AGOPINE SR TABLETS

Indications

• Hypertension
• Angina pectoris (prophylaxis)

Dosage

Children: Not licensed for use in children.

Adults: Initially 5 mg three times a day, which may be adjusted according to response, with a typical maintenance dose of 10-20 mg three times a day. For modified-release formulations, the initial dose is often 20 mg twice daily.

Mechanism of action

Nifedipine blocks voltage-gated L-type calcium channels in vascular smooth muscle and myocardial cells. This action prevents calcium ions from entering the cells during depolarization, reducing peripheral arterial resistance and dilating coronary arteries. This results in lowered blood pressure and increased oxygen delivery to the heart, alleviating angina symptoms. The mechanism by which nifedipine inhibits calcium influx is not completely understood, but it is believed to involve interference with ion-control gating mechanisms of the calcium channels.

Pharmacodynamics

Nifedipine is an inhibitor of L-type voltage-gated calcium channels, which reduces blood pressure and increases oxygen supply to the heart. The immediate-release formulations require dosing three times daily due to their shorter duration of action. The typical daily dose ranges from 10 to 120 mg, with careful monitoring for excessive hypotension and potential angina exacerbation.

Pharmacokinetics

Nifedipine is rapidly absorbed following oral administration, with peak plasma concentrations typically occurring within 30 minutes to 2 hours for immediate-release forms. Its bioavailability is affected by first-pass metabolism, and it is extensively metabolized in the liver. The half-life of nifedipine varies, but it generally ranges from 2 to 5 hours. The drug is primarily excreted as metabolites in the urine, with only a small fraction excreted unchanged.

Contra-indications

• Cardiogenic shock
• Aortic stenosis
• Severe maternal hypotension
• Fatal fetal hypoxia in pregnancy

Adverse effects

• Constipation
• Malaise
• Oedema
• Allergic reactions
• Angioedema
• Hypotension
• Reflex tachycardia

Interactions

• Grapefruit juice (severe increase in exposure)
• Rifampicin (severe decrease in exposure)
• Enzalutamide (moderate decrease in exposure)
• Dronedarone (moderate increase in exposure)
• Antifungal azoles (moderate increase in exposure)
• Miconazole (moderate increase in exposure)
• Cobicistat (moderate increase in exposure)
• Crizotinib (moderate increase in exposure)
• Dabrafenib (moderate decrease in exposure)
• Idelalisib (moderate increase in exposure)

Precautions

• Monitor blood pressure and heart rate regularly
• Use with caution in patients with significant left ventricular dysfunction
• Avoid excessive decrease in blood pressure
• Consider initial low doses in patients with renal impairment

Pregnancy

May inhibit labour; not to be used in multiple pregnancies unless no other acceptable alternative.

Breast-feeding

Manufacturer advises to avoid; present in breast milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Immediate-release capsules
• Modified-release formulations
• Oral suspension
• Solution for infusion

Dosage

Children: Refer to specific drug guidelines for dosing information, as it varies by medication.

Adults: Refer to specific drug guidelines for dosing information, as it varies by medication.

Mechanism of action

The mechanism of action would depend on the specific drug referred to as 'released'. Generally, pharmacological agents may act through various pathways such as receptor binding, enzyme inhibition, or modulation of physiological processes. For example, some medications may function as agonists or antagonists at specific receptors, influencing cellular signaling pathways and physiological responses.

Pharmacodynamics

Pharmacodynamics describes the effects of the drug on the body, including the relationship between drug concentration and effect. This may vary significantly based on the specific medication. Factors such as drug-receptor interactions, therapeutic index, and side effects are crucial to understanding its pharmacodynamics. Typically, the efficacy and potency of the drug are assessed through clinical outcomes and dose-response relationships.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion of the drug. The specific pharmacokinetic profile would depend on the drug in question. Generally, pharmacokinetic parameters such as bioavailability, half-life, volume of distribution, and clearance rates are essential for determining dosing regimens and predicting therapeutic outcomes.

