Peripheral vascular disease

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Receptor blockade | | > Blood pressure | Indapamide, 1.25–2.5 mg each time, once daily. (3) Effects on lowering blood pressure: After oral administration, hydrochlorothiazide reaches peak effect within 2–6 hours, and its effect lasts for 12 hours; after 3–4 weeks of medication, the effect peaks. Indapamide reaches peak effect 24 hours after oral administration, and the effect peaks after 3–4 weeks of medication. (4) Main side effects: Related to dosage; using a small dose can reduce side effects. ① Volume depletion and hyponatremia. ② Hypokalemia. ③ Elevated fasting blood glucose. ④ Other: Increased serum uric acid levels, as well as decreased serum magnesium levels, etc. (5) Clinical applications: Hydrochlorothiazide is a basic antihypertensive drug. It is particularly effective for mild to moderate hypertension, “salt-sensitive” hypertension, especially in patients with low renin levels (such as the elderly and those with diabetes) and those presenting with metabolic syndrome. It is often used in combination with other antihypertensive drugs to synergistically lower blood pressure and reduce the side effects of water and sodium retention. It is especially suitable for patients with concurrent heart failure. (6) Contraindications: Do not use in patients allergic to sulfonamides, those with hypokalemia, or those with primary hyperaldosteronism; Patients with diabetes and a history of gout or hypercalcemia should use with caution. (7) Drug interactions: Hydrochlorothiazide is often used in combination with other antihypertensive drugs, such as ACEIs, ARBs, beta-blockers, central-acting drugs, calcium antagonists, and other diuretics. Indapamide combined with perindopril has been clinically proven to prevent recurrence of stroke. Nonsteroidal anti-inflammatory drugs can weaken the antihypertensive effect of thiazides. Combining thiazides with beta-blockers can increase fatigue and drowsiness as side effects. (8) Additional note: Thiazide diuretics can reduce the incidence and mortality of hypertension-related complications such as stroke and heart failure. ① When using thiazides alone for antihypertensive treatment, the dosage should be kept as low as possible: Patients can achieve antihypertensive effects with as little as 12.5 mg of hydrochlorothiazide; exceeding 25 mg does not necessarily enhance the antihypertensive effect, but may instead increase the incidence of adverse reactions. Therefore, it is recommended that the dosage when using diuretics alone for antihypertension should not exceed 25 mg. If 25 mg still cannot effectively control blood pressure, then combination therapy or switching to other types of antihypertensive drugs should be considered. ② When treating with thiazides alone, especially for long-term use, potassium-sparing diuretics or angiotensin-converting enzyme inhibitors should be used concurrently. ③ Long-term, high-dose use of thiazides can have adverse effects on lipid metabolism and glucose metabolism. ④ Indapamide has fewer adverse reactions and does not cause changes in blood lipids, so patients with hyperlipidemia can use indapamide instead of thiazide diuretics.

2. Potassium-sparing diuretics (1) Mechanism of antihypertensive action: Selectively blocking the sodium transport channels in the renal tubular epithelium, thereby reducing the sodium-potassium exchange in the distal convoluted tubule, increasing urinary sodium excretion while relatively retaining potassium. The mechanism of vasodilation is also considered. (2) Common preparations and dosages: Triamterene, 50–100 mg each time, 1–2 times daily; Amiloride, 5–10 mg each time, once daily. (3) Main side effects: Mild and transient, including hyperkalemia, diarrhea, nausea, vomiting, calf cramps, and irregular menstruation; triamterene may induce kidney stones. (4) Clinical applications: Alone, the antihypertensive effect is relatively weak, making it suitable for hypertensive patients with hypokalemia, while also preserving magnesium ions. Often used in combination with hydrochlorothiazide, it can effectively lower blood pressure and correct the hypokalemia and hypomagnesemia caused by thiazide diuretics. (5) Contraindications: Patients with diabetes or renal insufficiency, as well as those currently taking ACEIs and potassium supplements, should use this drug with caution. Patients with gout should not use it. (6) Drug interactions: Often used in combination with thiazide diuretics.
3. Aldosterone antagonists ( 1 ) Mechanism of antihypertensive action: Blocking the effects of aldosterone, including reducing extracellular fluid volume and dilating blood vessels. It has protective effects on cardiovascular target organs (especially fibrosis). Eplerenone exhibits stronger selectivity in blocking aldosterone. (2) Common formulations and dosages: Spironolactone 20–40 mg each time, 1–3 times daily. (3) Main side effects: Erectile dysfunction, gynecomastia (in males), menstrual irregularities. (4) Clinical applications: Spironolactone can effectively control blood pressure in most hypertensive patients, especially those with low-renin hypertension (elderly patients and diabetic patients). It is also suitable for patients with bilateral adrenal hyperplasia in primary aldosteronism who are ineligible for surgery, as well as for those whose blood pressure continues to rise after surgery. (5) Contraindications: Patients with hyperkalemia and renal insufficiency should not use it. (6) Drug interactions: Can be used concurrently with thiazide diuretics.
