Toxico Overdose Lec07.

Poisons & Drug Poisoning Dr Mohamad shaikhani.

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 O 2 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 If comatose consider; DON’T( Dextrose,O2,Naloxone,Thaimine). 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

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: 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 8-10 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. D iazepam , 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 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. 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

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. 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 "being in a snowstorm," blindness (end result). S&ss Methanol POISONING WITH METHANOL OR ETHYLENE GLYCOL

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

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 s elective s erotonin r euptake i nhibitors (SSRIs) and monoamine oxidase inhibitors is now being reported.

Toxico Overdose Lec07.

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