Pregnancy

Safety during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use with caution. It is not known whether released is excreted in human milk.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Indications

• Chronic pain management
• Hypertension
• Diabetes management
• Attention-deficit hyperactivity disorder (ADHD)
• Chronic obstructive pulmonary disease (COPD)

Dosage

Children: Refer to specific drug formulations and guidelines for paediatric dosing, as it varies between different medications.

Adults: Refer to specific drug formulations and guidelines for adult dosing, as it varies between different medications.

Mechanism of action

Sustained release formulations utilize various physical and chemical mechanisms to control the rate of drug release. These may include the use of matrix systems, reservoir systems, or osmotic devices, which modulate the release of the active ingredient based on diffusion, erosion, or osmotic pressure. This controlled release can help to maintain therapeutic drug concentrations and improve efficacy.

Pharmacodynamics

The pharmacodynamic properties of sustained release drugs depend on the specific drug involved, but generally, they aim to provide a consistent therapeutic effect over time. The goal is to maintain plasma drug concentrations within the therapeutic window, avoiding the peaks and troughs often associated with immediate release formulations. This can result in improved clinical outcomes, reduced side effects, and enhanced patient quality of life.

Pharmacokinetics

Sustained release formulations typically exhibit altered pharmacokinetic profiles compared to immediate release forms. The onset of action may be delayed, but the duration of effect is prolonged. The absorption rate is modified to ensure a steady release of the drug, which can lead to reduced peak plasma concentrations and less frequent dosing. Key pharmacokinetic parameters such as bioavailability, half-life, and clearance may be influenced by the formulation design.

Pregnancy

Consult healthcare provider for advice on use during pregnancy.

Breast-feeding

Consult healthcare provider for advice on use while breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight.

Mechanism of action

Nifedipine blocks voltage gated L-type calcium channels in vascular smooth muscle and myocardial cells. This blockage prevents the entry of calcium ions into cells during depolarization, reducing peripheral arterial vascular resistance and dilating coronary arteries. These actions reduce blood pressure and increase the supply of oxygen to the heart, alleviating angina. The principal physiologic action of nifedipine is to inhibit the transmembrane influx of extracellular calcium ions across the membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations. Calcium plays important roles in the excitation-contraction coupling processes of the heart and vascular smooth muscle cells and in the electrical discharge of the specialized conduction cells of the heart. The membranes of these cells contain numerous channels that carry a slow inward current and that are selective for calcium. Activation of these slow calcium channels contributes to the plateau phase (phase 2) of the action potential of cardiac and vascular smooth muscle cells. The exact mechanism whereby nifedipine inhibits calcium ion influx across the slow calcium channels is not known, but the drug is thought to inhibit ion-control gating mechanisms of the channel, deform the slow channel, and/or interfere with release of calcium from the sarcoplasmic reticulum. By inhibiting calcium influx, nifedipine inhibits the contractile processes of cardiac and vascular smooth muscle, thereby dilating the main coronary and systemic arteries. Nifedipine is a peripheral arterial vasodilator which acts directly on vascular smooth muscle. The binding of nifedipine to voltage-dependent and possibly receptor-operated channels in vascular smooth muscle results in an inhibition of calcium influx through these channels. Stores of intracellular calcium in vascular smooth muscle are limited and thus dependent upon the influx of extracellular calcium for contraction to occur. The reduction in calcium influx by nifedipine causes arterial vasodilation and decreased peripheral vascular resistance which results in reduced arterial blood pressure.

Pharmacodynamics

Nifedipine is an inhibitor of L-type voltage gated calcium channels that reduces blood pressure and increases oxygen supply to the heart. Immediate release nifedipine's duration of action requires dosing 3 times daily. Nifedipine dosing is generally 10-120mg daily. Patients should be counselled regarding the risk of excessive hypotension, angina, and myocardial infarction.