which ccb is contraindicated in heart failure?

Non-dihydropyridines are contraindicated in those with heart failure with reduced ejection fraction, second or third-degree AV blockade, and sick sinus syndrome because of the possibility of causing bradycardia and worsening cardiac output.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2] Edzel Lorraine Co, DMD, MD[3]

Although calcium channel blockers cause vasodilation and may reduce afterload in the setting of heart failure, their overall benefit in heart failure is minimized by the fact that they have a negative inotropic effect and by the reflex activation of the sympathetic nervous system. These agents are therefore not recommended as vasodilators in patients with systolic dysfunction, however they may be useful as antihypertensive agents in patients with diastolic dysfunction.

Normally, vascular smooth muscle contraction initiates when calcium enters the cell via voltage-dependent L-type calcium channels. The calcium binds to intracellular calmodulin, which binds to and activates myosin light-chain kinase (MLCK). MLCK is responsible for the phosphorylation of the myosin light chain, ultimately leading to muscle contraction and vasoconstriction. The vascular smooth muscle contraction becomes further amplified by calcium-induced calcium release from the sarcoplasmic reticulum. This sequence of events leads to a decreased vascular cross-sectional area, increased vascular resistance, and increased blood pressure.

Amlodipine works by blocking the voltage-dependent L-type calcium channels, thereby inhibiting the initial influx of calcium. Reduced intracellular calcium leads to decreased vascular smooth muscle contractility, increased smooth muscle relaxation, and resultant vasodilation. Additionally, amlodipine has improved vascular endothelial function in hypertensive patients. Amlodipine decreases blood pressure by inducing smooth muscle relaxation and vasodilatation.[3]

Amlodipine's role in relieving stable angina is due to the lowering of afterload secondary to its vasodilatory and antihypertensive properties. Reducing afterload leads to lowering myocardial oxygen demand at any level of exertion, as the heart does not need to work as hard to pump blood into the systemic circulation. Amlodipine also alleviates Prinzmetal or variant angina by blocking coronary spasms and restoring blood flow in the coronary arteries.[12]

Raynaud phenomenon (RP) is an excessive vascular response to cold temperature, manifested clinically by color changes of the distal skin of the digits and toes, nose, and earlobes. Amlodipine induces smooth muscle relaxation and is an effective short-term treatment for patients with Raynaud's phenomenon.[13]

ACE inhibitors(ACE-I)/angiotensin receptor blockers(ARBs) are the initial treatment of choice for diabetic nephropathy. However, clinical trials have shown that combined antihypertensive therapy with either amlodipine plus an ARBs/ACE-I plus exerts a greater antiproteinuric effect in patients with type 2 diabetic nephropathy[14][15]

ASCOT (Anglo-Scandinavian Outcome Trial) demonstrated that an amlodipine-based blood pressure regimen decreased the long-term incidence of stroke compared with atenolol, but further research is still required.[16]

Pharmacokinetics

Absorption:  The absolute bioavailability of amlodipine is between 64% and 90%. Food doesn't alter the bioavailability of amlodipine. Peak plasma concentrations are achieved between 6 and 12 hours. Steady-state plasma levels are achieved after 7 to 8 days of daily dosing of amlodipine. Patients with hepatic dysfunction have decreased clearance of amlodipine; accordingly, there is an increase in AUC of approximately 40% to 60%.

Distribution: Amlodipine has high plasma protein binding(93%).

Metabolism: Amlodipine is extensively metabolized by the liver to inactive metabolites.