination – Specific antidotes
  • Principles of therapy: 1. Prevention of drug absorption • Washing to remove cutaneous contamination by acid or base or organophosphorous insecticides. • Induction of vomiting to remove poison from stomach by: – a. Mechanical stimulation as inducing gag. – b. Ipecac syrup. – c. Apomorphine. – d. Warm salt water or biarbonate gastric lavage .
  • Principles of therapy: 1. Prevention of drug absorption • Binding of the poison by specific chelating agents e.g. EDTA inn heavy metal poisoning as lead poisoning or deferxamine in Iron poisoning. • Adsorption of the poison onto activated charcoal – Should be given within 30 mm of ingestion – Charcoal has no toxicity, may be given before inducing vomiting or gastric lavage – It is with a universal antidote (activated charcoal: magnesium oxide: tannic acid 2:1:1) – 50 g single or repeated dose (↑ elimination) – Doesn’t bind heavy metals, ethanol, acids
  • Drugs not adsorb to activated charcoal: • Iron. • Lithium. • Methanol. • Ethylene glycol ( antifreze). • Acids – alkalis. • Petrolium distilates.
  • ↓ Absorption • Gastric lavage – Only if within 1 hour & if life-threatening amount – Never for corrosives as it may cause respiratory irritation& more GIT damage specially esophage. – If ↓ LOC intubate before gastric lavage.
  • ↑ Elimination • Methods to inrease elimination: • Multiple dose activated charcoal – Can bind Quinine, phenobarbitone • Charcoal haemoperfusion – Can bind Barbiturates, theophylline • Diuresis • Urinary alkalinization: increase excretion of aspirin. • Dialysis: can remove many substances from blood.
  • Drugs adsorb to activated charcoal: • Aspirin. • Carbamezepine. • Dapsone. • Digoxin. • Phenytoin. • Quinine. • Theophyline. • Barbiturates.
  • Principles of therapy: 2. Alteration of drug metabolism • The enhancement of metabolism for drugs inactivated by metabolism e.g. use of thiosulfate in cyanide poisoning • The inhibition of metabolism of drugs which produce toxic metabolites e.g. use of ethanol for methanol poisoning
  • Principles of therapy: 3. Enhancement of excretion • Ion trapping & alteration of urinary pH forced diuresis ,dialysis [hemodialysis), peritoneal dialysis, gastric dialysis (add acidic solution to stomach, pump out)] • Hemoperfusion, pass blood over charcoal • Laxatives (cathartics) e.g. sodium sulfate, magnesium sulfate, citrate or phosphate
  • Principles of therapy: 4. Specific pharmacological intervention • Direct chemical antagonism e.g acid-base • Receptor competition e.g. nalorphine in morphine overdose • Blockade of receptors that causes the toxic effects e.g. atropine in organophosphate poisoning, Flumazenil in benzodiazepin poisoning. • Restoration of normal function using an agent exerting a direct opposite effect e.g. barbiturate in CNS stimulant poisoning
  • Antidotes in most common use in clinical toxicology: • Paracetamol: n-acetyl cystein or methionine. • Opoid: Naloxone. • Benzodiazepines: Flumazenil. • Iron: dexferoxamine.
  • Treatment of shock • Shock is in all serious accidental poisoning • Arterial blood pressure is low in shock • The problem of shock is poor tissue perfusion • Present treatment: provide fluid, increase arteriolar relaxation & C.O. using a adrenergic blocker (isoproterenol) & antiinflammatomy steroids.
  • Causes of hypotension in poisoning: • Volume depletion from vomiting, diarrhea, GITB. • Drug-induced dilation of the venous bed. • Myocardial depresion as in TAD & BB poisoning. • Severe brady or tahyrrhthmias. • Drug-induced metabolic acidosis as in aspirin poisoning.
  • Treatment of convulsion • Many drugs stimulate CNS causing convulsion. • Diazepam (Valium), a tranquilizer, is the drug of choice
  • Specific drug poisoning:
  • Paracetamol Overdose • Acetaminophen is a leading OTC analgesics • Is one of the leading causes of drug overdose in the US & UK& a leading cause of liver failure. • It is metabolized in the liver & relatively safe in therapeutic doses. • A small fraction is converted to a reactive toxic metabolite, N- acetyl-p-benzoquinoneimine (NAPQI), by the cytochrome P-450 hepatic enzymes. • With therapeutic doses, glutathione stores can detoxify NAPQI by conjugation. • Glutathione stores are depleted in overdoses, & NAPQI binds to cellular proteins, producing hepatocellular necrosis. • Toxicity occur after a minimum of 140 mg/kg, or about 10 g(20tabs) in an adult & much less in high risk persons( alcoholics, ,on enzyme inducing drugs as antipileptics& in malnaurished& eating disorders.
