Major Groups of Drugs Used in the Treatment of Hypertension
Several distinct drug classes target different physiological mechanisms involved in blood pressure regulation. Here is a list of the major groups, along with a representative example for each:
- Diuretics: Increase excretion of sodium and water by the kidneys, reducing blood volume and thus blood pressure.
- Example: Hydrochlorothiazide (HCTZ) – a commonly used thiazide diuretic.
- Angiotensin-Converting Enzyme Inhibitors (ACE-I): Block the enzyme that converts angiotensin I to angiotensin II, a powerful vasoconstrictor. This leads to vasodilation and reduced aldosterone secretion, decreasing sodium and water retention.
- Example: Lisinopril.
- Angiotensin II Receptor Blockers (ARBs): Block angiotensin II from binding to its receptors in blood vessels and other tissues. This also results in vasodilation and reduced aldosterone effects. Often used as an alternative for patients who develop a cough with ACE-I.
- Example: Losartan.
- Calcium Channel Blockers (CCBs): Block calcium entry into smooth muscle cells in blood vessels, causing relaxation and vasodilation. Some types also reduce heart rate and contractility.
- Example: Amlodipine (a dihydropyridine CCB primarily affecting blood vessels).
- Beta-Adrenergic Blockers (Beta Blockers): Block the effects of adrenaline (epinephrine) and noradrenaline (norepinephrine) on beta-adrenergic receptors in the heart, blood vessels, and kidneys. This typically reduces heart rate, contractility, renin release, and can lead to vasodilation.
- Example: Metoprolol (a selective beta-1 blocker).
- Alpha-Adrenergic Blockers (Alpha Blockers): Block the effects of noradrenaline on alpha-1 adrenergic receptors in blood vessels, causing vasodilation and reducing peripheral vascular resistance.
- Example: Doxazosin.
- Combined Alpha and Beta Blockers: Block both alpha and beta adrenergic receptors.
- Example: Labetalol.
- Centrally Acting Agents: Stimulate alpha-2 adrenergic receptors in the brainstem, reducing sympathetic outflow from the central nervous system. This decreases heart rate, contractility, and peripheral resistance.
- Example: Clonidine.
- Direct Renin Inhibitors: Block renin, an enzyme that initiates the renin-angiotensin-aldosterone system (RAAS). This prevents the formation of angiotensin I and subsequently angiotensin II.
- Example: Aliskiren.
The Value of Diuretics in the Treatment of Hypertension
Diuretics, particularly thiazide diuretics like hydrochlorothiazide or chlorthalidone, hold significant value in the management of hypertension due to several factors:
- Established Effectiveness: Thiazide diuretics have a long history of safe and effective use in lowering blood pressure. They are often recommended as first-line therapy, either alone or in combination with other agents.
- Cost-Effectiveness: Many diuretics, especially thiazides, are available as inexpensive generic medications, making them an accessible treatment option for a wide range of patients.
- Mechanism of Action: By promoting the excretion of sodium and water, diuretics reduce the volume of blood circulating in the body. This reduction in blood volume leads to decreased pressure on the arterial walls. Over time, they may also have a mild vasodilatory effect.
- Reduction of Cardiovascular Events: Large clinical trials have demonstrated that diuretic-based antihypertensive regimens are effective in reducing major cardiovascular events, including stroke, heart attack, and heart failure.
- Synergy with Other Agents: Diuretics are frequently used in combination therapies. Their mechanism complements other drug classes (like ACE-I, ARBs, or beta blockers) by addressing the volume component of blood pressure, often enhancing the overall antihypertensive effect and counteracting potential sodium/water retention caused by other drugs.
- Treatment of Comorbidities: They are particularly valuable in patients with hypertension accompanied by conditions where volume reduction is beneficial, such as heart failure or edema.
The Value of Centrally Acting Antihypertensive Drugs: Indications and Adverse Effects
Centrally acting antihypertensive drugs play a role in hypertension management, though they are typically not first-line agents due to their side effect profile.
- Value: Their primary value lies in their mechanism, which directly reduces sympathetic nervous system activity originating from the brain. This can be particularly effective in patients whose hypertension is significantly driven by sympathetic overactivity. They can be useful in more complex cases, including resistant hypertension (high blood pressure that does not respond adequately to three or more different classes of medications, including a diuretic).
- Indications:
- Resistant Hypertension: Often used as an add-on therapy when other drug classes have failed to achieve target blood pressure.
