Common Drug Poisonings: Tricyclic Antidepressants, Benzodiazepines, and Antipsychotics

2. مسمومیتهاي شايعداروئی منابع • -1- Goldfrank’sToxicologic Emergencies2015 • 2- www.emedicine / Emergency Medicine / Toxicology

3. فراواني مسموميت های دارویی • Mixed drug ingestion • مواد مخدر –مواد محرک • ضد افسردگي سه حلقه اي • أنتي سايكوتيكها • بنزو ديازپين ها • بتابلوکرها • مسكن ها

4. Tricyclic antidepressant poisoning داروهاي ضد افسردگي

5. داروهاي ضد افسردگي • آ مي تريپتيلين - نورتريپتيلين...ما پروتيلين -آموكساپين • > 1 g : Life treatening • one pill can kill (children) • شروع علائم سريع )خطرناکترین لحظات 1-2 ساعت اول پس از خوردن تا 6 ساعت ) • تغییر وضعیت ناگهانی

6. Clinical manifestations Delirium, Hallucination, Hypertermia, ….

7. Hypotension Wide QRS (> 0.10 s) Ventricular Tachycardia

8. Tricyclic AntidepressantsSymptoms • 1- Midriasis ; Tachycardia • 2- Coma, 3- Delirium • 4- Seizures • 5- Hypotension • 6- QRS > 0.1s ; R avR>= 3 mm ; Right Axis deviation ; Arrhythmias (VT) • ECG is the single most important test to determine diagnosis and prognosis

9. Management of TCA poisoning 1- ABCD ( Antidote) • A:Airway compromise (Artificial airway, Intubation) • B: Breathing difficulties (Oxygen, Intubation, Mechanical ventilation) • C:Circulation Problems (IV line; ECG, Manage hypotension, VT) • D: Drugs (Coma : Thiamine- Glucose-Naloxone –Oxygen)

10. Antidote: Sodium Bicarbonate Hypotension Arrythmia, Wide QRS > 0.1 s, R avR 3 mm Seizure (wide QRS) 1-2 mEq / kg bolus , Infusion (50-150 mEq / L D5W) + repeated bolus (ABG) End point: Serum pH ( 7.45-7.55)

11. Seizure: Diazepam 0.1-0.2 mg/kg (5-10 mg), Midazolam 0.1 mg/kg, NaHCO3 • Hyotension: N.S., NaHCO3, Norepinephrine (0.1-0.2 ug/kg/min), Dopamine (10-20 ug/kg/min) • Wide QRS, R/avR>3 mm: NaHCO3 • Coma: Glucose, Naloxone, Thiamine • Delirium: Benzodiazepines

12. Ventricular Arrhythmias (VT) • NaHCO3 (1-2 meq/kg) 5 min • Lidocaine: 1-1.5 mg/kg slow IV bolus over 2-3 min • up to 3 mg/kg total • infusion: 1-4 mg/min IV • IO/ET • Monitor: ECG • PH: 7.45-7.55

13. Management of TCA Poisoning • ABCD , Antidote • Gastric Lavage (GL) • Activated Charcoal(AC) 1 g/kg, 50-100 g • urine toxicology screen

14. Contraindicated medications • beta-blockers, • calcium channel blockers, • class IA (procainamide, quinidine, disopyramide, moricizine), • class IC (flecainide, propafenone), • and possibly class III (bretylium, amiodarone,sotalol) antidysrhythmics.

15. Management of TCA Poisoning • Rapidly transport all patients with possible TCA ingestion to the hospital because clinical deterioration often occurs rapidly after overdose. • Supplemental oxygen and airway support (Intubation,..) • Intravenous access, Cardiac monitoring • Rapid glucose determination (finger stick) • GL + Activated charcoal • Sodium bicarbonate should be considered in life-threatening circumstances in the pre-hospital setting.

16. Antipsychotics • Large toxic to therapeutic ratio • Clinical manifestations • Antichlinergic (midriasis, Tachycardia,….) •  receptor blocking (Hypotension, Miosis):Chlorpromazine • CNS (Coma, seizure,…) • Dystonic reaction (Thiotexene, halloperidol, Perphenazine, Trifluperazine,..) • Cardiovascular (Mesoridazime, Thioridazine, Chlorpromazine, Halloperidol) • Respiratory depression ( Coma)

17. Management ABCD اكسيژن لوله گذاري داخل تراشه + ساكشن كردن بررسي نياز به گلوكز ((Counsciousness نالوكسان (Respiratory depression , pin point pupil ) Gastric Evacuation دادن زغالفعال 1 g/kg Close Observation; Supportive treatment

