Diltiazem works by relaxing thesmooth muscle in the walls ofarteries, resulting in them opening and allowing blood to flow more easily.[9] Additionally, it acts on theheart to prolong the period until it can beat again.[10] It does this by blocking the entry of calcium into the cells of the heart and blood vessels.[11] It is aclass IV antiarrhythmic.[12]
Diltiazem was approved for medical use in the United States in 1982.[9] It is available as ageneric medication.[9] In 2023, it was the 106th most commonly prescribed medication in the United States, with more than 6million prescriptions.[13][14] An extended release formulation is also available.[5][6][9]
Because of itsvasodilatory effects, diltiazem is useful for treatinghypertension. Calcium channel blockers are well tolerated, and especially effective in treating low-renin hypertension.[19]
It is also used as topical application foranal fissures because it promotes healing due to its vasodilatory property.[20]
Incongestive heart failure, patients with reduced ventricular function may not be able to counteract the negative inotropic and chronotropic effects of diltiazem, the result being an even higher compromise of function.
WithSA 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.
A reflex sympathetic response, caused by theperipheral dilation of vessels and the resulting drop in blood pressure, works to counteract the negative inotropic, chronotropic and dromotropic effects of diltiazem. Undesirable effects includehypotension,bradycardia,dizziness,flushing, fatigue, headaches and edema.[21] Rare side effects are congestive heart failure, myocardial infarction, and hepatotoxicity.[22]
Because of its inhibition ofhepaticcytochromesCYP3A4,CYP2C9 andCYP2D6, there are a number of drug interactions.[23] 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 ofdysrhythmia andAV node block.[24]
Quinidine should not be used concurrently with calcium channel blockers because of reduced clearance of both drugs and potentialpharmacodynamic effects at the SA and AV nodes.[25]
Concurrent use of fentanyl with diltiazem, or any other CYP3A4 inhibitors, as these medications decrease the breakdown of fentanyl and thus increase its effects.[26]
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.[27]Diltiazem is a potentvasodilator, increasing blood flow and variably decreasing theheart rate via strong depression ofA-V node conduction. It binds to the alpha-1 subunit of L-type calcium channels in a fashion somewhat similar toverapamil, another nondihydropyridine (non-DHP) calcium channel blocker.[28] Chemically, it is based upon a1,4-thiazepinering, making it abenzothiazepine-type calcium channel blocker.
Diltiazem has negativeinotropic,chronotropic, anddromotropic effects. This means diltiazem causes a decrease inheart muscle contractility – how strong the beat is, lowering of heart rate – due to slowing of thesinoatrial node, and a slowing of conduction through theatrioventricular node – increasing the time needed for each beat. Each of these effects results in reducedoxygen consumption by the heart, reducing angina, typicallyunstable angina, symptoms. These effects also reduce blood pressure by causing less blood to be pumped out.
Diltiazem is also being used in the treatment ofanal fissures. It can be taken orally orapplied topically with increased effectiveness.[40] When applied topically, it is made into a cream form using either petrolatum or Phlojel. Phlojel absorbs the diltiazem into the problem area better than the petrolatum base. It has good short-term success rates.[41][42]
^Claas SA, Glasser SP (May 2005). "Long-acting diltiazem HCl for the chronotherapeutic treatment of hypertension and chronic stable angina pectoris".Expert Opinion on Pharmacotherapy.6 (5):765–776.doi:10.1517/14656566.6.5.765.PMID15934903.S2CID39272285.
^Gabrielli A, Gallagher TJ, Caruso LJ, Bennett NT, Layon AJ (October 2001). "Diltiazem to treat sinus tachycardia in critically ill patients: a four-year experience".Critical Care Medicine.29 (10):1874–1879.doi:10.1097/00003246-200110000-00004.PMID11588443.S2CID25104288.
^Wattanasuwan N, Khan IA, Mehta NJ, Arora P, Singh N, Vasavada BC, et al. (February 2001). "Acute ventricular rate control in atrial fibrillation: IV combination of diltiazem and digoxin vs. IV diltiazem alone".Chest.119 (2):502–506.doi:10.1378/chest.119.2.502.PMID11171729.
