Diltiazem Hydrochloride for Angina: A Comprehensive Review

Overview

Diltiazem hydrochloride belongs to the family of medicines known as calcium channel blockers. It is frequently used to treat a variety of cardiovascular diseases, including angina. Angina is a type of chest pain or discomfort caused by insufficient blood and oxygen to the heart muscle. Diltiazem inhibits the inflow of calcium ions into smooth muscle cells in the heart and blood arteries. This helps to relax and broaden the blood arteries, lowering the burden on the heart and increasing blood flow to the heart muscle. Diltiazem hydrochloride was approved by the Food and Drug Administration on August 15th, 1999.

Drug Group

Diltiazem hydrochloride is a calcium channel blocker. It belongs to the subclass of Benzothiazepines. Calcium channel blockers are a varied class of drugs that modulate the entrance of calcium ions into cardiac and smooth muscle cells. They are used to treat hypertension (increased blood pressure), angina, and certain arrhythmias.

Indications

Diltiazem hydrochloride is used to treat a variety of cardiovascular diseases. The key indicators are:

• Angina Pectoris (Stable Angina): Diltiazem is used to treat stable angina, a kind of chest pain or discomfort that persists consistently after physical activity or stress. It relieves angina symptoms by dilating blood vessels and lowering the burden on the heart.

• Chronic Stable Angina: Diltiazem is useful in the long-term therapy of chronic stable angina, reducing chest discomfort associated with the illness.

• Control of Rapid Ventricular Response in Atrial Fibrillation or Atrial Flutter: Diltiazem is used to regulate heart rate in individuals suffering from atrial fibrillation or atrial flutter, which are disorders characterized by abnormal heart rhythms.

The medication's ability to dilate blood vessels and reduce myocardial oxygen demand makes it useful in the treatment of various cardiovascular diseases. Individuals should take Diltiazem under the supervision of a healthcare professional, who will establish the proper dosage and monitor their reaction to therapy.

Contraindications

Diltiazem hydrochloride has certain contraindications, and its usage may be limited or avoided in certain medical situations. Contraindications to Diltiazem hydrochloride include:

• Hypersensitivity: Individuals who have a history of hypersensitivity or allergic reactions to Diltiazem or similar chemicals should avoid using this drug.

• Severe Hypotension: Diltiazem may drop blood pressure, and its usage is typically not recommended in those with severe hypotension (extremely low blood pressure).

• Sick Sinus Syndrome (without a pacemaker): Individuals with sick sinus syndrome (a condition in which the heart's natural pacemaker fails to function correctly) who do not have a pacemaker should not take Diltiazem.

• Second or Third-Degree Atrioventricular (AV) Block (Without a Pacemaker): Diltiazem is typically contraindicated in people with second or third-degree AV block (conditions affecting electrical conduction in the heart) who do not have a pacemaker.

Dosage Forms and Available Strengths

Diltiazem hydrochloride is available in a variety of dose forms and strengths to meet the needs of patients and achieve their therapeutic objectives. Common dose forms include:

• Immediate-Release Tablets: These tablets are intended to quickly release the drug into the bloodstream after intake. Diltiazem immediate-release tablets are commonly available in strengths of 30 mg (milligrams), 60 mg, 90 mg, and 120 mg.

• Extended-Release Capsules: Extended-release formulations provide the drug in a regulated and sustained manner over a longer time, allowing for less frequent administration. Diltiazem extended-release capsules are available in several strengths, including 120 mg, 180 mg, 240 mg, 300 mg, and 360 mg.

• Intravenous (IV) Formulations: Diltiazem can also be given intravenously in some therapeutic situations, such as hospitals. This enables a quicker beginning of activity. The concentration of the intravenous fluid might vary depending on the clinical condition and the healthcare provider's prescription.

Warnings and Precautions

When taking Diltiazem hydrochloride, patients and healthcare professionals should be aware of the following risks and precautions:

• Hypotension: Diltiazem may produce a drop in blood pressure, particularly when first starting the medicine or with dose modifications. Regular blood pressure monitoring is required, and people with pre-existing hypotension should proceed with care.

• Heart Block: Diltiazem can induce or worsen heart block, especially in patients with pre-existing conduction problems. Patients with second- or third-degree AV block should take Diltiazem with care, while those without a pacemaker should avoid it.

• Worsening Heart Failure: Diltiazem can worsen congestive heart failure, so use it with care. The medication's unfavorable inotropic effects have the potential to aggravate heart failure in sensitive patients.