18. Seizure: Diazepam 0.1-0.2 mg/kg (5-10 mg), Midazolam 0.1 mg/kg • Hyotension: N.S., Norepinephrine (0.1-0.2 ug/kg/min), Dopamine (10-20 ug/kg/min) • Coma: Glucose, Naloxone, Thiamine • Dystonic reaction: Diphenhydramine or Biperdine or Benzodiazepine (alternative) • Wide QRS: NaHCO3

19. Benzodiazepine Poisoning • CNS Depression (Somnolence, Stupor, Coma), Miosis, Ataxia • Deep Coma, respiratory arrest (rare)

20. Symptoms of BZD overdose may include the following • Dizziness • Confusion • Drowsiness • Blurred vision • Anxiety • Agitation

21. Findings on physical examination may include the following: • Nystagmus, Slurred speech • Ataxia, Coma, Hypotonia • Weakness, impairment of cognition • Amnesia, Paradoxical agitation • urine toxicology screen

22. Managment of BZD Poisoning ABCD Antagonist: Flumazenil pure BZD overdose + verbally unresponsive +no history of long-term BZD use or seizure disorder not recommended for use by pre-hospital personnel Contraindication(past history of seizure, co ingestion with drugs induced seizure e.g. TCA; BZD addiction) • Decontamination within 1-2 h of ingestion Gastric Lavage + Activated charcoal

23. Flumazenil • 0.1-0.2 mg IV over 15-30 sec • IF no response after 30 sec, administer 0.3 mg over 30 sec 1 min later • Rarely patient may require titration up to total dose 5 mg; IF no response after 5 min, sedation unlikely to be secondary to benzodiazepines

24. Beta-Adrenergic Receptor Antagonists

25. In use for nearly 50 years. • treating hypertension and other cardiovascular disorders • migraine headaches, • anxiety, • and various other disorders. • As a result of their expanded use, the incidence of overdose with these agents has also increased.

26. Table 1-1* B-Adrenergic Receptor Antagonist Pharmacologic Profile

27. Clinical Manifestations of B-Adrenergic Antagonist Toxicity

28. Increased PR intervals • Loss of atrial activity • Atrioventricularjunctional rhythm • Widening of the QRS complex • Atrioventricular block • Asystole • prolonged QT interval: sotalol overdose. • VF, VT: uncommon (sotalol)

29. Diagnosis • History • Clinical presentation • ECG, ABG/VBG • serum glucose and potassium levels.

30. Treatment end points • HR>60 • SBP>90mmHg • Evidence of good organ perfusion Evidence of good organ perfusion (improved mentation or urine output)

31. Mangement • ABCD Bradycardia • Atropine (1 mg..>3 mg) • Pace

32. Mangement (Hypotension) • Isotonic IV fluid (20 mL/kg) • Glucagon (5-10 mg IV slow) (50-150 mcg/kg IV over 1 minute) Infusion: 3-5 mg/hr or 50-100 mcg/kg/hrIV titrate to response • Epinephrine for hypotension, bradycardiaUnresponsive to atropine or pacing: 2-10 mcg/min by IV infusion or 0.1-0.5 mcg/kg/min (7-35 mcg/min in 70 kg patient); titrate to response • Calcium Chloride (1g IV central line/ over 10-20 min (emergent 5 min) slow infusion • Insulin: 0.1-1 U/kg/h + Hypertonic glucose (10%,20,%, 50% 1 g/kg, check BS/30min) (Dextrose infusion of 10-75 g/h may be required) • Dopamine (5-20 ug/kg/min),Norepinephrine (0.1-0.2 ug/kg/min)

33. Insulin-Glucose • should be considered for overdoses that are refractory to crystalloids, glucagon, and catecholamine infusions. • monitoring serum glucose and potassium levels • Monitoring must be conducted regularly during high-dose insulin therapy and for up to 24 hours after its discontinuation. • Dextrose supplementation is typically required to maintain euglycemia

34. Benzodiazepines : if seizures occur. • Hemodialysis: severe cases of atenolol overdoses because atenolol is less than 5% protein bound and 40-50% is excreted unchanged in urine. Nadolol, sotalol, and atenolol (low lipid solubility, low protein binding) reportedly are removed by hemodialysis. Acebutolol is dialyzable. • Consider hemodialysis or hemoperfusiononly when treatment with glucagon and other pharmacotherapy fails. • Cardiac pacing: Cardiac pacing may be effective in increasing the rate of myocardial contraction. • cardiac pacing for patients unresponsive to pharmacologic therapy torsade de pointes unresponsive to magnesium • Resuscitation should be aggressive and prolonged.

