Toxico Overdose Lec07.


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Medical college lectures: toxicology/poisoning 5nd year.

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Toxico Overdose Lec07.

  1. 1. Poisons & Drug Poisoning Dr Mohamad shaikhani.
  2. 2. Accidental?                                                                                 
  3. 4. Poisoning classifiation: <ul><li>Accidental: most common in children < 5 years, less common in adults as occupational exposure. </li></ul><ul><li>Deliberate self poisoning: common in adults > 15 ys ( parasuicide). </li></ul><ul><li>Non accidental: deliberate poisoning of a child by one of parents( manchausen by proxy). </li></ul><ul><li>Misadventure: By medical staff or nurse, usually error in dose or admintration. </li></ul><ul><li>Homicide: rare. </li></ul>
  4. 5. Incidence: <ul><li>Relatively a common problem in the our ER. </li></ul><ul><li>Young persons specially females. </li></ul><ul><li>In UK: </li></ul><ul><li>15-20% of all emergency medical admissions. </li></ul><ul><li>~6,300 suicides /year </li></ul><ul><ul><li>20% of deaths in young people </li></ul></ul><ul><ul><li>Important way of committing suicide. </li></ul></ul><ul><li>~140,000 attempted suicides (parasuicides) </li></ul><ul><ul><li>Most common 15-19 year old females </li></ul></ul><ul><ul><li>Most common method is poisoning </li></ul></ul><ul><ul><ul><li>50% paracetamol </li></ul></ul></ul>
  5. 6. Incidence: <ul><li>30% involve > 1 drug. </li></ul><ul><li>Involve alcohol in addition of the ingested drug in 60% males & 40% females. </li></ul><ul><li>60% ingest drugs prescribed for themselves or a relative. </li></ul><ul><li>The mortality from drug poisoning is < 1% & should be < 2% in severely ill patient by effective ICU. </li></ul>
  6. 8. <ul><li>Drugs play an important role in suicidal &accidental poisoning </li></ul><ul><li>Common drugs used in poisoning include: </li></ul><ul><li>Analgesics (salicylates) > sedatives & hypnotics (barbiturates) > psychotherapeutics (tranquilizers) > CNS stimulants &depressants (amphetamines) </li></ul><ul><li>Narcotics - Lomotilt, an antidiarrhetic with a similar lethal dose as morphine; due to CNS depression. </li></ul><ul><ul><li>Propoxyphene , similar effect as methadone </li></ul></ul><ul><ul><li>Overdose treated with Naloxone. </li></ul></ul>
  7. 9. <ul><li>Major drugs involved in poisoning: </li></ul><ul><li>Paracetamol. </li></ul><ul><li>Aspirin. </li></ul><ul><li>Benzodiazepines. </li></ul><ul><li>SSRIs. </li></ul><ul><li>TADs. </li></ul><ul><li>Antionvulsants. </li></ul><ul><li>Other analgesics inculding NSAIDs. </li></ul>
  8. 10. <ul><li>Poisoing by substanes other than drugs: </li></ul><ul><li>Petrolium distilates. </li></ul><ul><li>Nature toxines as mushrooms. </li></ul><ul><li>Industrial chemicals. </li></ul><ul><li>Toiletries. </li></ul><ul><li>Household products. </li></ul><ul><li>Agrochemicals. </li></ul><ul><li>Others. </li></ul>
  9. 11. General Comments <ul><li>Try &get as much history as possible including witnesses </li></ul><ul><li>People truly wanting to commit suicide often lie </li></ul><ul><li>Remember the ABCs: </li></ul><ul><ul><li>Airway Clear mouth & throat, gag reflex </li></ul></ul><ul><ul><li>Breathing O 2 saturation, ABGs </li></ul></ul><ul><ul><li>Circulation Venous access, IV fluids if shocked </li></ul></ul><ul><li>Assess GCS </li></ul><ul><li>Examination </li></ul>
  10. 12. History <ul><li>When, what, how much ? </li></ul><ul><li>Why? </li></ul><ul><li>Circumstances </li></ul><ul><li>PMHx, Drug history </li></ul><ul><li>Psychiatric history </li></ul><ul><li>Assess mental status & capacity </li></ul>
  11. 13. Care with names: Generic vs Chemical name! <ul><li>Dolostop: paracetamol+dextropropoxiphen. </li></ul><ul><li>Valium: diazepan. </li></ul><ul><li>Fluout: paraetamol + diphenhydramine. </li></ul>
  12. 14. Investigations <ul><li>Always check blood glucose. </li></ul><ul><li>Send blood & urine for toxicology screening. </li></ul><ul><li>ALWAYS measure paracetamol & salicylate levels </li></ul><ul><ul><li>Failure to diagnose & treat is negligent. </li></ul></ul><ul><li>CBP, LFTs, glucose, ABG, clotting, bicarbonate </li></ul><ul><li>ECG, CXR </li></ul><ul><li>Specific blood levels </li></ul>
  13. 15. Toxins for which emegency blood levels measurements needed: <ul><li>Paracetamol. </li></ul><ul><li>Aspirin. </li></ul><ul><li>Iron. </li></ul><ul><li>Lthium. </li></ul><ul><li>Theophylin. </li></ul><ul><li>Methanol. </li></ul><ul><li>Ethylene glycol. </li></ul>
  14. 16. Management <ul><li>Supportive </li></ul><ul><ul><li>Correct hypoxia, hypotension, dehydration, hypo- hyperthermia, and acidosis </li></ul></ul><ul><ul><li>Control seizures </li></ul></ul><ul><ul><li>If comatose consider; DON’T( Dextrose,O2,Naloxone,Thaimine). </li></ul></ul><ul><li>Monitor </li></ul><ul><ul><li>PR, BP, ECG, Oxygenation, GCS </li></ul></ul><ul><li>General </li></ul><ul><ul><li> Absorption </li></ul></ul><ul><ul><li> Elimination </li></ul></ul><ul><ul><li>Specific antidotes </li></ul></ul>
