Drugs Used in the Treatment of Cardiovascular Disorders

These drugs are used in the treatment of conditions such as:

• Hypertension
• Angina pectoris
• Heart failure
• Hyperlipidemia
• Arrhythmias

Hypertension

Hypertension is the persistent elevation of blood pressure higher than normal (140/90 mmHg) .

Common Terms Used in Hypertension

• Blood Pressure : This is the pressure of blood against the walls of the main arteries.
• Diastolic Blood Pressure: This is the pressure exerted in the vessels when the ventricles are relaxing and refilling.
• Systolic Pressure : This is the pressure exerted in the vessels when the ventricles are contracting.
• Orthostatic Hypotension (Postural Hypotension) : This is the decrease in blood pressure that occurs when a person stands erect.
• Peripheral Vascular Resistance: This is the pressure that blood must overcome as it flows in the vessels.
• Isolated Systolic Hypertension: This is defined as systolic blood pressure greater than or equal to 140 mmHg with diastolic blood pressure less than 90 mmHg. It is common in elderly patients.
• Malignant Hypertension: This is a rapidly progressing, potentially fatal form of hypertension with diastolic pressure exceeding 120 mmHg.
• Hypertensive Emergency : This is characterized by severe elevation in blood pressure > 180/120 mmHg complicated by target organ dysfunction. These situations require immediate reduction of blood pressure to limit target organ damage.
• Hypertensive Urgency : This is a situation with severe elevation of blood pressure without target organ dysfunction.

Table 1: Stages of Hypertension

• Category Systolic Diastolic
• Normal < 130 < 80
• High Normal (Pre-hypertension) 130-139 81-89
• Mild Hypertension (Stage I) 140-159 90-99
• Moderate Hypertension (Stage 2) 160-179 100-109
• Severe Hypertension (Stage 3) 180-209 110-119
• Very Severe Hypertension (Stage 4) > 209 > 119

Classification of Hypertension

Hypertension may be classified as:

• Essential (Primary) Hypertension
• Secondary Hypertension

Essential Hypertension

Essential hypertension is the most common type of hypertension, contributing to over 90% of the cases of hypertension encountered in medical practice. The cause of essential hypertension is not known.

Secondary Hypertension

Secondary hypertension is an elevation of blood pressure due to an identifiable cause such as:

• Renal disease
• Drugs like oral contraceptives
• Pre-eclampsia
• Renovascular disease

Treatment is directed at elimination of the cause.

Management of Hypertension

Non-Pharmacological Measures

• Encourage regular exercise (e.g., walking, jogging)
• Advise the patient to lose weight (if overweight)
• Advise the patient to limit alcohol intake
• Advise the patient to restrict salt intake
• Advise the patient to stop smoking
• Encourage a diet high in fruits and vegetables
• Advise the patient to relax and manage stress
• Diet should be low in saturated fats and cholesterol

Note: Non-pharmacological measures may be employed alone in pre-hypertension or in combination with drugs in mild to severe hypertension.

Drugs used in the treatment of hypertension may be classified as follows:

• Beta blockers
• ACE inhibitors
• Alpha-II blockers
• Diuretics
• Centrally acting antihypertensives
• Calcium channel blockers
• Angiotensin II antagonists
• Direct vasodilators

Table 2: Choice of Antihypertensives in Different Conditions

• Comorbid Disease Drugs Recommended
• Diabetes mellitus Calcium channel blockers, ACE inhibitors
• Congestive heart failure Diuretics, ACE inhibitors
• Angina pectoris Beta blockers, calcium channel blockers, ACE inhibitors, and diuretics as alternative
• Asthma, chronic pulmonary disease Calcium channel blockers, diuretics, and ACE inhibitors
• Hyperlipidemia ACE inhibitors, calcium channel blockers
• Previous myocardial infarction Beta blockers, calcium channel blockers, ACE inhibitors, and diuretics
• Chronic renal disease Diuretics, calcium channel blockers, beta blockers, and ACE inhibitors

These drugs are recommended in the treatment of hypertension, angina pectoris, and post-myocardial infarction.

Beta blockers are classified as follows:

Non-selective beta blockers

• Propranolol
• Sotalol

Selective beta-1 blockers

• Atenolol
• Bisoprolol
• Metoprolol

Alpha and beta blockers

• Carvedilol
• Labetalol

Mode of Action

Beta blockers competitively block the response to beta receptors, resulting in a decrease in heart rate and heart contractility, thereby lowering blood pressure.

Atenolol

Available Preparations:

• Tablets : 25 mg, 50 mg, 100 mg

Available Brands : Tenormin®, Totamol®, Velorin®, Atelor®, Betagard®, Cardinol®, Tensimin®

Combinations :

• Tenoret® (Atenolol/Chlorthalidone) 50/12.5 mg
• Tenoretic® (Atenolol/Chlorthalidone) 100/25 mg

Pharmacokinetics

About half of the dose is absorbed following oral administration, crosses the placenta, and is distributed into breast milk. Atenolol undergoes little or no hepatic metabolism and is excreted unchanged in the urine.

