Common toxic syndromes -

Common toxic syndromes -

Common toxic syndromes Domina Petric, MD Acetaminophen Acute ingestion of more than 150-200 mg/kg for children and 7 g total for adults is considered potentially toxic.

Acetaminophen Initially, the patient is asymptomatic or has mild gastrointestinal upset (nausea, vomiting). After 24-36 hours, evidence of liver injury appears. There are elevated aminotransferase levels and hypoprothrombinemia. In severe cases, fulminant liver

failure occurs, leading to hepatic encephalopathy and death. Acetaminophen Serum acetaminophen concentration measurement: If the level is greater than 150-200 mg/L approximately 4 hours after ingestion, the

Acetaminophen Chronic alcoholics Chronic alcoholics or patients taking drugs that enhance P450 production of toxic metabolites are at risk with lower levels.

Acetaminophen The antidote is acetylcysteine. It acts as a glutathione substitute and binds the toxic metabolite as it is produced. It is most effective when given orally within 8-10 hours if possible. Liver transplantation: for the patients with fulminant hepatic

failure. Amphetamines and others Stimulant drugs commonly abused: methamphetamine (crank, crystal) methylenedioxymethamphet

amine (MDMA, ecstasy) cocaine (crack) Amphetamines and others Caffeine is often added to dietary supplemets sold as fat burners. 3,4methylenedioxypyrovalerone

(MDPV) and various derivatives of methcathinone are becoming popular: Ivory Wave, Bounce, Bubbles, Mad Amphetamines and others At lower doses, euphoria and wakefulness are

accompanied by a sense of power and well-being. At higher doses, restlessness, agitation and acute psychosis may occur, accompanied by hypertension and Amphetamines and others

Prolonged muscular hyperactivity or seizures may contribute to hyperthermia and rhabdomyolysis. Body temperature as high as 42O C may develop. Hyperthermia can cause brain damage, hypotension,

Amphetamines and others There is no specific antidote. Seizures and hyperthermia are the most dangerous manifestations and must be trated aggressively.

Iv. benzodiazepines Amphetamines and others Temperature reduction: removing clothing, spraying with tepid water, encouraging evaporative cooling with fanning.

For very high body temperatures, neuromuscular paralysis is used to abolish muscle Anticholinergic agents Classic anticholinergic (antimuscarinic) syndrome: red as a beet (skin flushed) hot as a hare (hyperthermia) dry as a bone (dry mucous

membranes, no sweating) blind as a bat (blurred vision, cycloplegia) mad as a hatter (confusion, Anticholinergic agents Patients usually have sinus tachycardia and the pupils are usually dilated. Agitated delirium or

coma may be present. Muscle twitching is Anticholinergic agents Diphenhydramine can cause seizures. Tricyclic antidepressants can also cause seizures and severe cardiovascular toxicity. These drugs have also

anticholinergic effects. Anticholinergic agents Agitated patients may require sedation with a benzodiazepine or an antipsychotic agent (haloperidol). The specific antidote for peripheral and central anticholinergic syndrome is

Anticholinergic agents Physostigmine is given in small intravenous doses 0,5-1 mg with careful monitoring. It can cause bradycardia and seizures if given too rapidly. Anticholinergic agents

Physostigmine should not be given to a patient with suspected tricyclic antidepressant overdose because it can aggravate cardiotoxicity. Cardiotoxicity can result in heart block or asystole. Catheterization may be needed to prevent excessive distension of the bladder.

Antidepressants Tricyclic antidepressants are amitriptyline, desipramine and doxepin. Ingestion of more than 1 g of a tricyclic drug (about 15-20 mg/kg) is considered potentially lethal. Antidepressants

Tricyclic antidepressants are competitive antagonists at muscarinic cholinergic receptors. Anticholinergic findings (tachycardia, dilated pupils, dry mouth) are common even at Antidepressants Some tricyclics are also

strong blockers, which can lead to vasodilatation. Centrally mediated agitation and seizures may be followed by Antidepressants Tricyclics have quinidinelike cardiac depressant effects on the sodium channel.

