Calcium channel blockers

Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

Calcium channel blockersCalcium channel blockers

Professor Ian Whyte

Hunter Area Toxicology Service


Cardiac arrhythmia Cardiac arrhythmia

Primary – quinidine–like drugs, sympathomimetic

drugs, calcium channel blockers, β–blockers, digitalis, chloroquine

Secondary to metabolic/electrolyte abnormalities – salicylates, methanol, ethylene glycol


Cardiotoxic drugs 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


Cardiac arrest 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



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



Hypotension– peripheral vasodilatation and myocardial

depression Bradycardia

– AV and SA node block


CCB caseCCB 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


CCB caseCCB case On arrival in ED

– PR 120, BP 110/80, RR 20, afebrile– drowsy but oriented and cooperative


CCB caseCCB case

GI decontamination– emesis before arrival– lavaged with return of green tablets– 50 g of charcoal with sorbitol repeated 4 h later


CCB caseCCB 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


CCB caseCCB case

16 hours post overdose– BP fell to 70/40 and then 50/30– PR 50– oxygen saturation dropped to 75 %


CCB caseCCB case

16 hours post overdose– ECG

absent p waves prominent u waves normal QRS duration and QT interval


CCB caseCCB case

Treatment– IV atropine 0.6 mgs – no response


CCB caseCCB 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



CCB caseCCB case

Outcome– non–cardiogenic pulmonary oedema– twenty four hours post admission

largely recovered , sinus rhythm PR 60, BP 115/70


CCB caseCCB 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


CCB caseCCB 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


CCB caseCCB 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


CCB caseCCB case

Outline your initial management


CCB caseCCB 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


CCB caseCCB 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!)


CCB caseCCB 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


CCB caseCCB 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


CCB caseCCB 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


CCB caseCCB 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?


CCB caseCCB 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


CCB treatmentCCB 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



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



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


In su l in 1 U /k g

In su l in 0 .5U /k g/h

S B P < 9 0 a fte r 1 h

0 .5 g/h 5 0 %glu co se

2 5 m L (1 2 .5 g)5 0 % glu co se

In su l in 1 U /k g/h

S to p in su lin

S B P > 1 0 0 fo r 6 h

B S L > 1 1 m m o l/LB S L < 5 .5 m m o l/L

O ff in su l in , ea t in g , B S L > 5 .5 m m o l/L

glu co se glu co se

S to p glu co se

A N D


Cardiopulmonary bypassCardiopulmonary bypass

As a last resort extracorporeal blood pressure support eg cardiopulmonary bypass may be considered


Antidotes: asystole & Antidotes: asystole & bradycardiabradycardia

Atropine everything Bicarbonate tricyclic antidepressants Calcium calcium channel blockers Diazepam chloroquine, organochlorines Epinephrine everything, β–blockers Fab fragments digoxin Glucagon β–blockers, CCBs

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Calcium channel blockers