Metoprolol

BRAND NAMES

Kapspargo Sprinkle: It is available in capsule form, with dose ranges of metoprolol 25 mg, 50 mg, 100 mg, and 200 mg. It relaxes the blood vessels, easing the frequency of angina attacks, allowing blood to circulate freely throughout your body, and ensuring the heart gets enough oxygen. It lowers your chances of experiencing chest pain caused by angina. This drug can help you exercise and go about your regular activities by decreasing the frequency of angina attacks. 

Cortel M 50: The combination of Telmisartan 40 mg and Metoprolol 50 mg tablet is mostly used to treat hypertension. It helps to control blood pressure by blocking the effects of angiotensin II and adrenaline, reducing the strain on the heart, and relaxing blood vessels. 

Lopressor HCT: The Lopressor HCT tablet is a combination of hydrochlorothiazide (25–50 mg) and metoprolol (50–100 mg). It reduces your heart rate and allows the heart to beat with less force. It also eliminates extra water from the body and stimulates urine production. 

Dutoprol: A dutoprol tablet is a combination of hydrochlorothiazide (12.5 mg) and metoprolol (25–100 mg).

MECHANISM OF ACTION

Metoprolol is a cardio-selective β-blocker medicine that targets β-1 adrenergic receptors in the heart. It inhibits the effects of catecholamines on cardiac function. The mechanism of action of metoprolol might be described in the following steps:

• Specifically in the ventricular myocardium, atrioventricular node, and sinoatrial node, metoprolol binds to β-1 adrenergic receptors on cardiac cells. 
• Metoprolol reduces intracellular signaling pathways mediated by cyclic adenosine monophosphate and protein kinase A by inhibiting catecholamine receptor activation through competition for the same receptors.
• Metoprolol lowers the slope of the nodal action potential's phase 4, which is the heart rate-determining spontaneous depolarization phase. Metoprolol decreases the sodium influx during this phase, which slows down the pacemaker cell's rate of firing and lowers the heart rate.
• Metoprolol delays the nodal action potential's phase 3 repolarization when potassium efflux returns the membrane potential to its resting state. Metoprolol prolongs the cardiac cells' refractory period and lowers their excitability and conduction velocity by postponing this phase.
• Metoprolol additionally reduces the ventricular myocardium's contractility by blocking the influx of calcium through PKA-regulated L-type calcium channels. Metoprolol decreases the force of contraction and cardiac output by reducing the calcium available for the sarcomeres.

PHARMACOKINETICS:

Absorption: Metoprolol is rapidly and completely absorbed by the gastrointestinal tract following oral administration. Metoprolol's bioavailability is approximately 50% due to extensive first-pass metabolism in the liver. The peak plasma concentration of metoprolol occurs 1 to 2 hours after an oral dose. Metoprolol absorption is not affected by food, but it may be slightly delayed.

Distribution: Metoprolol's distribution volume is overall, ranging from 3.2 to 5.6 L/kg. This medication accumulates in many tissues and organs, including the heart, brain, lungs, kidneys, and liver. Metoprolol crosses the blood-brain barrier and the placenta and gets eliminated in breast milk. Metoprolol is about 12% bound to plasma proteins, primarily albumin.

Metabolism: The liver extensively metabolizes metoprolol via the cytochrome P450 enzyme CYP2D6. Then it goes through oxidative deamination and O-demethylation, resulting in several inactive metabolites like alpha-hydroxy-metoprolol and 4'-hydroxy-metoprolol. Metoprolol is a racemic mixture of the R and S enantiomers, which have distinct pharmacokinetic and pharmacodynamic characteristics. The R-enantiomer has higher potency and selectivity for β-1 receptors than the S-enantiomer, but it is more susceptible to CYP2D6 metabolism. The S-enantiomer has a longer half-life and higher plasma levels than the R-enantiomer.

Elimination: Metoprolol and its metabolites are primarily excreted in the urine, accounting for approximately 95% of the oral dose. Less than 5% to 10% of an oral dose is excreted unchanged in urine, but this figure can rise to 30% to 40% in poor CYP2D6 metabolizers. The renal clearance of metoprolol is approximately 1 L/h/kg. Metoprolol has an elimination half-life of 3 to 7 hours, depending on the dose, formulation, enantiomer, and metabolic phenotype.

PHARMACODYNAMICS:

It is commonly known that administering metoprolol to normal subjects results in a dose-dependent reduction in heart rate and cardiac output. This effect results from decreased cardiac excitability, cardiac output, and myocardial oxygen demand. Metoprolol works in arrhythmias by lowering the slope of the pacemaker potential and slowing cardiovascular conduction.

DOSAGE AND ADMINISTRATION

Metoprolol is available in two formulations: metoprolol tartrate and metoprolol succinate. Metoprolol tartrate is an immediate-release tablet taken orally twice or thrice daily. Metoprolol succinate is an extended-release tablet or capsule taken orally once daily. The following dosage strengths of metoprolol tartrate tablets are available: 25 mg, 37.5 mg, 50 mg, 75 mg, and 100 mg. The following strengths of metoprolol succinate tablets or capsules are available: 50, 100, 200, and 25 mg. The strengths of metoprolol injection are as follows: 1mg/ml.

CONTRAINDICATIONS:

Cardiogenic shock, decompensated cardiac failure, sick sinus syndrome, severe bradycardia, and heart blocks greater than first-degree are contraindications for metoprolol succinate extended-release tablets.

DRUG INTERACTIONS:

Metoprolol, a β-blocker medication, can interact with various drugs and substances. Some of these interactions may impair the efficacy, safety, or duration of metoprolol or other medications.

Metoprolol is extensively metabolized in the liver, with CYP2D6 acting as the primary enzyme. Co-administration with substances that modulate CYP2D6 activity can result in altered metoprolol concentrations; these include: 

• Inhibitors like fluoxetine and paroxetine can raise metoprolol levels, potentially causing β-blockade and negative effects. 
• CYP2D6 inducers: In contrast, CYP2D6 inducers (such as rifampin) may speed up metoprolol metabolism, potentially decreasing its therapeutic efficacy. Dose adjustments or other treatment options may be necessary. 
• Calcium Channel Blockers: Taking calcium channel blockers simultaneously, particularly verapamil and diltiazem, can have additional negative inotropic and chronotropic effects, potentially exacerbating bradycardia and hypotension.

SIDE EFFECTS:

Metoprolol's common side effects may include blurred vision, chest pain, slow or irregular heartbeat, sweating, inability to speak, bleeding gums, blood in the urine, nausea, nervousness, shakiness, yellow eyes, skin, bloody vomiting, or weakness.

TOXICITY:

An overdose of metoprolol can have serious consequences for the heart, blood pressure, breathing, and nervous system. The signs and symptoms of metoprolol overdose can differ depending on the amount taken, the time passed, and the presence of other drugs or medical conditions. Hypotension (low blood pressure) can cause lightheadedness, dizziness, and fainting, as well as severe bradycardia, which is frequently accompanied by varying degrees of heart block, shortness of breath, gasping, and wheezing from bronchospasm.

STORAGE CONDITIONS:

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.