  • Paracetamol Overdose
  • Paracetamol Overdose: features. • Acetaminophen poisoning clinically produces only nausea, vomiting, & anorexia 12 to 24 hours after ingestion. • Hepatic coma & coagulopathy do not occur until 48 to 96 hours after ingestion, after irreversible hepatic necrosis has occurred. • Patient with significant paracetamol overdose should not be discharged early from Hospital, even if appearing clinically well in the first 48-96 hours.
  • Paracetamol Overdose: Treatment. • N-acetylcysteine is the drug of choice. • It effectively prevents hepatotoxicity if given within 8 hours. • It is strongly effective if given within 16 hours & may be effective up to & beyond 24 hours. • N-acetylcysteine therapy should be instituted with a 4-hour acetaminophen level of 150 mg/mL, an 8-hour level of 75 mg/mL, or a 12-hour level of 37.5 mg/mL. • Because this therapy may be effective 24 hours after ingestion, the presence of any measurable acetaminophen or biochemical evidence of hepatic injury at 24 hours is an indication to start N- acetylcysteine therapy.
  • Paracetamol Overdose: Treatment. • It causes hepatic damage in overdose& rarely renal failure. • If presents within 1 hour of overdose, activated charcoal given in addition to NAC. • Antidote is IV N-acetylcysteine, provides complete protection if given within 10 hours of overdose;efficacy declines thereafter. • So, if a patient presents > 8 hours after ingestion, N-acetylcysteine should not be delayed to await a paracetamol blood result, so it is given & only stopped if the level subsequently shown to be below the treatment line. • Methionine 12 g orally 4-hourly, to a total of four doses, is a suitable alternative when N-acetylcysteine is not available. • If a patient presents > 15 hours after ingestion, liver function tests, PT (or INR) & renal function tests should be performed& the antidote started. • In some cases ABGs will need to be taken. • Liver transplantation should be considered in individuals who develop acute liver failure.
  • Paracetamol Overdose: Treatment. • Because the P-450 enzyme is present in the fetus by the 14th week of pregnancy, acetaminophen is highly toxic to the fetus, & N- acetylcysteine therapy should be given to the pregnant patient as soon as possible.
  • Do not check a paracetamol level before 4 hours have elapsed; it is uninterpretable. If more than 8 hours since ingestion, start N-acetylcysteine immediately & only stop it if the concentration is below the treatment line
  • The salicylates (aspirin). • Is a leading cause of analgesic drug overdose. • The association of Reye's syndrome with aspirin produced a dramatic fall in use & accidental poisoning in the pediatric age group. • Salicylates inhibit the cyclooxygenase enzyme of the prostaglandin synthetase complex, uncouple oxidative phosphorylation, & produce respiratory alkalosis & a high anion gap metabolic acidosis. • Salicylates are metabolized by first-order kinetics & are conjugated with glycine & glucuronic acid; as plasma concentrations rise in overdose & glycine stores are depleted, zero-order kinetics prevail & renal excretion of salicylate becomes prominent.
  • The salicylates (aspirin). • Salicylate ingestion at doses > 150, 250 & 500 mg aspirin/kg body weight produces mild, moderate & severe poisoning respectively. • Salicylate poisoning can also occur with ingestion of oil of wintergreen or when salicylic ointment (e.g. wart remover) is applied extensively to skin.