  15. 17. Principles of therapy: 1. Prevention of drug absorption <ul><li>Washing to remove cutaneous contamination by acid or base or organophosphorous insecticides. </li></ul><ul><li>Induction of vomiting to remove poison from stomach by: </li></ul><ul><ul><li>a. Mechanical stimulation as inducing gag. </li></ul></ul><ul><ul><li>b. Ipecac syrup. </li></ul></ul><ul><ul><li>c. Apomorphine. </li></ul></ul><ul><ul><li>d. Warm salt water or biarbonate gastric lavage . </li></ul></ul>
  16. 18. Principles of therapy: 1. Prevention of drug absorption <ul><li>Binding of the poison by specific chelating agents e.g. EDTA inn heavy metal poisoning as lead poisoning or deferxamine in Iron poisoning. </li></ul><ul><li>Adsorption of the poison onto activated charcoal </li></ul><ul><ul><li>Should be given within 30 mm of ingestion </li></ul></ul><ul><ul><li>Charcoal has no toxicity, may be given before inducing vomiting or gastric lavage </li></ul></ul><ul><ul><li>It is with a universal antidote (activated charcoal: magnesium oxide: tannic acid 2:1:1) </li></ul></ul><ul><ul><li>50 g single or repeated dose (  elimination) </li></ul></ul><ul><ul><li>Doesn’t bind heavy metals, ethanol, acids </li></ul></ul>
  17. 19. Drugs not adsorb to activated charcoal: <ul><li>Iron. </li></ul><ul><li>Lithium. </li></ul><ul><li>Methanol. </li></ul><ul><li>Ethylene glycol ( antifreze). </li></ul><ul><li>Acids – alkalis. </li></ul><ul><li>Petrolium distilates. </li></ul>
  18. 20.  Absorption <ul><li>Gastric lavage </li></ul><ul><ul><li>Only if within 1 hour & if life-threatening amount </li></ul></ul><ul><ul><li>Never for corrosives as it may cause respiratory irritation& more GIT damage specially esophage. </li></ul></ul><ul><ul><li>If  LOC intubate before gastric lavage. </li></ul></ul>
  19. 21.  Elimination <ul><li>Methods to inrease elimination: </li></ul><ul><li>Multiple dose activated charcoal </li></ul><ul><ul><li>Can bind Quinine, phenobarbitone </li></ul></ul><ul><li>Charcoal haemoperfusion </li></ul><ul><ul><li>Can bind Barbiturates, theophylline </li></ul></ul><ul><li>Diuresis </li></ul><ul><li>Urinary alkalinization: increase excretion of aspirin. </li></ul><ul><li>Dialysis: can remove many substances from blood. </li></ul>
  20. 22. Drugs adsorb to activated charcoal: <ul><li>Aspirin. </li></ul><ul><li>Carbamezepine. </li></ul><ul><li>Dapsone. </li></ul><ul><li>Digoxin. </li></ul><ul><li>Phenytoin. </li></ul><ul><li>Quinine. </li></ul><ul><li>Theophyline. </li></ul><ul><li>Barbiturates. </li></ul>
  21. 23. Principles of therapy: 2. Alteration of drug metabolism <ul><li>The enhancement of metabolism for drugs inactivated by metabolism e.g. use of thiosulfate in cyanide poisoning </li></ul><ul><li>The inhibition of metabolism of drugs which produce toxic metabolites e.g. use of ethanol for methanol poisoning </li></ul>
  22. 24. Principles of therapy: 3. Enhancement of excretion <ul><li>Ion trapping & alteration of urinary pH forced diuresis ,dialysis [hemodialysis), peritoneal dialysis, gastric dialysis (add acidic solution to stomach, pump out)] </li></ul><ul><li>Hemoperfusion, pass blood over charcoal </li></ul><ul><li>Laxatives (cathartics) e.g. sodium sulfate, magnesium sulfate, citrate or phosphate </li></ul>
  23. 25. Principles of therapy: 4. Specific pharmacological intervention <ul><li>Direct chemical antagonism e.g acid - base </li></ul><ul><li>Receptor competition e.g. nalorphine in morphine overdose </li></ul><ul><li>Blockade of receptors that causes the toxic effects e.g. atropine in organophosphate poisoning, Flumazenil in benzodiazepin poisoning. </li></ul><ul><li>Restoration of normal function using an agent exerting a direct opposite effect e.g. barbiturate in CNS stimulant poisoning </li></ul>
  24. 26. Antidotes in most common use in clinical toxicology: <ul><li>Paracetamol: n-acetyl cystein or methionine. </li></ul><ul><li>Opoid: Naloxone. </li></ul><ul><li>Benzodiazepines: Flumazenil. </li></ul><ul><li>Iron: dexferoxamine. </li></ul>
  25. 27. Treatment of shock <ul><li>Shock is in all serious accidental poisoning </li></ul><ul><li>Arterial blood pressure is low in shock </li></ul><ul><li>The problem of shock is poor tissue perfusion </li></ul><ul><li>Present treatment: provide fluid, increase arteriolar relaxation & C.O. using a adrenergic blocker (isoproterenol) & antiinflammatomy steroids. </li></ul>
  26. 28. Causes of hypotension in poisoning: <ul><li>Volume depletion from vomiting, diarrhea, GITB. </li></ul><ul><li>Drug-induced dilation of the venous bed. </li></ul><ul><li>Myocardial depresion as in TAD & BB poisoning. </li></ul><ul><li>Severe brady or tahyrrhthmias. </li></ul><ul><li>Drug-induced metabolic acidosis as in aspirin poisoning. </li></ul>
  27. 29. Treatment of convulsion <ul><li>Many drugs stimulate CNS causing convulsion. </li></ul><ul><li>Diazepam (Valium), a tranquilizer, is the drug of choice </li></ul>
