2 Dihydropyridines may cause ankle edema and gingival hyperplasia.

(2) Dihydropyridines may cause ankle edema and gingival hyperplasia. (3) Non-dihydropyridines such as diltiazem and verapamil can suppress sinoatrial node function, cardiac conduction, and ventricular function. 5. Clinical applications (1) Long-acting calcium antagonists (including both dihydropyridines and non-dihydropyridines) can effectively control blood pressure whether used alone or in combination with other antihypertensive drugs, thereby reducing the incidence of cardiovascular and cerebrovascular events. Rapid-acting short-term preparations should be avoided. (2) Diltiazem and verapamil are also suitable for hypertensive patients with atrial arrhythmias. (3) Calcium antagonists have the following advantages: better antihypertensive efficacy in elderly patients; high sodium intake does not affect antihypertensive efficacy; nonsteroidal anti-inflammatory drugs do not interfere with antihypertensive effects; significant antihypertensive effect in patients who drink heavily; can be used in patients with comorbid diabetes, coronary heart disease, or peripheral vascular disease; long-term treatment also has anti-atherosclerotic effects. 6. Contraindications (1) Pregnant women should avoid using them. (2) Individuals with impaired sinoatrial node function or cardiac conduction block, as well as those with congestive heart failure, should use diltiazem and verapamil with caution. 7. Drug interactions (1) Can be used in combination with diuretics, ACE inhibitors. (2) Verapamil, diltiazem, nicardipine, and amlodipine increase cyclosporine plasma levels. (3) Verapamil and diltiazem increase digoxin plasma levels. A drawback is that reflex sympathetic activity increases at the beginning of treatment, especially when using short-acting preparations, leading to increased heart rate, facial flushing, headache, and lower extremity edema. Non-dihydropyridines inhibit myocardial contraction,自律性和传导性, so they are not suitable for patients with heart failure, impaired sinoatrial node function, or cardiac conduction block. (IV) Angiotensin-converting enzyme inhibitors (ACEI) 1. Mechanism of antihypertensive action (1) Primarily by inhibiting ACE in the periphery and tissues, reducing the production of angiotensin I (Ang I), while also inhibiting kininase to reduce bradykinin degradation, thereby dilating blood vessels and lowering blood pressure. (2) Due to the blockade of aldosterone, the effect of diuretics can be enhanced. (3) Has a mild potassium-retaining effect. 2. Common formulations and dosages Captopril 12.5–50 mg each time, two to three times daily; Enalapril 2.5–20 mg each time, twice daily; Cilazapril 2.5–5 mg each time, once daily; Benazepril 10–20 mg each time, once daily; Perindopril 4–8 mg each time, once daily; Ramipril 2.5–10 mg each time, once daily; Fosinopril 10–20 mg each time, once daily; Lisinopril 10–20 mg each time, once daily. 3. Antihypertensive effects Onset is slow, gradually strengthening, reaching maximum effect in 3–4 weeks. Limiting sodium intake or combining with diuretics can accelerate onset and enhance effects. 4. Main side effects (1) Common: Dry cough. (2) Rare: Angioedema, hyperkalemia, rash, taste abnormalities, leukopenia. 5. Clinical applications (1) Clinically applied to various degrees of hypertension, especially suitable for patients with heart failure, left ventricular dysfunction, post-myocardial infarction, or diabetic nephropathy. (2) ACEIs improve insulin resistance and reduce proteinuria, showing relatively good efficacy in obese, diabetic, and hypertensive patients with cardiac and renal target organ damage, particularly suitable for hypertensive patients with heart failure, post-myocardial infarction, impaired glucose tolerance, or diabetic nephropathy. 6. Contraindications Pregnancy, hyperkalemia, and bilateral renal artery stenosis are contraindications. 7. Drug interactions Can be used in combination with diuretics, calcium antagonists, and beta-blockers, etc. (V) Angiotensin I receptor blockers (ARBs)

