LOGIMAX 5/50 MG TABLETS

Indications

• Hypertension
• Short-term treatment of supraventricular arrhythmias
• Atrial fibrillation
• Atrial flutter
• Sinus tachycardia
• Tachycardia and hypertension in the perioperative period
• Symptomatic relief in hyperthyroidism

Dosage

Children: In children, the usual dose is 1 to 2 mg/kg daily in 2 to 4 divided doses, with a maximum of 8 mg/kg daily.

Adults: 200 mg once daily, increased if necessary to 400 mg once daily.

Mechanism of action

Metoprolol tartrate selectively blocks beta-1 adrenergic receptors, which results in a decrease in heart rate and myocardial contractility. This action reduces the workload on the heart and decreases oxygen demand, thereby lowering blood pressure.

Pharmacodynamics

As a beta-1 blocker, metoprolol exhibits negative chronotropic (decreasing heart rate) and inotropic (decreasing force of contraction) effects. This results in lower cardiac output and, consequently, reduced blood pressure. The drug also has a mild effect on reducing renin release from the kidneys, contributing further to its antihypertensive effects.

Pharmacokinetics

Metoprolol is well absorbed from the gastrointestinal tract but undergoes significant first-pass metabolism in the liver, which reduces its bioavailability to approximately 50%. It has a half-life of about 3 to 7 hours, allowing for once or twice daily dosing. Metoprolol is primarily eliminated by hepatic metabolism, and renal excretion of metabolites also occurs. Dose adjustments may be necessary in patients with hepatic impairment but are generally not required for mild renal impairment.

Contra-indications

• Severe bradycardia
• Heart block greater than first degree
• Cardiogenic shock
• Uncontrolled heart failure
• Hypersensitivity to metoprolol or any component of the formulation

Adverse effects

• Dizziness
• Fatigue
• Hypotension
• Bradycardia
• Heart block
• Depression
• Insomnia
• Nausea
• Diarrhea
• Cold extremities
• Peripheral edema

Interactions

• Other antihypertensive drugs may enhance the hypotensive effect
• Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce antihypertensive effect
• Caution with other beta-blockers
• Concurrent use with calcium channel blockers may increase the risk of bradycardia and heart block
• Caution with drugs that affect CYP2D6 metabolism

Precautions

• Caution in patients with asthma or reactive airway disease
• Caution in patients with diabetes mellitus, as it may mask signs of hypoglycemia
• Monitor in patients with hepatic impairment
• Gradual withdrawal is advised to avoid acute tachycardia, hypertension, or ischemic symptoms

Pregnancy

Metoprolol should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Consult guidelines for specific recommendations.

Breast-feeding

Manufacturers advise avoidance during breastfeeding due to potential adverse effects on the infant.

Storage

Store below 25°C, protect from light and moisture. Keep out of reach of children.

Formulations

• Metoprolol tartrate 25 mg tablets
• Metoprolol tartrate 50 mg tablets
• Metoprolol tartrate 100 mg tablets

Indications

• Essential hypertension
• Chronic stable angina

Dosage

Children: Refer to the BNF for Children for paediatric dosing guidance.

Adults: The usual adult dosage for hypertension is 5 mg once daily, which may be increased to 10 mg depending on clinical response.

Mechanism of action

Felodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels. It reversibly competes against dihydropyridine calcium channel blockers for binding sites in vascular smooth muscle, leading to reduced contractile activity and vasodilation.

Pharmacodynamics

Felodipine belongs to the dihydropyridine class of calcium channel blockers, primarily targeting L-type calcium channels in muscle cells. It also inhibits T-type calcium channels and calmodulin-dependent calcium release, although these interactions appear to have minor pharmacologic significance. Its vasodilatory effects contribute to lowering blood pressure and improving blood flow.

Pharmacokinetics

Felodipine is well absorbed following oral administration, with peak plasma concentrations occurring about 2-5 hours after dosing. It undergoes extensive hepatic metabolism and has a long half-life, allowing for once-daily dosing. Its bioavailability is affected by food, particularly grapefruit juice, which can significantly increase plasma levels.