  28. 30. <ul><li>Specific drug poisoning: </li></ul>
  29. 31. Paracetamol Overdose <ul><li>Acetaminophen is a leading OTC analgesics </li></ul><ul><li>Is one of the leading causes of drug overdose in the US & UK& a leading cause of liver failure. </li></ul><ul><li>It is metabolized in the liver & relatively safe in therapeutic doses. </li></ul><ul><li>A small fraction is converted to a reactive toxic metabolite, N -acetyl- p -benzoquinoneimine (NAPQI), by the cytochrome P-450 hepatic enzymes. </li></ul><ul><li>With therapeutic doses, glutathione stores can detoxify NAPQI by conjugation. </li></ul><ul><li>Glutathione stores are depleted in overdoses, & NAPQI binds to cellular proteins, producing hepatocellular necrosis. </li></ul><ul><li>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. </li></ul>
  30. 32. Paracetamol Overdose
  31. 33. Paracetamol Overdose: features. <ul><li>Acetaminophen poisoning clinically produces only nausea, vomiting, & anorexia 12 to 24 hours after ingestion. </li></ul><ul><li>Hepatic coma & coagulopathy do not occur until 48 to 96 hours after ingestion, after irreversible hepatic necrosis has occurred. </li></ul><ul><li>Patient with significant paracetamol overdose should not be discharged early from Hospital, even if appearing clinically well in the first 48-96 hours. </li></ul>
  32. 34. Paracetamol Overdose: Treatment. <ul><li>N - acetylcysteine is the drug of choice. </li></ul><ul><li>It effectively prevents hepatotoxicity if given within 8 hours. </li></ul><ul><li>It is strongly effective if given within 16 hours & may be effective up to & beyond 24 hours. </li></ul><ul><li>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. </li></ul><ul><li>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 . </li></ul>
  33. 35. Paracetamol Overdose: Treatment. <ul><li>It causes hepatic damage in overdose& rarely renal failure. </li></ul><ul><li>If presents within 1 hour of overdose, activated charcoal given in addition to NAC. </li></ul><ul><li>Antidote is IV N-acetylcysteine, provides complete protection if given within 8-10 hours of overdose;efficacy declines thereafter. </li></ul><ul><li>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. </li></ul><ul><li>Methionine 12 g orally 4-hourly, to a total of four doses, is a suitable alternative when N-acetylcysteine is not available. </li></ul><ul><li>If a patient presents > 15 hours after ingestion, liver function tests, PT (or INR) & renal function tests should be performed& the antidote started. </li></ul><ul><li>In some cases ABGs will need to be taken. </li></ul><ul><li>Liver transplantation should be considered in individuals who develop acute liver failure. </li></ul>
  34. 36. Paracetamol Overdose: Treatment. <ul><li>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. </li></ul>
  35. 37. 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
  36. 38. The salicylates ( aspirin ) . <ul><li>Is a leading cause of analgesic drug overdose. </li></ul><ul><li>The association of Reye's syndrome with aspirin produced a dramatic fall in use & accidental poisoning in the pediatric age group. </li></ul><ul><li>Salicylates inhibit the cyclooxygenase enzyme of the prostaglandin synthetase complex, uncouple oxidative phosphorylation, & produce respiratory alkalosis & a high anion gap metabolic acidosis. </li></ul><ul><li>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. </li></ul>
  37. 39. The salicylates ( aspirin ) . <ul><li>Salicylate ingestion at doses > 150, 250 & 500 mg aspirin/kg body weight produces mild, moderate & severe poisoning respectively. </li></ul><ul><li>Salicylate poisoning can also occur with ingestion of oil of wintergreen or when salicylic ointment (e.g. wart remover) is applied extensively to skin. </li></ul>
  38. 40. Salicylates ( aspirin ): Clinical presentation . <ul><li>Includes nausea, vomiting, tinnitus, hearing loss,sweating, facial flushing, hyperpyrexia, & hyperventilation. </li></ul><ul><li>With severe poisoning: progressive dehydration, hypernatremia, pulmonary edema, purpura, GIB & death. </li></ul><ul><li>Direct stimulation of respiratory centre produces hyperventilation </li></ul><ul><li>Peripheral vasodilatation with bounding pulses & profuse sweating occurs in moderately severe poisoning. </li></ul><ul><li>Petechiae &subconjunctival haemorrhages can occur due to reduced platelet aggregation but this is self-limiting. </li></ul><ul><li>Signs of serious poisoning include metabolic acidosis, renal failure & CNS effects as agitation, confusion, coma& fits. </li></ul><ul><li>Rarely, pulmonary& cerebral oedema occur. </li></ul><ul><li>Death can occur as a result of CNS depression&CV collapse. </li></ul><ul><li>The development of a metabolic acidosis is a bad prognostic sign, because acidosis results in increased salicylate transfer across the blood-brain barrier </li></ul><ul><li>A plasma level of > 30 mg/dL indicates salicylate toxicity& 80-100 mg/dL indicates critical salicylate poisoning. </li></ul>
