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Diltiazem, sold under the brand name Cardizem among others, is a nondihydropyridine calcium channel blocker medication used to treat high blood pressure, angina, and certain heart arrhythmias.<ref name=AHFS2018>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It may also be used in hyperthyroidism if beta blockers cannot be used.<ref name=AHFS2018/> It is taken by mouth or given by injection into a vein.<ref name=AHFS2018/> When given by injection, effects typically begin within a few minutes and last a few hours.<ref name=AHFS2018/>

Common side effects include swelling, dizziness, headaches, and low blood pressure.<ref name=AHFS2018/> Other severe side effects include an overly slow heart beat, heart failure, liver problems, and allergic reactions.<ref name=AHFS2018/> Use is not recommended during pregnancy.<ref name=AHFS2018/> It is unclear if use when breastfeeding is safe.<ref name="Drugs.com pregnancy" />

Diltiazem works by relaxing the smooth muscle in the walls of arteries, resulting in them opening and allowing blood to flow more easily.<ref name=AHFS2018/> Additionally, it acts on the heart to prolong the period until it can beat again.<ref>Template:Cite book</ref> It does this by blocking the entry of calcium into the cells of the heart and blood vessels.<ref>Template:Cite book</ref> It is a class IV antiarrhythmic.<ref>Template:Cite book</ref>

Diltiazem was approved for medical use in the United States in 1982.<ref name=AHFS2018/> It is available as a generic medication.<ref name=AHFS2018/> In 2022, it was the 100th most commonly prescribed medication in the United States, with more than 6Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> An extended release formulation is also available.<ref name="Cardizem CD FDA label" /><ref name="Cardizem LA FDA label" /><ref name=AHFS2018/>

Medical usesEdit

Diltiazem is indicated for:

For supraventricular tachycardias (PSVT), diltiazem appears to be as effective as verapamil in treating re-entrant supraventricular tachycardia.<ref>Template:Cite journal</ref>

Atrial fibrillation<ref name="pmid11171729">Template:Cite journal</ref> or atrial flutter is another indication. The initial bolus should be 0.25 mg/kg, intravenous (IV).

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.<ref>Template:Cite journal</ref>

It is also used as topical application for anal fissures because it promotes healing due to its vasodilatory property.<ref>Template:Cite journal</ref>

Contraindications and precautionsEdit

Diltiazem is relatively contraindicated in the presence of sick sinus syndrome, atrioventricular node conduction disturbances, bradycardia, impaired left ventricle function, peripheral artery occlusive disease, and chronic obstructive pulmonary disease.

Side effectsEdit

A reflex sympathetic response, caused by the peripheral dilation of vessels and the resulting drop in blood pressure, works to counteract the negative inotropic, chronotropic and dromotropic effects of diltiazem. Undesirable effects include hypotension, bradycardia, dizziness, flushing, fatigue, headaches and edema.<ref>Template:Cite journal</ref> Rare side effects are congestive heart failure, myocardial infarction, and hepatotoxicity.<ref name=Diltiazem2019>Template:Cite book</ref>


Drug interactionsEdit

Because of its inhibition of hepatic cytochromes CYP3A4, CYP2C9 and CYP2D6, there are a number of drug interactions.<ref name="dilt-inhibit1">Template:Cite journal</ref> Some of the more important interactions are listed below.

Beta-blockersEdit

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.<ref>Template:Cite journal</ref>

QuinidineEdit

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.<ref>Template:Cite journal</ref>

FentanylEdit

Concurrent use of fentanyl with diltiazem, or any other CYP3A4 inhibitors, as these medications decrease the breakdown of fentanyl and thus increase its effects.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Mechanism of actionEdit

File:000197lg cardizem 180mg.jpg
180 mg Cardizem capsule

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.<ref name=synthesis>Template:Cite book</ref> 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.<ref>Template:Cite journal</ref> 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,<ref name="Gordon Kittleson 2008 pp. 380–457">Template:Cite book</ref> which reduces peripheral resistance and afterload, though not as potent as the dihydropyridine (DHP) calcium channel blockers. This results in minimal reflexive sympathetic changes.Template:Citation needed

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.

ResearchEdit

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.<ref name="Calcium antagonists"/><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>Template:Update inline

Recent researchTemplate:When has shown diltiazem may reduce cocaine cravings in drug-addicted rats.<ref>Common Heart Drug May Reduce Cocaine Cravings Template:Webarchive. Sciencedaily.com (28 February 2008). Retrieved on 21 October 2012.</ref> This is believed to be due to the effects of calcium blockers on dopaminergic and glutamatergic signaling in the brain.<ref>Template:Cite journal</ref> Diltiazem also enhances the analgesic effect of morphine in animal tests, without increasing respiratory depression,<ref>Template:Cite journal</ref> and reduces the development of tolerance.<ref>Template:Cite journal</ref>

Diltiazem is also being used in the treatment of anal fissures. It can be taken orally or applied topically with increased effectiveness.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

ReferencesEdit

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