Toxidromes.pptx

A brief account on major toxidrome and an explanation about how the clinical features occur. anticholinergic, cholinergic, sympathomimetic, opiate, sedative toxidrome and serotonin syndrome and neuroleptic malignant syndrome are explained with the management.

1. TOXIDROMES DR KTD PRIYADARSHANI REGISTRAR IN EMERGENCY MEDICINE TEACHING HOSPITAL- PERADENIYA 2023/04/17

2. Toxidromes Toxic syndromes Group drugs together according to the signs and symptoms they generally produce in patients (so when encounter a patient presenting a certain way, easy to recognize the toxidrome) Help to move toward final diagnosis

3. What are the major Toxidromes? Anticholinergics Cholinergic / Anticholinesterase Sympathomimetics / Withdrawal Opiate Sedative/ hypnotic ( Hypnosedative ) Serotonin syndrome/ neuroleptic malignant syndrome

4. Anti-cholinergic toxidrome

5. Anti-cholinergic toxidrome Antagonize Ach receptors (muscarinic / nicotinic) Major blockage – muscarinic High doses – nicotinic at NMJ & autonomic ganglia

6. Anti- cholinergics Hot as a Hare : warm skin Dry as a bone : dry skin and mouth Blind as a Bat : cycloplegia, mydriasis Red as a beet : flushed skin Mad as a Hatter : altered mental status, hallucinations

7. Anticholinergic TCA, SSRI Antihistamines Carbamazepine antipsychotics, Antispasmodics atropine

8. Management – Resus-RSI-DEAD Supportive BDZ for agitation or seizures Antidote – physostigmine (centrally acting reversible AChE inhibitor) Avoid Rx agitation with Anticholinergics (haloperidol)

9. Cholinergic toxidrome

10. Cholinergic toxidrome Increased Ach activity Both central and peripheral Both nicotinic and muscarinic

11. Anticholinesterases Organophosphate & carbamate insecticides Nerve gas (sarin) Cholinergic ( Cholinomymetics ) Nicotine Mushrooms Pilocarpine

12. DUMBELS Diaphoresis, Diarrhea, Decreased blood pressure Urination Miosis Bronchorrhea , Bronchospasm, Bradycardia Emesis, Excitation of skeletal muscles Lacrimation (tearing) Salivation, Seizures SLUDGE Salivation Lacrimation Urination Defecation GI Stress Emesis

13. Management - Resus-RSI-DEAD Decontamination Atropine – until dry secretions Pralidoxime

14. Opioid toxidrome

15. Opioid toxidrome Due to narcotics & narcotic derivatives Bind to opioid receptors in CNS & bowel Classic presentation CNS depression Respiratory depression Miosis

16. Commonly used opioids Heroin, Morphine, Hydromorphone, Codeine, Hydrocodone, Oxycodone, Fentanyl

17. Treatment - RSI- DEAD Naloxone Competitive opioid antagonist (mu, kappa & delta) Bolus 400 mcg IV/IM Rpt 100mcg every 30-60 seconds until spontaneous respiration 2/3 of initial dose per hour infusion if patient not conscious

18. Sympathomimetic toxidrome

19. Sympathomimetic toxidrome Act on sympathetic nervous system Direct or indirect effect on catecholamines Direct act – alpha agonists, dopaminergic agents Indirect – increase catecholamine release, inhibit breakdown/delay reuptake (amphetamines, cocaine)

20. Clinical Features Tachycardia Hypertension Hyperthermia Hyperreflexia Mydriasis Diaphoresis Normal bowel sounds Tremors Chest pain Rhabdomyolysis

21. Treatment Supportive IV Fluids CVS (HT/Tachycardia) BDZ phentolamine Vasodilator infusion (GTN) No β blockers Seizures/Agitation BDZ Cooling- Dantrolene

22. Hypno-sedative toxidrome

23. Hypno-sedative toxidrome Modulate activity of GABA neurotransmitter complex Include in Benzodiazepines Barbiturates Zolpidem, zopliclone Baclofen Gamma-hydroxybutyrate Chloral hydrate paraldehyde

24. Clinical Features CNS depression sedation, confusion, amnesia Respiratory depression CVS depression Nystagmus Ataxia/ loss of coordination Loss of bladder control

25. Treatment Largely supportive Extreme caution with antidotes Flumazenil can reverse benzodiazepines, but can also cause intractable seizures and so is not used routinely.

26. Contraindications to Flumazenil Overdose of unknown agents. Suspected or known physical dependence on benzodiazepines. Suspected cyclic antidepressant overdose. Co-ingestion of seizure-inducing agents. Known seizure disorder Suspected increased intracranial pressure .

27. SS & NMS

28. Serotonin syndrome MAOI : phenelzine, tranylcypromine, isocarboxazid , pargyline, rasagiline , and selegiline SSRI : fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram SNRI : venlafaxine, desvenlafaxine, levomilnacipran , and duloxetine TCA : amitriptyline, clomipramine, desipramine , doxepin, imipramine, nortriptyline, protriptyline, and trimipramine Miscellaneous: trazodone (moderate potency), bupropion (low potency),tramadol , Lithium, meperidine

29. Severity Pattern Category Clinical features Mild Mild agitation, mild fever (<40°C), tremor, myoclonus, hyperreflexia, diaphoresis, mydriasis, elevated blood pressure and heart rate Moderate Marked agitation, hyperthermia (>40°C), myoclonus, hyperreflexia, ocular clonus, increased bowel sounds Severe Hyperthermia (>41.1°C), delirium, marked muscle rigidity, marked swings in blood pressure and heart rate

30. Treatment Stop all serotonergic therapy Initiate cardiopulmonary monitoring, establish peripheral IV access, and obtain ECG IV fluid rehydration External cooling measures for hyperthermia Benzodiazepines for agitation Use short-acting IV antihypertensives (nitroprusside or esmolol) for severe hypertension Use direct-acting IV vasopressors (norepinephrine, epinephrine, or phenylephrine) for hypotension resistant to IV fluid resuscitation Consider cyproheptadine for moderate to severe clinical features refractory to supportive care.

31. Neuroleptic Malignant Syndrome An idiosyncratic drug reaction to antipsychotics Occurs with in 3-9 days of starting drug Due to central dopaminergic blockade

32. Clinical Features Major criteria – fever, muscle rigidity, psychomotor slowing and altered mental status, sympathetic nervous system liability, recent dopaminergic antagonist exposure or dopamine agonist withdrawal Minor criteria- Increased CK levels or myoglobinuria, tachycardia, tachypnea, hypersalivation, tremor, muscle cramps Exclude No other infection, toxic, metabolic or neurologic cause identified both major and at least 5 minor criteria must be present

33. Treatment Supportive. Withdraw any potentiating drugs Exclude DD Airway and breathing difficulties nondepolarizing agents (e.g., rocuronium) are preferred over depolarizing agents (e.g., succinylcholine).

34. Temperature external cooling measures; pharmacologic antipyretics are not beneficial Sedation - to decrease agitation and sympathetic activity; a benzodiazepine, such as lorazepam. Hypertension- GTN or Nitroprusside Antidote-Dantrolene and Bromocriptine in severe cases.

35. Summary

36. Tackling Toxidromes Good history Directed physical examination Vital signs,Pupils,Skin , bowel bladder Simple tests Rapid glucose, ECG, ABG, SE, RFT etc Simple interventions

37. References Tintinali EM 9Edition Life in the fast lane FRCEM Intermediate- text books

38. Thank you