AMLOCIP NB

Indications

• Hypertension
• Chronic stable angina
• Vasospastic angina (Prinzmetal's angina)

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Amlodipine selectively inhibits the influx of calcium ions into vascular smooth muscle and cardiac muscle during depolarization. This results in relaxation of vascular smooth muscle, leading to vasodilation, decreased peripheral vascular resistance, and subsequently lowered blood pressure. Additionally, it reduces the oxygen demand of the heart, alleviating angina.

Pharmacodynamics

The pharmacodynamic effects of amlodipine include a significant decrease in systemic vascular resistance and diastolic BP. Amlodipine's effects may persist for up to 24 hours, allowing for once-daily dosing. The drug is well-tolerated and does not typically lead to reflex tachycardia due to its gradual onset and sustained action. Long-term use has been shown to improve exercise tolerance in patients with angina.

Pharmacokinetics

Amlodipine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring 6 to 12 hours post-administration. It has a long half-life of approximately 30 to 50 hours, allowing for once-daily dosing. Amlodipine is extensively metabolized in the liver, primarily via CYP3A4, and its metabolites are excreted mainly in the urine. The drug's bioavailability is approximately 64-90%, and it is not significantly affected by food intake.

Contra-indications

• Severe hypotension
• Shock (cardiogenic or hypovolemic)
• Aortic stenosis
• Known hypersensitivity to amlodipine or any of its components

Adverse effects

• Peripheral edema
• Headache
• Flushing
• Palpitations
• Fatigue
• Abdominal pain
• Nausea
• Dizziness
• Rash
• Gingival hyperplasia

Interactions

• CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) may increase amlodipine levels
• CYP3A4 inducers (e.g., rifampicin, St. John's Wort) may decrease amlodipine levels
• Other antihypertensive agents may have an additive effect, leading to increased hypotension

Precautions

• Use with caution in patients with hepatic impairment
• Monitor blood pressure regularly during treatment
• Caution in patients with heart failure or severe coronary artery disease

Pregnancy

Amlodipine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Limited data on its safety in pregnant women.

Breast-feeding

Amlodipine is excreted in breast milk, and caution is advised when administered to nursing mothers.

Storage

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

Formulations

• Tablets: 2.5 mg, 5 mg, 10 mg

Indications

• Essential hypertension
• Migraine prophylaxis
• Hypertension in patients with renal impairment
• Adjunct treatment in stable mild to moderate heart failure
• Management of arrhythmias during anesthesia

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations.

Adults: Initially 5 mg once daily, with a maximum of 40 mg daily depending on clinical response and tolerance.

Mechanism of action

Nebivolol selectively antagonizes beta-1 adrenergic receptors, leading to decreased heart rate, myocardial contractility, and blood pressure. Additionally, it stimulates beta-3 adrenergic receptors, causing increased nitric oxide production and subsequent vasodilation. This reduces vascular resistance and enhances cardiac output while minimizing adverse effects commonly associated with non-selective beta blockers.

Pharmacodynamics

Nebivolol decreases vascular resistance and increases stroke volume and cardiac output without negatively impacting left ventricular function. Its effects can persist for up to 48 hours after discontinuation of the drug. It possesses a wide therapeutic window, with typical doses ranging from 5 to 40 mg daily. Patients, especially those with coronary artery disease, should not stop treatment abruptly as this may exacerbate their condition. Additionally, diabetic patients should monitor blood glucose levels, as nebivolol may mask hypoglycemic symptoms.

Pharmacokinetics

Nebivolol is well absorbed and undergoes extensive first-pass metabolism. It has a half-life that allows for once-daily dosing, making it convenient for patient adherence. The drug is primarily metabolized by the liver, and its elimination is influenced by renal function. The pharmacokinetic profile supports its use in various patient populations, including the elderly, who may require dose adjustments.

Contra-indications

• Acute or decompensated heart failure requiring intravenous inotropes
• Severe bradycardia
• Heart block (greater than first degree) unless a functioning pacemaker is present
• Cardiogenic shock
• Severe hepatic impairment

Adverse effects

• Constipation
• Oedema
• Postural hypotension
• Dyspepsia
• Flatulence
• Skin reactions
• Palpitations
• Alopecia
• Arrhythmia
• Conjunctivitis
• Dry eyes
• Fatigue
• Thrombocytopenia
• Sexual dysfunction

Interactions

• Propafenone: Severe (increases exposure)
• Dacomitinib: Severe (increases exposure)
• Berotralstat: Moderate (increases exposure)
• Fedratinib: Moderate (increases exposure)
• Givosiran: Moderate (increases exposure)
• Panobinostat: Moderate (increases exposure)
• Bupropion: Unknown (increases exposure)
• Cinacalcet: Unknown (increases exposure)
• Terbinafine: Unknown (increases exposure)
• Ropeginterferonalfa: Unknown (increases exposure)

Precautions

• Use with caution in patients with diabetes, as beta-blockers may mask signs of hypoglycemia
• Monitor blood pressure and heart rate regularly
• Taper off the medication gradually to avoid exacerbation of coronary artery disease
• Caution in patients with a history of bronchospastic disease

Pregnancy

Use only if the benefits outweigh the risks, as safety in pregnancy has not been established.

Breast-feeding

Manufacturers advise avoidance due to potential effects on the infant.

Storage

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

Formulations

• Nebivolol 1.25 mg tablet
• Nebivolol 5 mg tablet
• Nebivolol 10 mg tablet
• Nebivolol solution for injection

Mechanism of action

Nebivolol is a highly selective beta-1 adrenergic receptor antagonist with weak beta-2 adrenergic receptor antagonist activity. Blocking beta-1 adrenergic receptors by d-nebivolol leads to decreased resting heart rate, exercise heart rate, myocardial contracility, systolic blood pressure, and diastolic blood pressure. The selectivity of d-nebivolol limits the magnitude of beta blocker adverse effects in the airways or relating to insulin sensitivity. Nebivolol also inhibits aldosterone, and beta-1 antagonism in the juxtaglomerular apparatus also inhibits the release of renin. Decreased aldosterone leads to decreased blood volume, and decreased renin leads to reduced vasoconstriction. l-nebivolol is responsible for beta-3 adrenergic receptor agonist activity that stimulates endothelial nitric oxide synthase, increasing nitric oxide levels; leading to vasodilation, decreased peripheral vascular resistance, increased stroke volume, ejection fraction, and cardiac output. The vasodilation, reduced oxidative stress, and reduced platelet volume and aggregation of nebivolol may lead to benefits in heart failure patients.

Pharmacodynamics

Nebivolol is a selective beta-1 adrenergic receptor antagonist that decreases vascular resistance, increases stroke volume and cardiac output, and does not negatively affect left ventricular function. It has a long duration of action as effects can be seen 48 hours after stopping the medication and a wide therapeutic window as patients generally take 5-40mg daily. Patients should not abruptly stop taking this medication as this may lead to exacerbation of coronary artery disease. Diabetic patients should monitor their blood glucose levels as beta blockers may mask signs of hypoglycemia.