That causes slowed conduction with a wide QRS interval and depressed cardiac Antidepressants Tricyclics cardiac toxicity may result in serious arrhythmias like ventricular

conduction block and ventricular tachycardia. Lifeinthefastlane. com Antidepressants Treatment of tricyclic antidepressant overdose: endotracheal intubation

and assisted ventilation iv. fluids for hypotension dopamine or norepinephrine Antidepressants Norepinephrine can be used as inital drug of choice for tricyclic-induced hypotension. The antidote for quinidinelike cardiac toxicity (wide

QRS complex) is sodium bicarbonate: 50-100 mmol (or 1-2 mmol/kg) iv. bolus. Antidepressants Sodium bicarbonate provides a rapid increase in extracellular sodium that helps overcome sodium channel blockade. Physostigmine is

contraindicated because it can aggravate depression of cardiac conduction and Antidepressants Monoamine oxidase inhibitors (tranylcypromine, phenelzine) are sometimes used for resistant depression. They can cause severe

hypertensive reactions when interacting with drugs (for example with SSRIs) Antidepressants Newer antidepressants (fluoxetine, paroxetine, citalopram, venlafaxine) are generally safer than the tricyclic antidepressants and monoamine oxidase

inhibitors. SSRIs (selective serotonine reuptake inhibitors) can Antidepressants Bupropion has caused seizures even in therapeutic doses. SSRIs may interact with each other or especially with monoamine oxidase

inhibitors to cause the serotonin syndrome: agitation, muscle Antipsychotics Older phenothiazines, butyrophenones and newer atypical drugs can cause CNS depression, seizures and hypotension. Some of antipsychotics

can cause QT prolongation. Antipsychotics The potent dopamine D2 blockers are also associated with parkinsonian movement disorders (dystonic reactions). In rare cases these drugs can cause neuroleptic malignant

syndrome: lead-pipe rigidity, hyperthermia and autonomic Aspirin (salicylate) Acute ingestion of more than 200 mg/kg is likely to produce intoxication. Poisoning can also result from chronic overmedication:

Aspirin (salicylate) Poisoning causes uncoupling of oxidative phosphorylation and disruption of normal cellular metabolism. The first sign of salicylate toxicity is often hyperventilation and respiratory alkalosis due to medullary stimulation.

Aspirin (salicylate) Metabolic acidosis follows. An increased anion gap results from accumulation of lactate and from excretion of bicarbonate by the kidney to compensate for

Aspirin (salicylate) Arterial blood gas testing: mixed respiratory alkalosis and metabolic acidosis. Body temperature may be elevated because of uncoupling of oxidative phosphorylation. Severe hyperthermia may occur.

Aspirin (salicylate) Vomiting, hyperpnea and hyperthermia contribute to fluid loss and dehydration. Very severe poisoning: profound metabolic acidosis, seizures, coma, pulmonary edema and Aspirin (salicylate)

Absorption of salicylate and signs of toxicity may be delayed after very large overdoses or ingestion of enteric coated tablets. Aspirin (salicylate) Massive aspirin

ingestions (more than 100 tablets): aggressive gut decontamination with gastric lavage, repeated doses of activated charcoal and whole bowel irrigation (if necessary). Aspirin (salicylate) Intravenous fluids: replacing

fluid losses caused by tachypnea, vomiting and fever. Moderate intoxications: iv. sodium bicarbonate to alkalinize the urine and promote salicylate excretion by trapping the salicylate in Aspirin (salicylate)

Severe poisoning (patients with severe acidosis, coma, serum salicylate level>100 mg/dL): emergency hemodialysis to remove the salicylate more quickly and to restore acid-base balance and fluid status.

Beta blockers In overdose, blockers inhibit both 1 and 2 adrenoreceptors. Selectivity is lost at high doses. The most toxic blocker is PROPRANOLOL. Beta blockers

As little as two to three times the therapeutic dose of propranolol can cause serious toxicity. Propranolol in high doses may cause sodium channel blocking effects similar to those seen with quinidinelike drugs. Beta blockers Propranolol is lipophilic

and enters the CNS. Seizures and cardiac conduction block (wide QRS complex) may be seen with propranolol overdose. Beta blockers Bradycardia and hypotension are the most common

manifestations of toxicity. Agents with partial agonist activity Beta blockers Glucagon is a useful antidote. It acts on cardiac cells to raise intracellular cAMP, but does so independent of

adrenoreceptors. It can improve heart rate and blood pressure when given in high doses (5-20 mg iv.). Calcium channel blockers Calcium antagonists can cause serious toxicity or

death with relatively small overdoses. These drugs depress sinus node automaticity and slow AV node conduction. Calcium channel blockers They also reduce

cardiac output and blood pressure. Serious hypotension is mainly seen with nifedipine and related dihydropyridines. Calcium channel Initiating whole bowel blockers

irrigation and oral activated charcoal as soon as possible, before calcium antagonist-induced ileus intervenes, is very important step in treatment. Calcium channel blockers

Calcium given iv. in doses of 2-10 g, is a useful antidote for depressed cardiac Calcium is less effective contractility. for nodal block or peripheral vascular collapse.

