Undesirable effects include hypotension, bradycardia, dizziness, flushing, fatigue, headaches and edema. Rare side effects are congestive heart failure, myocardial infarction, and hepatotoxicity.Diltiazem is one of the most common drugs that cause drug-induced lupus, along with hydralazine, procainamide, isoniazid, minocycline. Drug interactions
Because of its inhibition of hepatic cytochromes CYP3A4, CYP2C9 and CYP2D6, there are a number of drug interactions. Some of the more important interactions are listed below. Beta-blockers
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
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. Fentanyl
Concurrent use of fentanyl with diltiazem, or any other CYP3A4 inhibitors, as these medications decrease the breakdown of fentanyl and thus increase its effects. Mechanism
Diltiazem, also known as (2S,3S)-3-acetoxy-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one hydrochlorid has a vasodilating activity attributed to the (2S,3S)-isomer. Diltiazem is a potent vasodilator, increasing blood flow and variably decreasing the heart rate via strong depression of A-V node conduction. It binds to the alpha-1 subunit of L-type calcium channels in a fashion 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 potent and mild vasodilator of coronary and peripheral vessels, respectively, 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, typically unstable angina, symptoms. These effects also reduce blood pressure by causing less blood to be pumped out. Research
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.Recent research has shown diltiazem may  reduce cocaine cravings in drug-addicted rats. This is believed to be due to the effects of calcium blockers on dopaminergic and glutamatergic signaling in the brain. Diltiazem also enhances the analgesic effect of morphine in animal tests, without increasing respiratory depression, and reduces the development of tolerance.Diltiazem is also being used in the treatment of anal fissures. It can be taken orally or applied topically with increased effectiveness. When applied topically, it is made into a cream form using either vaseline or Phlojel. Phlojel absorbs the diltiazem into the problem area better than the vaseline base. It has good short-term success rates. References
External links
"Diltiazem". Drug Information Portal. U.S. National Library of Medicine.