Calcium Channel Blockers

Calcium channel blockers or CCBs are another common class of drugs used to treat hypertension. They reduce blood pressure by causing vasodilation. This is because they block voltage-activated Calcium channels in vascular smooth muscle.

They not used as prevalently as other drug types such as Thiazide-type diuretics, but are a still widely used, especially in the treatment of essential hypertension in the elderly. Elderly patients tend to respond better to CCBs because often loss of elasticity in vascular walls is a prominent cause of their hypertension, so they respond well to treatments that target this problem.

Typical Calcium Channel Blockers include:

Nisoldipine, Nicardipine, Amlodipine, Lercanidipine, Nifedipine, Lacidipine, Felodipine ,Isradipine, Diltiazem, Verapamil.

Mechanism of Action

Calcium entry into smooth muscle causes contraction. In smooth muscle, voltage-activate calcium channels respond to stimulation from nerves by opening these channels, and causing entry of calcium into the smooth muscle cells, causing contraction.

Generally, in peripheral vascular tissue, the nervous system sends tonic output (long lasting, sustained signals) that regulates vasodilation by altering the contraction of the ring of smooth muscle around these vessels.

In the heart, voltage-activated calcium channels are also present in cardiac muscle, where they are also responsible for contraction. Here, CCBs exert negative chronotropic, inotropic and dromotropic effects.

•  Negative Chronotropic: They reduce the heart rate.
• Negative Inotropic: They reduce the force of contraction of the muscle.
• Negative Dromotropic: They reduce the rate of cardial action potential conduction through the muscle.

By causing vasodilation in the periphery, remember that according to Poisseuille’s law, the resistance in a vessel is a function of the radius to the power of four. As such CCBs reduce the total peripheral resistance in the vasculature. Reducing both the rate and force of contraction of the heart reduces cardiac output.

• Remember that blood pressure is proportional to cardiac output multiplied by the total peripheral resistance, so blood pressure drops.

Different CCBs exert different effects, because they all work slightly different according to their properties – some easily pass into cardiac tissue and so exert stronger cardiac effects whereas others do not, they also all have different affinities for different calcium channels. You can categorise CCBs into groups according to their structure and function.

• Dihydropyridines are the biggest class. These include amlodipine, nisoldipine, isradipine, nicardipine, nifedipine, felodipine, lacidipine, lercanidipine. These are considered to work more via peripheral vasodilation rather than causing effects on cardiac tissue.
•  The only drugs that do not fit into this class are Verapamil, which is targets the myocardium more than peripheral calcium channels, and Diltiazem which seems to have both cardiac and vascular effects.

Other Uses for CCBs

Verapamil and other CCBs are also useful for the treatment of Angina Pectoris – chest pain associated with a reduction of blood flow to the heart, because it penetrates into heart tissue better than dihydropyridines. Angina is commonly caused by atherosclerosis in the cardiac vasculature, so causing vasodilation in these tissues is useful for aiding blood flow to the myocardium. Because it stabilises contractions of the heart muscle, it is also useful for treating cardiac arrhythmias, especially arrhythmias with tachycardia (fast heart rate).
 

Calcium Channel Blockers for treatment of Hypertension in the Elderly

With increasing age, there is a tendency for loss of elasticity in vascular tissue, and increased stiffness is a common cause of hypertension with increasing age. This increased stiffness causes a raised systolic blood pressure, rather than diastolic because there is more resistance in vessels in the periphery rather than an increased “resting tension” of the blood caused by a change in fluid volumes.
For this reason, CCBs, especially dihydropyridine CCBs, are recommended for treatment in the elderly. It is often quite difficult to treat elderly patients, as they often have other complications to their treatment, including a generalised reduction in physiological function with age. Patients with low renin hypertension, as is commonly seen with persons of Afro-Caribbean origin, also respond well to CCBs.

Adverse Effects and Contraindications

• Because they cause vasodilation, CCBs and especially dihydropyridines can cause flushing, redness and headaches.
• Another common side effect is that due to their negative chronotropic effects, the body may respond by increasing sympathetic stimulation via the baroceptor. This can cause tachycardia.
• Verapamil also exerts effects on smooth muscle in the gut. Because it reduces contractions, it can reduce gut motility and cause constipation.
• Because of their dromotropic effects, they are not recommended for patients with heart blocks (irregularities in conduction in cardiac tissue).

References

• NICE Guidelines 2004 "Hypertension (CG34): Management of hypertension in adults in primary care"
• Mark Nelson (2010). "Drug Treatment of Elevated Blood Pressure" Australian Prescriber. Volume4 - 33:108-112. 
• Pestana M. "Hypertension in the elderly." International Urology and Nephrology 33:3, 563-569
• Smulyan H (1999). "Clinical studies and therapeutic trials in systolic hypertension" Pathologie-biologie (Paris) 47(7):752-9.
• British Hypertension Society web page: "Calcium Channel Blockers"

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