  39. 41. Salicylates ( aspirin ): treatment . <ul><li>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. </li></ul><ul><li>The salicylate concentration needs to be interpreted in conjunction with the clinical features& acid-base status. </li></ul><ul><li>The treatment of choice for salicylate poisoning is an alkaline diuresis with sodium bicarbonate . </li></ul><ul><li>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. </li></ul><ul><li>Patients are often very dehydrated& fluid loss from vomiting & sweating &must be replaced, but over use of IVF may precipitate pulmonary oedema. </li></ul><ul><li>The use of multiple doses of activated charcoal in salicylate poisoning is controversial, but this approach is currently recommended unless salicylate level has peaked. </li></ul><ul><li>Urinary alkalinisation is indicated for adult patients with salicylate concentrations of 600-800 mg/l. </li></ul>
  40. 42. Salicylates ( aspirin ): treatment . <ul><li>Haemodialysis is very effective at removing salicylate &correcting acid-base and fluid balance abnormalities & considered when: </li></ul><ul><li>1.Serum concentrations are > 800 mg/l in adults &> 700 mg/l in the elderly. </li></ul><ul><li>2.Metabolic acidosis resistant to correction. </li></ul><ul><li>3.Severe CNS effects as coma or convulsions, pulmonary oedema & acute renal failure </li></ul><ul><li>Vitamin K supplementation should be given. </li></ul><ul><li>Supportive care is paramount. </li></ul>
  41. 43. Other (NSAID) poisoning . <ul><li>Ibuprofen is the leading (NSAID). </li></ul><ul><li>Usually causes little more than minor GI upset including mild abdominal pain, vomiting & diarrhoea. </li></ul><ul><li>10-20% have convulsions; usually self-limiting & needs only airway protection & oxygen, if persist IV diazepam. </li></ul><ul><li>Serious features include coma, prolonged fits, apnoea , bradycardia but very rare. </li></ul><ul><li>Deaths have been reported after massive overdose of ibuprofen, but not with mefenamic acid. </li></ul><ul><li>Rarely, renal failure ensues. </li></ul><ul><li>Features of toxicity tend to occur early & unlikely to develop later than 6 hours after the overdose. </li></ul><ul><li>Liver/renal function may be affected, so electrolytes, liver functions &CBP should be checked in all unless trivial overdoses. </li></ul><ul><li>The 1/2t of most NSAIDs are < 12 hours, so elimination methods are not needed. </li></ul><ul><li>Activated charcoal should be given if > 100 mg/kg BW ibuprofen or > 10 tablets of any other NSAID taken in the last hour. </li></ul><ul><li>GI irritation is treated with oral H2-blockers (e.g. ranitidine). </li></ul>
  42. 44. Anticholinergic poisoning. <ul><li>The classic anticholinergic syndrome is produced by blockade of acetylcholine with central & peripheral effects: </li></ul><ul><li>Psychosis, delirium, seizures, flushing, dry mucous membranes & skin, hyperpyrexia, dilated pupils & urinary retention. </li></ul><ul><li>The antidote physostigmine should be reserved for severe cases of pure anticholinergic poisoning. </li></ul><ul><li>Physostigmine should not be used for agents with only some anticholinergic properties, as tricyclic antidepressants. </li></ul><ul><li>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. </li></ul><ul><li>Cardiac monitoring is essential, because physostigmine has caused asystole, bradycardia, & seizures. </li></ul>
  43. 45. Barbiturates poisoning. <ul><li>Still constitute a major source of overdose & mortality although largely replaced as sleep medication by benzodiazepines. </li></ul><ul><li>They are still present in headache prescriptions & sleep medications & remain common drugs of abuse. </li></ul><ul><li>Phenobarbital is one of the leading anticonvulsant medications. </li></ul><ul><li>Thiopental is used as an IV anesthetic for in-hospital rapid-sequence intubation or as a sedative before cardioversion & surgery. </li></ul><ul><li>Phenobarbital is excreted primarily unchanged by the kidney, whereas most other barbiturates are metabolized by the liver. </li></ul>
  44. 46. Barbiturates poisoning: features. <ul><li>Overdose is associated with depression of CNS & CV system, coma, hypotension, loss of reflexes, hypothermia, respiratory arrest & death. </li></ul><ul><li>2 characteristic of a barbiturate overdose is: </li></ul><ul><li>1. The persistence of the pupillary light reflex even with stage IV coma. </li></ul><ul><li>2. Bullous skin lesions often occur over pressure areas. </li></ul>
  45. 47. Barbiturates poisoning: treatment. <ul><li>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. </li></ul><ul><li>An alkaline diuresis with sodium bicarbonate is specifically indicated for phenobarbital , which is a weak acid that is excreted unchanged in the urine. </li></ul><ul><li>Multiple-dose activated charcoal every 4 -6 hours is also specifically indicated for phenobarbital , as it diffuses into the GIT lumen. </li></ul><ul><li>Charcoal hemoperfusion & hemodialysis have a role in barbiturate overdose for critical patients who do not respond to conservative therapy. </li></ul>
