Calcium channel blockers (CCB)

Preface

CCBs are widely used in anti-hypertensive therapies. In overdose, CCB's exhibit a profoundly toxic effect. Acting to block calcium uptake in the myocardium and vascular smooth muscle, toxicity can quickly lead to cardiovascular collapse and death.

Mechanism of action

CCBs are can classed as dihydropyridine and non-dihydropyridine types. All CCBs inhibit voltage-gated L-type calcium channels in the myocardium and vascular smooth muscle. Voltage-gated calcium channels are responsible for for excitation-contraction coupling of skeletal, smooth, and cardiac muscles. Blockade of calcium influx therefore directly decreases vascular smooth muscle and cardiac muscle contraction. They also play a large role in the conduction of cardiac pacemaker signals. At therapeutic doses, dihydropyridine's are selective for blood vessels, where as non-dihydropyridine's act both on reducing vascular contraction (peripheral resistance) and have specific effect on cardiac tissue. Non-dihydropyridine's further depress myocardial contractility, reduce sinus node firing rate and AV-node conduction.

Dihydropyridines

nifedipine
felodipine
Amlodipine

Non-Dihydropyridines

diltiazem
verapamil

Non-Dihydropyridines are the most lethal CCBs due to their non-selective nature, although dihydropyridines loose receptor selectivity in large overdose. The coformulation trandolapril (ACE inhibitor) + verapamil will have profound effects as congestion will potentiate the effects of overdose.

Clinical presentation

Cardiovascular

Sinus bradycardia, conduction delays (First-degree heart block, junctional and idioventricular rhythms)
Hypotension due to bradycardia, myocardial depression and vasoplegia
Cardiogenic shock
Pulmonary oedema

CNS

Drowsiness
Confusion
Agitation
Seizure

Metabolic

Hyperglycaemia
Acidosis

Onset of symptoms

Immediate-release formulations: Symptoms typically occur within 1-2 hours of ingestion
Extended-release formulations: Symptoms may be delayed, occurring up to 12-24 hours after ingestion

Prehospital Management

Symptomatic management of CCB overdose is the forefront of pre-hospital care. Rapid transport to a tertiary hospital is necessary.

Bradycardia

Atropine - 600mcg undiluted bolus, RPT: 1min, Max Dose: 3mg
Adrenaline - 50mcg bolus 1:1000, RPT: 1min, NO MAX
Adrenaline infusion
Calcium Gluconate 10%
Trans cutaneous pacing - May be difficult to obtain capture

Hypotension

20ml/kg Bolus, whilst indicated, NO MAX
Calcium Gluconate 10%

Calcium Gluconate

Calcium gluconate can have useful temporising effects on HR and BP.
Calcium gluconate is only indicated for hyperkalemia in NSWA.

A VCP will need to be completed if calcium gluconate is used in the setting of CCB overdose.

Early activation of ICP resources would be of great benefit. Although not always available, it is always advised to ask!