calcium channel blockers

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Calcium Channel Blockers

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  • 1. Calcium ChannelBlocking Drugs

2. Outline

  • Introduction
  • CCB binding sites
  • Heterogeneity of action
  • Cardiac & hemodynamic
  • differentiation
  • Pharmacokinetics
  • Adverse effects
  • Contraindications
  • Summary

3. Three Classes of CCBs Chemical Type Chemical Names Brand Names Phenylalkylamines verapamil Calan, Calna SR, Isoptin SR, Verelan Benzothiazepines diltiazem Cardizem CD, Dilacor XR 1,4-Dihydropyridines Nifedipine nicardipine isradipine felodipine amlodipine Adalat CC, Procardia XL Cardene DynaCirc Plendil Norvasc 4.

  • Angina pectoris
  • Hypertension
  • Treatment of supraventricular
  • arrhythmias
  • -Atrial Flutter
  • - Atrial Fibrillation
  • - Paroxysmal SVT

Widespread use of CCBs 5. Outline

  • Introduction
  • CCB binding sites
  • Heterogeneity of action
  • Cardiac & hemodynamic
  • differentiation
  • Pharmacokinetics
  • Adverse effects
  • Contraindications
  • Summary

6. The Three Classes of CCBs Bind to Different Sites 1,4- Dihydropyridines (nifedipine) Phenylalkylamines (verapamil) Benzothiazepines (diltiazem) Ca 2+ pore - - - - + + - 7.

  • Increase the time that Ca 2+channels are closed
  • Relaxation of the arterial smooth muscle but not
  • much effect on venous smooth muscle
  • Significant reduction in afterload but not preload

CCBs Mechanisms of Action 8. Outline

  • Introduction
  • CCB binding sites
  • Heterogeneity of action
  • Cardiac & hemodynamic
  • differentiation
  • Pharmacokinetics
  • Adverse effects
  • Contraindications
  • Summary

9. Why Do CCBs Act Selectivelyon Cardiac and Vascular Muscle? 10. N-type and P-type Ca 2+channels mediateneurotransmitter release in neuronspostsynaptic cell Ca 2+ Ca 2+ Ca 2+ Ca 2+ Ca 2+ 11. Skeletal muscle relies on intracellular Ca 2+for contraction Myofibril Plasma membrane Transversetubule Terminalcisterna of SR Tubules of SR Triad T SR 12. Cardiac cells rely on L-type Ca 2+channels for contraction and for the upstroke of the AP in slow response cells Contractile Cells (atria, ventricle) L-Type Ca 2+ Ca 2+ Ca 2+ Slow Response Cells (SA node, AV node) L-Type Ca 2+ Ca 2+ 13. Vascular smooth muscle relies on Ca 2+influx through L-type Ca 2+channels for contraction (graded, Ca 2+dependent contraction) L-Type Ca 2+ 14. CCBs Act Selectively on Cardiovascular Tissues

  • Neurons rely on N-and P-type Ca 2+channels
  • Skeletal muscle relies primarily on [Ca] i
  • Cardiac muscle requires Ca 2+influx through
  • L-type Ca 2+channels
  • - contraction (fast response cells)
  • - upstroke of AP (slow response cells)
  • Vascular smooth muscle requires Ca 2+influx
  • through L-type Ca 2+channels for contraction

15. Outline

  • Introduction
  • CCB binding sites
  • Heterogeneity of action
  • Cardiac & hemodynamic
  • differentiation
  • Pharmacokinetics
  • Adverse effects
  • Contraindications
  • Summary

16. Differential effects of different CCBs on CV cells AV SN AV SN Potential reflex increase in HR, myocardial contractility and O 2demand Coronary VD Dihydropyridines: Selective vasodilators Non -dihydropyridines: equipotent for cardiac tissue and vasculature Heart rate moderating Peripheral and coronary vasodilation Reduced inotropism Peripheral vasodilation 17. Hemodynamic Effects of CCBs Effect Verapamil Diltiazem Nifedipine Peripheral vasodilatation Coronary vasodilatation Preload 0 0 0/ Afterload Contractility 0/ / * Heart rate 0/ /0 AV conduction 0 18. Outline

  • Introduction
  • CCB binding sites
  • Heterogeneity of action
  • Cardiac & hemodynamic
  • differentiation
  • Pharmacokinetics
  • Adverse effects
  • Contraindications
  • Summary

19. CCBs: Pharmacokinetics Agent Oral Absorption (%) Bioavail- Ability (%) Protein Bound (%) EliminationHalf-Life (h) Verapamil >90 10-35 83-92 2.8-6.3* Diltiazem >90 41-67 77-80 3.5-7 Nifedipine >90 45-86 92-98 1.9-5.8 Nicardipine -100 35 >95 2-4 Isradipine>90 15-24 >95 8-9 Felodipine -100 20 >99 11-16 Amlodipine >90 64-90 97-99 30-50 20. Outline

  • Introduction
  • CCB binding sites
  • Heterogeneity of action
  • Cardiac & hemodynamic
  • differentiation
  • Pharmacokinetics
  • Adverse effects
  • Contraindications
  • Summary

21. Comparative Adverse Effects Diltiazem Verapamil Dihydropyridines Overall 0-3% 10-14% 9-39% Hypotension ++ ++ +++ Headaches 0 + +++ Peripheral Edema ++ ++ +++ Constipation 0 ++ 0 CHF (Worsen) 0 + 0 AV block + ++ 0 Caution w/beta blockers + ++ 0 22.

  • heart rate
  • blood pressure
  • anginal symptoms
  • signs of CHF
  • adverse effects

CCBs - Monitoring 23. Outline

  • Introduction
  • CCB binding sites
  • Heterogeneity of action
  • Cardiac & hemodynamic
  • differentiation
  • Pharmacokinetics
  • Adverse effects
  • Contraindications
  • Summary

24. Contradications for CCBs Contraindication Verapamil Nifedipine Diltiazem Hypotension + ++ + Sinus bradycardia + 0 + AV conduction defects ++ 0 ++ Severe cardiac failure ++ + + 25. Outline

  • Introduction
  • CCB binding sites
  • Heterogeneity of action
  • Cardiac & hemodynamic
  • differentiation
  • Pharmacokinetics
  • Adverse effects
  • Contraindications
  • Summary

26. Which CCB is most likely to causehypotension and reflex tachycardia?

  • Diltiazem
  • Nifedipine
  • Verapamil

27. Contraindications for CCBs include (choose allappropriate):

  • Supraventricular tachycardias
  • Hypotension
  • AV heart block
  • Hypertension
  • Congestive heart failure

28. CCBs may improve cardiac function by:

  • Reducing cardiac afterload
  • Increasing O 2supply
  • Decreasing cardiac preload
  • Normalizing heart rate in patients with
  • supraventricular tachycardias

29. Thank you!

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