See also [[high dose insulin euglycemia therapy|HIET]] > [!danger] Key Points > **leading cause of death from cardiovascular drugs** > > - ingestion of as little as 2-3 times the normal dose of verapamil or diltiazem can cause severe tox in susceptible people > - ingestion of > 10 tablets of verapamil or diltiazem is likely to cause life-threatening toxicity > > **Antidote**:: [[Calcium Gluconate]], [[high dose insulin euglycemia therapy|HIET]], pacing @60BPM, catacholamines rarely effective, [[ECMO]], consider [[Intralipid]], [[Decontamination#Whole bowl irrigation]] **Timeframe:** *Standard release*: symptoms occur within 1-2 hours *Modified release*: symptoms may be delayed up to 12 hours # Risk doses ## Diltiazem - comes in 60mg tablets - 600mg high risk ## Verapamil - comes in 40, 80, up to 240mg SR - would be concerned starting with 1g - 10 tablets (eg 2.4g) life threatening ## amlodipine, nifedipine, lercanidipine, felodipine - dihydropyridine CCBs cause high degree of vasodilation but less myocardial depression and conduction delays than verapamil and diltiazem - combine with ACE-I/ARB or massive ingestions can produce serious toxicity and profound vasoplegia # Mechanism - Ca channel blockers prevent influx of calcium - leads to: - smooth muscle relaxation - slowing of cardiac conduction - reduced force of cardiac contraction > verapamil and diltiazem cause **central cardiac effects** and **periperhal vasodilation** # clinical features - hypotension - bradycardia - sometimes [[hyperglycaemia|increase glucose]] - in contrast to [[beta blocker overdose]], which can decrease glucose - prevents insulin release by blocking Ca channels in pancreas - this is an *early sign of significant toxicity* - lactic acidosis # Treatment http://hqmeded-ecg.blogspot.com/2023/05/20-something-with-huge-verapamil.html - activated charcoal to all intubated patients — [[Decontamination#Multi dose activated charcoal]] if modified release prep - ==calcium gluconate== 2.2mmol x 3 (3 bottles to get to 6.6 mmol) IV over 5-15 min - repeat x3 in first 60 min - target ionized Ca concentration 1.5-2 mmol/L - Give 2 g (20 mL) of calcium chloride IV or 6 g (60 mL) of calcium gluconate IV over 5–10 minutes. This dose may be repeated every 20 minutes for up to three doses. - [[high dose insulin euglycemia therapy]] as an ionitrope - Takes 45 min to work so start with noradrenaline/adrenaline then ween - [[Decontamination#Whole bowl irrigation]] aim within first 4 hours - usually cannot do because too hypotensive or illeus - can be vasoplegic → norad/methylene blue in addition to adrenaline - +/- ECMO - +/- [[Transcutaneous pacing]] ## Issues - *Bradycardia* --> tx **adrenaline** - low cardiac ouptput --> [[high dose insulin euglycemia therapy|HIET]] - this is an ionodilator, can **worsen** vasoplegia - takes 30 min to take effect - *vasoplegia* --> **noradrenaline** - decontamination - usually too hypotensive to do whole bowel irrigation - whole bowel irrigation --> may do with BP and bowel sounds, but *stop if illeus* - airway --> gets worse cuz drowsy, ==intubate early== - drowsy usually secondary to low brain perfusion, but **consider a co-ingestion as well** - may need [[ECMO]] - +/- methylene blue - +/- vasopresssn - +/- atropine to speed them up - +/- [[Intralipid]] # Related Questions ## calcium channel blocker - [ ] 3Q: [Calcium Channel Blocker overdose](x-devonthink-item://F0498813-9350-484C-AD5B-6FF7C3AE9015?page=25) -- [Answer](x-devonthink-item://A491A3F6-FD6D-492F-BCBE-7F7BAE101EDF?page=24) - [x] 4Q: [Verapamil Overdose](x-devonthink-item://7FCD3940-4BB4-45FE-86A6-E5707E82D5B5?page=42) -- [Answer](x-devonthink-item://3263A68A-96A6-43EC-985B-43260C3509BF?page=15) ## diltiazem - [ ] 6Q: [Diltiazem Overdose](x-devonthink-item://09CFA1A7-00F1-4151-979E-8F3984924D54?page=11) -- [Answer](x-devonthink-item://CF5E9C2B-42F9-4F9C-AC29-877E20134927?page=6) ## overdose - [ ] 78Q: [Overdose](x-devonthink-item://5DC0999B-D537-4002-86AF-FD7B54B45E2E?page=64) -- [Answer](x-devonthink-item://406AF611-5CD4-4B3B-9795-327E8F4E3626?page=31)