calcium channel blockers acem 2003
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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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Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Calcium channel blockersCalcium channel blockers
Phenylalkylamines
verapamil
Benzothiazepines diltiazem
Dihydropyridines
nifedipine, felodipine, nimodipine,nicardipine, amlodipine, lercanidipine
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Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Calcium channel blockersCalcium channel blockers
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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Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
Calcium channel blockersCalcium channel blockers
Hypotension
peripheral vasodilatation and myocardial
depression Bradycardia
AV and SA node block
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Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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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Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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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Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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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Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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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Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
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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Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
InsulinInsulin--EuglycaemiaEuglycaemia
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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Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
InsulinInsulin--EuglycaemiaEuglycaemia
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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Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital
InsulinInsulin--EuglycaemiaEuglycaemia
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
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