• Hepatic Impairment: Diltiazem is processed by the liver, and people with hepatic impairment may have a slower clearance rate. Dosage changes may be required in patients with hepatic impairment.

• Renal Impairment: Although Diltiazem is not predominantly eliminated by the kidneys, individuals with severe renal impairment may require dose changes.

• Elderly Patients: Elderly patients may be more vulnerable to the effects of Diltiazem. When providing this drug to the elderly, use caution and monitor closely.

• Peripheral Edema: Diltiazem can induce peripheral edema (swelling of the extremities). Monitoring for indications of edema, changing the dose, or exploring alternate therapies may be required.

• Concomitant Use with Beta-Blockers or Digoxin: Combining Diltiazem with beta-blockers or Digoxin should be done with caution, as there is an increased risk of atrioventricular conduction abnormalities.

• Pregnancy and Lactation: Diltiazem should only be taken during pregnancy if the possible advantages outweigh the dangers. The medicine may be secreted in breast milk, therefore use caution during breastfeeding.

For Patients

What Is the Clinical Condition?

Diltiazem hydrochloride is often used to treat cardiovascular diseases, particularly those involving blood pressure and cardiac rhythm control. The medicine is primarily used to treat:

• Angina Pectoris (Stable Angina): Diltiazem is used to treat stable angina, which is characterized by chest pain or discomfort that occurs reliably following physical activity or stress. Diltiazem helps reduce angina symptoms by dilating blood vessels and lowering the strain on the heart.

• Chronic Stable Angina: Diltiazem is used to treat chronic stable angina, giving long-term relief from the chest discomfort associated with this cardiovascular disease.

• Control of Rapid Ventricular Response in Atrial Fibrillation or Atrial Flutter: Diltiazem is used to regulate heart rate in people who have atrial fibrillation or atrial flutter, which are disorders marked by irregular heart rhythms that originate in the atria.

How Effective Is the Drug?

Diltiazem hydrochloride is widely regarded as an excellent medicine for the treatment of different cardiovascular diseases, including angina and certain arrhythmias. Its efficacy is based on its capacity to modify calcium channels, which results in vasodilation (blood vessel relaxation) and lower myocardial oxygen demand. Here are a few examples of its effectiveness:

• Angina Pectoris (Stable Angina): Diltiazem reduces the frequency and severity of angina events in patients with stable angina. It relieves chest discomfort associated with this illness by increasing blood flow to the heart and lowering the burden on the heart muscle.

• Chronic Stable Angina: Diltiazem is successful in the long-term therapy of chronic stable angina by giving consistent relief from chest discomfort.

• Atrial Fibrillation or Atrial Flutter: Diltiazem is commonly used to regulate the heart rate in people with atrial fibrillation or atrial flutter, which helps to normalize the heart rhythm.

What Are the Clinical Uses of the Drug?

Diltiazem hydrochloride has a variety of therapeutic advantages and applications, the majority of which are connected to its effects as a calcium channel blocker. Here are the primary advantages and therapeutic applications of the drug:

• Angina Pectoris (Stable Angina): Diltiazem is frequently used to treat angina pectoris (stable angina). It relieves angina symptoms by dilating coronary arteries and lowering myocardial oxygen demand. The vasodilatory impact increases blood flow to the heart muscle, which improves oxygen delivery.

• Chronic Stable Angina: Diltiazem gives long-term relief from chest discomfort, contributing to an enhanced quality of life for people suffering from this condition.

• Control of Rapid Ventricular Response in Atrial Fibrillation or Atrial Flutter: Diltiazem is used to regulate heart rate in individuals with atrial fibrillation or atrial flutter. Slowing down the electrical impulses in the heart helps maintain a more regular cardiac rhythm and alleviates symptoms associated with certain arrhythmias.

• Hypertension (Off-label Use): While not a main indication, Diltiazem can be used off-label to treat hypertension (high blood pressure) in some circumstances. Its vasodilatory actions aid in lowering blood pressure.

• Raynaud's Phenomenon (Off-label Use): Diltiazem may be used off-label to treat symptoms of Raynaud's phenomenon, a disorder marked by decreased blood flow to certain parts of the body, most often the fingers and toes.

Dietary Considerations:

A healthy and balanced diet is typically recommended when taking Diltiazem. Certain dietary concerns may be important owing to possible interactions or effects on the cardiovascular system. Patients should get individualized guidance from their healthcare practitioner. Here are some general tips:

• Grapefruit Interaction: Grapefruit and grapefruit juice may interact with Diltiazem, affecting its metabolism. It is commonly advised to avoid grapefruit products when taking Diltiazem.