Contra-indications

• Severe hypotension
• Cardiogenic shock
• Unstable angina
• Severe aortic stenosis

Adverse effects

• Peripheral edema
• Headache
• Flushing
• Palpitations
• Dizziness
• Nausea
• Abdominal pain

Interactions

• Grapefruit juice: Severe (increases exposure)
• Enzalutamide: Moderate (decreases exposure)
• Apalutamide: Moderate (decreases exposure)
• Dronedarone: Moderate (increases exposure)
• Antifungals (azoles): Moderate (increases exposure)
• Miconazole: Moderate (increases exposure)
• Cenobamate: Moderate (decreases exposure)
• Cobicistat: Moderate (increases exposure)
• Crizotinib: Moderate (increases exposure)
• Dabrafenib: Moderate (decreases exposure)

Precautions

• Use with caution in patients with hepatic impairment
• Monitor blood pressure regularly
• Consider the risk of hypotension in patients on other antihypertensives

Pregnancy

Felodipine should only be used in pregnancy if the potential benefit justifies the potential risk to the fetus. Consult specific guidelines for use during pregnancy.

Breast-feeding

Felodipine is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Felodipine 2.5 mg tablets
• Felodipine 5 mg tablets
• Felodipine 10 mg tablets
• Felodipine extended-release 2.5 mg tablets
• Felodipine extended-release 5 mg tablets
• Felodipine extended-release 10 mg tablets

Indications

• Hypertension
• Angina pectoris
• Heart failure
• Arrhythmias
• Myocardial infarction prevention

Dosage

Children: Paediatric dosing of metoprolol is not provided in the BNF text supplied. It is essential to refer to the BNF for Children for appropriate paediatric dosing recommendations.

Adults: The typical dose of metoprolol for adults varies based on the specific indication and patient factors. For hypertension, the initial dose is often 50 mg once daily, which may be adjusted based on response. For angina, the usual starting dose is also 50 mg, taken twice daily. It is recommended to refer to the BNF for specific dosing guidelines.

Mechanism of action

Metoprolol selectively inhibits beta-1-adrenergic receptors in cardiac cells, leading to negative chronotropic and inotropic effects. It reduces automaticity, decreases conduction velocity, and enhances refractoriness in accessory pathways. By blocking adrenergic stimulation, metoprolol lowers heart rate and myocardial contractility, contributing to its antihypertensive effects.

Pharmacodynamics

Administration of metoprolol results in a dose-dependent decrease in heart rate and cardiac output. It reduces cardiac excitability and myocardial oxygen demand, improving outcomes in patients with arrhythmias by suppressing atrioventricular conduction. Clinical trials indicate that metoprolol significantly reduces mortality and reinfarction risk in post-myocardial infarction patients.

Pharmacokinetics

Metoprolol is rapidly absorbed and undergoes extensive first-pass metabolism in the liver, leading to variable bioavailability. Peak plasma concentrations occur approximately 1-2 hours post-administration. The drug is primarily excreted by the kidneys, with a half-life of around 3-7 hours. Individual pharmacokinetic profiles may vary based on genetic factors and co-administered medications.

Contra-indications

• Severe bradycardia
• Heart block greater than first degree
• Cardiogenic shock
• Uncontrolled heart failure
• Hypersensitivity to metoprolol or any component of the formulation

Adverse effects

• Bradycardia
• Hypotension
• Fatigue
• Dizziness
• Depression
• Cold extremities
• Gastrointestinal disturbances
• Shortness of breath
• Sleep disturbances

Interactions

• dacomitinib+metoprolol: Severe (increases exposure)
• eliglustat+metoprolol: Moderate (increases exposure)
• fedratinib+metoprolol: Moderate (increases exposure)
• panobinostat+metoprolol: Moderate (increases exposure)
• abiraterone+metoprolol: Unknown (increases exposure)
• propafenone+metoprolol: Unknown (increases exposure)
• bupropion+metoprolol: Unknown (increases exposure)
• cinacalcet+metoprolol: Unknown (increases exposure)
• mirabegron+metoprolol: Unknown (increases exposure)
• snris+metoprolol: Unknown (increases exposure)