  46. 48. The benzodiazepines poisoning. <ul><li>Extremely popular & have replaced other sedative-hypnotics. </li></ul><ul><li>All are effective anxiolytics & sedatives& are muscle relaxants, anticonvulsants & amnestics. </li></ul><ul><li>D iazepam , lorazepam , & midazolam, have major therapeutic roles as IV drugs for in-hospital use as anticonvulsants, preanesthetics & sedatives. </li></ul><ul><li>Although common agents of overdose, cause only coma & ataxia; mortality is rare & supportive care is all that usually necessary. </li></ul><ul><li>The antidote flumazenil is reserved only for reversing pure in-hospital benzodiazepine conscious analgesia&reversing coma in zolpidem overdose. </li></ul><ul><li>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. </li></ul>
  47. 49. Cardiotoxic drugs:
  48. 50. Cardiotoxic drug poisoning: <ul><li>CCBs. </li></ul><ul><li>BBs. </li></ul><ul><li>Digoxin. </li></ul><ul><li>TAD. </li></ul>
  49. 51. The calcium channel blockers poisoning. <ul><li>Common antihypertensive agents </li></ul><ul><li>the most common cause of cardiovascular drug death by overdose. </li></ul><ul><li>A special problem is presented by the sustained-release preparations, which allow for continued absorption. </li></ul><ul><li>Persistent hypotension, bradycardia with atrioventricular block (especially with verapamil), coma, pulmonary edema, & cardiac arrest constitute the clinical picture. </li></ul>
  50. 52. The calcium channel blockers poisoning. <ul><li>Treatment must be aggressive if these patients are to survive. </li></ul><ul><li>Whole-bowel irrigation with polyethylene glycol is indicated if sustained-release preparations have been ingested. </li></ul><ul><li>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. </li></ul>
  51. 53. The calcium channel blockers poisoning. <ul><li>For patients who do not respond to high-dose calcium therapy, dopamine, dobutamine, amrinone, epinephrine, and/or glucagon. </li></ul><ul><li>Glucagon is indicated in patients with concomitant b-blocker overdose. </li></ul><ul><li>Pacing may be necessary, especially with verapamil overdose. </li></ul><ul><li>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. </li></ul>
  52. 54. Digitalis poisoning. <ul><li>Still common. </li></ul><ul><li>Patients who suffer yellow or blurred vision, nausea or vomiting, & sinus bradycardia may improve simply by stopping the drug. </li></ul><ul><li>Significant digitalis intoxication is heralded by hyperkalemia & a variety of major cardiac arrhythmias. </li></ul><ul><li>Digoxin-specific Fab antibodies (Digibind) offer a definitive means of therapy &are indicated for: </li></ul><ul><li>Life-threatening cardiac arrhythmia. </li></ul><ul><li>Hyperkalemia. </li></ul><ul><li>Aserum digoxin level of 10 ng/mL, </li></ul><ul><li>A massive overdose of 10 mg or greater in adults or 4 mg in children. </li></ul><ul><li>Antidotal therapy should be instituted before conventional therapy in life-threatening situations. </li></ul>
  53. 55. Antidiabetics: <ul><li>Sulphonylureas (e.g. chlorpropamide, glibenclamide, gliclazide, glipizide, tolbutamide) </li></ul><ul><li>Biguanides (metformin, phenformin) </li></ul><ul><li>Insulins. </li></ul><ul><li>Cause hypoglycaemia when taken in overdose. </li></ul><ul><li>The onset & duration of hypoglycaemia vary, but can last for several days with long-acting agents as chlorpropamide& isophane / lente insulins. </li></ul><ul><li>Hypoglycaemia may manifest as agitation, sweating, confusion, tachycardia, hypothermia, drowsiness, coma or convulsions </li></ul><ul><li>Permanent neurological damage can occur if the hypoglycaemia is prolonged. </li></ul>
  54. 56. Antidiabetics: <ul><li>Metformin can cause a lactic acidosis in overdose, particularly in elderly & those with renal or hepatic impairment, or when co-ingested with ethanol. </li></ul><ul><li>It is associated with a > 50% mortality. </li></ul><ul><li>Metformin overdose may also cause nausea / vomiting, diarrhoea, abdominal pain, drowsiness, coma, hypotension & CV collapse. </li></ul>
  55. 57. Antidiabetics: Management <ul><li>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. </li></ul><ul><li>Formal measurement of venous blood glucose (not just visually read strips or meter) , urea & electrolytes should be performed &repeated regularly. </li></ul><ul><li>For medico-legal purposes , a blood sample may be required for subsequent measurement of insulin, pro-insulin and C-peptide. </li></ul><ul><li>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. </li></ul><ul><li>Potassium replacement should be guided by frequent measurement of urea &electrolytes. </li></ul>