  • Salicylates (aspirin): Clinical presentation. • Includes nausea, vomiting, tinnitus, hearing loss,sweating, facial flushing, hyperpyrexia, & hyperventilation. • With severe poisoning: progressive dehydration, hypernatremia, pulmonary edema, purpura, GIB & death. • Direct stimulation of respiratory centre produces hyperventilation • Peripheral vasodilatation with bounding pulses & profuse sweating occurs in moderately severe poisoning. • Petechiae &subconjunctival haemorrhages can occur due to reduced platelet aggregation but this is self-limiting. • Signs of serious poisoning include metabolic acidosis, renal failure & CNS effects as agitation, confusion, coma& fits. • Rarely, pulmonary& cerebral oedema occur. • Death can occur as a result of CNS depression&CV collapse. • The development of a metabolic acidosis is a bad prognostic sign, because acidosis results in increased salicylate transfer across the blood-brain barrier • A plasma level of > 30 mg/dL indicates salicylate toxicity& 80-100 mg/dL indicates critical salicylate poisoning.
  • Salicylates (aspirin): treatment. • It is important to measure a plasma level in all but the most trivial overdose, best at 6 hours or later after ingestion because of continued absorption of the drug. • The salicylate concentration needs to be interpreted in conjunction with the clinical features& acid-base status. • The treatment of choice for salicylate poisoning is an alkaline diuresis with sodium bicarbonate. • Any significant metabolic acidosis should be treated with IV sodium bicarbonate (8.4%)&the volume given titrated to give an arterial Ph of 7.4-7.5. • Patients are often very dehydrated& fluid loss from vomiting & sweating &must be replaced, but over use of IVF may precipitate pulmonary oedema. • The use of multiple doses of activated charcoal in salicylate poisoning is controversial, but this approach is currently recommended unless salicylate level has peaked. • Urinary alkalinisation is indicated for adult patients with salicylate concentrations of 600-800 mg/l.
  • Salicylates (aspirin): treatment. • Haemodialysis is very effective at removing salicylate &correcting acid-base and fluid balance abnormalities & considered when: • 1.Serum concentrations are > 800 mg/l in adults &> 700 mg/l in the elderly. • 2.Metabolic acidosis resistant to correction. • 3.Severe CNS effects as coma or convulsions, pulmonary oedema & acute renal failure • Vitamin K supplementation should be given. • Supportive care is paramount.
  • Other (NSAID) poisoning. • Ibuprofen is the leading (NSAID). • Usually causes little more than minor GI upset including mild abdominal pain, vomiting & diarrhoea. • 10-20% have convulsions; usually self-limiting & needs only airway protection & oxygen, if persist IV diazepam. • Serious features include coma, prolonged fits, apnoea , bradycardia but very rare. • Deaths have been reported after massive overdose of ibuprofen, but not with mefenamic acid. • Rarely, renal failure ensues. • Features of toxicity tend to occur early & unlikely to develop later than 6 hours after the overdose. • Liver/renal function may be affected, so electrolytes, liver functions &CBP should be checked in all unless trivial overdoses. • The 1/2t of most NSAIDs are < 12 hours, so elimination methods are not needed. • Activated charcoal should be given if > 100 mg/kg BW ibuprofen or > 10 tablets of any other NSAID taken in the last hour. • GI irritation is treated with oral H2-blockers (e.g. ranitidine).
  • Anticholinergic poisoning. • The classic anticholinergic syndrome is produced by blockade of acetylcholine with central & peripheral effects: • Psychosis, delirium, seizures, flushing, dry mucous membranes & skin, hyperpyrexia, dilated pupils & urinary retention. • The antidote physostigmine should be reserved for severe cases of pure anticholinergic poisoning. • Physostigmine should not be used for agents with only some anticholinergic properties, as tricyclic antidepressants. • The initial dose of physostigmine is 0.5 - 2 mg IV slowly in adults &0.02 mg/kg in children, maximum dose is not to exceed 4 mg in 30 minutes in adults. • Cardiac monitoring is essential, because physostigmine has caused asystole, bradycardia, & seizures.
  • Barbiturates poisoning. • Still constitute a major source of overdose & mortality although largely replaced as sleep medication by benzodiazepines. • They are still present in headache prescriptions & sleep medications & remain common drugs of abuse. • Phenobarbital is one of the leading anticonvulsant medications. • Thiopental is used as an IV anesthetic for in-hospital rapid- sequence intubation or as a sedative before cardioversion & surgery. • Phenobarbital is excreted primarily unchanged by the kidney, whereas most other barbiturates are metabolized by the liver.
  • Barbiturates poisoning: features. • Overdose is associated with depression of CNS & CV system, coma, hypotension, loss of reflexes, hypothermia, respiratory arrest & death. • 2 characteristic of a barbiturate overdose is: • 1. The persistence of the pupillary light reflex even with stage IV coma. • 2. Bullous skin lesions often occur over pressure areas.