- Hypertension in Pregnancy: Methyldopa is considered one of the safest antihypertensive medications for use during pregnancy.
- Less common/specific uses: Clonidine can sometimes be used in specific situations like hypertensive urgency (with careful monitoring) or to manage withdrawal symptoms from opioids or alcohol (off-label).
- Adverse Effects: Centrally acting agents are associated with several common and sometimes limiting side effects:
- Central Nervous System Effects: Sedation, drowsiness, fatigue, dizziness, difficulty concentrating.
- Anticholinergic Effects: Dry mouth, constipation.
- Bradycardia: Slow heart rate.
- Orthostatic Hypotension: Dizziness upon standing due to a sudden drop in blood pressure.
- Rebound Hypertension (especially with Clonidine): A potentially severe and rapid increase in blood pressure if the medication is stopped abruptly. Dose must be tapered gradually.
- Other: Nasal congestion, erectile dysfunction, depression.
The Value of Adrenoceptor Agents in the Treatment of Hypertension
Adrenoceptor blocking agents target the body’s sympathetic nervous system by interfering with the actions of adrenaline and noradrenaline at various receptor sites (alpha and beta receptors). Their value stems from their diverse mechanisms and applicability in patients with specific comorbidities.
- Beta Blockers: Primarily block beta-1 receptors (mostly in the heart) and/or beta-2 receptors (in lungs, peripheral blood vessels, etc.). Their value in hypertension includes:
- Reducing heart rate and contractility, decreasing cardiac output.
- Inhibiting renin release from the kidneys, affecting the RAAS.
- Often used in patients with concomitant conditions like angina, post-myocardial infarction, certain arrhythmias (e.g., atrial fibrillation), or heart failure (specific beta blockers).
- Alpha Blockers: Block alpha-1 receptors in the smooth muscle of peripheral blood vessels, causing vasodilation and reducing peripheral vascular resistance. Their value includes:
- Effective for reducing peripheral resistance.
- Also used to manage symptoms of benign prostatic hyperplasia (BPH) due to relaxation of smooth muscle in the prostate and bladder neck, making them a valuable choice for hypertensive men with BPH.
- Combined Alpha and Beta Blockers: Offer a combination of effects, reducing heart rate and contractility (beta blockade) while also causing peripheral vasodilation (alpha blockade). Their value lies in providing a broader sympathetic blockade, useful in conditions like hypertensive emergencies (e.g., Labetalol IV) or hypertension associated with pheochromocytoma.
Major Indications, Contraindications, Pharmacokinetics, and Adverse Effects of Commonly Used Adrenoceptor Agents
Let’s look in more detail at the commonly used sub-classes of adrenoceptor agents.
A. Beta-Adrenergic Blockers (Beta Blockers)
- Common Examples: Metoprolol, Atenolol (selective Beta-1); Propranolol, Nadolol (non-selective Beta-1 & Beta-2); Carvedilol (non-selective Beta & Alpha-1).
- Major Indications:
- Hypertension (especially with concomitant conditions like angina, post-MI, supraventricular arrhythmias).
- Angina Pectoris.
- Post-Myocardial Infarction.
- Heart Failure (specific agents like Metoprolol succinate, Carvedilol, Bisoprolol).
- Certain Arrhythmias.
- Migraine Prophylaxis (Propranolol).
- Tremor.
- Anxiety/Performance Anxiety.
- Contraindications:
- Severe Bradycardia (very slow heart rate).
- High-degree Heart Block (second or third degree AV block) without a pacemaker.
- Cardiogenic Shock.
- Decompensated Heart Failure.
- Non-selective beta blockers are generally contraindicated or used with extreme caution in patients with Bronchial Asthma or severe Chronic Obstructive Pulmonary Disease (COPD) due to the risk of bronchospasm (blocking Beta-2 receptors in the lungs).
- Pharmacokinetics (General):
- Absorption varies; some have significant first-pass metabolism (e.g., Propranolol, Metoprolol), requiring higher oral doses compared to IV.
- Generally well-distributed in the body. Lipophilic agents (e.g., Propranolol, Metoprolol) cross the blood-brain barrier more readily, potentially leading to more CNS side effects. Hydrophilic agents (e.g., Atenolol, Nadolol) have less CNS penetration.
- Metabolism is primarily hepatic for lipophilic beta blockers, and excretion is mainly renal for hydrophilic ones. This is important for dosing in patients with liver or kidney dysfunction.
