DYNACIRC-SRO 5MG CAPSULE

Indications

• Hypertension
• Essential hypertension

Dosage

Children: Refer to BNF for Children for specific dosing information.

Adults: The usual starting dose is 2.5 mg taken orally twice daily, which may be increased based on patient response and tolerability.

Mechanism of action

Isradipine binds to inactive L-type calcium channels, stabilizing their inactive conformation. This binding inhibits the influx of calcium ions into vascular smooth muscle cells, which decreases contractility and promotes vasodilation. The drug exhibits arterial selectivity due to alternative splicing of the alpha-1 subunit of the calcium channel, allowing for reduced effects on cardiac myocytes.

Pharmacodynamics

By inhibiting calcium influx through L-type calcium channels, isradipine decreases arterial smooth muscle contractility, leading to vasodilation. This mechanism reduces blood pressure by preventing the calcium-induced activation of myosin light chain kinase (MLCK), a key enzyme in muscle contraction. The vasodilatory effects result in decreased peripheral vascular resistance and overall blood pressure reduction without significantly affecting heart rate.

Pharmacokinetics

Isradipine is well absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It undergoes extensive hepatic metabolism, primarily via cytochrome P450 enzymes, and has a variable half-life, generally ranging from 6 to 12 hours. Excretion occurs mainly through urine, with only a small amount eliminated unchanged.

Contra-indications

• Severe hypotension
• Aortic stenosis
• Cardiogenic shock
• Unstable angina
• Pregnancy

Adverse effects

• Headache
• Dizziness
• Flushing
• Peripheral edema
• Gingival hyperplasia
• Palpitations
• Nausea

Interactions

• Caution with other antihypertensive agents
• May enhance the effects of analgesics
• Caution with CYP3A4 inhibitors and inducers

Precautions

• Monitor blood pressure regularly
• Use with caution in patients with hepatic impairment
• Avoid abrupt withdrawal

Pregnancy

Isradipine is not recommended during pregnancy due to potential risks to the fetus.

Breast-feeding

It is unknown whether isradipine is excreted in human breast milk. Exercise caution.

Storage

Store at room temperature, away from moisture and light.

Formulations

• Isradipine 2.5 mg capsules
• Isradipine 5 mg capsules

Mechanism of action

Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in <i>Homo sapiens</i>: L-, N-, P/Q-, R- and T-type. CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction. Similar to other DHP CCBs, isradipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives isradipine additional arterial selectivity. At therapeutic sub-toxic concentrations, isradipine has little effect on cardiac myocytes and conduction cells.

Pharmacodynamics

Isradipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of isradipine result in an overall decrease in blood pressure.