  • Barbiturates poisoning: treatment. • Treatment of the critically ill patient involves mechanical ventilation, resuscitation of CV status, gastric lavage & activated charcoal (after securing the airway) & supportive care in an ICU. • An alkaline diuresis with sodium bicarbonate is specifically indicated for phenobarbital, which is a weak acid that is excreted unchanged in the urine. • Multiple-dose activated charcoal every 4 -6 hours is also specifically indicated for phenobarbital, as it diffuses into the GIT lumen. • Charcoal hemoperfusion & hemodialysis have a role in barbiturate overdose for critical patients who do not respond to conservative therapy.
  • The benzodiazepines poisoning. • Extremely popular & have replaced other sedative-hypnotics. • All are effective anxiolytics & sedatives& are muscle relaxants, anticonvulsants & amnestics. • Diazepam, lorazepam, & midazolam, have major therapeutic roles as IV drugs for in-hospital use as anticonvulsants, preanesthetics & sedatives. • Although common agents of overdose, cause only coma & ataxia; mortality is rare & supportive care is all that usually necessary. • The antidote flumazenil is reserved only for reversing pure in- hospital benzodiazepine conscious analgesia&reversing coma in zolpidem overdose. • Its use in the general overdose patient or in a patient with head injury or coma of unknown etiology is not recommended, reported to cause seizures in patients who have co-ingested benzodiazepines & cyclic antidepressants & has caused increased intracranial pressure in patients with head injury.
  • Cardiotoxic drugs:
  • Cardiotoxic drug poisoning: • CCBs. • BBs. • Digoxin. • TAD.
  • The calcium channel blockers poisoning. • Common antihypertensive agents • the most common cause of cardiovascular drug death by overdose. • A special problem is presented by the sustained-release preparations, which allow for continued absorption. • Persistent hypotension, bradycardia with atrioventricular block (especially with verapamil), coma, pulmonary edema, & cardiac arrest constitute the clinical picture.
  • The calcium channel blockers poisoning. • Treatment must be aggressive if these patients are to survive. • Whole-bowel irrigation with polyethylene glycol is indicated if sustained-release preparations have been ingested. • An intravenous 10% calcium chloride 1-g bolus (over 5 minutes) may be life-saving, and 1 gram IV every 15 minutes over the first hour may be necessary in critically ill patients, followed by 10% calcium chloride via continuous intravenous infusion (the dosage and rate depending on the clinical condition) until blood pressure stabilizes.
  • The calcium channel blockers poisoning. • For patients who do not respond to high-dose calcium therapy, dopamine, dobutamine, amrinone, epinephrine, and/or glucagon. • Glucagon is indicated in patients with concomitant b-blocker overdose. • Pacing may be necessary, especially with verapamil overdose. • Symptomatic patients and patients who have ingested sustained- release preparations should be admitted to the critical care unit for continuous ECG monitoring for at least 24 hours after stabilization.
  • Digitalis poisoning. • Still common. • Patients who suffer yellow or blurred vision, nausea or vomiting, & sinus bradycardia may improve simply by stopping the drug. • Significant digitalis intoxication is heralded by hyperkalemia & a variety of major cardiac arrhythmias. • Digoxin-specific Fab antibodies (Digibind) offer a definitive means of therapy &are indicated for: • Life-threatening cardiac arrhythmia. • Hyperkalemia. • Aserum digoxin level of 10 ng/mL, • A massive overdose of 10 mg or greater in adults or 4 mg in children. • Antidotal therapy should be instituted before conventional therapy in life-threatening situations.
  • Antidiabetics: • Sulphonylureas (e.g. chlorpropamide, glibenclamide, gliclazide, glipizide, tolbutamide) • Biguanides (metformin, phenformin) • Insulins. • Cause hypoglycaemia when taken in overdose. • The onset & duration of hypoglycaemia vary, but can last for several days with long-acting agents as chlorpropamide& isophane / lente insulins. • Hypoglycaemia may manifest as agitation, sweating, confusion, tachycardia, hypothermia, drowsiness, coma or convulsions • Permanent neurological damage can occur if the hypoglycaemia is prolonged.