- Half-lives vary, allowing for once-daily dosing for many agents (e.g., Atenolol, Metoprolol succinate ER).
- Adverse Effects:
- Fatigue, weakness, dizziness.
- Bradycardia, hypotension.
- Cold extremities.
- Bronchospasm (especially non-selective agents).
- Masking of hypoglycemia symptoms in diabetic patients (except sweating).
- Erectile dysfunction.
- Depression, sleep disturbances, nightmares (especially lipophilic agents).
- Worsening of intermittent claudication/peripheral artery disease in some cases.
- Withdrawal syndrome if stopped abruptly (rebound angina, hypertension, palpitations, MI), particularly with short-acting agents. Must be tapered.
B. Alpha-Adrenergic Blockers (Alpha Blockers)
- Common Examples: Prazosin, Terazosin, Doxazosin.
- Major Indications:
- Hypertension (often as add-on therapy).
- Benign Prostatic Hyperplasia (BPH) symptoms.
- Contraindications:
- Hypotension (though paradoxically used to treat hypertension, caution required).
- History of orthostatic hypotension with syncope.
- Pharmacokinetics (General):
- Well absorbed orally.
- Mostly hepatic metabolism.
- Excreted primarily in feces.
- Varying half-lives (Prazosin requires twice/thrice daily dosing, Terazosin and Doxazosin are once daily).
- Adverse Effects:
- First-dose phenomenon: Severe orthostatic hypotension (dizziness, fainting) after the first dose or initial dose increases. Usually managed by starting with a low dose at bedtime.
- Orthostatic hypotension.
- Dizziness, headache.
- Palpitations.
- Nasal congestion.
- Lack of energy/weakness.
- Priapism (rare).
- Intraoperative Floppy Iris Syndrome (IFIS) during cataract surgery.
C. Combined Alpha and Beta Blockers
- Common Examples: Labetalol, Carvedilol (Carvedilol was listed under beta blockers, but notably has significant alpha-1 blocking activity as well, making it a combined blocker).
- Major Indications:
- Hypertension (especially Labetalol in hypertensive emergencies – IV formulation).
- Hypertension in pregnancy (Labetalol is a common choice).
- Hypertension associated with pheochromocytoma (after alpha blockade is established).
- Heart Failure (Carvedilol is one of the specific agents indicated).
- Contraindications:
- Similar to beta blockers (severe bradycardia, high-degree heart block, decompensated heart failure).
- Bronchial asthma (especially Labetalol).
- Pharmacokinetics (General):
- Oral absorption varies, significant first-pass metabolism (e.g., Labetalol).
- Hepatic metabolism is significant.
- Excretion primarily via urine and feces.
- Half-lives allow for twice-daily dosing (e.g., Labetalol, Carvedilol).
- Adverse Effects:
- Combination of beta and alpha blocker side effects.
- Orthostatic hypotension more prominent than with pure beta blockers.
- Dizziness, fatigue, headache.
- Bradycardia.
- Scalp tingling (transient, with Labetalol).
- Erectile dysfunction.
- Bronchospasm risk.
Conclusion
The pharmacologic treatment of hypertension is a complex and individualized process. Understanding the major drug classes – including diuretics, agents affecting the renin-angiotensin system, calcium channel blockers, centrally acting agents, and adrenoceptor blockers – and their specific properties is essential for effective management. Adrenoceptor agents, comprising beta, alpha, and combined blockers, represent a diverse group with unique indications, contraindications, pharmacokinetic profiles, and potential adverse effects that must be carefully considered when selecting therapy for patients with high blood pressure. Successful management often involves a combination approach, tailoring medications to meet the patient’s specific needs and clinical profile.
The Role of Peripheral Vasodilators in Treating Hypertension
Peripheral vasodilators are a class of drugs that directly relax the smooth muscle of blood vessels, leading to vasodilation. This dilation can occur in arterioles (reducing arterial pressure) or veins (reducing preload on the heart), or both. By reducing peripheral resistance, these drugs decrease afterload (the resistance the heart must pump against), which in turn lowers blood pressure and improves cardiac function in some conditions like heart failure.
While not typically first-line therapy for uncomplicated hypertension, direct peripheral vasodilators are valuable agents, particularly in resistant hypertension, hypertensive emergencies, or when other agents are ineffective or contraindicated. Other drug classes, like ACEIs and ARBs, also cause vasodilation, but often through more indirect mechanisms involving hormonal pathways.
