Calcium Channel Blockers (CCBs)

Calcium channel blockersare drugs that block the entry ofcalciuminto themusclecells of theheartand arteries.

• The entry of calcium is critical for the conduction of the electrical signal that passes from musclecellto muscle cell of the heart, and signals the cells to contract.
• It also is necessaryinorder for the muscle cells to contract and thereby pumpblood．
• In the arteries, the entry of calcium into muscle cells constricts the arteries.

Thus, by blocking the entry of calcium, calcium channel blockers reduce electrical conduction within the heart, decrease the force ofcontraction(work) of the muscle cells, anddilatearteries.

• Dilationof the arteries reducesblood pressureand thereby the effort the heart must exert to pump blood.
• Combined with decreases in the force of contraction, this leads to a reduced requirement foroxygenby the heart.
• Dilation of the arteries provides more oxygen-carrying blood to the heart.
• The combination of reduced demand for oxygen and increased delivery of oxygen prevents心绞痛or heartpain．(心绞痛发生在心脏is not getting enough oxygen relative to the amount of work it is doing.)
• In addition, calcium channel blockers slow electrical conduction through the heart and thereby correctabnormalrapid heartbeats.

Calcium channel blockers are approved for treating:

• high blood pressure,
• 心绞痛,
• abnormal heart rhythms (for example,atrialfibrillation, paroxysmalsupraventricular tachycardia) andsubarachnoid hemorrhage．

They are also used for treating other conditions such as:

• high blood pressure in thepulmonaryarteries (pulmonary hypertension),
• Raynaud's phenomenon,cardiomyopathy(diseaseof the heart's muscle), and
• preventingmigraineheadaches.

Although calcium channel blockers have a similar mechanism of action, they differ in their ability toaffectheart musclevs. arteries, and they differ in their ability to affectheart rateand contraction. These differences determine how they are used and their side effects.

For example:

• verapamil(Covera-HS,Verelan PM,Calan),维iltiazem (Cardizem LA,Tiazac) reduce the strength and rate of the heart's contraction and are used in treating abnormal heart rhythms; and
• amlodipine(Norvasc) has very little effect on the heart rate and contraction. Therefore, amlodipine is not used for treating abnormal heart rhythm, but it is preferred whenheart failureis present and dilation of arteries is desired.

Common side effects of calcium channel blockers include:

• headache,
• constipation,
• rash,
• nausea,
• flushing,
• 水肿(fluid accumulation in tissues),
• drowsiness,
• low blood pressure, and
• dizziness．

Sexualdysfunction,overgrowthof gums, andliverdysfunction also have been associated with calcium channel blockers. Verapamil (Covera-HS,VerelanPM, Calan) and diltiazem (CardizemLA, Tiazac) worsen heart failure because they reduce the ability of the heart to contract and pump blood.

Calcium channel blockers interact with several drugs.

• Verapamil (Covera-HS, Verelan PM, Calan) and diltiazem (Cardizem LA, Tiazac) reduce the elimination and increase the blood levels ofcarbamazepine(Tegretol),simvastatin(Zocor),atorvastatin(Lipitor), andlovastatin(洛伐他汀). This can lead totoxicityfrom these drugs.
• Several calcium channel blockers [for example, diltiazem (Cardizem LA, Tiazac),felodipine(Plendil)] increase the level ofcyclosporine(Sandimmune,Neoral,Restasis) and similarly lead to toxicity of cyclosporine.
• Grapefruitjuice (1 glass, approximately 200ml) may elevateserumconcentrations of verapamil (Covera-HS, Verelan PM, Calan), felodipine (Plendil),nifedipine(Adalat,Procardia), nicardipine (Cardene), nisoldipine (Sular), and possibly amlodipine (Norvasc).

The calcium channel blockers available in the U. S. are:

• amlodipine (Norvasc),
• diltiazem (Cardizem LA, Tiazac),
• felodipine (Plendil),
• isradipine (Dynacirc),
• nifedipine (Adalat, Procardia),
• nicardipine (Cardene),
• nimodipine (Nimotop),
• nisoldipine (Sular), and
• verapamil (Covera-HS, Verelan PM, Calan).

Verapamil, diltiazem and nicardipine (Cardene IV) also are available inintravenousformulations.