Diltiazem
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Diltiazem
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| Systematic (IUPAC) name | |
| [2-(2-dimethylaminoethyl)-5-(4-methoxyphenyl) -3-oxo-6-thia-2-azabicyclo[5.4.0]undeca-7,9, 11-trien-4-yl]ethanoate |
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| Identifiers | |
| CAS number | |
| ATC code | C08 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C22H26N2O4S |
| Mol. mass | 414.519 g/mol |
| 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 |
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 a class 3 anti-anginal drug, and a class IV antiarrhythmic. It incites very minimal reflex sympathetic changes.
Diltiazem is a potent vasodilator, increasing blood flow and variably decreasing the heart rate via strong depression of A-V node conduction. Its pharmacolgical activity is somewhat similar to verapamil.[1]
Diltiazem is metabolized by and acts as an inhibitor of the CYP3A4 enzyme.
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.
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[edit] Brand names
- Herben
- Cardizem
- Cartia XT
- Tiazac
- Tiazac XC
- Tiamate
- Tildiem in particular in Europe
- Adizem
- Viazem
- Dilatam
- Dilzem
- Angiozem
- Dilatem
- Dilcardia
- Diltelan
- Diltime
- Dyalec
- Filazem
- Tildiem
- Vasmulax
- Zandil
- Zemtrial
[edit] Therapeutic effects
Potent vasodilator of coronary vessels.
Vasodilator of peripheral vessels. This reduces peripheral resistance and afterload.
Negative inotropic effect. Diltiazem causes a modest decrease in 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 node. It results in reduced myocardium oxygen consumption.
Negative dromotropic effect. By slowing conduction through the AV node, diltiazem increases the time needed for each beat. This results in reduced myocardium oxygen consumption.
[edit] Nontherapeutic effects and toxicities
Reflex sympathetic response. Caused by the peripheral dilatation of vessels and the resulting drop in BP; the response works to counteract the inotropic, chronotropic and dromotropic effects of diltiazem. Symptoms include hypotension, bradycardia, dizziness, flushing.[2]
[edit] Indications
Stable (exercise-induced) Angina. 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 dilatation.
Unstable (preinfarction, crescendo) Angina. 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 or flutter.
Hypertension. Because of its vasodilatatory effects, diltiazem is useful for treating hypertension. Calcium channel blockers are well-tolerated, and especially effective in treating low-renin hypertension.[6]
[edit] 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.
[edit] Drug interactions
Beta-blockers
Intravenous diltiazem should never be used concurrently with a beta-blocker as AV node block may result.
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.
[edit] 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.[7] Diltiazem also enhances the analgesic effect of morphine in animal tests, without increasing respiratory depression,[8] and reduces the development of tolerance.[9]
Diltiazem is also being used to aid in the treatment of anal fissures and hemhorroids. However, it is not taken orally. 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 excellent success rates.[10][11]
[edit] References
- ^ O'Connor SE, Grosset A, Janiak P. The pharmacological basis and pathophysiological significance of the heart rate-lowering property of diltiazem. Fundamental and Clinical Pharmacology. 1999;13(2):145-53. PMID 10226758
- ^ Ramoska EA, Spiller HA, Winter M, Borys D. A one-year evaluation of calcium channel blocker overdoses: toxicity and treatment. Annals of Emergency Medicine. 1993 Feb;22(2):196-200. PMID 8427431
- ^ Grossman E, Messerli FH. Calcium antagonists. Progress in Cardiovascular Disease. 2004 Jul-Aug;47(1):34-57. PMID 15517514
- ^ Claas SA, Glasser SP. Long-acting diltiazem HCl for the chronotherapeutic treatment of hypertension and chronic stable angina pectoris. Expert Opinion on Pharmacotherapy. 2005 May;6(5):765-76. PMID 15934903
- ^ Gabrielli A, Gallagher TJ, Caruso LJ, Bennett NT, Layon AJ. Diltiazem to treat sinus tachycardia in critically ill patients: a four-year experience. Critical Care Medicine. 2001 Oct;29(10):1874-9. PMID 11588443
- ^ Basile J. The role of existing and newer calcium channel blockers in the treatment of hypertension. Journal of Clinical Hypertension. 2004 Nov;6(11):621-29. PMID 15538095
- ^ Mills K, Ansah TA, Ali SF, Mukherjee S, Shockley DC. Augmented behavioral response and enhanced synaptosomal calcium transport induced by repeated cocaine administration are decreased by calcium channel blockers. Life Sciences. 2007 Jul 26;81(7):600-8. PMID 17689567
- ^ Kishioka S, Ko MC, Woods JH. Diltiazem enhances the analgesic but not the respiratory depressant effects of morphine in rhesus monkeys. European Journal of Pharmacology. 2000 May 26;397(1):85-92. PMID 10844102
- ^ Verma V, Mediratta PK, Sharma KK. Potentiation of analgesia and reversal of tolerance to morphine by calcium channel blockers. Indian Journal of Experimental Biology. 2001 Jul;39(7):636-42. PMID 12019755
- ^ Nash GF, Kapoor K, Saeb-Parsy K, Kunanadam T, Dawson PM. The long-term results of diltiazem treatment for anal fissure. International Journal of Clinical Practice. 2006 Nov;60(11):1411-3. PMID 16911570
- ^ Sajid MS, Rimple J, Cheek E, Baig MK. The efficacy of diltiazem and glyceryltrinitrate for the medical management of chronic anal fissure: a meta-analysis. International Journal of Colorectal Disease. 2008 Jan;23(1):1-6. PMID 17846781
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