Calcium channel blockers Other treatment options are glucagon and high-dose insulin (0,5-1 unit/kg/h) plus glucose supplementation to maintain euglycemia. Lipid emulsion (Intralipid) may be useful for severe

verapamil overdose. Carbon monoxide and other CO is a colorless, odorless gas that is ubiquitous. It is created whenever carbon-containing materials are burned. Specific antidote is

Carbon monoxide CO binds to hemoglobin, reducing oxygen delivery to tissues. Clinical features: headache, dizziness, nausea, vomiting, seizures and coma. Treatment: 100% oxygen, hyperbaric oxygen.

Irritant gases Irritant gases are chlorine, ammonia, sulfur dioxide, nitrogen oxides Mechanism of toxicity: corrosive effect on upper and lower airways. Clinical features: cough, stridor, wheezing, pneumonia. Treatment: humidified oxygen, bronchodilators.

Cyanide Cyanide (CN-) salts and hydrogen cyanide (HCN) are highly toxic chemicals used in chemical synthesis and as rodenticides. Hydrogen cyanide is formed from the burning of plastics, wool and many other synthetic and natural

Cyanide Cyanide is also released after ingestion of various plants (cassava) and seeds of apple, peach and apricot. Cyanide binds readily to cytochrome oxidase, inhibiting oxygen utilization within the cell and leading to cellular hypoxia and lactic

Cyanide Cyanide binds to cytochrome and blocks cellular oxygen use. Clinical features are headache, nausea, vomiting, syncope, seizures and coma. Cyanide

Symptoms of cyanide poisoning are: shortness of breath agitation tachycardia seizures, coma hypotension, death Cyanide Severe metabolic acidosis is

characteristic. The venous oxygen content may be elevated because oxygen is not being Cyanide Initial treatment is rapid

administration of activated charcoal and general supportive care. Cyanide Conventional antidote kit consists of: NITRITES to induce methemoglobinemia (which

binds cyanide) THIOSULFATE which hastens conversion of cyanide to less toxic thiocyanate Cyanide Newer antidote kit (Cyanokit) consists of: concetrated HYDROXOCOBALAMIN which directly converts

cyanide into cyanocobalamin Cholinesterase inhibitors Organophosphate and carbamate cholinesterase inhibitors are widely used to kill insects and other pests.

Causes of poisoning are suicid, intoxication at work (pesticide application or packaging), food contamination and terrorist Cholinesterase inhibitors Stimulation of muscarinic receptors causes: abdominal cramps

diarrhea excessive salivation sweating urinary frequency increased bronchial Cholinesterase inhibitors Stimulation of

nicotinic receptors causes generalized ganglionic activation, which can lead to hypertension and either tachycardia or bradycardia. Cholinesterase inhibitors

Muscle twitching and fasciculations may progress to weakness and respiratory muscle paralysis. CNS effects include agitation, confusion Cholinesterase inhibitors


EXCITATION LACRIMATION SEIZURES, SWEATING, SALIVATION Cholinesterase inhibitors Antidotal treatment consists of atropine and pralidoxime. Atropine is an effective competitive inhibitor at

muscarinic sites, but has no effect at nicotinic sites. Pralidoxime given early enough may restore the cholinesterase activity and it is active at both muscarinic and nicotinic sites. Digoxin Digitalis, other cardiac glycosides and cardenolides are found in many plants and

in the skin of some toads. Causes of toxicity: acute overdose, accumulation of digoxin in a patient with renal insufficiency, taking a drug that interferes with Digoxin Patients receiving long-term digoxin

treatment are often taking diuretics (especially loopdiuretics) which can lead to electrolyte depletion (especially potassium). Digoxin Vomiting is common in patients with digitalis overdose. Hyperkalemia may be caused by

acute digitalis overdose or severe poisoning. Hypokalemia may be present in patients as a result of long-term diuretic treatment. Digoxin Cardiac rhythm disturbances are: sinus bradycardia AV block

atrial tachycardia with block accelerated junctional rhythm premature ventricular beats Digitalis (digoxin) toxic effects