Precautions

• Use with caution in patients with asthma or chronic obstructive pulmonary disease due to potential for bronchoconstriction at high doses
• Monitor heart rate and blood pressure regularly
• Caution in patients with diabetes as it may mask hypoglycemic symptoms
• Taper dose gradually to avoid rebound hypertension

Pregnancy

Metoprolol is classified as a category C drug. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Metoprolol is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Tablets: 25 mg, 50 mg, 100 mg

Mechanism of action

Felodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels. It reversibly competes against nitrendipine and other DHP CCBs for DHP binding sites in vascular smooth muscle and cultured rabbit atrial cells. 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 felodipine result in an overall decrease in blood pressure. Felodipine may be used to treat mild to moderate essential hypertension.

Pharmacodynamics

Felodipine 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 Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction; however, some studies have shown that felodipine also binds to and inhibits T-type calcium channels. T-type calcium channels are most commonly found on neurons, cells with pacemaker activity and on osteocytes. The pharmacologic significance of T-type calcium channel blockade is unknown. Felodipine also binds to calmodulin and inhibits calmodulin-dependent calcium release from the sarcoplasmic reticulum. The effect of this interaction appears to be minor. Another study demonstrated that felodipine attenuates the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) by binding to the PDE-1B1 and PDE-1A2 enzyme subunits. CaMPDE is one of the key enzymes involved in cyclic nucleotides and calcium second messenger systems. Felodipine also acts as an antagonist to the mineralcorticoid receptor by competing with aldosterone for binding and blocking aldosterone-induced coactivator recruitment of the mineralcorticoid receptor. Felodipine is able to bind to skeletal and cardiac muscle isoforms of troponin C, one of the key regulatory proteins in muscle contraction. Though felodipine exhibits binding to many endogenous molecules, its vasodilatory effects are still thought to be brought about primarily through inhibition of voltage-gated L-type calcium channels. Similar to other DHP CCBs, felodipine 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 felodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, felodipine has little effect on cardiac myocytes and conduction cells.

Mechanism of action

Metoprolol is a beta-1-adrenergic receptor inhibitor specific to cardiac cells with negligible effect on beta-2 receptors. This inhibition decreases cardiac output by producing negative chronotropic and inotropic effects without presenting activity towards membrane stabilization nor intrinsic sympathomimetics. Beta-adenoreceptor blocking property the amount of beta1 and beta2 effect depends on the cardioselectivity of the drug. Decreased automaticity. Reduced conduction velocity and increased refractoriness in accessory bundles (Wolff- Parkinson-White syndrome). /Class II- beta-Blocking Agents/ At low doses, metoprolol is a selective inhibitor of beta 1-adrenergic receptors. Like propranolol, metoprolol inhibits response to adrenergic stimuli by competitively blocking b1-adrenergic receptors within the myocardium. Unlike propranolol, however, metoprolol blocks b2-adrenergic receptors within bronchial and vascular smooth muscle only in high doses. The precise mechanism of metoprolol's hypotensive action has not been determined. It has been postulated that beta-adrenergic blocking agents reduce blood pressure by blocking peripheral (especially cardiac) adrenergic receptors (decreasing cardiac output), by decreasing sympathetic outflow from the CNS, and/or by suppressing renin release. In the management of angina pectoris, the mechanism of action of metoprolol is thought to be blockage of catecholamine-induced increases in heart rate, velocity and extent of myocardial contraction, and blood pressure, which results in a net decrease in myocardial oxygen consumption. For more Mechanism of Action (Complete) data for METOPROLOL (7 total), please visit the HSDB record page.

Pharmacodynamics

Administration of metoprolol in normal subjects is widely reported to produce a dose-dependent reduction on heart rate and cardiac output. This effect is generated due to a decreased cardiac excitability, cardiac output, and myocardial oxygen demand. In the case of arrhythmias, metoprolol produces its effect by reducing the slope of the pacemaker potential as well as suppressing the rate of atrioventricular conduction. The Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) trial showed a significant improvement in sudden cardiac death and myocardial infarction when patients were given with metoprolol as compared with diuretics. As well, in clinical trials performed in 1990, metoprolol reduces mortality and re-infarction in 17% of the individuals when administered chronically after an episode of myocardial infarction.