• High-Fiber Diet: Getting enough fiber might help with constipation, which is a side effect of Diltiazem.

Missed Dose:

• If one misses a dosage of Diltiazem, take it as soon as recalled.

• However, if it is nearing the next planned dosage, the missed dose should be omitted.

• Do not take double doses to make up for missing ones.

Overdose:

• Overdosing on Diltiazem might cause significant consequences.

• Symptoms may include dizziness, fainting, trouble breathing, and an abnormally slow or irregular heartbeat.

• In the event of an overdose, seek emergency medical treatment right away.

Storage:

• Diltiazem should be kept at room temperature, free from light and moisture.

• Keep the medicine out of the reach of youngsters.

• Specific storage instructions may differ depending on the formulation (tablets, capsules, intravenous solution), thus it is critical to follow the guidelines on the drug label.

Handling:

• Tablets and capsules must be handled with clean, dry hands.

• It is critical to follow the healthcare provider's recommendations regarding the precise kind of Diltiazem prescribed.

• Intravenous solutions should only be given by skilled healthcare professionals in a clinical environment.

For Doctors

Pharmacodynamics

Mechanism of Action:

• Diltiazem is a calcium channel blocker that predominantly targets L-type calcium channels.

• It prevents calcium ions from entering vascular smooth muscle cells and cardiac myocytes during depolarization.

Vasodilation:

• Diltiazem relaxes the vascular smooth muscle, which leads to vasodilation.

• This action decreases peripheral vascular resistance, resulting in lower afterloads.

Cardiac Effects:

• In the heart, Diltiazem reduces the sinoatrial (SA) node's automaticity.

• It slows down the conduction via the atrioventricular (AV) node, resulting in a negative chronotropic impact.

Myocardial Oxygen Demand:

• Diltiazem reduces the myocardium's oxygen demand via decreasing afterload and cardiac contractility.

Antiarrhythmic Effects:

• Diltiazem's actions on calcium channels help to explain its antiarrhythmic capabilities, notably in regulating the fast ventricular response in atrial fibrillation or atrial flutter.

Coronary Vasodilation:

• Diltiazem dilates the coronary arteries, increasing blood flow to the myocardium.

• This coronary vasodilation adds to its ability to treat angina.

Hemodynamic Effects:

• The combined effects of vasodilation, negative chronotropy, and inotropic modulation reduce blood pressure and cardiac strain.

Onset and Duration:

• Immediate-release formulations provide a quick beginning of action, whilst extended-release ones have a longer-lasting impact.

Individual Variation:

• Diltiazem response may vary across individuals, needing personalized doses and monitoring.

Chemical Taxonomy of Diltiazem Hydrochloride:

• Chemical Name: Diltiazem Hydrochloride

• Chemical Formal: C22H26N2O4S · HCl.

• Chemical Structure: Diltiazem hydrochloride is a Benzothiazepine derivative with a complicated chemical structure that contains a benzene ring, a thiazepine ring, and an aminoethyl chain.

• Molecular Weight: The molecular weight of Diltiazem hydrochloride is around 450.98.

Mechanism of Action of Diltiazem Hydrochloride:

Diltiazem hydrochloride is a calcium channel blocker that predominantly targets L-type calcium channels in cardiac and smooth muscle cells. Its mode of action includes the control of calcium ion influx, which influences a variety of biological processes.

Inhibition of Calcium Inflow:

• Diltiazem inhibits L-type calcium channels, which are voltage-dependent channels that enable calcium ions into cells during depolarization.

• Diltiazem inhibits these channels, reducing the entry of calcium ions into vascular smooth muscle cells and cardiac myocytes.

Vasodilation:

• Inhibiting calcium entrance in vascular smooth muscle causes relaxation, resulting in peripheral artery dilatation.

• Vasodilation lowers peripheral vascular resistance, which lessens the heart's afterload.

Negative Chronotropy and Dromotropy:

• Diltiazem reduces the automaticity of the sinoatrial (SA) node in the heart, causing negative chronotropic effects (slowed heart rate).

• It also delays conduction via the atrioventricular (AV) node, which causes unfavorable dromotropic effects.

Toxicity

Diltiazem hydrochloride is typically well tolerated when taken at therapeutic levels; nevertheless, like with any medicine, it can cause toxicity if overused or overdosed. Toxicity symptoms can vary and affect the cardiovascular, central nervous, and gastrointestinal systems. Here are the major factors about Diltiazem toxicity:

• Cardiovascular Effects: Excessive Diltiazem doses can cause severe hypotension (low blood pressure) and bradycardia. Toxicity can cause conduction abnormalities, including varying degrees of heart block.

