1 / 17

Calcium channel blockers

Calcium channel blockers. Professor Ian Whyte Hunter Area Toxicology Service. Calcium channel blockers. Phenylalkylamines verapamil Benzothiazepines diltiazem Dihydropyridines nifedipine, felodipine, nimodipine, nicardipine, amlodipine, lercanidipine. Calcium channel blockers.

ddixon
Télécharger la présentation

Calcium channel blockers

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Calcium channel blockers Professor Ian Whyte Hunter Area Toxicology Service

  2. Calcium channel blockers • Phenylalkylamines • verapamil • Benzothiazepines • diltiazem • Dihydropyridines • nifedipine, felodipine, nimodipine, nicardipine, amlodipine, lercanidipine

  3. Calcium 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

  4. Calcium channel blockers • Hypotension • peripheral vasodilatation and myocardial depression • Bradycardia • AV and SA node block

  5. Antidotes • Correction of acidosis • Calcium loading • Glucagon • Insulin-dextrose euglycaemia • Atropine • Inotropic agents • Cardiac pacing • Bay K 8644 (calcium channel agonist)

  6. Correction 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 a swine model of verapamil poisoning

  7. Calcium loading • Calcium loading is the most logical and appears to be the most effective agent to use in calcium channel blocker poisoning • It is primarily indicated in patients with heart block (who have usually taken verapamil or diltiazem)

  8. Glucagon • Glucagon is a well-accepted antidote for beta-blocker poisoning • The rationale for its use in CCB poisoning is that it activates myosin kinase independent of calcium flux • Clinical experience suggests it is less effective in this setting than in beta-blocker poisoning

  9. Insulin-dextrose euglycaemia • Insulin infusions should be used to treat hyperglycaemia or hyperkalaemia • Insulin-dextrose euglycaemia is more effective in animal models than calcium, adrenaline or glucagon • Effective in a case series of clinically serious poisonings • Hypotension that is refractory to volume loading, correction of acidosis and calcium salts

  10. Insulin-Euglycaemia • Insulin as an inotrope • myocardial ischaemia/infarction • endotoxic shock • cardiogenic shock post cardiopulmonary bypass • CCB and –blocker induced myocardial depression • Yuan TH, Kerns WP, Tomaszewski CA,Ford MD, Kline JA. Insulin-glucose as adjunctive therapy for severe calcium channel antagonist poisoning. J Tox Clin Tox 1999; 37(4): 463–474

  11. Insulin-Euglycaemia • Rationale • In unstressed, aerobic state the myocardium relies primarily on free fatty acids (FFAs) for mechanical energy • During shock, substrate preference shifts from FFAs to carbohydrate oxidation

  12. Insulin-Euglycaemia • 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

  13. Insulin-Euglycaemia • 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+ 2.8–3.2 • Replace if K+ < 2.5

  14. Atropine • Vagal tone is increase by vomiting and gastrointestinal decontamination • Atropine should be given to all patients who are vomiting or having GI decontamination • Atropine should be given to all patients with bradycardia • A response may only occur after calcium loading

  15. Inotropic agents • Dopamine is the initial pressor agent of choice (75% response) for diltiazem overdose • Isoprenaline produces a therapeutic response in 50% of patients • Action is predominantly through increasing the frequency of impulses originating in the SA node • These agents are often ineffective as chronotropic agents when there is a high degree of conduction block

  16. Cardiac pacing • Ventricular rather than atrial pacing • In severe poisoning the heart may fail to capture and pharmacological therapy will still be required

  17. Calcium 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

More Related