  56. 58. Antidiabetics: Management <ul><li>Failure to regain consciousness within a few minutes of normalisation of the blood glucose indicate either: </li></ul><ul><li>1. CNS depressant has also been ingested </li></ul><ul><li>2. Hypoglycaemia has been prolonged. </li></ul><ul><li>3. Another cause for the coma (e.g. cerebral haemorrhage) or cerebral oedema. </li></ul><ul><li>In cases of severe sulphonylurea overdose resistant to dextrose infusions, use of IV octreotide as an antidote may be considered. </li></ul>
  57. 59. Carbon monoxide poisoning. <ul><li>Is the leading cause of death from poisoning in US. </li></ul><ul><li>CO is a colorless, odorless, tasteless gas produced by incomplete combustion of carbon materials. </li></ul><ul><li>CO has a 200 times greater affinity for hemoglobin than oxygen & thus produces cellular hypoxia & death. </li></ul><ul><li>Fires, smoke, wood-burning stoves, gas space heaters& engine exhaust are sources of unintentional poisoning. </li></ul>
  58. 60. Carbon monoxide poisoning. <ul><li>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. </li></ul><ul><li>Mild CO poisoning often is mistaken for influenza, as both occur primarily in the winter months & cause headache/GI symptoms. </li></ul><ul><li>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. </li></ul><ul><li>In general, the deeper the level of coma, the greater the chance of neuropsychiatric sequelae. </li></ul>
  59. 61. Carbon monoxide poisoning. <ul><li>CO poisoning is treated with oxygen: </li></ul><ul><li>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. </li></ul><ul><li>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 </li></ul>
  60. 62. Carbon monoxide poisoning. 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 SPECIFIC INDICATIONS FOR HYPERBARIC OXYGEN THERAPY
  61. 63. Caustic alkali poisoning. <ul><li>Accidentally swallowing button batteries larger than 20 mm in diameter & intentional ingestion of alkali substances are the major causes of morbidity. </li></ul><ul><li>Because solid crystals adhere to the tongue & cause burning, they uncommonly produce esophageal burn. </li></ul><ul><li>Drooling in children &inability to swallow are highly suggestive. </li></ul><ul><li>Mouth burns are also suggestive, but the absence of mouth burns does not exclude esophageal burn. </li></ul>
  62. 64. Caustic alkali poisoning. <ul><li>Milk is the only possible home antidote, but it must be given immediately. </li></ul><ul><li>To detect significant burns, some suggest UGI esophagoscopy within 12 hours, whereas others prefer to wait 24-2 hours following ingestion. </li></ul><ul><li>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. </li></ul><ul><li>Esophageal dilation & gastric tube esophageal replacement are indicated for treating esophageal stricture. </li></ul>
  63. 65. Cyanide poisoning. <ul><li>Most commonly is due to smoke inhalation. </li></ul><ul><li>One public source is acetonitrile in acrylic nail remover. </li></ul><ul><li>Hydrogen cyanide gas is a fumigant rodenticide. </li></ul><ul><li>Prolonged administration of nitroprusside can result in elevated cyanide levels. </li></ul>
  64. 66. Cyanide poisoning. <ul><li>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. </li></ul><ul><li>Rapidly develop coma, shock, seizures, lactic acidosis, respiratory & cardiac arrest. </li></ul><ul><li>Mild exposures following smoke inhalation may be difficult to diagnose& Emergency administration of antidote may be life-saving. </li></ul><ul><li>Cyanide poisoning should be suspected in patients who have inhaled smoke &who have evidence of lactic acidosis. </li></ul>
  65. 67. Cyanide poisoning. <ul><li>The cyanide antidote kit contains amyl nitrite , ampules of sodium thiosulfate , & ampules of sodium nitrite. </li></ul><ul><li>The body has a natural enzyme, rhodanese, that can complex cyanide & sulfur to form thiocyanate, which is only mildly toxic. </li></ul><ul><li>IV sodium thiosulfate provides the sulfur necessary to produce thiocyanate & is relatively safe. </li></ul><ul><li>Because sodium nitrite causes hypotension & methemoglobinemia, its use is reserved for the most critical cases. </li></ul><ul><li>The new antidote hydroxocobalamin (initial adult dosage 5 g IV), not yet approved, is a safer alternative. </li></ul>
  66. 68. Iron poisoning. <ul><li>Has a direct corrosive action on the stomach & proximal small bowel </li></ul><ul><li>Once absorbed, produces shock, metabolic acidosis, liver failure& death. </li></ul><ul><li>Initially, GIsymptoms prevail with persistent vomiting, abdominal pain& hemorrhage. </li></ul><ul><li>A quiescent phase may be observed, followed by shock, coma, metabolic acidosis& liver failure. </li></ul><ul><li>Laboratory data may reveal leukocytosis, hyperglycemia& radiopaque tablets on a flat plate of the abdomen. </li></ul>
  67. 69. Iron poisoning. <ul><li>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. </li></ul>
  68. 70. Iron poisoning. <ul><li>Management of iron poisoning includes gastric lavage with normal saline. </li></ul><ul><li>Whole-bowel irrigation may be indicated after ingestion of sustained-release capsules. </li></ul><ul><li>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. </li></ul>