^Griffin N, Acheson AG, Jonas M, Scholefield JH (October 2002). "The role of topical diltiazem in the treatment of chronic anal fissures that have failed glyceryl trinitrate therapy".Colorectal Disease.4 (6):430–435.doi:10.1046/j.1463-1318.2002.00376.x.PMID12790914.S2CID32959944.
^Ramoska EA, Spiller HA, Winter M, Borys D (February 1993). "A one-year evaluation of calcium channel blocker overdoses: toxicity and treatment".Annals of Emergency Medicine.22 (2):196–200.doi:10.1016/S0196-0644(05)80202-1.PMID8427431.
^Talreja O, Cassagnol M (2019). "Diltiazem".StatPearls. Treasure Island (FL): StatPearls Publishing.PMID30422532.
^Ohno Y, Hisaka A, Suzuki H (2007). "General framework for the quantitative prediction of CYP3A4-mediated oral drug interactions based on the AUC increase by coadministration of standard drugs".Clinical Pharmacokinetics.46 (8):681–696.doi:10.2165/00003088-200746080-00005.PMID17655375.S2CID41343222.
^Narimatsu A, Taira N (August 1976). "Effects of atrio-ventricular conduction of calcium-antagonistic coronary vasodilators, local anaesthetics and quinidine injected into the posterior and the anterior septal artery of the atrio-ventricular node preparation of the dog".Naunyn-Schmiedeberg's Archives of Pharmacology.294 (2):169–177.doi:10.1007/bf00507850.PMID1012337.S2CID21986119.
^O'Connor SE, Grosset A, Janiak P (1999). "The pharmacological basis and pathophysiological significance of the heart rate-lowering property of diltiazem".Fundamental & Clinical Pharmacology.13 (2):145–153.doi:10.1111/j.1472-8206.1999.tb00333.x.PMID10226758.S2CID20440286.
^Montastruc JL, Senard JM (April 1992). "[Calcium channel blockers and prevention of migraine]" [Calcium channel blockers and prevention of migraine].Pathologie-Biologie (in French).40 (4):381–388.PMID1353873.
^Kim KE (February 1991). "Comparative clinical pharmacology of calcium channel blockers".American Family Physician.43 (2):583–588.PMID1990741.
^Paterna S, Martino SG, Campisi D, Cascio Ingurgio N, Marsala BA (July 1990). "[Evaluation of the effects of verapamil, flunarizine, diltiazem, nimodipine and placebo in the prevention of hemicrania. A double-blind randomized cross-over study]".La Clinica Terapeutica.134 (2):119–125.PMID2147612.
^Smith R, Schwartz A (May 1984). "Diltiazem prophylaxis in refractory migraine".The New England Journal of Medicine.310 (20):1327–1328.doi:10.1056/NEJM198405173102015.PMID6144044.
^Kishioka S, Ko MC, Woods JH (May 2000). "Diltiazem enhances the analgesic but not the respiratory depressant effects of morphine in rhesus monkeys".European Journal of Pharmacology.397 (1):85–92.doi:10.1016/S0014-2999(00)00248-X.PMID10844102.
^Verma V, Mediratta PK, Sharma KK (July 2001). "Potentiation of analgesia and reversal of tolerance to morphine by calcium channel blockers".Indian Journal of Experimental Biology.39 (7):636–642.PMID12019755.
^Jonas M, Neal KR, Abercrombie JF, Scholefield JH (August 2001). "A randomized trial of oral vs. topical diltiazem for chronic anal fissures".Diseases of the Colon and Rectum.44 (8):1074–1078.doi:10.1007/BF02234624.PMID11535842.S2CID40406260.
^Sajid MS, Rimple J, Cheek E, Baig MK (January 2008). "The efficacy of diltiazem and glyceryltrinitrate for the medical management of chronic anal fissure: a meta-analysis".International Journal of Colorectal Disease.23 (1):1–6.doi:10.1007/s00384-007-0384-x.PMID17846781.S2CID13015745.
