Calcium Channel Blocker Toxicity: A Practical Approach

Figures & data

Table 1 Examples of Common Drug–Drug Interactions with CCBs

Mechanism of Interaction	Interacting Medications
Induction of CYP3A isoenzyme (Higher doses of CCBs maybe needed)	Carbamazepine
	Oxcarbazepine
	Phenytoin
	Barbiturates
	Nevirapine
	Rifampicin
	Pioglitazone
Inhibition of CYP3A isoenzyme (Lower doses of CCBs maybe needed)	Cimetidine
	Erythromycin
	Clarithromycin
	Azole antifungals
	HIV-protease inhibitors
	Grapefruit juice
CYP3A isoenzyme inhibition by verapamil and diltiazem (Lower doses of interacting medication maybe needed)	Ciclosporin
	Statins
	Benzodiazepines
	Buspirone
	Sildenafil
P-glycoprotein inhibition by verapamil and diltiazem (Lower doses of interacting medication maybe needed)	Digoxin
	Ciclosporin
	Fexofenadine
	Daunorubicin
	Doxorubicin
	Etoposide
	Vinca alkaloids
Added antihypertensive effects	All antihypertensive medications
Added negative chronotropic effects	Digoxin
	Beta blockers
	Amiodarone
Added negative inotropic effects	Beta blockers
	Flecainide

Abbreviation: CCBs, calcium-channel blockers.

Table 2 Summary of the Pharmacokinetics of Commonly Prescribed CCB Agents

Medication	Usual Adult Daily Dose (mg)	Absorption (%)	Bioavailability (%)	Protein Binding (%)	Terminal Half-Life (hr)
Verapamil	120–480	90	20–35	90	2.8–7.4
Diltiazem	120–540	95	40	70–80	3–4.5
Amlodipine	2.5–10	100	64–90	93	30–50
Nicardipine	20–40	100	35	>95	8.6
Felodipine	2.5–10	100	20	>99	11–16

Table 3 Common Monitoring Parameters for Selected Reversal Agents

Treatment	Monitoring Parameter
Atropine	- Heart rate - Blood pressure - Pulse oxygenation - Mental status
Calcium	- Vital signs - Electrocardiograph - Serum calcium
Insulin	- Electrolytes - Blood glucose - Mean arterial pressure - Hypersensitivity and allergic reactions
Norepinephrine	- Blood pressure every 2 minutes until desired hemodynamic effect, and every five minutes for duration of infusion after desired effect is achieved - Cardiac function - Changes to skin of extremities - Signs of extravasation
Epinephrine	- Blood pressure (or mean arterial pressure) - Heart rate - Cardiac output (as appropriate) - Intravascular volume status - Pulmonary capillary wedge pressure (as appropriate) - Urine output Peripheral perfusion Infusion site
Dobutamine	- Electrocardiograph - Blood pressure (or mean arterial pressure) - Heart rate - Pulmonary wedge pressure -Cardiac output - Electrolytes (ie, potassium)
Glucagon	- Blood glucose
Lipid emulsion	- Allergic reactions - Triglycerides levels - Monitor for pancreatitis
Methylene blue	- Electrocardiograph - Serotonin syndrome - Anaphylaxis - Vital signs - Toxicity in patients with renal/hepatic impairment
Dialysis	- Blood pressure - Electrolytes - Coagulopathy - Drug serum level
ECMO	- Heart rhythm - Mean arterial pressure - Blood flow - Gas exchange

Figure 1 Algorithmic structure for managing patients with calcium channel blocker toxicity.

Abbreviations: CCB, calcium channel blocker; EKG, electrocardiogram; MAP, mean arterial pressure; GI, gastrointestinal; ABGs, arterial blood gases; PaO2, partial pressure of oxygen; HIET, high insulin euglycemia therapy; HR, heart rate; BPM, beat per minute; SBP, systolic blood pressure; VA, venous arterial; ECMO, extracorporeal membrane oxygenation.