  • Antidiabetics: • Metformin can cause a lactic acidosis in overdose, particularly in elderly & those with renal or hepatic impairment, or when co- ingested with ethanol. • It is associated with a > 50% mortality. • Metformin overdose may also cause nausea / vomiting, diarrhoea, abdominal pain, drowsiness, coma, hypotension & CV collapse.
  • Antidiabetics: Management • Activated charcoal should be given & gastric lavage considered in all patients who present within 1 hour of ingestion of more than the normal therapeutic dose of an oral hypoglycaemic agent. • Formal measurement of venous blood glucose (not just visually read strips or meter) , urea & electrolytes should be performed &repeated regularly. • For medico-legal purposes , a blood sample may be required for subsequent measurement of insulin, pro-insulin and C-peptide. • Hypoglycaemia should be corrected urgently with 50 ml 50% dextrose, given i.v. if the patient is unconscious or with a sugary drink if the patient is conscious, followed by an infusion of 10% or 20% dextrose titrated to the blood glucose to prevent further hypoglycaemia&may be necessary for several days, depending on the agent ingested or injected. • Potassium replacement should be guided by frequent measurement of urea &electrolytes.
  • Antidiabetics: Management • Failure to regain consciousness within a few minutes of normalisation of the blood glucose indicate either: • 1. CNS depressant has also been ingested • 2. Hypoglycaemia has been prolonged. • 3. Another cause for the coma (e.g. cerebral haemorrhage) or cerebral oedema. • In cases of severe sulphonylurea overdose resistant to dextrose infusions, use of IV octreotide as an antidote may be considered.
  • Carbon monoxide poisoning. • Is the leading cause of death from poisoning in US. • CO is a colorless, odorless, tasteless gas produced by incomplete combustion of carbon materials. • CO has a 200 times greater affinity for hemoglobin than oxygen & thus produces cellular hypoxia & death. • Fires, smoke, wood-burning stoves, gas space heaters& engine exhaust are sources of unintentional poisoning.
  • Carbon monoxide poisoning. • Because the heart & brain are the most sensitive to hypoxic insult, clinical presentation usually involves CNS or cardiac symptoms— headache, altered mental status, convulsions, chest pain, cardiac arrhythmia, &/or AMI. • Mild CO poisoning often is mistaken for influenza, as both occur primarily in the winter months & cause headache/GI symptoms. • Because most patients receive oxygen in an ambulance on the way to the hospital, the carboxyhemoglobin level is usually an unreliable indicator of the extent of poisoning. • In general, the deeper the level of coma, the greater the chance of neuropsychiatric sequelae.
  • Carbon monoxide poisoning. • CO poisoning is treated with oxygen: • Breathing room air, it takes a patient 6 hours to halve carboxyhemoglobin level (T½); breathing 100% oxygen, 90 minutes; with hyperbaric oxygen at 2.5 atmospheres of pressure absolute, < 1 hour. • Hyperbaric oxygen therapy reduces the incidence of neurologic sequelae & has become the standard of care for treating CO- poisoned patients with coma & altered mental status
  • Carbon monoxide poisoning. SPECIFIC INDICATIONS FOR HYPERBARIC OXYGEN THERAPY All comatose patients Patients with neurologic impairment by examination or psychometric testing Patients with carboxyhemoglobin levels >40% Cardiovascular involvement (chest pain, ECG changes, arrhythmias) Pregnant patients with carbon monoxide levels >15% Patients who do not respond to 100% oxygen Patients with recurrent symptoms up to 3 weeks after exposure
  • Caustic alkali poisoning. • Accidentally swallowing button batteries larger than 20 mm in diameter & intentional ingestion of alkali substances are the major causes of morbidity. • Because solid crystals adhere to the tongue & cause burning, they uncommonly produce esophageal burn. • Drooling in children &inability to swallow are highly suggestive. • Mouth burns are also suggestive, but the absence of mouth burns does not exclude esophageal burn.
  • Caustic alkali poisoning. • Milk is the only possible home antidote, but it must be given immediately. • To detect significant burns, some suggest UGI esophagoscopy within 12 hours, whereas others prefer to wait 24-2 hours following ingestion. • A 3-week course of methylprednisolone, 2.5 mg/kg/day, to prevent esophageal stricture has been the mainstay of therapy, but its efficacy has been questioned. • Esophageal dilation & gastric tube esophageal replacement are indicated for treating esophageal stricture.
