CLASSIFICATION OF ANTIHYPERTENSIVE DRUGS

Antihypertensive drugs are medications used to treat hypertension (high blood pressure).
They work through various mechanisms to lower blood pressure and prevent complications
such as stroke, myocardial infarction, and kidney damage. The following is a detailed
classification of antihypertensive drugs:

1. Diuretics

• Thiazide Diuretics: Hydrochlorothiazide, Chlorthalidone, Indapamide

• Loop Diuretics: Furosemide, Bumetanide, Torsemide
• Potassium-Sparing Diuretics: Spironolactone, Eplerenone, Amiloride, Triamterene

2. Beta-Blockers

• Non-Selective Beta-Blockers: Propranolol, Nadolol, Timolol

• Cardioselective Beta-Blockers: Metoprolol, Atenolol, Bisoprolol
• Beta-Blockers with Alpha-Blocking Activity: Carvedilol, Labetalol

3. Angiotensin-Converting Enzyme (ACE) Inhibitors

• Common ACE Inhibitors: Lisinopril, Enalapril, Ramipril, Captopril, Benazepril

4. Angiotensin II Receptor Blockers (ARBs)

• Common ARBs: Losartan, Valsartan, Irbesartan, Telmisartan, Olmesartan

5. Calcium Channel Blockers (CCBs)

• Dihydropyridines: Amlodipine, Nifedipine, Felodipine, Nicardipine

• Non-Dihydropyridines: Verapamil, Diltiazem

6. Alpha-1 Blockers

• Common Alpha-1 Blockers: Prazosin, Doxazosin, Terazosin

7. Central Alpha Agonists

• Common Central Alpha Agonists: Clonidine, Methyldopa, Guanfacine

8. Direct Vasodilators

• Common Direct Vasodilators: Hydralazine, Minoxidil

9. Renin Inhibitors

• Common Renin Inhibitors: Aliskiren

Diuretics in Hypertension Management

Diuretics are a class of medications that help eliminate excess fluid and sodium from the
body, thereby reducing blood pressure. They are often the first line of treatment for
hypertension and are categorized into three main types: thiazide diuretics, loop diuretics, and
potassium-sparing diuretics. Each type acts at different sites within the kidneys and has
distinct mechanisms of action.

1. Thiazide Diuretics

Examples: Hydrochlorothiazide, Chlorthalidone, Indapamide

Mechanism of Action: Thiazide diuretics act on the distal convoluted tubule of the nephron.
They inhibit the sodium-chloride symporter, reducing sodium reabsorption. As a result, more
sodium and water are excreted in the urine, decreasing blood volume and blood pressure.

Clinical Use:

• Often used as a first-line treatment for hypertension.

• Particularly effective in elderly patients and African American patients.
• May be combined with other antihypertensives for better control.

Side Effects:

• Hypokalemia (low potassium levels)

• Hyponatremia (low sodium levels)
• Hypercalcemia (high calcium levels)
• Hyperuricemia (high uric acid levels, which can exacerbate gout)
• Hyperglycemia (high blood sugar levels)

Monitoring:

• Electrolytes (especially potassium and sodium)

• Renal function
• Blood pressure

2. Loop Diuretics

Examples: Furosemide, Bumetanide, Torsemide

Mechanism of Action: Loop diuretics act on the thick ascending limb of the loop of Henle.
They inhibit the sodium-potassium-chloride cotransporter (NKCC2), leading to a significant
increase in the excretion of sodium, potassium, chloride, and water. This results in a
substantial reduction in blood volume and pressure.

Clinical Use:

• Typically used in conditions with fluid overload, such as heart failure, chronic kidney
disease, and acute pulmonary edema.
 • Less commonly used for long-term management of hypertension due to potent
diuretic effects and the need for close monitoring.

