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8/8/2019 Calcium Channel Blockers ACEM 2003

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Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

Calcium channel blockersCalcium channel blockers

Professor Ian Whyte

Hunter Area Toxicology Service


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Phenylalkylamines

verapamil

Benzothiazepines diltiazem

Dihydropyridines

nifedipine, felodipine, nimodipine,nicardipine, amlodipine, lercanidipine


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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


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Hypotension

peripheral vasodilatation and myocardial

depression Bradycardia

AV and SA node block


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AntidotesAntidotes

Correction of acidosis

Calcium loading

Glucagon Insulin-dextrose euglycaemia

Atropine

Inotropic agents Cardiac pacing

Bay K 8644 (calcium channel agonist)


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Correction of acidosisCorrection of acidosis

Correct acidosis to a pH within the normal

range

L calcium channel function is impaired when the

pH falls outside the physiological range

acidosis enhances the effect of verapamil and

decreases the effect of calcium

sodium bicarbonate significantly improved

myocardial contractility and cardiac output in aswine model of verapamil poisoning


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Calcium loadingCalcium loading

Calcium loading is the most logical

and appears to be the most effective

agent to use in calcium channelblocker poisoning

It is primarily indicated in patients

with heart block (who have usually

taken verapamil or diltiazem)


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GlucagonGlucagon

Glucagon is a well-accepted antidote

for beta-blocker poisoning

The rationale for its use in CCBpoisoning is that it activates myosin

kinase independent of calcium flux

Clinical experience suggests it is lesseffective in this setting than in beta-

blocker poisoning


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InsulinInsulin--dextrose euglycaemiadextrose euglycaemia

Insulin infusions should be used to treathyperglycaemia or hyperkalaemia

Insulin-dextrose euglycaemia is more

effective in animal models than calcium,adrenaline or glucagon

Effective in a case series of clinicallyserious poisonings

Hypotension that is refractory to volumeloading, correction of acidosis and calciumsalts


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InsulinInsulin--EuglycaemiaEuglycaemia

Insulin as an inotrope

myocardial ischaemia/infarction

endotoxic shock cardiogenic shock post cardiopulmonary bypass

CCB andFblocker induced myocardial depression Yuan TH, Kerns WP, Tomaszewski CA,Ford MD, Kline

JA. Insulin-glucose as adjunctive therapy for severe calciumchannel antagonist poisoning. J Tox Clin Tox 1999; 37(4):

463474


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Rationale

In unstressed, aerobic state the

myocardium relies primarily on free fattyacids (FFAs) for mechanical energy

During shock, substrate preference shifts

from FFAs to carbohydrate oxidation


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In the presence of

inhibition of insulin release

insulin resistance poor tissue perfusion

impaired glycolysis and carbohydrate

delivery

Systemic hyperglycaemia and

inefficient myocardial energy transfer

myocardial depression


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Hypokalaemia

Shift of extracellular K+ to intracellular via

Na+/K+pump

Na+ shift means resting membrane potential

becomes more negative (hyperpolarisation)

decrease arrhythmias

Prolongs plateau phase of action potential increases calcium entry

Aim for K+ 2.83.2

Replace if K+ < 2.5


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AtropineAtropine

Vagal tone is increase by vomiting andgastrointestinal decontamination

Atropine should be given to allpatients who are vomiting or havingGI decontamination

Atropine should be given to all

patients with bradycardia A response may only occur after

calcium loading


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Inotropic agentsInotropic agents

Dopamine is the initial pressor agent ofchoice (75% response) for diltiazemoverdose

Isoprenaline produces a therapeutic responsein 50% of patients

Action is predominantly through increasingthe frequency of impulses originating in theSA node

These agents are often ineffective aschronotropic agents when there is a highdegree of conduction block


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Cardiac pacingCardiac pacing

Ventricular rather than atrial pacing

In severe poisoning the heart may fail

to capture and pharmacologicaltherapy will still be required


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Calcium channel agonistsCalcium channel agonists

Calcium channel agonists (eg. Bay K

8644) would appear to be a logical

antidote Animal studies using these compounds

have not been very promising