Emergent Care / Stabilization:

• Assess for airway, breathing, and circulation (ABCs) with a focus on supportive care.
• Neurology checks must be performed frequently in case patients need to be intubated.
• Patients may have refractory hypotension or bradycardia despite adequate treatment. Hemodynamically unstable patients or those with severe symptoms with rapid deterioration may need to be intubated.
• More stable patients can be placed on continuous cardiac monitoring in the intensive care unit (ICU).

In the United States, the phone number for poison control is 800-222-1222 (available 24/7).

Diagnosis Overview:
Calcium channel blockers (CCBs) are used to treat cardiovascular conditions including hypertension, coronary spasm, angina pectoris, supraventricular dysrhythmias (eg, paroxysmal supraventricular tachycardia), hypertrophic cardiomyopathy, and pulmonary hypertension. CCBs may also be used for Raynaud phenomenon, subarachnoid hemorrhage, and migraine headache.

Severe toxicity from CCBs can occur due to accidental or intentional overingestion in adults as well as experimental ingestion in children. Other causes include drug interactions leading to toxicity as well as prolonged exposure due to changes in drug metabolism or elimination.

• Intake of immediate-release formulations can show effects within about 2-3 hours of ingestion, and most experience symptoms in about 6 hours.
• In extended-release CCBs, toxicity can take up to 16 hours to manifest.

Beta blockers and CCBs are the primary contributors to cardiovascular drug overdose deaths, with verapamil as the most commonly implicated medication. Verapamil acts on both cardiac myocytes and peripheral smooth muscle cells. It inhibits the sinoatrial (SA) and atrioventricular (AV) nodes, decreases cardiac contractility, and causes peripheral vasodilation. Diltiazem has similar effects with less prominent vasodilatory effects. In cases of toxicity, excessive drug concentrations can lead to negative chronotropic and dromotropic effects, hypotension, and escape rhythms for both verapamil and diltiazem. Dihydropyridines like nifedipine can cause hypotension and reflex tachycardia.

All subclasses of CCBs decrease insulin secretion, resulting in hyperglycemia, which can be an indicator for severity of poisoning. Acidosis can also occur due to insulin resistance, calcium-dependent mitochondrial activity, and glucose catabolism, leading to lactic acidosis and ATP hydrolysis.

About CCBs:
CCBs are classified into dihydropyridines and nondihydropyridines and are available in immediate and long-acting formulations. CCBs exert their effects by blocking the influx of intracellular cytosolic calcium through the long-acting L-type voltage-gated calcium channels (L-VGCCs). These channels are predominantly found in the SA node, AV node, and peripheral vessels. Nondihydropyridines selectively inhibit myocardial channels, impeding depolarization of the SA node and impulse conduction in the AV node; this causes reduced cardiac chronotropy, dromotropy, and inotropy. Dihydropyridines preferentially inhibit L-type calcium channels in peripheral vessels, functioning as peripheral vasodilators.

CCBs are primarily absorbed orally but have low bioavailability, mainly due to hepatic first-pass metabolism mediated by the CYP3A4 enzyme. In cases of overdose or repetitive dosing, saturation of the enzyme can occur, reducing the first-pass effect. This leads to increased absorption of the drug's active form, decreased clearance, and protracted half-life. Sustained-release formulations have inestimable absorption and longer periods of toxicity. Extended-release formulations, high protein binding, and the lipophilic nature of CCBs contribute to their prolonged half-life and large distribution volume. Consequently, these drugs are not effectively eliminated by hemodialysis, urinary alkalinization, or hemofiltration.