Digoxin Atropine is often effective for bradycardia or AV block. Digoxin antibodies are administered intravenously. Symptoms usually improve within 30-60 minutes after antibody administration. Digoxin Digoxin antibodies may

also be useful in cases of poisoning with other glycosides (digitoxin, oleander), but larger doses may be needed due to incomplete crossreactivity. Ethanol, sedative-hypnotic drugs Sedative-hypnotic drugs (SHD): benzodiazepines, barbiturates,

carisoprodol, -hydroxybutyrate (GHB) Patients with ethanol or SHD overdose may be euphoric and rowdy (DRUNK) or in a state of stupor/coma (DEAD Ethanol, sedative-hypnotic drugs

Comatose patients often have depressed respiratory drive. Depression of protective airway reflexes may result in pulmonary aspiration of gastric contents leading to Ethanol, sedative-hypnotic drugs

Hypothermia may be present because of environmental exposure and depressed shivering. Ethanol blood levels greater than 300 mg/dL usually cause deep coma. Ethanol, sedative-hypnotic drugs

Patients with GHB overdose are often deeply comatose for 3-4 hours and then awaken fully in a matter of minutes. Ethanol, sedative-hypnotic drugs Protecting the airway (endotracheal intubation)

and assisting ventilation until the drug effects wear off. Hypotension usually responds to intravenous fluids, body warming (if there is hypothermia) and Ethanol, sedative-hypnotic drugs

Patients with isolated benzodiazepine overdose may awaken after intravenous flumazenil (benzodiazepine antagonist). Flumazenil may precipitate seizures in patients who are addicted to benzodiazepines. Ethanol, sedative-hypnotic drugs

Flumazenil is contraindicated in patient that ingested a convulsant drug like tricyclic antidepressant. There are no specific antidotes for ethanol, barbiturates or most Ethylene glycol, methanol

Ethylene glycol and methanol are alcohols that are important toxins because of their metabolism to highly toxic organic acids. They are capable of causing CNS depression and a drunken state similar to ethanol overdose.

Ethylene glycol, methanol Formic acid (from methanol); hippuric, oxalic and glycolic acids (from ethylene glycol) cause a severe metabolic acidosis and can lead to: coma and blindness (formic acid)

renal failure (oxalic and glycolic acid) Ethylene glycol, methanol Initially, the patient appears drunk. After a delay of up to several hours, a severe

anion gap metabolic acidosis becomes apparent, accompanied by hyperventilation and Ethylene glycol, Patients with methanol methanol

poisoning may have visual disturbances ranging from blurred vision to blindness. Ethylene glycol, methanol

Metabolism of ethylene glycol and methanol to their toxic products can be blocked by inhibiting the enzyme alcohol dehydrogenase with a competing drug: fomepizole. Iron salts Deferoxamine!

If poisoning is severe, give 15 mg/ kg/h iv. 100 mg of deferoxamine binds 8,5 mg of iron. Narcotic drugs, other opioid derivatives Naloxone is specific antagonist of opioids. Give 0,4-2 mg initially by iv., im. or

sc. injection. Larger doses may be needed to reverse the effects of overdose with propoxyphene, codeine or fentanyl derivatives. Duration of action (2-3 hours) may be significantly shorter than that of the opioid being antagonized. Theophylline Theophylline is used for

the treatment of bronchospasm by some patients with asthma and bronchitis. A dose of 20-30 tablets can cause serious or fatal poisoning. Theophylline Chronic or subacute

theophylline poisoning can also occur as a result of accidental overmedication or use of a drug that interferes with theophylline metabolism (cimetidine, ciprofloxacin, erythromycin). Theophylline

Initial symtpoms of overdose are tremor, tachycardia and vomiting. Hypotension, tachycardia, hypokalemia and hyperglycemia are result of 2-adrenergic activation. Theophylline Cardiac arrhythmias

include: atrial tachycardias premature ventricular contractions ventricular tachycardia Theophylline In severe poisoning (acute overdose with serum level>100 mg/L), seizures

often occur and are usually resistant to common anticonvulsants. Toxicity may be delayed in onset for many hours after ingestion of sustained- Theophylline Aggressive gut decontamination should be carried out using repeated

doses of activated charcoal and whole bowel irrigation. Propranolol or other blockers (esmolol) are useful antidotes for -mediated hypotension and Theophylline Phenobarbital is preferred for convulsions. Hemodialysis is indicated

for serum concentrations greater than 100 mg/L and for intractable seizures in patients with lower levels. Literature Katzung, Masters, Trevor. Basic and clinical pharmacology.

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