ISORDIL 30MG TABLET

Indications

• Angina pectoris
• Heart failure
• Acute coronary syndrome
• Hypertensive emergencies

Dosage

Children: Refer to the BNF for Children for specific dosage in paediatric patients.

Adults: Refer to the BNF for specific dosage guidelines.

Mechanism of action

Isosorbide dinitrate is converted in the body to nitric oxide, which activates guanylate cyclase, leading to increased levels of cyclic GMP. This results in relaxation of smooth muscle in the vascular wall, causing vasodilation. The primary effects include reduced preload and afterload on the heart, leading to decreased myocardial oxygen demand.

Pharmacodynamics

The pharmacodynamic effects of isosorbide dinitrate include vasodilation, which reduces cardiac workload and improves oxygen supply to the heart muscle. The onset of action is typically within 20 to 30 minutes when administered orally, with peak effects occurring around 1 to 2 hours. The duration of action can last several hours, depending on the formulation.

Pharmacokinetics

Isosorbide dinitrate is rapidly absorbed from the gastrointestinal tract, with bioavailability ranging from 20% to 30% due to first-pass metabolism. Peak plasma concentrations are reached approximately 1 hour after oral administration. The drug is metabolized in the liver to active and inactive metabolites, with a half-life of 1 to 4 hours. It is primarily excreted through the kidneys as metabolites.

Contra-indications

• Hypersensitivity to dinitrates or any of their components
• Severe anemia
• Closed-angle glaucoma
• Cardiogenic shock
• Severe hypotension
• Concurrent use with phosphodiesterase type 5 inhibitors (e.g., sildenafil)

Adverse effects

• Headache
• Dizziness
• Flushing
• Hypotension
• Tachycardia
• Nausea
• Palpitations

Interactions

• May enhance the hypotensive effects of antihypertensive agents
• Concurrent use with other nitrates can lead to additive effects
• Increased risk of hypotension when used with alcohol
• May interact with drugs that affect hepatic metabolism

Precautions

• Use with caution in patients with hepatic or renal impairment
• Monitor blood pressure regularly
• Taper doses gradually to prevent withdrawal symptoms
• Consider potential for tolerance with long-term use

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Dinitrate is excreted in breast milk. Caution should be exercised when administered to a nursing mother.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Sublingual tablets
• Oral tablets
• Topical ointments
• Transdermal patches

Indications

• Angina pectoris
• Chronic heart failure
• Hypertension
• Myocardial ischemia

Dosage

Children: Refer to the BNF for Children for appropriate dosing in pediatric patients.

Adults: Refer to specific clinical guidelines or pharmacy references for appropriate dosing based on the clinical condition being treated.

Mechanism of action

Isosorbide is converted to nitric oxide (NO) in the body, which relaxes smooth muscle and dilates blood vessels. This vasodilation decreases preload and afterload on the heart, thus reducing cardiac workload and oxygen consumption. The drug primarily affects venous capacitance vessels, leading to a decrease in venous return (preload) to the heart.

Pharmacodynamics

The pharmacodynamic effects of isosorbide include the relaxation of vascular smooth muscle, leading to vasodilation and a reduction in myocardial oxygen demand. Isosorbide has a rapid onset of action, typically within 30 minutes, and its effects can last for several hours, depending on the formulation used. Tolerance may develop with prolonged use, necessitating dosing adjustments or drug-free intervals.

Pharmacokinetics

Isosorbide is well-absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 2 hours after oral administration. It undergoes extensive first-pass metabolism, which can significantly reduce its bioavailability. The drug is primarily metabolized in the liver, and its metabolites are eliminated via the kidneys. The half-life of isosorbide varies between 4 and 6 hours, depending on the specific formulation and individual patient factors.

Contra-indications

• Hypersensitivity to isosorbide or any of its components
• Severe hypotension
• Cardiogenic shock
• Acute myocardial infarction with right ventricular involvement

Adverse effects

• Headache
• Dizziness
• Hypotension
• Tachycardia
• Flushing
• Nausea
• Vomiting
• Palpitations

Interactions

• Nitrates (increased hypotensive effect)
• Antihypertensives (enhanced blood pressure lowering)
• Alcohol (potentiation of vasodilatory effects)

Precautions

• Use with caution in patients with pre-existing hypotension
• Monitor blood pressure regularly during therapy
• Caution in patients with renal impairment
• May cause syncope in susceptible individuals

Pregnancy

Isosorbide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare provider.

Breast-feeding

Isosorbide is excreted in breast milk. Caution should be exercised when administering to a nursing mother.

Storage

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

Formulations

• Isosorbide dinitrate tablets
• Isosorbide mononitrate extended-release tablets
• Isosorbide dinitrate sublingual tablets