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Diltiazem ( INN ) ( / d ɪ l ˈ t aɪ ə z ɛ m / ) is a nondihydropyridine (non-DHP) calcium channel blocker used in the treatment of hypertension, angina pectoris, and some types of arrhythmia. It relaxes the smooth muscles in the walls of arteries, which opens (dilates) the arteries, allows blood to flow more easily, and lowers blood pressure. Additionally, it lowers blood pressure by acting on the heart itself to reduce the rate, strength, and conduction speed of each beat.
It is also used off-label as a preventive medication for migraine. It is a Class 3 antianginal drug, and a Class IV antiarrhythmic.
Diltiazem is metabolized by, and acts as an inhibitor of the CYP3A4 enzyme, which can cause it to interact with a variety of other medications.
2 Nontherapeutic effects and toxicities
4 Contraindications and precautions
5 Drug interactions
6 Potential future indications
8 External links
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Diltiazem is a potent vasodilator, increasing blood flow and variably decreasing the heart rate via strong depression of A-V node conduction. Its pharmacological activity is somewhat similar to verapamil, another nondihydropyridine (non-DHP) calcium channel blocker. Chemically, it is based upon a 1,4-thiazepine ring, making it a benzothiazepine -type calcium channel blocker.
It is a vasodilator of coronary and peripheral vessels, which reduces peripheral resistance and afterload, though not as potent as the dihydropyridine (DHP) calcium channel blockers. This results in minimal reflexive sympathetic changes.
Diltiazem has negative inotropic, chronotropic, and dromotropic effects. This means diltiazem causes a decrease in heart muscle contractility – how strong the beat is, lowering of heart rate – due to slowing of the sinoatrial node, and a slowing of conduction through the atrioventricular node – increasing the time needed for each beat. Each of these effects results in reduced oxygen consumption by the heart, reducing angina symptoms. These effects also reduce blood pressure by causing less blood to be pumped out.
Nontherapeutic effects and toxicities
A reflex sympathetic response, caused by the peripheral dilation of vessels and the resulting drop in blood pressure, works to counteract the negative inotropic, chronotropic and dromotropic effects of diltiazem. Undesirable effects include hypotension, bradycardia, dizziness, and flushing.
Diltiazem is indicated for:
Stable angina (exercise-induced) – diltiazem increases coronary blood flow and decreases myocardial oxygen consumption, secondary to decreased peripheral resistance, heart rate, and contractility.
Variant angina – it is effective owing to its direct effects on coronary dilation.
Unstable angina ( preinfarction, crescendo ) – diltiazem may be particularly effective if the underlying mechanism is vasospasm.
For supraventricular tachycardias ( PSVT ), diltiazem appears to be as effective as verapamil in treating re-entrant supraventricular tachycardia.
Atrial fibrillation or atrial flutter is another indication. The initial bolus should be 0.25 mg/kg, intravenous (IV).
Because of its vasodilatory effects, diltiazem is useful for treating hypertension. Calcium channel blockers are well tolerated, and especially effective in treating low- renin hypertension.
Contraindications and precautions
In congestive heart failure, patients with reduced ventricular function may not be able to counteract the inotropic and chronotropic effects of diltiazem, the result being an even higher compromise of function.
With SA node or AV conduction disturbances, the use of diltiazem should be avoided in patients with SA or AV nodal abnormalities, because of its negative chronotropic and dromotropic effects.
Low blood pressure patients, with systolic blood pressures below 90 mm Hg, should not be treated with diltiazem.
Diltiazem may paradoxically increase ventricular rate in patients with Wolff-Parkinson-White syndrome because of accessory conduction pathways.
Diltiazem is relatively contraindicated in the presence of sick sinus syndrome, atrioventricular node conduction disturbances, bradycardia, impaired left ventricle function, peripheral artery occlusive disease, and chronic obstructive pulmonary disease.
Because of its inhibition of hepatic cytochromes CYP3A4, CYP2C9 and CYP2D6, there are a significant number of drug interactions. Some of the more important interactions are listed below.
Intravenous diltiazem should be used with caution with beta-blockers because, while the combination is most potent at reducing heart rate, there are rare instances of dysrhythmia and AV node block.
Quinidine should not be used concurrently with calcium channel blockers because of reduced clearance of both drugs and potential pharmacodynamic effects at the SA and AV nodes.
Potential future indications
Diltiazem is prescribed off-label by doctors in the US for prophylaxis of cluster headaches. Some research on diltiazem and other calcium channel antagonists in the treatment and prophylaxis of migraine is ongoing.
Diltiazem is also being used in the treatment of anal fissures. It can be taken orally or applied topically with increased effectiveness.
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