Dilacor XR  

Diltiazem
Systematic (IUPAC) name
cis-(+)-[2-(2-dimethylaminoethyl)-5-(4-methoxyphenyl) -3-oxo-6-thia-2-azabicyclo[5.4.0]undeca-7,9, 11-trien-4-yl]ethanoate
Identifiers
CAS number	42399-41-7
ATC code	C08DB01
PubChem	39186
DrugBank	APRD00473
ChemSpider	35850
Chemical data
Formula	C22H26N2O4S
Mol. mass	414.519 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	40%
Metabolism	Hepatic
Half life	3-4.5 hours
Excretion	Renal Biliary Lactic (in lactiferous females)
Therapeutic considerations
Pregnancy cat.	D: (USA)
Legal status
Routes	Oral
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Diltiazem is a member of the group of drugs known as benzothiazepines, which are a class of calcium channel blockers, used in the treatment of hypertension, angina pectoris, and some types of arrhythmia. It is also an effective preventive medication for migraine. It is a class 3 anti-anginal drug, and a class IV antiarrhythmic. It incites very minimal reflex sympathetic changes. It is based upon a 1,4-thiazepine ring.

Diltiazem is metabolized by and acts as an inhibitor of the CYP3A4 enzyme.

Brand names

Mechanism

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.^[1]

Potent vasodilator of coronary vessels.

Vasodilator of peripheral vessels. This reduces peripheral resistance and afterload.

Negative inotropic effect. Diltiazem causes a modest decrease in heart muscle contractility and reduces myocardium oxygen consumption.

Negative chronotropic effect. Diltiazem causes a modest lowering of heart rate. This effect is due to slowing of the SA (sinoatrial) node. It results in reduced myocardium oxygen consumption.

Negative dromotropic effect. By slowing conduction through the AV (atrioventricular) node, diltiazem increases the time needed for each beat. This results in reduced myocardium oxygen consumption by the body.

Nontherapeutic effects and toxicities

Reflex sympathetic response. Caused by the peripheral dilation of vessels and the resulting drop in BP; the response works to counteract the negative inotropic, chronotropic and dromotropic effects of diltiazem. Symptoms include hypotension, bradycardia, dizziness, flushing.^[2]

Indications

Angina:

• Stable angina (exercise-induced) . Diltiazem increases coronary blood flow and decreases myocardial oxygen consumption, secondary to decreased peripheral resistance, heart rate, and contractility.^[3][4]

• Variant angina. Diltiazem is effective due to its direct effects on coronary dilation.

• Unstable angina (preinfarction, crescendo). Diltiazem may be particularly effective if the underlying mechanism is vasospasm.

Supraventricular tachycardias. Diltiazem appears to be as effective as verapamil in treating reentrant supraventricular tachycardia.^[5]

Atrial fibrillation^[6] or atrial flutter.

Hypertension. 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.^[7]

Contraindications and precautions

CHF. 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.

SA node or AV conduction disturbances. 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.

Wolff-Parkinson-White syndrome. Diltiazem may paradoxically increase ventricular rate in patients with WPW 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, chronic obstructive pulmonary disease, and Prinzmetal's angina.

Drug interactions

Beta-blockers

Intravenous diltiazem should be used with caution with beta-blockers, because while the combination is most therauputically beneficial, there are rare instances of dysrhythmia and AV node block ^[8].

Quinidine

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.

Miscellaneous

Inhibition of hepatic enzymes. Diltiazem and verapamil inhibit hepatic cytochromes CYP3A4, CYP2C9 and CYP2D6, possibly resulting in drug interactions.

Potential future indications

Recent research has shown that diltiazem is able to reduce cocaine cravings in drug-addicted rats.[1] This is believed to be due to the effects of calcium blockers on dopaminergic and glutamatergic signalling in the brain.^[9] Diltiazem also enhances the analgesic effect of morphine in animal tests, without increasing respiratory depression,^[10] and reduces the development of tolerance.^[11]

Diltiazem is also being used in the treatment of anal fissures. It can be taken orally or applied topically with equal effectiveness. When applied topically, it is made into a cream form using either vaseline or Phlogel. Phlogel absorbs the diltiazem into the problem area better than the vaseline base. It has good short term success rates. ^[12][13] Like all non-surgical treatments of anal fissure it does not address the long term problem of increased basal anal tone and does not decrease the subsequent recurrence rate that can vary between 40 to 60%.

References