Side Effects:

• Hypokalemia
• Hyponatremia
• Hypocalcemia (low calcium levels)
• Hypomagnesemia (low magnesium levels)
• Ototoxicity (hearing damage, particularly with high doses or rapid infusion)
• Dehydration

Monitoring:

• Electrolytes (potassium, sodium, calcium, magnesium)

• Renal function
• Fluid status
• Blood pressure

3. Potassium-Sparing Diuretics

Examples: Spironolactone, Eplerenone, Amiloride, Triamterene

Mechanism of Action:

• Spironolactone and Eplerenone: These are aldosterone antagonists. They inhibit the
action of aldosterone on the distal nephron, reducing sodium reabsorption and
potassium excretion.
• Amiloride and Triamterene: These block sodium channels in the distal nephron,
reducing sodium reabsorption and minimizing potassium loss.

Clinical Use:

• Often used in combination with other diuretics to prevent hypokalemia.

• Spironolactone and eplerenone are beneficial in conditions like heart failure, primary
hyperaldosteronism, and resistant hypertension.

Side Effects:

• Hyperkalemia (high potassium levels)

• Gynecomastia (breast enlargement in men, particularly with spironolactone)
• Menstrual irregularities
• Gastrointestinal disturbances

Monitoring:

• Potassium levels
• Renal function
• Blood pressure
General Considerations for Diuretics

Efficacy:

• Thiazide diuretics are particularly effective for long-term management of

hypertension and are often recommended as the initial therapy.
• Loop diuretics are powerful diuretics suitable for acute management of severe
hypertension or fluid overload conditions but require careful monitoring due to their
potent effects.
• Potassium-sparing diuretics are useful as adjunctive therapy to counteract potassium
loss from other diuretics.

Combination Therapy:

• Diuretics are frequently used in combination with other antihypertensive agents such
as ACE inhibitors, ARBs, beta-blockers, or calcium channel blockers for better blood
pressure control and to mitigate side effects.

Beta Blockers in Hypertension Management

Beta blockers are a class of medications used to treat hypertension and various cardiovascular
conditions. They work by blocking the effects of the hormone epinephrine (adrenaline) on
beta-adrenergic receptors, which are found in the heart and blood vessels. This leads to a
decrease in heart rate, cardiac output, and blood pressure.

Classification of Beta Blockers

1. Non-Selective Beta Blockers

2. Cardioselective Beta Blockers
3. Beta Blockers with Alpha-Blocking Activity

1. Non-Selective Beta Blockers

Examples: Propranolol, Nadolol, Timolol

Mechanism of Action: Non-selective beta blockers inhibit both beta-1 and beta-2 receptors.
Beta-1 receptors are primarily found in the heart, while beta-2 receptors are located in the
lungs, vascular smooth muscle, and other tissues.

Clinical Use:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Essential tremor
Side Effects:

• Bronchoconstriction (caution in asthma and COPD)

• Bradycardia (slow heart rate)
• Fatigue
• Cold extremities
• Masking of hypoglycemia symptoms in diabetic patients

2. Cardioselective Beta Blockers

Examples: Metoprolol, Atenolol, Bisoprolol

Mechanism of Action: Cardioselective beta blockers preferentially block beta-1 receptors in

the heart. At higher doses, they may also inhibit beta-2 receptors.

Clinical Use:

• Hypertension
• Angina pectoris
• Heart failure
• Myocardial infarction (heart attack)
• Arrhythmias

Side Effects:

• Bradycardia
• Fatigue
• Dizziness
• Reduced exercise tolerance

3. Beta Blockers with Alpha-Blocking Activity

Examples: Carvedilol, Labetalol

Mechanism of Action: These beta blockers inhibit both beta and alpha-adrenergic receptors.
The alpha-blocking effect leads to vasodilation, further reducing blood pressure.

Clinical Use:

• Hypertension
• Heart failure
• Hypertensive emergencies (labetalol)

Side Effects:

• Orthostatic hypotension (drop in blood pressure when standing up)

• Dizziness
• Fatigue
• Bradycardia
Angiotensin-Converting Enzyme (ACE) Inhibitors in Hypertension
Management

Angiotensin-converting enzyme (ACE) inhibitors are a class of medications used to treat

hypertension and other cardiovascular conditions. They work by inhibiting the enzyme that
converts angiotensin I to angiotensin II, a potent vasoconstrictor. This results in vasodilation,
reduced blood volume, and decreased blood pressure.