  • Cyanide poisoning. • Most commonly is due to smoke inhalation. • One public source is acetonitrile in acrylic nail remover. • Hydrogen cyanide gas is a fumigant rodenticide. • Prolonged administration of nitroprusside can result in elevated cyanide levels.
  • Cyanide poisoning. • Produces cellular hypoxia by binding with the ferric iron of mitochondrial cytochrome oxidase & disrupting the electron transport chain & the ability of cells to use oxygen. • Rapidly develop coma, shock, seizures, lactic acidosis, respiratory & cardiac arrest. • Mild exposures following smoke inhalation may be difficult to diagnose& Emergency administration of antidote may be life- saving. • Cyanide poisoning should be suspected in patients who have inhaled smoke &who have evidence of lactic acidosis.
  • Cyanide poisoning. • The cyanide antidote kit contains amyl nitrite, ampules of sodium thiosulfate, & ampules of sodium nitrite. • The body has a natural enzyme, rhodanese, that can complex cyanide & sulfur to form thiocyanate, which is only mildly toxic. • IV sodium thiosulfate provides the sulfur necessary to produce thiocyanate & is relatively safe. • Because sodium nitrite causes hypotension & methemoglobinemia, its use is reserved for the most critical cases. • The new antidote hydroxocobalamin (initial adult dosage 5 g IV), not yet approved, is a safer alternative.
  • Iron poisoning. • Has a direct corrosive action on the stomach & proximal small bowel • Once absorbed, produces shock, metabolic acidosis, liver failure& death. • Initially, GIsymptoms prevail with persistent vomiting, abdominal pain& hemorrhage. • A quiescent phase may be observed, followed by shock, coma, metabolic acidosis& liver failure. • Laboratory data may reveal leukocytosis, hyperglycemia& radiopaque tablets on a flat plate of the abdomen.
  • Iron poisoning. • A serum iron level should be determined (during peak levels) at 2 -4 hours after ingestion: > 300 mg/dL indicates mild intoxication, ,> 500 mg/dL indicates serious intoxication, but a serum iron level in excess of the total iron-binding capacity does not serve as a useful predictor of iron poisoning.
  • Iron poisoning. • Management of iron poisoning includes gastric lavage with normal saline. • Whole-bowel irrigation may be indicated after ingestion of sustained-release capsules. • The treatment of choice is the antidote deferoxamine, which chelates free serum iron in the plasma to form ferrioxamine, which is readily excreted & imparts a vin rosé color to the urine.
  • Iron poisoning. • Deferoxamine is indicated for: • All critical patients who present with coma, shock, or hemorrhage, • All patients with a serum iron level higher than 500 mg/dL, • Patients who are symptomatic with a serum iron > 300 mg/dL. • IV deferoxamine 15 mg/kg/hour is the preferred; up to 6 g may be given in 24 hours.
  • Iron poisoning. • Chelation therapy should continue until: • The patient becomes stable for at least 24 hours. • Vntil the vin rosé urine (when present) becomes clear. • Until the serum iron level has fallen <300 mg/dL. • Exchange transfusion may be indicated for the unusual patient who is critically ill & does not respond to chelation therapy.
  • Methanol & ethylene glycol poisoning. • True medical emergencies. • Methanol is most commonly found as the active ingredient in windshield washer fluid& ethylene glycol constitutes antifreeze. • Moth are also found in many commercial & marine products. • Methanol, or wood alcohol, is converted by alcohol dehydrogenase to formaldehyde &then to formic acid.
  • Methanol & ethylene glycol poisoning. • Signs & symptoms develop over a 24-hour period & may include infarction of the putamen. • Severe high anion gap metabolic acidosis occurs with an increase in the osmolal gap. • Treatment emphasizes IV ethanol, sodium bicarbonate & hemodialysis.
  • Methanol & ethylene glycol poisoning. • The diagnosis of ethylene glycol poisoning in adults, commonly from antifreeze, is generally, but not always, evident from the history. • Metabolism of ethylene glycol by alcohol dehydrogenase causes poisoning by producing severe metabolic acidosis due to aldehyde, glycolate& lactate formation & deposition of oxalate crystals in the lungs, heart& kidneys • (4-methylpyrazole) inhibits alcohol dehydrogenase & may be an alternative to intravenous alcohol for the treatment of ethylene glycol poisoning. • Hemodialysis is the treatment of choice for ethylene glycol poisoning & should be instituted as early as possible once the diagnosis is made.