• Central Nervous System Effects: Diltiazem poisoning can cause dizziness, disorientation, and, in severe cases, loss of consciousness. Central nervous system depression may occur, especially at large dosages.

• Gastrointestinal Effects: Nausea, vomiting, and abdominal pain are all possible gastrointestinal symptoms. Constipation is a typical adverse effect of Diltiazem, however it might be more severe in situations of overdose.

• Metabolic Acidosis: Severe poisoning can cause metabolic acidosis, characterized by an elevated anion gap and respiratory correction (hyperventilation).

Management of Toxicity:

• In situations of overdose, supportive treatment is required. This may include stomach lavage, the administration of activated charcoal, and other absorption-reducing techniques.

• Intravenous fluids may be supplied to keep blood pressure stable, and vasopressors may be used in severe situations.

• Atropine can be used to treat bradycardia. In severe situations, temporary pacing may be required.

Drug Interactions

Diltiazem hydrochloride can interact with a variety of drugs, potentially reducing their efficacy or increasing the risk of unwanted effects. Healthcare professionals must be mindful of potential medication interactions while prescribing Diltiazem. Here are some important medication interactions:

Beta-Blockers:

• Concurrent usage with beta-blockers can lead to further unfavorable chronotropic and inotropic effects.

• Caution is suggested owing to the risk of bradycardia, heart block, or hypotension.

Digoxin:

• Diltiazem can raise Digoxin levels by lowering renal clearance.

• Monitor Digoxin levels regularly; dose modifications may be required.

Antiarrhythmics (Class IA and III):

• Concomitant usage may raise the risk of ventricular arrhythmia.

• When used together, close monitoring is suggested.

Cyclosporine:

• Diltiazem may raise Cyclosporine levels, potentially leading to toxicity.

• Monitor Cyclosporine levels and alter the dosage as needed.

Statins (HMG-CoA Reductase Inhibitors):

• Diltiazem can raise the plasma concentrations of statins like Simvastatin and Lovastatin.

• Consider taking statins at lower doses and keeping an eye out for statin-related side effects.

Rifampin:

• Rifampin can lower Diltiazem plasma levels, potentially lowering its effectiveness.

• When using Diltiazem with rifampin, adjust the dose as needed.

Cimetidine:

• Cimetidine may raise Diltiazem levels, potentially leading to toxicity.

• Keep track of any Diltiazem-related side effects and modify the dose as needed.

Carbamazepine:

• Carbamazepine can lower Diltiazem levels, thereby reducing its effectiveness.

• Check for decreasing therapeutic effects and alter the dose as appropriate.

Other Calcium Channel Blockers:

• Concurrent usage of calcium channel blockers may result in cumulative cardiovascular consequences.

• Combining calcium channel blockers should be done with caution.

Use in Specific Populations

Pregnancy: Diltiazem belongs to the category C drug and should only be used when pregnant if the possible benefits outweigh the dangers. There is limited human evidence, however, animal research indicates that there may be negative consequences for the fetus. A consultation with a healthcare practitioner is required to consider the risks and advantages.

Lactation: Diltiazem is excreted in human breast milk. Use care during nursing; weigh the significance of the medicine to the mother against the potential dangers to the newborn. Breastfeeding women should check with their healthcare professional.

Pediatric Use: Safety and efficacy in pediatric patients have not been demonstrated. Diltiazem is typically not advised for usage in children unless closely monitored by a pediatric expert.

Geriatric Use: Dosage adjustments may be required in older individuals due to age-related changes in pharmacokinetics. Close monitoring for side effects, particularly hypotension, is essential.

Renal Impairment: Diltiazem is eliminated by the kidneys. Dosage changes may be necessary in people with renal impairment. Regular monitoring of renal function is recommended.

Concomitant Use with Beta Blockers: Combining Diltiazem with beta blockers should be done with caution, especially in individuals with compromised cardiac function. Keep an eye out for any potential additive negative inotropic or chronotropic effects.

Conduction Abnormalities: Use with care in individuals with conduction anomalies (such as sick sinus syndrome or AV block). In specific circumstances, a pacemaker may be required.

Diabetes: Diltiazem may affect diabetics' glucose management. Regular blood glucose monitoring is indicated for diabetic people using Diltiazem.