Common ACE Inhibitors

• Lisinopril
• Enalapril
• Ramipril
• Captopril
• Benazepril
• Quinapril
• Perindopril

Mechanism of Action

ACE inhibitors block the conversion of angiotensin I to angiotensin II by inhibiting the

angiotensin-converting enzyme. This leads to several beneficial effects:

1. Vasodilation: Angiotensin II is a potent vasoconstrictor. By reducing its formation,

ACE inhibitors cause relaxation of blood vessels, which lowers blood pressure.
2. Decreased Aldosterone Secretion: Angiotensin II stimulates the release of
aldosterone from the adrenal glands. Aldosterone promotes sodium and water
retention, increasing blood volume. ACE inhibitors reduce aldosterone secretion,
leading to decreased sodium and water retention and further lowering blood pressure.
3. Reduction in Sympathetic Nervous System Activity: Angiotensin II enhances
sympathetic nervous system activity. By decreasing angiotensin II levels, ACE
inhibitors reduce sympathetic nervous system outflow, contributing to lower blood
pressure.

Clinical Uses

• Hypertension: ACE inhibitors are effective in reducing blood pressure and are often
used as first-line therapy, especially in patients with coexisting conditions like
diabetes or chronic kidney disease.
• Heart Failure: They help reduce the workload on the heart and improve symptoms in
patients with heart failure.
• Post-Myocardial Infarction: ACE inhibitors reduce mortality and improve outcomes
in patients who have had a heart attack.
• Diabetic Nephropathy: They provide renal protection by reducing intraglomerular
pressure and slowing the progression of kidney disease in diabetic patients.
Side Effects

1. Cough: A persistent dry cough is a common side effect due to increased bradykinin
levels, which can irritate the respiratory tract.
2. Hyperkalemia: Elevated potassium levels can occur due to decreased aldosterone
activity, which can lead to dangerous cardiac arrhythmias.
3. Hypotension: Excessive lowering of blood pressure, especially after the first dose,
can cause dizziness or fainting.
4. Angioedema: A rare but serious side effect involving swelling of the deeper layers of
the skin, often around the eyes and lips, and potentially the airways.
5. Renal Impairment: ACE inhibitors can cause a decline in renal function, particularly
in patients with pre-existing kidney disease or those who are dehydrated.

Contraindications

1. Pregnancy: ACE inhibitors can cause fetal injury or death and are contraindicated in
pregnancy.
2. Bilateral Renal Artery Stenosis: Patients with this condition can experience acute
renal failure with ACE inhibitor use.
3. History of Angioedema: Due to the risk of recurrence, ACE inhibitors are
contraindicated in patients with a history of angioedema related to previous ACE
inhibitor therapy.
4. Hyperkalemia: Patients with high baseline potassium levels should avoid ACE
inhibitors due to the risk of further increasing potassium levels.

Angiotensin II Receptor Blockers (ARBs)

Angiotensin II receptor blockers (ARBs) are a class of medications used to treat hypertension
and other cardiovascular conditions. They work by blocking the action of angiotensin II on its
receptors, which helps relax blood vessels and reduce blood pressure.

Common ARBs

• Losartan
• Valsartan
• Irbesartan
• Candesartan
• Olmesartan
• Telmisartan
• Eprosartan

Mechanism of Action

ARBs specifically block the binding of angiotensin II to the angiotensin II type 1 (AT1)
receptors on blood vessels and other tissues. This action leads to several beneficial effects:
 1. Vasodilation: By inhibiting the action of angiotensin II, ARBs cause relaxation of
blood vessels, which lowers blood pressure.
2. Reduced Aldosterone Secretion: Blocking angiotensin II reduces aldosterone release
from the adrenal glands, decreasing sodium and water retention and further lowering
blood pressure.
3. Reduction in Sympathetic Nervous System Activity: Angiotensin II enhances
sympathetic nervous system activity. By blocking its action, ARBs reduce
sympathetic outflow, contributing to lower blood pressure.
4. Cardiovascular and Renal Protection: ARBs help reduce the risk of heart and
kidney damage by lowering blood pressure and decreasing the workload on these
organs.