Commonly Used Vasodilating Drugs
The term “vasodilator” can encompass various drug classes. When discussing peripheral vasodilators specifically, one often refers to agents that have a primary, direct effect on smooth muscle. However, for a comprehensive understanding in hypertension management, it’s important to include other major classes that induce vasodilation.
Commonly used drugs and classes with significant vasodilating effects used in hypertension include:
- Direct Peripheral Vasodilators:
- Hydralazine
- Minoxidil
- Sodium Nitroprusside (primarily for hypertensive emergencies)
- Angiotensin-Converting Enzyme Inhibitors (ACEIs): (Indirect vasodilation by blocking Angiotensin II formation)
- Lisinopril
- Enalapril
- Ramipril
- Captopril
- Angiotensin Receptor Blockers (ARBs): (Indirect vasodilation by blocking Angiotensin II receptors)
- Losartan
- Valsartan
- Olmesartan
- Candesartan
- Calcium Channel Blockers (CCBs): (Some types cause vasodilation)
- Dihydropyridines (e.g., Amlodipine, Nifedipine) – Primarily arterial vasodilators.
- Alpha-Adrenergic Blockers: (Block vasoconstricting effects of norepinephrine)
- Prazosin, Terazosin, Doxazosin
This guide will focus in detail on the Direct Peripheral Vasodilators listed under point 1 (Hydralazine, Minoxidil) and then dedicate separate steps to the ACEIs and ARBs (points 2 and 3), as requested by the prompt.
Direct Peripheral Vasodilators: Pharmacokinetics, Indications, Contraindications, and Adverse Effects
Direct peripheral vasodilators cause relaxation of arterial and/or venous smooth muscle independent of autonomic innervation or specific receptor blockade (though their exact cellular mechanisms vary).
A. Hydralazine
- Mechanism of Action: Directly relaxes arteriolar smooth muscle, reducing peripheral vascular resistance and lowering blood pressure. It has less effect on venous smooth muscle. The precise cellular mechanism is not fully understood but may involve interference with calcium metabolism within the muscle cell.
- Pharmacokinetics:
- Oral bioavailability is variable (30-50%), influenced by first-pass metabolism in the liver, which in turn depends on a patient’s acetylation phenotype (slow vs. fast acetylators).
- Rapidly absorbed, peak plasma levels within 1-2 hours.
- Protein binding is high (~85-90%).
- Metabolized extensively in the liver by acetylation. Plasma half-life is 2-4 hours, but its duration of action can be longer due to tissue binding.
- Excreted primarily in the urine as metabolites.
- Indications:
- Moderate to severe hypertension, often used in combination with other antihypertensives (like beta-blockers and diuretics) to counteract reflex tachycardia and fluid retention.
- Hypertensive emergencies (IV formulation).
- Preeclampsia and eclampsia (IV).
- Heart failure (in combination with nitrates, e.g., BiDil).
- Contraindications:
- Coronary artery disease (can precipitate angina due to reflex tachycardia).
- Mitral valvular rheumatic heart disease.
- Known hypersensitivity to hydralazine.
- Adverse Effects:
- Common: Headache, nausea, flushing, palpitations, reflex tachycardia (often requiring co-administration of a beta-blocker), dizziness.
- Less Common but Serious: Lupus-like syndrome (dose-related, reversible upon discontinuation), peripheral neuropathy, blood dyscrasias.
B. Minoxidil
- Mechanism of Action: A very potent direct arterial vasodilator. It is a prodrug that is converted to an active metabolite (minoxidil N-O-sulfate) which opens adenosine triphosphate-sensitive potassium channels (KATP channels) in vascular smooth muscle membranes. This causes hyperpolarization of the cell membrane, preventing calcium influx and leading to relaxation and vasodilation.
- Pharmacokinetics:
- Rapidly and almost completely absorbed orally.
- Not significantly protein- bound.
- Widely distributed in the body, including into breast milk.
- Metabolized primarily by conjugation in the liver.
- Elimination half-life is approximately 4.2 hours, but its antihypertensive effect is longer.
- Excreted mainly in the urine as metabolites and unchanged drug.
- Indications:
- Severe, refractory hypertension that has not responded to maximal doses of a diuretic and two other antihypertensive agents. Note: Due to significant side effects, it is reserved for severe cases.
- Topical formulation is used to treat hair loss (alopecia).