  • Methanol & ethylene glycol poisoning. POISONING WITH METHANOL OR ETHYLENE GLYCOL Methanol S&ss Altered mental status; coma; seizures; gastrointestinal disturbance with abdominal pain; pancreatitis in some; visual disturbances: blurred vision, diplopia, photophobia, sensation of quot;being in a snowstorm,quot; blindness (end result). Treat Aggressively prevent methanol conversion by infusing IV ethanol. Correct metabolic acidosis with sodium bicarbonate; Hemodialysis to remove methanol/metabolites—indicated for patients with visual disturbance, serum methanol >50 mg/dL, or with intractable metabolic acidosis.
  • Methanol & ethylene glycol poisoning. Ethylene Glycol Signs and symptoms Early Altered mental status; seizures; hypocalcemic tetany 12 hr after ingestion Congestive heart failure 24–72 hr after ingestion Profound renal failure Treatment Treat ethylene glycol with: aggressive gastric lavage; ethanol infusion or 4-methylpyrazole, sodium bicarbonate to correct metabolic acidosis, Correct hypocalcemia with calcium chloride, Hemodialysis
  • The organophosphates poisoning. • Highly popular insecticides because they are effective, disintegrate within days of application & do not persist in the environment • Even minute quantities can penetrate the skin & be lethal, as evidenced by the use of organophosphate nerve gases sarin, soman, tabun, & VX in chemical weapons.
  • The organophosphates poisoning. • The organophosphates irreversibly inhibit acetylcholinesterase, resulting in an overabundance of acetylcholine at synapses & the myoneural junction. • The acetylcholine initially excites & then paralyzes the CNS, the parasympathetic nerve endings & the sweat glands (muscarinic effects), somatic nerves & ganglionic synapses of autonomic ganglia (nicotinic effects). • Initial symptoms resemble a flulike syndrome with abdominal pain, vomiting, headache, dizziness. • The full-blown picture generally develops by 24 hours ,includes coma, convulsions, confusion, or psychosis; fasciculation , weakness or paralysis; dyspnea, cyanosis,pulmonary edema; sometimes pancreatitis. • Torsades de pointes VF has also been described.
  • The organophosphates poisoning. • Emergency management includes decontamination of the skin,& removal of clothes; establishing an airway & ensuring proper ventilatory support , cardiac monitoring; & administering the specific antidote pralidoxime & the physiologic antidote atropine. • A 25% reduction in red blood cell cholinesterase confirms organophosphate poisoning. • Atropine should be given as a physiologic antidote to reverse the muscarinic effects & to dry the excessive pulmonary secretions seen in patients with respiratory distress. • Atropine use requires cardiac monitoring& proper oxygenation. • Pralidoxime is the treatment of choice for organophosphate poisoning & should be begun on clinical grounds before return of any blood studies. • To be effective, pralidoxime must be given in the first 48 hours before irreversible binding of acetylcholinesterase occurs.
  • The organophosphates poisoning. • The initial dose is 1 g IV given over 15 to 30 minutes; the effect may be dramatic. • Pralidoxime by continuous infusion of up to 500 mg/hour may be necessary in critically ill patients. • Pralidoxime may obviate the need for high-dose atropine therapy & reduce the incidence of late-onset paralysis. • Neither therapies exclude the use of the other.
  • The organophosphates poisoning. • The carbamate insecticides include carbaril, methomyl, & propoxur • are reversible cholinesterase inhibitors. • They produce clinical effects similar to those of the organophosphates but without CNS signs; • They are considerably more benign & shorter duration. • Atropine is the drug of choice for carbamate poisoning. • Pralidoxime is not indicated because the carbamate- cholinesterase complex is quite reversible.
  • Theophylline poisoning. • Mortality from both plain & sustained-release preparations occur from acute overdose & long-term unintentional intoxication. • Vomiting is often the first symptom, sinus tachycardia is the most common sign in both acute - chronic toxicity. • Seizures may be common when the serum concentration is higher than 40 mg/mL in chronic toxicity or higher than 80 to 100 mg/mL in acute overdose. • Cardiac arrhythmia, CVcollapse, respiratory arrest are seen infrequently unless the concentration is higher than 50 mg/mL in chronic toxicity or higher than 100 mg/mL in acute overdose. • Profound hypokalemia, hyperglycemia, metabolic acidosis are also seen. • Serum theophylline is higher in acute overdose compared with those in chronic toxicity.