Side Effects

1. Hyperkalemia: Elevated potassium levels can occur, especially in patients with renal
impairment or those taking potassium supplements or potassium-sparing diuretics.
2. Hypotension: Excessive lowering of blood pressure, particularly after the first dose,
can cause dizziness or fainting.
3. Renal Impairment: ARBs can cause a decline in renal function, particularly in
patients with pre-existing kidney disease or those who are dehydrated.
4. Angioedema: While less common than with ACE inhibitors, ARBs can still cause
angioedema.
5. Gastrointestinal Symptoms: Nausea, diarrhea, and abdominal pain can occur but are
generally mild.

Contraindications

1. Pregnancy: ARBs can cause fetal injury or death and are contraindicated in
pregnancy.
2. Bilateral Renal Artery Stenosis: Patients with this condition can experience acute
renal failure with ARB use.
3. History of Angioedema: While less common with ARBs than with ACE inhibitors,
patients with a history of angioedema related to ARBs should avoid these
medications.
4. Hyperkalemia: Patients with high baseline potassium levels should avoid ARBs due
to the risk of further increasing potassium levels.

Calcium Channel Blockers (CCBs) in Hypertension Management

Calcium channel blockers (CCBs) are a class of medications used to treat hypertension and
other cardiovascular conditions. They work by inhibiting the influx of calcium ions through
L-type calcium channels in the heart and vascular smooth muscle, leading to vasodilation and
decreased cardiac contractility.

Classification of Calcium Channel Blockers

1. Dihydropyridines (DHPs)
2. Non-Dihydropyridines (Non-DHPs)
1. Dihydropyridines (DHPs)

Examples: Amlodipine, Nifedipine, Felodipine, Nicardipine

Mechanism of Action: DHPs primarily act on vascular smooth muscle, causing vasodilation
and reducing peripheral resistance, which lowers blood pressure. They have minimal effects
on the heart.

Clinical Use:

• Hypertension
• Angina pectoris (particularly Prinzmetal's angina)
• Raynaud's phenomenon

Side Effects:

• Peripheral edema (swelling of the legs and ankles)

• Flushing
• Headache
• Dizziness
• Reflex tachycardia (especially with short-acting DHPs)

2. Non-Dihydropyridines (Non-DHPs)

Examples: Verapamil, Diltiazem

Mechanism of Action: Non-DHPs act on both the heart and vascular smooth muscle. They
reduce heart rate, decrease myocardial contractility, and cause vasodilation.

Clinical Use:

• Hypertension
• Angina pectoris
• Supraventricular tachycardia (SVT)
• Atrial fibrillation/flutter

Side Effects:

• Bradycardia
• Constipation (particularly with verapamil)
• Heart block
• Negative inotropic effect (reduced force of heart contraction)

Mechanism of Action

CCBs inhibit the influx of calcium ions through L-type calcium channels, leading to several
beneficial effects:

1. Vasodilation: By reducing calcium entry into vascular smooth muscle cells, CCBs
cause relaxation of these muscles, leading to vasodilation and lowered blood pressure.
 2. Decreased Cardiac Contractility: By inhibiting calcium influx into cardiac muscle
cells, non-DHP CCBs reduce the force of myocardial contraction, which decreases
cardiac output and blood pressure.
3. Slowed Heart Rate: Non-DHP CCBs decrease the heart rate by affecting the calcium
channels in the sinoatrial (SA) and atrioventricular (AV) nodes, which helps in
controlling arrhythmias and reducing blood pressure.

Clinical Uses

• Hypertension: CCBs are effective in reducing blood pressure and can be used as
first-line therapy, particularly in certain populations such as older adults and those of
African descent.
• Angina Pectoris: CCBs relieve angina by reducing myocardial oxygen demand
through decreased heart rate and contractility (non-DHPs) and by increasing oxygen
supply through vasodilation (DHPs).
• Arrhythmias: Non-DHP CCBs, such as verapamil and diltiazem, are used to manage
supraventricular tachycardia and control ventricular rate in atrial fibrillation/flutter.
• Raynaud's Phenomenon: DHP CCBs are used to treat Raynaud's phenomenon by
improving blood flow to extremities.

