Diltiazem

Source: Wikipedia, the free encyclopedia.

Diltiazem
Clinical data
Pronunciation/dɪlˈtaɪəzɛm/
Trade namesCardizem, Dilacor XR, Cartia XT, others
AHFS/Drugs.comMonograph
MedlinePlusa684027
License data
Pregnancy
category
intravenous
Drug classNondihydropyridine calcium channel blocker
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability40%
MetabolismLiver
Elimination half-life3–4.5 hours
ExcretionKidney
Bile duct
Identifiers
  • cis-(+)-[2-(2-Dimethylaminoethyl)-5-(4-methoxyphenyl)-3-oxo-6-thia-2-azabicyclo[5.4.0]undeca-7,9,11-trien-4-yl]ethanoate
JSmol)
  • O=C2N(c3c(S[C@@H](c1ccc(OC)cc1)[C@H]2OC(=O)C)cccc3)CCN(C)C
  • InChI=1S/C22H26N2O4S/c1-15(25)28-20-21(16-9-11-17(27-4)12-10-16)29-19-8-6-5-7-18(19)24(22(20)26)14-13-23(2)3/h5-12,20-21H,13-14H2,1-4H3/t20-,21+/m1/s1 checkY
  • Key:HSUGRBWQSSZJOP-RTWAWAEBSA-N checkY
  (verify)

Diltiazem, sold under the brand name Cardizem among others, is a

injection into a vein.[8] When given by injection, effects typically begin within a few minutes and last a few hours.[8]

Common side effects include swelling, dizziness, headaches, and

low blood pressure.[8] Other severe side effects include an overly slow heart beat, heart failure, liver problems, and allergic reactions.[8] Use is not recommended during pregnancy.[8] It is unclear if use when breastfeeding is safe.[1]

Diltiazem works by relaxing the

class IV antiarrhythmic.[11]

Diltiazem was approved for medical use in the United States in 1982.

generic medication.[8] In 2021, it was the 84th most commonly prescribed medication in the United States, with more than 8 million prescriptions.[12][13] An extended release formulation is also available.[8][14]

Medical uses

Diltiazem is indicated for:

For

PSVT), diltiazem appears to be as effective as verapamil in treating re-entrant supraventricular tachycardia.[17]

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.[19]

It is also used as topical application for

anal fissures because it promotes healing due to its vasodilatory property.[20]

Contraindications and precautions

Diltiazem is relatively contraindicated in the presence of

peripheral artery occlusive disease, and chronic obstructive pulmonary disease
.

Side effects

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.[21] Rare side effects are congestive heart failure, myocardial infarction, and hepatotoxicity.[22]


Drug interactions

Because of its inhibition of

cytochromes CYP3A4, CYP2C9 and CYP2D6, there are a number of drug interactions.[23]
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

AV node block.[24]

Quinidine

pharmacodynamic effects at the SA and AV nodes.[25]

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.[26]

Mechanism of action

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.[27] Diltiazem is a potent

1,4-thiazepine ring, making it a benzothiazepine
-type calcium channel blocker.

It is a potent and mild vasodilator of

dihydropyridine (DHP) calcium channel blockers. This results in minimal reflexive sympathetic changes.[citation needed
]

Diltiazem has negative

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.[15][30][31][32][33][34][35][needs update
]

Recent research[

respiratory depression,[38] and reduces the development of tolerance.[39]

Diltiazem is also being used in the treatment of

applied topically with increased effectiveness.[40] When applied topically, it is made into a cream form using either petroletum or Phlojel. Phlojel absorbs the diltiazem into the problem area better than the petroletum base. It has good short-term success rates.[41][42]

References

  1. ^ a b "Diltiazem Use During Pregnancy". Drugs.com. 4 May 2020. Retrieved 5 May 2020.
  2. ^ "Dilcardia SR 120 mg Prolonged-release hard capsules – Summary of Product Characteristics (SmPC)". emc. 22 March 2018. Archived from the original on 28 August 2021. Retrieved 13 April 2020.
  3. ^ "Angitil SR/XL Capsules – Summary of Product Characteristics (SmPC)". (emc). 7 May 2019. Retrieved 13 April 2020.
  4. ^ "Cardizem- diltiazem hydrochloride tablet, coated". DailyMed. 2 June 2020. Retrieved 23 October 2022.
  5. ^ "Cardizem CD- diltiazem hydrochloride capsule, coated, extended release". DailyMed. 30 April 2020. Retrieved 23 October 2022.
  6. ^ "Cardizem LA- diltiazem hydrochloride tablet, extended release". DailyMed. 2 May 2019. Retrieved 23 October 2022.
  7. ^ "Active substance(s): diltiazem" (PDF). European Medicines Agency. 11 January 2018.
  8. ^ a b c d e f g h i j k "Diltiazem Hydrochloride Monograph for Professionals". Drugs.com. AHFS. Retrieved 28 December 2018.
  9. ISBN 978-1-935395-62-1
    . Retrieved 28 December 2018.
  10. ISBN 978-0-7637-7900-9
    .
  11. ISBN 978-0-471-73661-5
    . Retrieved 28 December 2018.
  12. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  13. ^ "Diltiazem - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  14. ^ "Diltiazem hydrochloride – diltiazem hydrochloride extended-release tablets tablet, extended release". DailyMed. 1 April 2019. Retrieved 13 April 2020.
  15. ^
    PMID 15517514
    .
  16. S2CID 39272285
    .
  17. S2CID 25104288
    .
  18. PMID 11171729
    .
  19. S2CID 23440538
    .
  20. S2CID 32959944
    .
  21. PMID 8427431
    .
  22. PMID 30422532
    .
  23. S2CID 41343222
    .
  24. PMID 10774785
    .
  25. S2CID 21986119
    .
  26. ^ "Drug interactions: Interactions between fentanyl and drugs that inhibit CYP3A4". Archived from the original on 3 December 2017. Retrieved 26 June 2019.
  27. ISBN 978-0-471-79930-6
    .
  28. S2CID 20440286
    .
  29. ISBN 978-0-7020-2858-8
    .
  30. PMID 1353873
    .
  31. PMID 1990741
    .
  32. S2CID 13621196
    .
  33. PMID 2147612
    .
  34. PMID 6144044
    .
  35. S2CID 40215836
    .
  36. ^ Common Heart Drug May Reduce Cocaine Cravings. Sciencedaily.com (28 February 2008). Retrieved on 21 October 2012.
  37. PMID 17689567
    .
  38. PMID 10844102
    .
  39. PMID 12019755
    .
  40. S2CID 40406260
    .
  41. S2CID 23510129
    .
  42. S2CID 13015745
    .