WK 6 -2 Calcium Channel Blockers

JCU Introductory Pharmacology & Pharmacotherapy

Course Name: PC1320Institution: James Cook University, AustraliaCelebrating 50 Years (1970-2020)

Cardiovascular Pharmacology: Calcium Channel Blockers (CCBs)

Presentation by: Robiul Islam, PhDAcknowledgment: Assoc Prof John Smithson, Pharmacy, College of Medicine and Dentistry

Learning Outcomes

  • Understand the two different groups of calcium channel blockers: Dihydropyridine and Non-dihydropyridine.

  • Recognize the differences in mechanism, pharmacological use, and clinical implications for each group.

  • Comprehend the action of calcium channel blockers on smooth muscle tissue and their impact on cardiovascular physiology.

  • Gain in-depth knowledge of pharmacokinetics, common side effects, drug interactions, and contraindications associated with both groups of CCBs.

Copyright Information

The material is protected under the Commonwealth of Australia Copyright Regulations 1969.Original source: James Cook University. Reproduction may be subject to copyright protection.

Characteristics of Calcium Channel Blockers

Clinical Uses:

  • Primarily used for the management of hypertension (high blood pressure) and angina (chest pain due to reduced blood flow to the heart).

  • May also be utilized in the prevention of migraine attacks and certain arrhythmias.

Mechanism of Action:Calcium channel blockers exert their effects by acting on calcium channels located in myocardial and vascular smooth muscles, leading to:

  • Reduced heart rate (negative chronotropic effect): By weakening the electrical conduction system of the heart.

  • Reduced contractility (negative inotropic effect): Decreasing the force of heart contractions, which can be particularly beneficial for patients with heart failure.

  • Reduced vasoconstriction: Relaxing the vascular smooth muscle, leading to vasodilation and lowered systolic and diastolic blood pressure.

Examples of CCBs:

  • Dihydropyridines: amlodipine, clevidipine, felodipine, lercanidipine, nifedipine, nimodipine.

  • Non-dihydropyridines: diltiazem, verapamil.

  • Common Suffix: Dihydropyridines typically end with the suffix ‘-ipine’.

Classification of Calcium Channel Blockers

Non-dihydropyridine CCBs

  • Include: verapamil, diltiazem.

  • Primary Action: Target cardiac tissues as well as arteriolar smooth muscle.

  • Effects:

    • Decrease heart contractility.

    • Lower heart rate by reducing conduction velocity through the AV node.

    • Cause vasodilation of systemic arteries, thus enhancing blood flow.

  • Mechanism of Action:Blocks calcium movement into cells, leading to:

    • Decreased calcium availability from the sarcoplasmic reticulum.

    • Reduced actin-myosin interaction, causing decreased myocardial contraction strength.

Dihydropyridine CCBs

  • Includes: amlodipine, clevidipine, felodipine, lercanidipine, nifedipine, nimodipine.

  • Mechanism of Action:Block inward calcium flow specifically into coronary arteries and peripheral arterioles.

  • Effects:

    • Induce significant dilation of arterioles and coronary arteries.

    • Reduce peripheral vascular resistance, resulting in a decrease in afterload, which ultimately increases nutrient/oxygen supply to the heart.

Pharmacokinetics and Side Effects of Dihydropyridine CCBs

  • Amlodipine:

    • Known for its longer half-life, administered once daily, enhancing patient compliance.

    • Typically available in controlled-release form, providing stable blood levels.

    • Metabolized primarily by CYP3A4 in the liver, leading to potential drug interactions.

  • Common Adverse Effects:

    • Gastrointestinal: constipation.

    • Cardiovascular: bradycardia, hypotension.

    • Neurological: dizziness; risk of falls, especially in elderly patients.

    • Dermatological: skin flushing, rash, dry mouth.

    • Other: ankle edema, gingival hyperplasia.

Comparison of Cardiovascular Effects of CCBs

Key Trends:

  • Non-dihydropyridine CCBs notably reduce heart contractility more significantly than dihydropyridine CCBs.

  • All types produce coronary or peripheral vasodilation, beneficial in managing hypertension and angina.

  • Variability exists in effects on heart rate; non-dihydropyridines can significantly lower heart rate, whereas some dihydropyridines may cause reflex tachycardia.

Practice Points for Calcium Channel Blockers

  • It is crucial to recognize that non-dihydropyridine CCBs impose a pronounced negative impact on central cardiac tissue compared to their effects on arteriolar smooth muscle.

  • Dihydropyridines primarily target arteriolar smooth muscle, making them excellent choices for primarily lowering blood pressure.

  • Non-dihydropyridines are contraindicated when combined with other medications that may further lower contractility or heart rate (e.g., beta-blockers), as this can increase the risk of bradycardia and other adverse effects.

  • Clinical Note: Verapamil has a more significant effect on contractility and automaticity than other CCBs like diltiazem, necessitating careful monitoring of cardiac function in patients using these agents.

Summary of Calcium Channel Blockers

Classifications:

  • Dihydropyridine: e.g., amlodipine; primarily vascular effects with less impact on the heart rate and contractility.

  • Non-dihydropyridine: e.g., verapamil, diltiazem; have both cardiac and vascular effects, crucial for treating arrhythmias and controlling heart rate.General Effect:Calcium channel blockers facilitate the relaxation of smooth muscle and cardiac tissue through decreased calcium availability during muscle contraction; this leads to lower myocardial contractility and vasodilation effects.Variability in cardiovascular effects depends on the specific CCB prescribed and individual patient factors, highlighting the need for personalized medical approaches and careful titration of dosing in clinical practice.Caution: Exercise caution when combining non-dihydropyridine CCBs with other agents that reduce heart rate or contractility to prevent any adverse cardiovascular outcomes.