Diltiazem

Brand names: Cardizem®Cardizem® CDCardizem® LACardizem® Lyo-JectCardizem® SRCartia® XTDilacor XR®Diltia® XTTaztia XT™Tiamate®Tiazac®

Chemical formula:

Drug Forms:
• Diltiazem Hydrochloride Oral capsule, extended-release (below)
• Diltiazem Hydrochloride Solution for injection
• Diltiazem Hydrochloride Oral tablet
• Diltiazem tablets
• Diltiazem Hydrochloride Oral tablet, extended-release
• Diltiazem Maleate Oral tablet, extended-release

Español:
• Diltiazem Clorhidrato, Cápsula oral de liberación prolongada
• Clorhidrato de diltiazem, Solución para inyección
• Diltiazem Clorhidrato, Tableta oral
• Tabletas de diltiazem
• Diltiazem Clorhidrato, Tableta oral de liberación prolongada
• Maleato de Diltiazem, Tableta oral de liberación prolongada

Diltiazem Hydrochloride Oral capsule, extended-release

What is this medicine?

DILTIAZEM (dil TYE a zem) is a calcium-channel blocker. It affects the amount of calcium found in your heart and muscle cells. This relaxes your blood vessels, which can reduce the amount of work the heart has to do. This medicine is used to treat high blood pressure and chest pain caused by angina.
 
This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•heart problems, low blood pressure, irregular heartbeat
•liver disease
•previous heart attack
•an unusual or allergic reaction to diltiazem, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. Swallow whole, do not crush or chew. Ask your doctor or pharmacist if your should take this medicine with food. Take your doses at regular intervals. Do not take your medicine more often then directed. Do not stop taking except on the advice of your doctor or health care professional. Ask your doctor or health care professional how to gradually reduce the dose.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

Do not take this medicine with any of the following medications:
•cisapride
•hawthorn
•pimozide
•ranolazine
•red yeast rice

This medicine may also interact with the following medications:
•buspirone
•carbamazepine
•cimetidine
•cyclosporine
•digoxin
•local anesthetics or general anesthetics
•lovastatin
•medicines for anxiety or difficulty sleeping like midazolam and triazolam
•medicines for high blood pressure or heart problems
•quinidine
•rifampin, rifabutin, or rifapentine

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Check your blood pressure and pulse rate regularly. Ask your doctor or health care professional what your blood pressure and pulse rate should be and when you should contact him or her.

You may feel dizzy or lightheaded. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. To reduce the risk of dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient. Alcohol can make you more dizzy or increase flushing and rapid heartbeats. Avoid alcoholic drinks.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•confusion, mental depression
•feeling faint or lightheaded, falls
•redness, blistering, peeling or loosening of the skin, including inside the mouth
•slow, irregular heartbeat
•swelling of the feet and ankles
•unusual bleeding or bruising, pinpoint red spots on the skin

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•constipation or diarrhea
•difficulty sleeping
•facial flushing
•headache
•nausea, vomiting
•sexual dysfunction
•weak or tired

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Protect from humidity. Throw away any unused medicine after the expiration date.

Last updated: 5/19/2003 1:04:00 PM

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

A calcium-channel blocking agent used to produce peripheral and coronary vasodilation in the management of heart disease.

The noun has one meaning:

Meaning #1: a calcium blocker (trade name Cardizem) used in treating hypertension or angina or heart failure
  Synonym: Cardizem

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
Y(what is this?)  (verify)

Diltiazem is a non-DHP 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.