1. Mechanism of antihypertensive action Primarily by blocking the AT subtype of angiotensin I receptors in tissues, more fully and effectively blocking angiotensin I's water and sodium retention, vasoconstriction, and tissue remodeling effects.
2. Common formulations and dosages Losartan 50–100 mg each time, once daily; Valsartan 80–160 mg each time, once daily; Irbesartan 150–300 mg each time, once daily; Telmisartan 40–80 mg each time, once daily; Candesartan 8–16 mg each time, once daily. 3. Antihypertensive effects Onset is slow but lasting and stable, generally reaching maximum effect in 6–8 weeks, with effects lasting over 24 hours. Low-salt diet or combined use with diuretics can significantly enhance efficacy.
3. Main side effects Hyperkalemia, angioedema (rare). Because there is no cough side effect, it is superior to ACE inhibitors.
4. Clinical applications (1) Suitable for various mild to moderate hypertensive patients, especially those who cannot tolerate the cough caused by ACE inhibitors. (2) The biggest feature is that there are very few drug-related adverse reactions, no irritating dry cough, and high adherence to long-term treatment.
5. Contraindications Pregnancy, hyperkalemia, and bilateral renal artery stenosis are contraindications. 7. Drug interactions Same as ACEIs. (VI) Other antihypertensive drugs 1. α-receptor blockers (1) Mechanism of antihypertensive action: Prazosin, terazosin, doxazosin, and naphazoline selectively block postganglionic adrenergic α1 receptors, lowering blood pressure without changing cardiac output; whereas phenoxybenzamine and phentolamine non-selectively block α1 and α2 receptors, causing peripheral arteriolar dilation. (2) Common formulations and dosages: Terazosin 1–10 mg each time, one to two times daily; Prazosin 2–10 mg each time, two to three times daily; Phentolamine 5–10 mg each time, administered intramuscularly or intravenously. (3) Antihypertensive effects: Prazosin and similar drugs take effect slowly, reaching peak effect after 4–8 weeks of medication. Phentolamine’s effect is short-lived. (4) Main side effects: Headache, dizziness, fatigue, tachycardia, and orthostatic hypotension upon first dose (prazosin). Selective α1 receptor blockers have a certain water and sodium retention effect. (5) Clinical applications: ① Selective α-receptor blockers can effectively lower blood pressure whether used alone or in combination with other antihypertensive drugs, suitable for various degrees of hypertension, especially for hypertensive patients with prostatic hyperplasia, abnormal lipid metabolism, and abnormal glucose tolerance; ② Phenoxybenzamine is mainly used for treating hypertension caused by pheochromocytoma. (6) Contraindications: Elderly hypertensive patients with orthostatic hypotension should use with caution. (7) Drug interactions: Prazosin can be used in combination with diuretics and beta-blockers.
6. α-, β-receptor blockers (1) Mechanism of antihypertensive action: Blocking α- and β-adrenergic receptors. (2) Common formulations and dosages: Arotinolol 10 mg each time, twice daily; Carvedilol 12.5–25 mg each time, once or twice daily. (3) Antihypertensive effects: Slow onset. (4) Main side effects: Similar to beta-blockers. (5) Clinical applications: Effective for various degrees of hypertension. (6) Contraindications: Bronchial asthma, second- to third-degree atrioventricular block, bradycardia, peripheral arterial disease. (7) Drug interactions: Can be used in combination with diuretics. (VII) Central and peripheral sympathetic nerve inhibitors
7. Mechanism of antihypertensive action (1) Clonidine and methyldopa reduce sympathetic outflow by stimulating central α2 receptors, slowing heart rate, reducing cardiac output, decreasing peripheral vascular resistance, and inhibiting renin and aldosterone secretion. (2) Moxonidine is a second-generation central antihypertensive drug that acts on the rostral ventrolateral medulla, with high selectivity for imidazoline I2 receptors. By activating RVLM’s I2 imidazoline receptors, it reduces peripheral sympathetic activity, leading to vasodilation and blood pressure reduction. Compared with clonidine, its affinity for I2 receptors is weaker, so while lowering blood pressure, it does not significantly slow heart rate or produce central sedation. (3) Reserpine suppresses reflexive vasoconstriction by depleting norepinephrine from peripheral nerve endings, thereby exerting an antihypertensive effect.
8. Common formulations and dosages Clonidine 0.1 mg each time, twice daily; Reserpine 0.1–0.25 mg each time, once daily. 3. Antihypertensive effects (1) Clonidine begins to lower blood pressure 30 minutes after ingestion, with the strongest effect lasting 2–4 hours. The effect lasts 4–24 hours. It lowers both systolic and diastolic blood pressure in different body positions. (2) Reserpine’s effect is gentle and long-lasting, generally declining after one week of medication, reaching the lowest level after 2–3 weeks.
9. Main side effects (1) Central nervous system depressants can cause drowsiness, dry mouth, etc., and blood pressure may rebound after stopping the medication. (2) Reserpine’s side effects include nasal congestion, depression, increased gastric acid secretion and risk of ulcers, aggravation of ulcerative colitis, and induction of biliary colic.
10. Clinical applications (1) Central nervous system depressants are suitable for various degrees of hypertension, especially for patients with renal insufficiency and elevated plasma renin activity. (2) Reserpine can be used alone for mild hypertension, and in combination with other antihypertensive drugs for moderate to severe hypertension. Particularly suitable for patients with fast heart rate, mental tension, and high plasma renin activity.
11. Contraindications Pregnant women should not take clonidine, and those with ulcers or depression should use reserpine with caution.
12. Drug interactions Can be used in combination with diuretics and vasodilators. Propranolol, guanethidine, brompheniramine, and tricyclic antidepressants can counteract clonidine’s antihypertensive effect, so they should not be used together. Can be used in combination with other antihypertensive drugs, but not with monoamine oxidase inhibitor drugs. (VIII) Direct vasodilators Primarily dilate small arteries, with little effect on capacitance vessels. Due to the dilation of small arteries, peripheral resistance decreases, thus lowering blood pressure. At the same time, through pressure-sensitive reflexes, sympathetic nerves are stimulated, leading to increased heart rate, strengthened myocardial contractility, and increased cardiac output, partially counteracting its antihypertensive efficacy. Sodium nitroprusside has a vasodilatory effect on both arterioles and veins. Since it also dilates veins, reducing venous return, it does not increase cardiac output; however, it can reflexively stimulate the sympathetic nervous system. Hydralazine is not recommended for clinical use due to its numerous adverse reactions.

