Toxidromes Lecture Notes PDF

Dr. Hanan Anbar Associate Professor of Pharmacology and Toxicology  Toxidromes They are characteristic clinical signs and symptoms suggesting a specific drug class. They need high index of suspicion, history and good physical examination. Common Toxidromes include: Sympa...

Dr. Hanan Anbar Associate Professor of Pharmacology and Toxicology  Toxidromes They are characteristic clinical signs and symptoms suggesting a specific drug class. They need high index of suspicion, history and good physical examination. Common Toxidromes include: Sympathomimetic Cholinergic –anticholinergic Opiate Sedative hypnotic Withdrawal (alcohol, benzodiazepines and opiates). CPC-B-3H Opioid Toxidrome The toxidrome associated with opiate or opioid intoxication includes: Coma Pinpoint pupils Miotic Respiratory depression Bradycardia Hypotension Hypoxia (airway obstruction) fresh needle marks Hypothermia (clammy skin) →Use of 0.04 naloxone NB: Do not use excess naloxone, as this will precipitate opioid withdrawal in addicts. If patients become agitated or distressed following naloxone this may be managed by a small dose of diazepam, but beware of precipitating respiratory depression. morphine and an amphetamine over and under The combination of heroin & cocaine (“speedball”) produces virtually any size pupil, depending on the relative contribution by each xenobiotic. Body Packers In an attempt to transport illicit drugs from one country to another, body packers ingest large numbers of multiple-wrapped packages of concentrated cocaine or heroin. When the authorities discover such individuals or when individuals become ill, they may be brought to a hospital for evaluation and management. Although these patients generally are asymptomatic on arrival, they are at risk for delayed, prolonged, or lethal poisoning as a consequence of packet rupture.  https://www.youtube.com/watch?v=g- 9KyxMtGXg&t=104s  This toxidrome is not pathognomonic for opioid toxicity, and a similar presentation may suggest : α2- adrenergic agonist (e.g., clonidine) toxicity Barbiturate toxicity Intracranial hemorrhage Brain stem stroke Note: Naloxone has been reported to reverse some cases of clonidine toxicity. Naloxone has no effect in: intracranial hemorrhage stroke or barbiturate toxicity  Cholinergic toxidrome (Cholinergic Syndrome) Causes: - Organophosphate pesticides. - Electronic cigarettes →↑cholinergic toxicity due to the concentrated liquid nicotine. - Some chemical weapons (nerve agents) are highly potent cholinergic toxicants. - Clitocybe sp. and Inocybe sp. mushrooms contain significant concentrations of muscarine, a direct muscarinic receptor agonist.  The classic cholinergic toxidrome includes: - Diarrhea -Respiratory - Seizures (common due to ↑ - Miosis insufficiency cerebral ACh levels) - Salivation -Diaphoresis -Fasciculations → skeletal muscle - Vomiting paralysis -Urinary incontinence  Antimuscarinic Toxidrome ( anticholinergic syndrome ) The drug classes that exhibit antimuscarinic properties include: First-generation antihistamines Antipsychotics Class 1A antidysrhythmics Alkaloids (atropine, scopolamine, and hyoscyamine) derived from many plants in the Solanaceae family Deadly Nightshade (Atropa belladonna) Antimuscarinic poisoning symptoms: Atropine like action Tachycardia Anhidrosis Mild hypertension Mydriasis Mild hyperthermia Urinary retention Skin flushing Delirium Dry mouth Visual or tactile Muffled or garbled speech hallucinations The antidote for antimuscarinic toxicity: → physostigmine which is a reversible acetylcholinesterase inhibitor that crosses BBB.  Sympathomimetic Toxidrome Clinically, the sympathomimetic toxidrome is difficult to differentiate from antimuscarinic poisoning or alcohol withdrawal. Also Cocaine, amphetamines and methylxanthines all produce findings of sympathomimetic toxicity.  The sympathomimetic toxidrome includes: -Tachycardia -In severe cases→ -Hypertension agitated delirium -Diaphoresis seizures -Mydriasis -Hyperthermia  Serotonin Syndrome The serotonin syndrome is a fatal reaction resulting from drug interactions or intentional overdose involving drugs acting on central and peripheral serotonergic receptors. Serotonin toxidrome includes: - Autonomic instability - Fever (tachycardia & mild HTN) - Rigidity (the lower extremities) - Altered mental status Serotonin toxidrome includes: Alteration of mental status: (in 40% of patients) → agitation, confusion, delirium, hallucinations to drowsiness and coma. Neuromuscular hyperactivity: (in 50% of patients) →profound shivering, tremor, teeth grinding, inducible or spontaneous clonus, and hyper-reflexia. Autonomic instability: (in 40% of patients) → dilated pupils, diarrhea, profuse sweating, flushing, tachycardia, hypertension, or hypotension. In severe cases, hyperthermia, rhabdomyolysis, renal failure, and disseminated intravascular coagulopathy may develop. Note: Normally, reflexes are diminished in rigidity, but serotonin syndrome is accompanied with hyperreflexia despite rigidity. Cogwheel rigidity Unlike the neuroleptic malignant syndrome, serotonin syndrome develops suddenly within hours and resolves quickly within 24–48 h. Serotonin syndrome Neuroleptic malignant syndrome Hyperreflexia despite rigidity Skeletal muscle rigidity and hyporeflexia Develops suddenly within hours and Begins insidiously and worsens over days resolves quickly within 24–48 h - Serotonin syndrome may result from drug interactions with two or more serotonergic drugs during normal therapeutic use. - The most severe cases occur with the combination of : monoamine oxidase inhibitors (which inhibit the breakdown of serotonin) with selective serotonin re-uptake inhibitors (SSRIs), tricyclic antidepressants, or Serotonin/norepinephrine reuptake inhibitors. NB: Drugs of abuse CNS stimulant drugs of abuse, e.g., amphetamines and ‘ecstasy’ (MDMA, 3,4-methylenedioxymethamfetamine), directly stimulate serotonin release from neuronal vesicles and frequently cause features of serotonin toxicity in overdose.  Neuroleptic Malignant Syndrome Neuroleptic malignant syndrome is skeletal muscle rigidity and hyporeflexia, particularly when use: Lead pipe rigidity antipsychotic or with Dantrolene, bromocriptine, and diazepam dopaminergic withdrawal. It begins insidiously and worsens over days. There are autonomic instability, altered mental status, fever and rigidity with diminished reflexes (unlike serotonin syndrome). Serotonin syndrome Neuroleptic malignant syndrome Hyperreflexia despite rigidity Skeletal muscle rigidity and hyporeflexia Develops suddenly within Begins insidiously and worsens hours and resolves quickly over days within 24–48 h