  69. 71. Iron poisoning. <ul><li>Deferoxamine is indicated for: </li></ul><ul><li>All critical patients who present with coma, shock, or hemorrhage, </li></ul><ul><li>All patients with a serum iron level higher than 500 mg/dL, </li></ul><ul><li>Patients who are symptomatic with a serum iron > 300 mg/dL. </li></ul><ul><li>IV deferoxamine 15 mg/kg/hour is the preferred; up to 6 g may be given in 24 hours. </li></ul>
  70. 72. Iron poisoning. <ul><li>Chelation therapy should continue until: </li></ul><ul><li>The patient becomes stable for at least 24 hours. </li></ul><ul><li>Vntil the vin rosé urine (when present) becomes clear. </li></ul><ul><li>Until the serum iron level has fallen <300 mg/dL. </li></ul><ul><li>Exchange transfusion may be indicated for the unusual patient who is critically ill & does not respond to chelation therapy. </li></ul>
  71. 73. Methanol & ethylene glycol poisoning. <ul><li>True medical emergencies. </li></ul><ul><li>Methanol is most commonly found as the active ingredient in windshield washer fluid& ethylene glycol constitutes antifreeze. </li></ul><ul><li>Moth are also found in many commercial & marine products. </li></ul><ul><li>Methanol, or wood alcohol, is converted by alcohol dehydrogenase to formaldehyde &then to formic acid. </li></ul>
  72. 74. Methanol & ethylene glycol poisoning. <ul><li>Signs & symptoms develop over a 24-hour period & may include infarction of the putamen. </li></ul><ul><li>Severe high anion gap metabolic acidosis occurs with an increase in the osmolal gap. </li></ul><ul><li>Treatment emphasizes IV ethanol, sodium bicarbonate & hemodialysis. </li></ul>
  73. 75. Methanol & ethylene glycol poisoning. <ul><li>The diagnosis of ethylene glycol poisoning in adults, commonly from antifreeze, is generally, but not always, evident from the history. </li></ul><ul><li>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 </li></ul><ul><li>(4-methylpyrazole) inhibits alcohol dehydrogenase & may be an alternative to intravenous alcohol for the treatment of ethylene glycol poisoning. </li></ul><ul><li>Hemodialysis is the treatment of choice for ethylene glycol poisoning & should be instituted as early as possible once the diagnosis is made. </li></ul>
  74. 76. Methanol & ethylene glycol poisoning. 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. Treat 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). S&ss   Methanol POISONING WITH METHANOL OR ETHYLENE GLYCOL
  75. 77. Methanol & ethylene glycol poisoning. Treat ethylene glycol with: aggressive gastric lavage; ethanol infusion or 4-methylpyrazole, sodium bicarbonate to correct metabolic acidosis, Correct hypocalcemia with calcium chloride, Hemodialysis Treatment Early Altered mental status; seizures; hypocalcemic tetany 12 hr after ingestion Congestive heart failure 24 – 72 hr after ingestion Profound renal failure Signs and symptoms   Ethylene Glycol
  76. 78. The organophosphates poisoning. <ul><li>Highly popular insecticides because they are effective, disintegrate within days of application & do not persist in the environment </li></ul><ul><li>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. </li></ul>
  77. 79. The organophosphates poisoning. <ul><li>The organophosphates irreversibly inhibit acetylcholinesterase, resulting in an overabundance of acetylcholine at synapses & the myoneural junction. </li></ul><ul><li>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). </li></ul><ul><li>Initial symptoms resemble a flulike syndrome with abdominal pain, vomiting, headache, dizziness. </li></ul><ul><li>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. </li></ul><ul><li>Torsades de pointes VF has also been described. </li></ul>
  78. 80. The organophosphates poisoning. <ul><li>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. </li></ul><ul><li>A 25% reduction in red blood cell cholinesterase confirms organophosphate poisoning. </li></ul><ul><li>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. </li></ul><ul><li>Atropine use requires cardiac monitoring& proper oxygenation. </li></ul><ul><li>Pralidoxime is the treatment of choice for organophosphate poisoning & should be begun on clinical grounds before return of any blood studies. </li></ul><ul><li>To be effective, pralidoxime must be given in the first 48 hours before irreversible binding of acetylcholinesterase occurs. </li></ul>
  79. 81. The organophosphates poisoning. <ul><li>The initial dose is 1 g IV given over 15 to 30 minutes; the effect may be dramatic. </li></ul><ul><li>Pralidoxime by continuous infusion of up to 500 mg/hour may be necessary in critically ill patients. </li></ul><ul><li>Pralidoxime may obviate the need for high-dose atropine therapy & reduce the incidence of late-onset paralysis. </li></ul><ul><li>Neither therapies exclude the use of the other. </li></ul>