- Contraindications:
- Pheochromocytoma (may stimulate catecholamine release).
- Known hypersensitivity to minoxidil.
- Adverse Effects:
- Significant reflex tachycardia (requires co-administration of a beta-blocker).
- Significant fluid and sodium retention (requires co-administration of a potent loop diuretic like furosemide).
- Hypertrichosis (excessive hair growth, particularly on the face, arms, and back) – very common and often limits use.
- Pericardial effusion and tamponade (rare but serious).
- ECG changes (T-wave changes).
(Note: Sodium Nitroprusside is another powerful, direct vasodilator but is given intravenously for hypertensive emergencies and works via the release of nitric oxide. Its use is limited by its delivery route and potential for cyanide toxicity with prolonged use or higher doses.)
The Renin-Angiotensin-Aldosterone System (RAAS)
Before discussing ACEIs and ARBs, it is essential to understand the Renin-Angiotensin-Aldosterone System (RAAS), a key hormonal system that regulates blood pressure, fluid and electrolyte balance.
The RAAS pathway is initiated when the kidneys release the enzyme Renin in response to low blood pressure, reduced renal blood flow, or sympathetic nerve stimulation. Renin acts on Angiotensinogen (produced by the liver) to produce Angiotensin I. Angiotensin I is then converted to the highly active peptide Angiotensin II primarily by Angiotensin-Converting Enzyme (ACE), which is found in high concentrations in the lungs but also in endothelium throughout the body.
Angiotensin II is a potent vasoconstrictor, increasing total peripheral resistance. It also stimulates the release of Aldosterone from the adrenal cortex (which increases sodium and water retention by the kidneys) and Antidiuretic Hormone (ADH) from the pituitary gland (which increases water reabsorption). Furthermore, Angiotensin II facilitates norepinephrine release and reuptake inhibition, increases sympathetic outflow, and acts on the brain to increase thirst. All these effects contribute to increased blood pressure and blood volume.
The Role of Angiotensin-Converting Enzyme Inhibitors (ACEIs)
ACEIs are a major class of antihypertensive drugs that interrupt the RAAS cascade.
- Mechanism of Action: ACEIs competitively inhibit the Angiotensin-Converting Enzyme (ACE). By blocking ACE, they prevent the conversion of Angiotensin I to the potent vasoconstrictor Angiotensin II. This leads to:
- Reduced Angiotensin II levels, resulting in vasodilation (decreased arterial resistance, some venous dilation).
- Reduced Angiotensin II-mediated aldosterone release, leading to decreased sodium and water retention and reduced potassium excretion.
- Reduced sympathetic nervous system activation.
- Inhibition of the breakdown of Bradykinin, a potent vasodilator. The accumulation of bradykinin is thought to contribute to the vasodilatory effects and also some side effects like cough and angioedema.
- Role in Hypertension: ACEIs are first-line agents or preferred add-on therapy for many patients with hypertension, particularly those with compelling indications such as:
- Heart failure
- Left ventricular systolic dysfunction
- Post-myocardial infarction
- Diabetes mellitus (especially with nephropathy)
- Chronic kidney disease (CKD) – they have renoprotective effects.
- They lower blood pressure effectively and reduce cardiovascular morbidity and mortality.
- Examples of Commonly Used ACEIs:
- Lisinopril
- Enalapril
- Ramipril
- Benazepril
- Captopril
- Pharmacokinetics (General & Example – Lisinopril):
- Most are orally administered, often as prodrugs requiring hepatic activation (e.g., Enalapril is a prodrug converted to Enalaprilat, Ramipril to Ramiprilat). Lisinopril and Captopril are active as administered.
- Absorption varies (e.g., Captopril absorption is reduced by food).
- Variable half-lives, allowing for once-daily dosing for many (except Captopril, typically dosed 2-3 times daily).
- Primarily eliminated by the kidneys, with dose adjustments often needed in renal impairment (except for some that have dual elimination).
- Lisinopril Specifics: Oral administration, bioavailability about 25%; not metabolized by the liver; excreted unchanged in the urine; plasma half-life is about 12 hours, allowing for once-daily dosing.
- Indications: Hypertension, Heart Failure, Left Ventricular Dysfunction, Post-MI, Diabetic Nephropathy, Chronic Kidney Disease, Proteinuric renal disease.
- Contraindications:
- Pregnancy (causes fetal toxicity and death – ABSOLUTE CONTRAINDICATION).