Indications

• Hypertension
• Angina pectoris
• Cardiac arrhythmias
• Prophylaxis in migraine
• Acute myocardial infarction

Contraindications

• Hypersensitivity to atenolol
• Sinus bradycardia
• Second and third-degree heart block
• Symptomatic heart failure

Dosage

• Hypertension : 25-100 mg once daily (100 mg is only slightly better than 50 mg)
• Angina : 100 mg once daily or 50 mg twice daily
• Arrhythmias : 50-100 mg daily
• Migraine Prophylaxis : 50-100 mg daily

Side Effects

• Fatigue
• Hypotension
• Impotence
• Muscle ache
• Dizziness
• Wheezing
• Insomnia

Drug Interactions

• Cimetidine may increase atenolol blood concentration
• Diuretics and other antihypertensives may increase the hypotensive effect of atenolol
• Atenolol may mask the symptoms of hypoglycemia and prolong the hypoglycemic effect of insulin and oral hypoglycemics
• NSAIDs may decrease the antihypertensive effects of atenolol
• Alcohol enhances the hypotensive effect of atenolol
• Concurrent use with digoxin increases the risk of AV block and bradycardia
• Oral contraceptives antagonize the hypotensive effect of atenolol
• Concurrent use with verapamil results in severe hypotension and heart failure

Key Issues to Note

• Atenolol should be used with caution in patients with diabetes since it may mask symptoms of hypoglycemia
• Atenolol may be administered with or without food
• Abrupt withdrawal of the drug should be avoided; it should be discontinued over 1-2 weeks through gradual reduction of the dose

These drugs are used in the treatment of hypertension and angina pectoris and are safe for patients with asthma, hyperlipidemia, diabetes, and renal dysfunction. They are subdivided into two groups:

• Dihydropyridines
• Non-dihydropyridines

Dihydropyridines : Drugs in this group produce significant blockage of calcium channels in blood vessels and minimal in the heart.

Examples:

• Nifedipine
• Amlodipine
• Felodipine

Non-Dihydropyridines : These drugs act on vascular smooth muscle and the heart. Since they suppress AV conduction, they are useful in cardiac arrhythmias.

Examples:

• Verapamil
• Diltiazem

Mode of Action

Calcium channel blockers decrease the influx of calcium into smooth muscles, thereby reducing vascular tone, which results in a reduction of peripheral resistance and blood pressure.

Nifedipine

Available Preparations:

• Tablets : 10 mg, 20 mg retard, 30 mg long-acting

Available Brands : Adalat®, Nifelat®, Nifedipine-denk®

Pharmacokinetics

Nifedipine is rapidly and almost completely absorbed from the gastrointestinal tract, but bioavailability is reduced by first-pass metabolism. It is extensively metabolized in the liver and excreted in the urine as inactive metabolites.

Indications

• Hypertension
• Prophylaxis of angina pectoris

Contraindications

• Hypersensitivity to nifedipine
• Unstable or acute attacks of angina
• Porphyria
• Cardiogenic shock

Dosage

The dose and frequency of administration vary depending on the preparations used.

• Short-acting nifedipine is given 3 times a day
• Nifedipine retard is given twice daily
• Long-acting nifedipine is given once daily

Hypertension :

• Adults: 10-20 mg twice daily, increased to 20-40 mg twice daily (Nifedipine retard)
• Nifedipine long-acting: 30-90 mg once daily

Angina Pectoris :

• Nifedipine retard: 10-40 mg twice daily or nifedipine long-acting: 30-90 mg once daily

Side Effects

• Oedema of ankle
• Headache
• Flushing
• Dizziness
• Tachycardia
• Palpitations
• Impotence
• Tremors
• Muscle cramps
• Dry mouth
• Constipation
• Nausea

Drug Interactions

• Beta blockers may have additive hypotensive effects when given together with nifedipine
• Nifedipine may increase digoxin blood concentration
• Nifedipine increases the plasma concentration of digoxin
• Rifampicin increases the metabolism of nifedipine, leading to reduced plasma concentrations

Key Issues to Note

• Administer nifedipine with food and swallow sustained-release tablets without chewing
• Advise the patient to avoid alcohol
• Advise the patient to rise slowly from a prolonged sitting or lying position
• Advise the patient not to stop using the drug suddenly
• Inform the patient that excessive hypotension may occur, especially at the beginning of treatment

Amlodipine

Available Preparations:

• Tablets : 5 mg, 10 mg
• Capsules : 5 mg, 2.5 mg

Available Brands: Norvasc®, Amtas®, Asomex®, Amlong®, Lovasc®, Lofral®, Amlodac®, Amedin®

Pharmacokinetics

Amlodipine is well absorbed following oral administration. It is extensively metabolized in the liver and excreted in the urine.

Indications

• Hypertension
• Prophylaxis of angina pectoris

Contraindications

• Unstable angina
• Known hypersensitivity to amlodipine
• Breastfeeding

Dosage

• Hypertension or Angina : Initially 5 mg once daily, increased after 10-14 days to a max of 10 mg once daily if necessary

Side Effects

• Headache
• Dizziness
• Oedema
• Fatigue
• Flushes
• Hypotension
• Malaise
• Bradycardia
• Palpitations
• Taste disturbances
• Abdominal pain

Drug Interactions

• Cimetidine increases serum levels of amlodipine
• Rifampicin may decrease serum concentrations of amlodipine
• Erythromycin may reduce clearance of amlodipine
• Barbiturates reduce plasma concentrations of amlodipine

Key Issues to Note

• Amlodipine may be administered without regard to food but take with caution with grapefruit juice
• Inform the patient not to discontinue the drug abruptly