  80. 82. The organophosphates poisoning. <ul><li>The carbamate insecticides include carbaril, methomyl, & propoxur </li></ul><ul><li>are reversible cholinesterase inhibitors. </li></ul><ul><li>They produce clinical effects similar to those of the organophosphates but without CNS signs; </li></ul><ul><li>They are considerably more benign & shorter duration. </li></ul><ul><li>Atropine is the drug of choice for carbamate poisoning. </li></ul><ul><li>Pralidoxime is not indicated because the carbamate-cholinesterase complex is quite reversible. </li></ul>
  81. 83. Theophylline poisoning. <ul><li>Mortality from both plain & sustained-release preparations occur from acute overdose & long-term unintentional intoxication. </li></ul><ul><li>Vomiting is often the first symptom, sinus tachycardia is the most common sign in both acute - chronic toxicity. </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>Profound hypokalemia, hyperglycemia, metabolic acidosis are also seen. </li></ul><ul><li>Serum theophylline is higher in acute overdose compared with those in chronic toxicity. </li></ul>
  82. 84. Theophylline poisoning. <ul><li>Treatment includes </li></ul><ul><li>withdrawing the drug, cardiac monitoring, supportive care. </li></ul><ul><li>Gastric lavage &activated charcoal are indicated for acute overdose. </li></ul><ul><li>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. </li></ul><ul><li>Whole-bowel irrigation may be indicated for ingestion of sustained-release capsules. </li></ul><ul><li>Cardiac arrhythmias are often difficult to manage but may respond to IV propranolol. </li></ul><ul><li>Correction of hypokalemia, metabolic acidosis& fluid-electrolyte balance is indicated. </li></ul><ul><li>Although seizures may respond to IV diazepam , status epilepticus & rhabdomyolysis may occur & signify a poor outcome. </li></ul>
  83. 85. Theophylline poisoning. <ul><li>Charcoal hemoperfusion is the treatment of choice for significant theophylline toxicity. </li></ul><ul><li>Hemodialysis is becoming an option equal to charcoal hemoperfusion. </li></ul><ul><li>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. </li></ul>
  84. 86. Tricyclic (or cyclic) poisoning. <ul><li>Still the leading cause of prescription drug death. </li></ul><ul><li>CV toxicity (arrhythmia /hypotension), CNS effects (especially coma /seizures), anticholinergic signs are seen. </li></ul><ul><li>The cardiotoxic effects are seen with ingestion of 1 g (10 to 20 mg/kg) &account for the high mortality rate. </li></ul>
  85. 87. Tricyclic (or cyclic) poisoning. <ul><li>The hallmark on ECG is prolongation of the QRS complex. </li></ul><ul><li>A QRS complex > 100 ms is a sign of severe toxicity & correlates with a plasma level > 1000 ng/mL. </li></ul><ul><li>Although sinus tachycardia & anticholinergic signs are evident with mild toxicity, QRS complex prolongation is associated with the development of ventricular arrhythmias, seizures, death. </li></ul><ul><li>Ventricular tachycardia is the most common ventricular rhythm, although ventricular bigeminy, slow ventricular rhythms, torsades de pointes VF also have been described. </li></ul><ul><li>VF/ sudden cardiac arrest are not uncommon. </li></ul>
  86. 88. Tricyclic (or cyclic) poisoning. <ul><li>The treatment of choice IV sodium bicarbonate . </li></ul><ul><li>To maintain a blood pH of 7.5 reduce the incidence of cardiac arrhythmia. </li></ul><ul><li>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. </li></ul><ul><li>Sodium bicarbonate also may be useful for correcting hypotension, although vasopressors may be necessary. </li></ul><ul><li>Airway, proper oxygenation & ventilation, fluid replacement (but avoid pulmonary edema), gastric lavage with serially administered activated charcoal& supportive therapy are indicated. </li></ul>
  87. 89. Tricyclic (or cyclic) poisoning. <ul><li>Phenytoin reverse QRS complex prolongation, but reserved for managing seizures. </li></ul><ul><li>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. </li></ul><ul><li>Diazepam is quite effective in controlling seizures, although intensive therapy including thiopental & rapid-sequence intubation may be necessary to manage status epilepticus. </li></ul><ul><li>Physostigmine is no longer used in tricyclic overdose, because by itself it can cause seizures, bradycardia, asystole. </li></ul><ul><li>Death generally occurs within the first 24 hours after overdose. </li></ul><ul><li>Because sudden death has occurred after apparent stabilization, cardiac monitoring is indicated for at least 24 hours after stabilization & normalization of the QRS complex. </li></ul>
  88. 90. Tricyclic (or cyclic) poisoning. <ul><li>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 ), </li></ul><ul><li>generally cause only sedation in overdose. </li></ul><ul><li>Fatal serotonin syndrome from concomitant overdose of s elective s erotonin r euptake i nhibitors (SSRIs) and monoamine oxidase inhibitors is now being reported. </li></ul>
  89. 91. Tricyclic OD – Initial ECG
  90. 92. Tricyclic OD – Recovery ECG