Side Effects

1. Peripheral Edema: Common with DHPs due to vasodilation.

2. Flushing and Headache: Result from vasodilation.
3. Dizziness: Can occur due to lowered blood pressure.
4. Bradycardia and Heart Block: More common with non-DHPs due to their effects on
the heart.
5. Constipation: Particularly associated with verapamil.
6. Gingival Hyperplasia: Overgrowth of gum tissue, especially with long-term use of
DHPs.

Contraindications

1. Severe Hypotension: Use of CCBs can exacerbate low blood pressure.

2. Severe Heart Failure: Non-DHPs can worsen heart failure due to their negative
inotropic effects.
3. Bradycardia and Heart Block: Non-DHPs are contraindicated in patients with
significant bradycardia or AV block without a pacemaker.
4. Liver Dysfunction: CCBs are metabolized by the liver, and caution is required in
patients with liver impairment.

Alpha-1 Blockers in Hypertension Management

Alpha-1 blockers, also known as alpha-adrenergic antagonists, are a class of medications

used to treat hypertension and certain other conditions. They work by inhibiting the alpha-1
adrenergic receptors on vascular smooth muscle, leading to vasodilation and reduced blood
pressure.
Common Alpha-1 Blockers

• Prazosin
• Terazosin
• Doxazosin

Mechanism of Action

Alpha-1 blockers selectively block the alpha-1 adrenergic receptors on blood vessels. This
action leads to several beneficial effects:

1. Vasodilation: By blocking the alpha-1 receptors, these drugs cause relaxation of the
vascular smooth muscle, leading to vasodilation and reduced peripheral resistance,
which lowers blood pressure.
2. Reduced Blood Pressure: The primary effect is the lowering of blood pressure,
particularly by decreasing diastolic blood pressure.

Clinical Uses

• Hypertension: Alpha-1 blockers are effective in reducing blood pressure and can be
used as part of combination therapy for managing hypertension.
• Benign Prostatic Hyperplasia (BPH): These medications are often prescribed to
treat symptoms of BPH, such as difficulty in urination, by relaxing the smooth
muscles of the bladder neck and prostate.
• Pheochromocytoma: Alpha-1 blockers can be used in managing hypertension
associated with pheochromocytoma, a rare tumor of the adrenal gland.

Side Effects

1. Orthostatic Hypotension: A significant drop in blood pressure upon standing,

leading to dizziness or fainting. This effect is more pronounced with the first dose, so
patients are often advised to take the first dose at bedtime.
2. Dizziness and Lightheadedness: Common due to the blood pressure-lowering
effects.
3. Headache: Can occur due to vasodilation.
4. Fatigue: Some patients may experience tiredness.
5. Nasal Congestion: Due to vasodilation of nasal blood vessels.
6. Palpitations: Rapid or irregular heartbeat can occur as the body adjusts to the lower
blood pressure.

Contraindications

1. Hypotension: Alpha-1 blockers should be used with caution in patients with existing
low blood pressure or those prone to orthostatic hypotension.
2. Heart Failure: Although not a strict contraindication, caution is advised as these
drugs can exacerbate symptoms in some patients.
3. History of Syncope: Patients with a history of fainting spells should use alpha-1
blockers with caution.
Central Alpha Agonists

Central alpha agonists, also known as centrally acting alpha-2 adrenergic agonists, are a class
of medications used to treat hypertension by reducing sympathetic outflow from the central
nervous system. This leads to a decrease in blood pressure.