- History of angioedema related to previous ACEI therapy.
- Bilateral renal artery stenosis (can precipitate acute kidney injury).
- Severe hyperkalemia.
- Concomitant use with Aliskiren in patients with diabetes.
- Adverse Effects:
- Cough: Dry, persistent cough (most common, occurring in 5-20% of patients), thought to be due to bradykinin accumulation.
- Angioedema: Rare but potentially life-threatening swelling of the face, lips, tongue, glottis (occurs in ~0.1-0.7%, higher risk in African Americans).
- Hypotension: Especially with initial doses in volume-depleted patients.
- Hyperkalemia: More likely in patients with renal impairment, diabetes, or those taking potassium-sparing diuretics or potassium supplements.
- Acute Kidney Injury: Can occur in patients with pre-existing renal disease, bilateral renal artery stenosis, or severe volume depletion.
- Fatigue, dizziness, headache.
- Taste disturbance (Dysgeusia, more common with Captopril).
The Role of Angiotensin Receptor Blockers (ARBs)
ARBs are another major class of antihypertensives that target the RAAS, offering an alternative mechanism to ACEIs.
- Mechanism of Action: ARBs block the effects of Angiotensin II by preventing it from binding to its primary receptor, the Angiotensin II type 1 (AT1) receptor. By blocking the AT1 receptor, ARBs prevent Angiotensin II’s vasoconstricting effects, aldosterone-releasing effects, and other actions that increase blood pressure. Unlike ACEIs, ARBs do not affect bradykinin metabolism, which is why they have a lower incidence of cough and angioedema. There is some theoretical benefit from Angiotensin II acting on the AT2 receptor (which is not blocked by ARBs), potentially leading to vasodilation and anti-proliferative effects, although the clinical significance of this is still being studied.
- Role in Hypertension: ARBs are also first-line agents or preferred add-on therapy for hypertension and have similar indications to ACEIs (Heart failure, post-MI, diabetic nephropathy, CKD). They are often used when a patient cannot tolerate an ACEI, typically due to cough or angioedema (though a history of angioedema with an ACEI is a relative contraindication for ARBs due to a small cross-reactivity risk).
- Examples of Commonly Used ARBs:
- Losartan
- Valsartan
- Olmesartan
- Candesartan
- Telmisartan
- Irbesartan
- Pharmacokinetics (General & Example – Losartan):
- All are orally administered.
- Some are prodrugs requiring hepatic activation (e.g., Losartan is metabolized to an active metabolite, Eprosartan is a prodrug). Others are active as administered (e.g., Valsartan, Candesartan).
- Protein binding is high.
- Metabolized in the liver (often by CYP enzymes), with variable proportions of renal and/or biliary excretion. Dose adjustments may be needed in renal or hepatic impairment depending on the specific drug.
- Half-lives vary, allowing for convenient once-daily dosing for most.
- Losartan Specifics: Oral bioavailability is about 33%; undergoes significant first-pass metabolism to an active carboxylic acid metabolite, which is more potent and longer-acting than Losartan itself; parent drug half-life ~2 hours, active metabolite half-life ~6-9 hours; primarily metabolized by CYP2C9 and CYP3A4; excreted via both renal and biliary routes.
- Adverse Effects:
- Similar to ACEIs regarding hypotension, dizziness, hyperkalemia, and acute kidney injury, especially in susceptible patients (renal impairment, bilateral RAS, dehydration).
- Cough incidence is significantly lower than with ACEIs (similar incidence to placebo).
- Angioedema risk is much lower than with ACEIs, but still possible (cross-reactivity risk is about 5-10%).
- Fatigue, headache, nausea.
- Contraindications:
- Pregnancy (causes fetal toxicity and death – ABSOLUTE CONTRAINDICATION).
- Bilateral renal artery stenosis (can precipitate acute kidney injury).
- Severe hyperkalemia.
- Concomitant use with Aliskiren in patients with diabetes.
Conclusion
Peripheral vasodilators, ACE inhibitors, and Angiotensin Receptor Blockers are vital components of the pharmacological arsenal used to manage hypertension. While direct peripheral vasodilators like Hydralazine and Minoxidil are potent agents often reserved for more severe or refractory cases due to their side effect profiles, ACEIs and ARBs are foundational therapies for many patients, particularly those with comorbidities like heart failure, diabetes, or chronic kidney disease.
