Isradipine
{{Short description|Antihypertensive drug of the calcium channel blocker class}}
{{Drugbox
| verifiedrevid = 477495807
| IUPAC_name = 3-Methyl 5-propan-2-yl 4-(2,1,3-benzoxadiazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
| image = Isradipine.svg
| tradename = DynaCirc
| Drugs.com = {{drugs.com|monograph|isradipine}}
| MedlinePlus = a693048
| pregnancy_AU =
| pregnancy_US =
| pregnancy_category = C
| legal_AU =
| legal_UK = POM
| legal_US = Rx-only
| legal_status =
| routes_of_administration = Oral
| bioavailability = 15-24%
| protein_bound = 95%
| metabolism = 100% Hepatic
| elimination_half-life = 8 hours
| excretion = 70% Renal, 30% Fecal
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 75695-93-1
| ATC_prefix = C08
| ATC_suffix = CA03
| ATC_supplemental =
| PubChem = 3784
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00270
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3652
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = YO1UK1S598
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00349
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1648
| C=19 | H=21 | N=3 | O=5
| smiles = O=C(OC)\C3=C(\N\C(=C(\C(=O)OC(C)C)C3c1cccc2nonc12)C)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C19H21N3O5/c1-9(2)26-19(24)15-11(4)20-10(3)14(18(23)25-5)16(15)12-7-6-8-13-17(12)22-27-21-13/h6-9,16,20H,1-5H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = HMJIYCCIJYRONP-UHFFFAOYSA-N
}}
Isradipine (tradenames DynaCirc, Prescal) is a calcium channel blocker of the dihydropyridine class. It is usually prescribed for the treatment of high blood pressure in order to reduce the risk of stroke and heart attack.
It was patented in 1978 and approved for medical use in 1989.{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=465 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA465 |language=en}}
Medical uses
Side effects
Common side effects include:{{cite web|url=https://www.drugs.com/sfx/isradipine-side-effects.html|title=Isradipine Side Effects}}
- Dizziness
- Warmth, redness, or tingly feeling under your skin
- Headache
- Weakness, tired feeling
- Nausea, vomiting, diarrhea, upset stomach
- Skin rash or itching
- Lightheadedness or fainting
- Shortness of breath, especially from minimal physical activity
- Swelling in the hands and feet
- Rapid and/or heavy heartbeat
- Chest pain
Drug interactions
It is advised that those using isradipine not take dolasetron (Anzemet), as both agents can cause a dose-dependent PR interval and QRS complex prolongation.{{cite web|url=https://www.drugs.com/drug-interactions/isradipine-with-onmel-1405-0-1406-15779.html|title=Isradipine and Anzemet Drug Interactions}}
Itraconazole (Onmel/Sporanox) exhibits a negative inotropic effect on the heart and thus could spur an additive effect when used concomitantly with isradipine. Itraconazole also inhibits an important cytochrome liver enzyme (CYP 450 3A4) which is needed to metabolize isradipine and other calcium channel blockers. This will increase plasma levels of isradipine and could cause an unintentional overdose of the medication. Caution is advised when administering both agents together.{{cite web|url=https://www.drugs.com/drug-interactions/isradipine-with-onmel-1405-0-1406-15779.html|title=Isradipine and Onmel Drug Interactions}}
Tizanidine demonstrates anti-hypertensive effects and should be avoided in patients taking isradipine due to the possibility of synergism between both medications.{{cite web|url=https://www.drugs.com/drug-interactions/isradipine-with-zanaflex-1405-0-2205-1453.html|title=Isradipine and Zanaflex Drug Interactions}}
The antibiotic rifampin lowered plasma concentrations of isradipine to below detectable limits.
Cimetidine increased isradipine mean peak plasma levels. A downward dose adjustment may be necessary with this particular instance of polypharmacy.
Severe hypotension was reported with fentanyl anesthesia when it was combined with other calcium channel blockers. Even though isradipine, another calcium channel blocker, has not been used in conjunction with fentanyl anesthesia in any studies, caution is advised.
Overdose
Symptoms of an isradipine overdose include:{{cite web|url=http://www.druglib.com/activeingredient/isradipine/|title=Isradipine: Brands, Medical Use, Clinical Data|access-date=2013-01-21|archive-date=2019-09-13|archive-url=https://web.archive.org/web/20190913232514/http://www.druglib.com/activeingredient/isradipine|url-status=dead}}
- Lethargy
- Sinus tachycardia
- Transient hypotension
Stereochemistry
Isradipine contains a stereocenter and consists of two enantiomers, more precisely atropisomers. This is a racemate, i.e. a 1: 1 mixture of (R)- and the (S)-forms:Rote Liste Service GmbH (Hrsg.): Rote Liste 2017 – Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). Rote Liste Service GmbH, Frankfurt/Main, 2017, Aufl. 57, {{ISBN|978-3-946057-10-9}}, S. 193.
| class="wikitable" style="text-align:center" |
| class="hintergrundfarbe6"
! colspan="2"| Enantiomers of Isradipine |
| 200 px CAS-Nummer: 84260-63-9 | 200 px |
References
{{reflist}}
Further reading
{{ref begin}}
- {{cite journal |vauthors=Hattori T, Wang P | title = Calcium antagonist isradipine-induced calcium influx through nonselective cation channels in human gingival fibroblasts. | journal = Eur J Med Res | volume = 11 | issue = 3 | pages = 93–6 | year = 2006 | pmid = 16751108}}
- {{cite journal |vauthors=Ganz M, Mokabberi R, Sica D | title = Comparison of blood pressure control with amlodipine and controlled-release isradipine: an open-label, drug substitution study. | journal = The Journal of Clinical Hypertension | volume = 7 | issue = 4 Suppl 1 | pages = 27–31 | year = 2005 | pmid = 15858400 | doi = 10.1111/j.1524-6175.2005.04450.x| pmc = 8109349 | doi-access = free }}
- {{cite journal |vauthors=Johnson B, Roache J, Ait-Daoud N, Wallace C, Wells L, Dawes M, Wang Y | title = Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects. | journal = Int J Neuropsychopharmacol | volume = 8 | issue = 2 | pages = 203–13 | year = 2005 | pmid = 15850499 | doi = 10.1017/S1461145704005036| doi-access = free }}
- {{cite journal |vauthors=Fletcher H, Roberts G, Mullings A, Forrester T | title = An open trial comparing isradipine with hydralazine and methyl dopa in the treatment of patients with severe pre-eclampsia. | journal = J Obstet Gynaecol | volume = 19 | issue = 3 | pages = 235–8 | year = 1999 | pmid = 15512286 | doi = 10.1080/01443619964977}}
- {{cite journal |vauthors=Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ|authorlink8=D. James Surmeier | title = 'Rejuvenation' protects neurons in mouse models of Parkinson's disease. | journal = Nature | volume = 447 | issue = 3 | pages = 1081–1086 | year = 2007 | pmid = 17558391 | doi = 10.1038/nature05865|bibcode=2007Natur.447.1081C |s2cid=4429534 }}
{{refend}}
External links
- {{MedlinePlusDrugInfo|medmaster|a693048}}
- {{DiseasesDB|30003}}
- [http://news.bbc.co.uk/1/hi/health/6740109.stm Drug offers hope for Parkinson's] - BBC News, 11 June 2007.
- [http://www.nature.com/nature/journal/v447/n7148/full/4471059a.html] - Commentary of Chan et al. publication
- [https://arstechnica.com/science/news/2010/11/why-neurons-die-in-parkinsons-patients.ars] - ArsTechnica - Why neurons die in Parkinson's patients
{{Calcium channel blockers}}