Common Central Alpha Agonists

• Clonidine
• Methyldopa
• Guanfacine

Mechanism of Action

Central alpha agonists work by stimulating alpha-2 adrenergic receptors in the brain. This
action reduces the release of norepinephrine and decreases sympathetic outflow, which leads
to several effects:

1. Decreased Sympathetic Activity: By reducing norepinephrine release, central alpha

agonists decrease the activity of the sympathetic nervous system, leading to lower
heart rate and vasodilation.
2. Reduced Cardiac Output: The reduction in heart rate and contractility lowers
cardiac output, contributing to the antihypertensive effect.
3. Vasodilation: The decreased sympathetic tone leads to relaxation of the blood
vessels, reducing peripheral resistance and lowering blood pressure.

Clinical Uses

• Hypertension: Central alpha agonists are effective in lowering blood pressure and are
often used in patients with resistant hypertension or those who cannot tolerate other
antihypertensive medications.
• Attention Deficit Hyperactivity Disorder (ADHD): Guanfacine and clonidine are
sometimes used in the management of ADHD.
• Opioid Withdrawal: Clonidine is used to manage symptoms of opioid withdrawal by
reducing sympathetic overactivity.
• Hypertensive Crisis: Clonidine can be used in an emergency setting to rapidly lower
blood pressure.

Side Effects

1. Sedation: One of the most common side effects, particularly with clonidine and
methyldopa, is drowsiness or fatigue.
2. Dry Mouth: Reduced sympathetic outflow can lead to decreased saliva production.
3. Bradycardia: Lowered heart rate due to reduced sympathetic activity.
4. Orthostatic Hypotension: A drop in blood pressure upon standing, leading to
dizziness or fainting.
5. Depression: Central alpha agonists can sometimes exacerbate depressive symptoms.
6. Rebound Hypertension: Abrupt discontinuation of these medications can lead to a
rapid and dangerous increase in blood pressure.
Contraindications

1. Severe Bradycardia: Use with caution in patients with significantly low heart rates.
2. Depression: Central alpha agonists can worsen depression, so they should be used
cautiously in patients with a history of depressive disorders.
3. Severe Liver Disease: Particularly with methyldopa, which is metabolized in the
liver.

Direct Vasodilators
Direct vasodilators are a class of medications used to treat hypertension by directly relaxing
the smooth muscle in blood vessels, leading to vasodilation and a reduction in blood pressure.

Common Direct Vasodilators

• Hydralazine
• Minoxidil

Mechanism of Action

Direct vasodilators work by directly acting on the smooth muscle cells in the arterial walls,
causing them to relax. This results in vasodilation (widening of the blood vessels), which
reduces vascular resistance and lowers blood pressure.

Clinical Uses

• Hypertension: Used to manage high blood pressure, particularly in cases of severe or

resistant hypertension.
• Heart Failure: Hydralazine, in combination with nitrates, is used in heart failure,
especially in patients who cannot tolerate ACE inhibitors or ARBs.
• Alopecia (Hair Loss): Minoxidil is used topically to treat hair loss.

Side Effects

Hydralazine

1. Reflex Tachycardia: An increase in heart rate as a compensatory response to the

drop in blood pressure.
2. Fluid Retention: Sodium and water retention can occur, often requiring concurrent
use of a diuretic.
3. Lupus-Like Syndrome: Prolonged use can cause a syndrome resembling systemic
lupus erythematosus, especially at higher doses.
4. Headache: Due to vasodilation.
5. Dizziness: Common, particularly when standing up quickly.
6. Nausea: Gastrointestinal disturbances can occur.

Minoxidil
 1. Severe Fluid Retention: Leading to edema, which often necessitates the use of
diuretics.
2. Reflex Tachycardia: Significant increase in heart rate, often requiring beta-blockers
to control.
3. Hypertrichosis: Excessive hair growth, which is a desired effect when used topically
for hair loss but an unwanted side effect when used orally.
4. Pericardial Effusion: Accumulation of fluid around the heart, which can be severe.

Contraindications

1. Severe Coronary Artery Disease: Due to the risk of reflex tachycardia exacerbating
angina.
2. Mitral Valve Rheumatic Heart Disease: Specifically for hydralazine.
3. Pheochromocytoma: Due to potential severe blood pressure changes.
4. Heart Failure: Caution with minoxidil due to the risk of fluid retention and
pericardial effusion.