  • Theophylline poisoning. • Treatment includes • withdrawing the drug, cardiac monitoring, supportive care. • Gastric lavage &activated charcoal are indicated for acute overdose. • The serum half-life of theophylline can be reduced by serial administration of activated charcoal, as it diffuses into the GIT lumen; dosage is 1g/kg every 4 hours. • Whole-bowel irrigation may be indicated for ingestion of sustained-release capsules. • Cardiac arrhythmias are often difficult to manage but may respond to IV propranolol. • Correction of hypokalemia, metabolic acidosis& fluid-electrolyte balance is indicated. • Although seizures may respond to IV diazepam, status epilepticus & rhabdomyolysis may occur & signify a poor outcome.
  • Theophylline poisoning. • Charcoal hemoperfusion is the treatment of choice for significant theophylline toxicity. • Hemodialysis is becoming an option equal to charcoal hemoperfusion. • Charcoal hemoperfusion is most beneficial for patients with a serum theophylline > 80 to 100 mg/mL in acute overdose or > 40 mg/mL in chronic toxicity (especially in the elderly or patients with hepatic disease or other conditions that delay theophylline clearance) or patients in critical condition.
  • Tricyclic (or cyclic) poisoning. • Still the leading cause of prescription drug death. • CV toxicity (arrhythmia /hypotension), CNS effects (especially coma /seizures), anticholinergic signs are seen. • The cardiotoxic effects are seen with ingestion of 1 g (10 to 20 mg/kg) &account for the high mortality rate.
  • Tricyclic (or cyclic) poisoning. • The hallmark on ECG is prolongation of the QRS complex. • A QRS complex > 100 ms is a sign of severe toxicity & correlates with a plasma level > 1000 ng/mL. • Although sinus tachycardia & anticholinergic signs are evident with mild toxicity, QRS complex prolongation is associated with the development of ventricular arrhythmias, seizures, death. • Ventricular tachycardia is the most common ventricular rhythm, although ventricular bigeminy, slow ventricular rhythms, torsades de pointes VF also have been described. • VF/ sudden cardiac arrest are not uncommon.
  • Tricyclic (or cyclic) poisoning. • The treatment of choice IV sodium bicarbonate. • To maintain a blood pH of 7.5 reduce the incidence of cardiac arrhythmia. • IV bolus of sodium bicarbonate (1 to 2 mEq/kg) is the treatment of choice for the sudden onset of ventricular tachycardia, ventricular fibrillation& cardiac arrest. • Sodium bicarbonate also may be useful for correcting hypotension, although vasopressors may be necessary. • Airway, proper oxygenation & ventilation, fluid replacement (but avoid pulmonary edema), gastric lavage with serially administered activated charcoal& supportive therapy are indicated.
  • Tricyclic (or cyclic) poisoning. • Phenytoin reverse QRS complex prolongation, but reserved for managing seizures. • Prophylactic IV phenytoin (15 mg/kg) before the onset of seizures may be given in cases of amoxapine overdose, which has a high incidence of status epilepticus. • Diazepam is quite effective in controlling seizures, although intensive therapy including thiopental & rapid-sequence intubation may be necessary to manage status epilepticus. • Physostigmine is no longer used in tricyclic overdose, because by itself it can cause seizures, bradycardia, asystole. • Death generally occurs within the first 24 hours after overdose. • Because sudden death has occurred after apparent stabilization, cardiac monitoring is indicated for at least 24 hours after stabilization & normalization of the QRS complex.
  • Tricyclic (or cyclic) poisoning. • Newer antidepressants that are not structurally related to the cyclic agents include the serotonin reuptake inhibitors fluoxetine ( Prozac), sertraline (Zoloft), paroxetine (Paxil), and fluvoxamine ( Luvox), • generally cause only sedation in overdose. • Fatal serotonin syndrome from concomitant overdose of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors is now being reported.
  • Tricyclic OD – Initial ECG
  • Tricyclic OD – Recovery ECG