Isradipine

Antihypertensive drug of the calcium channel blocker class
  • C
Routes of
administrationOralATC code
  • C08CA03 (WHO)
Legal statusLegal status
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic dataBioavailability15-24%Protein binding95%Metabolism100% HepaticElimination half-life8 hoursExcretion70% Renal, 30% FecalIdentifiers
  • 3-methyl 5-propan-2-yl 4-(2,1,3-benzoxadiazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
CAS Number
  • 75695-93-1 checkY
PubChem CID
  • 3784
DrugBank
  • DB00270 checkY
ChemSpider
  • 3652 checkY
UNII
  • YO1UK1S598
KEGG
  • D00349 checkY
ChEMBL
  • ChEMBL1648 checkY
CompTox Dashboard (EPA)
  • DTXSID4023179 Edit this at Wikidata
ECHA InfoCard100.158.721 Edit this at WikidataChemical and physical dataFormulaC19H21N3O5Molar mass371.393 g·mol−13D model (JSmol)
  • Interactive image
  • O=C(OC)\C3=C(\N\C(=C(\C(=O)OC(C)C)C3c1cccc2nonc12)C)C
  • InChI=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 checkY
  • Key:HMJIYCCIJYRONP-UHFFFAOYSA-N checkY
  (verify)

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.[1]

Medical uses

Isradipine is given as either a 2.5 mg or 5 mg capsule.[2]

Side effects

Common side effects include: [3]

  • Dizziness
  • Warmth, redness, or tingly feeling under your skin
  • Headache
  • Weakness, tired feeling
  • Nausea, vomiting, diarrhea, upset stomach
  • Skin rash or itching

Serious side effects include: [3]

  • 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 Anzemet (Dolasetron), as both agents can cause a dose-dependent PR interval and QRS complex prolongation.[4]

Itraconazole exhibits a negative inotropic effect on the heart and thus could spur an additive effect when used concomitantly with Isradipine. Onmel/Sporanox 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.[5]

Tizanidine demonstrates anti-hypertensive effects and should be avoided in patients taking Isradipine due to the possibility of synergism between both medications.[6]

The antibiotic Rifampin lowered plasma concentrations of Isradipine to below detectable limits.[2]

Cimetidine increased Isradipine mean peak plasma levels. A downward dose adjustment may be necessary with this particular instance of polypharmacy.[2]

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.[2]

Overdose

Symptoms of an Isradipine overdose include:[2]

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 ) - Form:[7]

Enantiomers of Isradipine

CAS-Nummer: 84260-63-9
CAS-Nummer: 84260-64-0

References

  1. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 465. ISBN 9783527607495.
  2. ^ a b c d e "Isradipine: Brands, Medical Use, Clinical Data".
  3. ^ a b "Isradipine Side Effects".
  4. ^ "Isradipine and Anzemet Drug Interactions".
  5. ^ "Isradipine and Onmel Drug Interactions".
  6. ^ "Isradipine and Zanaflex Drug Interactions".
  7. ^ 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.

Further reading

  • Hattori T, Wang P (2006). "Calcium antagonist isradipine-induced calcium influx through nonselective cation channels in human gingival fibroblasts". Eur J Med Res. 11 (3): 93–6. PMID 16751108.
  • Ganz M, Mokabberi R, Sica D (2005). "Comparison of blood pressure control with amlodipine and controlled-release isradipine: an open-label, drug substitution study". The Journal of Clinical Hypertension. 7 (4 Suppl 1): 27–31. doi:10.1111/j.1524-6175.2005.04450.x. PMC 8109349. PMID 15858400.
  • Johnson B, Roache J, Ait-Daoud N, Wallace C, Wells L, Dawes M, Wang Y (2005). "Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects". Int J Neuropsychopharmacol. 8 (2): 203–13. doi:10.1017/S1461145704005036. PMID 15850499.
  • Fletcher H, Roberts G, Mullings A, Forrester T (1999). "An open trial comparing isradipine with hydralazine and methyl dopa in the treatment of patients with severe pre-eclampsia". J Obstet Gynaecol. 19 (3): 235–8. doi:10.1080/01443619964977. PMID 15512286.
  • Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ (2007). "'Rejuvenation' protects neurons in mouse models of Parkinson's disease". Nature. 447 (3): 1081–1086. doi:10.1038/nature05865. PMID 17558391. S2CID 4429534.

External links

  • MedlinePlus DrugInfo medmaster-a693048
  • Diseases Database (DDB): 30003
  • Drug offers hope for Parkinson's - BBC News, 11 June 2007.
  • [1] - Commentary of Chan et al. publication
  • [2] - ArsTechnica - Why neurons die in Parkinson's patients
  • v
  • t
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Calcium
VDCCsTooltip Voltage-dependent calcium channels
Blockers
Activators
Potassium
VGKCsTooltip Voltage-gated potassium channels
Blockers
Activators
IRKsTooltip Inwardly rectifying potassium channel
Blockers
Activators
  • GIRKTooltip G protein-coupled inwardly rectifying potassium channel-specific: ML-297 (VU0456810)
KCaTooltip Calcium-activated potassium channel
Blockers
  • BKCa-specific: Ethanol (alcohol)
  • GAL-021
Activators
K2PsTooltip Tandem pore domain potassium channel
Blockers
Activators
Sodium
VGSCsTooltip Voltage-gated sodium channels
Blockers
Activators
ENaCTooltip Epithelial sodium channel
Blockers
Activators
  • Solnatide
ASICsTooltip Acid-sensing ion channel
Blockers
Chloride
CaCCsTooltip Calcium-activated chloride channel
Blockers
Activators
CFTRTooltip Cystic fibrosis transmembrane conductance regulator
Blockers
Activators
Unsorted
Blockers
Others
TRPsTooltip Transient receptor potential channels
  • See here instead.
LGICsTooltip Ligand gated ion channels
  • See here instead.
See also: Receptor/signaling modulators • Transient receptor potential channel modulators