Contents 1 Brand names 2 Mechanism 3 Nontherapeutic effects and toxicities 4 Indications 5 Contraindications and precautions 6 Drug interactions 7 Potential future indications 8 References

Brand names

• Progor
• Herben
• Altiazem
• 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
• Angizem CD
• Angizem
• Dilcontin SR in India (Sustained Release)
• Dilt-CD
• Dilt-XR

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

1. ^ 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
2. ^ 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
3. ^ Grossman E, Messerli FH. Calcium antagonists. Progress in Cardiovascular Disease. 2004 Jul-Aug;47(1):34-57. PMID 15517514
4. ^ 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
5. ^ 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
6. ^ Wattanasuwan N, Khan IA, Mehta NJ, et al. (February 2001). "Acute ventricular rate control in atrial fibrillation: IV combination of diltiazem and digoxin vs. IV diltiazem alone". Chest 119 (2): 502–6. PMID 11171729. http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=11171729. 
7. ^ 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
8. ^ http://www.ncbi.nlm.nih.gov/pubmed/10774785
9. ^ 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
10. ^ 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
11. ^ 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
12. ^ 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
13. ^ 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

v • d • e Channel blocker: calcium channel blockers (C08) Selective Dihydropyridines ("-dipine") Amlodipine# • Aranidipine • Azelnidipine • Barnidipine • Benidipine • Cilnidipine • Clevidipine • Efonidipine • Felodipine • Isradipine • Lacidipine • Manidipine • Lercanidipine • Nicardipine • Nifedipine# • Nilvadipine • Nimodipine • Nisoldipine • Nitrendipine • Pranidipine Phenylalkylamines ("-pamil") Gallopamil • Verapamil 1-4 Benzothiazepines ("-tiazem") Diltiazem • Clentiazem Non-selective Fendiline • Bepridil • Lidoflazine • Perhexiline Other/ungrouped Amrinone  • Anandamide  • Anipamil  • Azimilide  • Bencyclane  • Bepridil  • Berbamine  • Bevantolol  • Canadine  • Carboxyamido-Triazole  • Caroverine  • Cinnarizine  • Conotoxins  • Darodipine  • Dauricine  • Devapamil  • Dimeditiapramine  • Dotarizine  • Emopamil  • Enpiperate  • Eperisone  • Falipamil  • Fantofarone  • Fasudil  • Fenamic acid  • Fendiline  • Flunarizine  • Fosfedil  • Gabapentin  • Lamotrigine  • Lidoflazine  • Magnesium sulfate  • Manoalide  • Mepirodipine  • Mibefradil  • Monatepil  • Naftopidil  • Niguldipine  • Niludipin  • Norverapamil  • Ochratoxin A  • Octylonium  • Osthol  • Oxodipine  • Perhexiline  • Pinaverium  • Piperidine  • Pregabalin  • Prenylamine  • Risedronic acid  • Ryodipine  • Sesamodil  • Stepholidine  • Terodiline  • Tetrahydropalmatine  • Tetrandrine  • Tolfenamic acid  • Tranilast #WHO-EM. ‡Withdrawn from market. CLINICAL TRIALS: †Phase III. §Never to phase III

v • d • e Antiarrhythmic agents (C01B) Channel blockers class I (Na+ channel blockers) class Ia (Phase 0→ and Phase 3→) Procainamide # • Quinidine # • Ajmaline • Disopyramide • Prajmaline • Sparteine class Ib (Phase 3←) IV (Lidocaine #) • enteral (Mexiletine, Tocainide, Aprindine) class Ic (Phase 0→) Encainide • Flecainide • Lorcainide • Moricizine • Propafenone class III (Phase 3→, K+ channel blockers) Amiodarone • Bretylium • Bunaftine • Dofetilide • Ibutilide • Nifekalant • Sotalol • Tedisamil • E-4031 class IV (Phase 4→, Ca2+ channel blockers) Verapamil # • Diltiazem Receptor agonists and antagonists class II (Phase 4→, β blockers) Propranolol • Nadolol • Pindolol • cardioselective (Atenolol, Metoprolol, Acebutolol, Esmolol) A1 agonist Adenosine M2 muscarinic antagonist: Atropine • Quinidine • Disopyramide muscarinic agonist: Digoxin α receptors Quinidine • Verapamil • Amiodarone • Bretylium Ion transporters Na+ / K+-ATPase Digoxin # = WHO-EM

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