35. Gastric lavagemay be beneficial if the patient presents to the ED within 1-2 hours of ingestion. • Activated charcoal • Although most useful if used within 4 h of ingestion, repeated doses may be used, especially with ingestions of sustained-released agents. • Adult:1 g/kg PO up to 50-100 g • Pediatric: 1-2 g/kg PO , up to 15-30 g

36. با تشكر

37. Glucagon can enhance myocardial contractility, heart rate, and atrioventricular conduction; • Load: 50-150 mcg/kg IV over 1 minute, THEN  • 3-5 mg/hr or 50-100 mcg/kg/hr IV; titrate infusion to achieve adequate clinical response

38. Dopamine • 5-15 mcg/kg/min IV (medium dose): May increase heart rate, and cardiac contractitlity • 20-50 mcg/kg/min IV (high dose): May increase blood pressure and stimulate vasoconstriction; may not have a beneficial effect in blood pressure; may increase risk of tachyarrhythmias • May increase infusion by 1-4 mcg/kg/min at 10-30 min intervals until optimum response obtained • Titrate to desired response

39. calcium • Beta-blocker Overdose, Refractory to Glucagon & High Dose Vasopressor • Calcium chloride 1000 mg IV bolus via central line  over 10-20 min (emergent 5 min)

40. Insulin-Glucose •  The currently recommended regimen is a 1 U/kg of an insulin bolus followed by continuous infusion of 1-10 U/kg/h, but boluses of up to 10 U/kg and continuous infusions as high as 22 U/kg/h have been used with good outcomes and minimal adverse events.  Dextrose infusion of 10-75 g/h may be require

41. Acetaminophen • Commonest drug used DANGEROUS , PEOPLE DON’T KNOW IT • YOU FEEL WELL AND THEN THE LIVER FAILURE SETS IN.. • NAPQI (TOXIC mtetabolite) • Glutathione • Toxic dose: 7.5 g , 150 mg/kg

42. Acetaminophen poisoning Phase 1 (0-24 h) Asymptomatic Anorexia, Nausea or vomiting, Malaise serum transaminases levels 12 hours postingestion Phase 2 (18-72 h) Right upper quadrant abdominal pain, anorexia, nausea, vomiting, rise in serum transaminases Phase 3 (72-96 h) Hepatic necrosis with continued abdominal pain, Jaundice , Coagulopathy, Hepatic encephalopathy, Renal failure, Fatality • Phase 4 (4 d to 3 wk) • Complete resolution of symptoms (7-10 days), or death, • Complete heaptic recovery (3-6 months)

43. Acetaminophen ingestion should be considered as a potential cause of illness in patients who present with hepatic dysfunction of unknown etiology. • Acetaminophen crosses the placenta, and the fetal liver is able to elaborate NAPQI by 14 weeks of gestation. A delay in treating pregnant patients with antidotal therapy is associated with fetal demise.

44. Acetaminophen Overdose-management • ABCD ( usually well systemically) • Gastric lavage, Activated charcoal • Antidote: N-Acetylcysteine, IV (20 h) • Shown to be advantageous if given in the first 8 hours • Early administration of NAC, within 8 hours of ingestion, is nearly 100% hepatoprotective • NAC should be administered if the patient presents close to or later than 8 hours after an acute ingestion or if the patient is pregnant. • Follow up

45. ارگانوفسفره • موارداستفا د ه • براي ازبين بردن حشرات دركشاورزي • پاراتيون ؛ديازينون؛مالاتيون • بعنوانگازهاي جنگي • گاز جنگيسارين ؛سومان

46. فارماكو كينتيك • جذب : گوارشي ؛ پوستي ؛ تنفسي ؛ چشمي • متابوليسم : كبد • دفع : دفعمتابوليتها ازطريق ادرار • نيمه عمر دفعي : 2/89ساعتدرمالاتيونو2/1روزدرمتيل پاراتيون

47. مكانيسم اثر • مهار كننده غیر قابل برگشت آنزيم كليناستراز • شروع علا ئم : در طي چند دقيقه تا چند ساعت

48. 1-علائم موسكاريني • افزايش ترشح بزاق (سيالوره)،اشكريزش • ابريزش از بيني • تعريق • ميوز • اسهال، درد شکمی • بی اختیاری ادرار و مدفوع • برادي كاردي ؛ هيپو تانسيون

49. 2-علائم نيكوتيني • ضعف • فاسيكولاسيون……….فلج عضلات • تاكيكاردي • هيپر تانسيون • ميدرياز

50. 3-علائم سيستمعصبي مركزي • اضطراب • گيجي • كما • تشنج • دپرسیون مركز تنفس و قلبي