Calcium channel blockers

1. Calcium channel blockers Professor Ian Whyte Hunter Area Toxicology Service

2. Cardiac arrhythmia • Primary • quinidine–like drugs, sympathomimetic drugs, calcium channel blockers, β–blockers, digitalis, chloroquine • Secondary to metabolic/electrolyte abnormalities • salicylates, methanol, ethylene glycol

3. Cardiotoxic drugs • All patients should have • oxygenation and protection of airway • decontamination of the GIT • atropine pre–medication • correction of electrolyte abnormalities • acid base balance • cardioversion when appropriate • consultation • PIC 131126

4. Cardiac arrest • Successful resuscitation has been well documented after 8 hours of CPR • Overdose patients usually have • a reversible cause for their arrest • good general health • novel treatments for arrhythmias • cerebral protection

5. Calcium channel blockers • Block calcium channels (L-type) in heart and blood vessels • prolong depolarisation • ↑QRS width • block SA and AV node conduction • heart block • asystole • vasodilators • cerebral protection

6. Calcium channel blockers • Hypotension • peripheral vasodilatation and myocardial depression • Bradycardia • AV and SA node block

7. CCB case • 18 yo female admitted 3 hours after self–poisoning with • 3.5 g of slow release verapamil (Isoptin SR) • 6 g of paracetamol • 4.5 g of tetracycline • 1 g of pseudoephedrine

8. CCB case • On arrival in ED • PR 120, BP 110/80, RR 20, afebrile • drowsy but oriented and cooperative

9. CCB case • GI decontamination • emesis before arrival • lavaged with return of green tablets • 50 g of charcoal with sorbitol repeated 4 h later

10. CCB case • Investigations • ECG • sinus tachycardia with normal QRS width • serum paracetamol at 4 h was 38 µmol/l • hepatotoxicity > 1300 µmol/l at 4 hours

11. CCB case • 16 hours post overdose • BP fell to 70/40 and then 50/30 • PR 50 • oxygen saturation dropped to 75 %

12. CCB case • 16 hours post overdose • ECG • absent p waves • prominent u waves • normal QRS duration and QT interval

13. CCB case • Treatment • IV atropine 0.6 mgs – no response

14. CCB case • Treatment • IV calcium gluconate • 6 g over 20 minutes • further 6 g over the next hour • pr 60, sinus rhythm, BP 100/80 • oxygen saturation > 95 % • infusion of 10% calcium gluconate at 2 G/h for 10 hours • she was also given 2.5 L IV fluids

16. CCB case • Outcome • non–cardiogenic pulmonary oedema • twenty four hours post admission • largely recovered , sinus rhythm PR 60, BP 115/70

17. CCB case • Outcome • peak serum Ca was 4.8 (2.18–2.47 mmol/l) • serial verapamil levels at 6, 18, 22 and 46 hours were 616, 2374, 2518 and 1006 ng/ml • range during usual therapy • 100–300 ng/ml

18. CCB case • A thirty one-year-old female is brought to the Emergency Department by relatives • She states that she ingested 25 x 240 mg sustained-release diltiazem tablets approximately one hour earlier as a suicide attempt

19. CCB case • The tablets do not belong to her and she has no significant intercurrent illnesses • She appears upset but otherwise well • Her pulse is 70/minute, her blood pressure 125/70 mmHg and her ECG shows normal sinus rhythm

20. CCB case • Outline your initial management

21. CCB case • Despite the relatively benign presentation, this is a life-threatening overdose • Aggressive gastrointestinal decontamination using whole bowel irrigation before clinical effects of poisoning develop

22. CCB case • Give oral polyethylene glycol solution (GoLYTELY) at a rate of 15–20 mL/kg/h • Few patients can drink it this fast so it is best to place a nasogastric tube (premedicate with atropine!)

23. CCB case • Then sit the patient on a commode chair and continue until the rectal effluent looks like the GoLYTELY solution • This may take several hours

24. CCB case • Institute appropriate monitoring • This includes establishing IV access, continuous ECG monitoring and frequent non-invasive blood pressure monitoring • This patient will need a minimum of 16 hours monitoring even if she remains completely asymptomatic

25. CCB case • Admission should be to a monitored bed and personnel should be available who are capable of placing an arterial line, transvenous pacemaker and Swan-Ganz catheter

26. CCB case • Some six hours later, the patient is noted to be drowsy with a pulse rate of 45/minute (first degree heart block) and blood pressure of 80/40 mmHg • How do you respond now?

27. CCB case • Despite the excellent decontamination, sufficient drug has been absorbed to result in a toxic syndrome • There is no way of knowing at present how severe it is going to be • Best to assume the worst • Management at this point includes

28. CCB treatment • Normal saline bolus (10–20 mL/kg) • Calcium • 5–10 mL of 10% calcium chloride or 10–20 mL of 10% calcium gluconate over 5 minutes • repeat every 3–5 minutes up to 3 to 5 doses • if response institute calcium infusion of 1–10 mL/h of 10% calcium chloride • monitor serum calcium after 30 mL of calcium chloride or equivalent

29. CCB treatment • Glucagon 0.05 mg/kg IV • repeat every 5–10 minutes as needed • if response consider infusion of 0.075–0.15 mg/kg/h • Atropine, isoprenaline and/or pacing may be tried if associated symptomatic bradycardia • Dopamine infusion if still persistent hypotension

30. CCB treatment • If no response to the above consider • insulin bolus 1 unit/kg with glucose 25 mL of 50% dextrose IV followed by • insulin infusion of 0.5 units/kg/hr with 50% dextrose infusion at 0.5 g/hr adjusted according to hourly glucose checks

32. Cardiopulmonary bypass • As a last resort extracorporeal blood pressure support eg cardiopulmonary bypass may be considered

33. Antidotes: asystole & bradycardia • Atropine everything • Bicarbonate tricyclic antidepressants • Calcium calcium channel blockers • Diazepam chloroquine, organochlorines • Epinephrine everything, β–blockers • Fab fragments digoxin • Glucagon β–blockers, CCBs