(9) Antihypertensive Treatment Regimens Patients without complications or comorbidities may be treated with thiazide diuretics, β-blockers, CCBs, ACEIs, or ARBs, either alone or in combination. Treatment should begin with a low dose and gradually increase as needed. For patients with stage 2 hypertension (>160/100 mmHg), two antihypertensive drugs can be used in combination from the outset, either as separate prescriptions or fixed-dose combinations, which helps achieve target blood pressure more quickly.

(10) Combination Use of Antihypertensive Drugs

1. Significance of Combination Therapy To reach the target blood pressure level, at least two antihypertensive drugs are required.

2. Indications for Combination Therapy Patients with stage 2 hypertension or those at high risk due to multiple risk factors, target organ damage, or clinical diseases often require two low-dose antihypertensive drugs as initial treatment. If the target level still cannot be achieved, additional drugs may be added, potentially up to three or even four or more. See Table 2-5.

3. Methods of Combination Therapy When combining two drugs, their mechanisms of action should be complementary, with additive effects, while also offsetting or mitigating adverse reactions.

4. Combination Therapy Schemes (1) ACEI or ARB + thiazide diuretic. Thiazide diuretics can activate the renin-angiotensin-aldosterone system, leading to some adverse effects that hinder blood pressure reduction. However, when combined with ACEI or ARB, these negative effects are counteracted. ACEI and ARB can slightly elevate serum potassium levels, thereby preventing this issue. Table 2-5: Indications for Commonly Used Antihypertensive Drugs