4. Loop diuretics (1) Mechanism of antihypertensive action: Acting on the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption in the urine. (2) Common formulations and dosages: Furosemide (Lasix) 20–100 mg each time, 1–2 times daily; Torasemide 5–10 mg daily. (3) Antihypertensive effects: Both diuretic and antihypertensive effects are stronger and faster than other diuretics. Lasix has a short duration of action, while Torasemide’s effect can last up to 24 hours. (4) Main side effects: ① Similar to thiazide diuretics; ② Excessive diuresis may lead to hypotension and hypokalemia. (5) Clinical applications: Suitable for patients with renal impairment due to kidney disease or heart failure (serum creatinine > 2.5 mg/dL), where its effect is stronger than that of thiazide diuretics. Also applicable to hypertension accompanied by congestive heart failure, edema caused by other reasons, and renal insufficiency. (6) Contraindications: ① Hyperuricemia and primary aldosteronism; ② Increased urinary calcium excretion makes it unsuitable for patients with osteoporosis. (7) Drug interactions: ① Drugs that affect prostaglandin synthesis (such as nonsteroidal anti-inflammatory drugs) can weaken the loop diuretic effect on the renal tubules; ② Can be used in combination with other antihypertensive drugs. (8) Additional note: For patients with azotemia or uremia, the highly effective diuretic furosemide can be selected. (II) Beta-blockers There are selective (1), non-selective (B and 2), and mixed beta-blockers. (1) Mechanism of antihypertensive action: Blocking sympathetic β receptors, slowing heart rate, reducing cardiac output, inhibiting renin release, etc. (2) Common formulations and dosages: Atenolol 25–100 mg each time, once daily; Metoprolol 25–50 mg each time, twice daily; Bisoprolol 5–10 mg each time, once daily. (3) Antihypertensive effects: Slow onset, taking effect within 1–2 weeks. (4) Main side effects: ① Bradycardia, heart failure, bronchospasm, nausea, diarrhea, convulsions, dizziness, fatigue, Raynaud’s phenomenon, etc.; ② May increase serum triglycerides (except for those with endogenous sympathomimetic effects), cholesterol levels, and decrease high-density lipoprotein cholesterol levels; ③ Sudden discontinuation in patients with coronary heart disease may induce angina pectoris. (5) Clinical applications: ① Whether used alone or in combination with other antihypertensive drugs, it can effectively lower blood pressure in patients with diastolic or isolated systolic hypertension; ② Can be the first-choice drug for mild to moderate hypertension, especially for young and middle-aged patients with exertional angina, post-myocardial infarction, or rapid arrhythmias; ③ Its efficacy is relatively poor in elderly patients with hypertension; ④ Water and sodium retention may occur during dose escalation, so diuretics can be added. (6) Contraindications: The following conditions generally make it inadvisable to use standard doses of beta-blockers: Asthma, chronic obstructive pulmonary disease, congestive heart failure, sick sinus syndrome, second- to third-degree atrioventricular block, peripheral arterial disease. Use with caution: Type 1 diabetes, abnormal lipid metabolism, angina caused by coronary artery spasm, athletes, and individuals engaged in heavy physical labor. (7) Drug interactions: ① Can be used in combination with diuretics, dihydropyridine calcium channel blockers, or other beta-blockers. ② Should not be used concurrently with diltiazem or verapamil. Concurrent use with reserpine may lead to severe bradycardia or even syncope. Concurrent use with pseudoephedrine, ephedrine, or epinephrine may raise blood pressure. Beta-blockers not only lower resting blood pressure but also suppress the sharp rise in blood pressure during physical stress and exercise. The main obstacles to beta-blocker therapy are bradycardia and some adverse reactions that affect quality of life. Sudden discontinuation of high-dose beta-blocker therapy may lead to withdrawal syndrome. Although diabetes is not a contraindication for using beta-blockers, it increases insulin resistance and may mask and prolong hypoglycemic episodes during glucose-lowering treatment, so caution should be exercised when using them. If they must be used, highly selective β1-blockers should be chosen. (III) Calcium channel blockers Also known as calcium antagonists, they are divided into dihydropyridines and non-dihydropyridines. 1. Mechanism of antihypertensive action (1) Primarily through blocking the entry of extracellular calcium ions into vascular smooth muscle cells via voltage-dependent L-type calcium channels, weakening excitation-contraction coupling and reducing the contractile responsiveness of resistance vessels. (2) Calcium antagonists can mitigate the vasoconstrictive effects of angiotensin I (AI) and α-adrenergic receptors, and reduce sodium reabsorption in the renal tubules.
5. Common formulations and dosages (1) Dihydropyridines: Nifedipine 5–10 mg each time, three times daily; Amlodipine 2.5–10 mg each time, once daily; Felodipine extended-release tablets 5–10 mg each time, once daily; Lacidipine 2–6 mg each time, once daily; Lercanidipine 10–20 mg each time, once daily; Nitrendipine 10 mg each time, twice daily. (2) Non-dihydropyridines: Diltiazem extended-release tablets 90–180 mg each time, once daily; Verapamil extended-release tablets 240 mg each time, once daily.
6. Antihypertensive effects (1) Nifedipine takes effect 30 minutes after oral administration, with a half-life of 2–5 hours, requiring three doses per day. (2) Long-half-life calcium antagonists or sustained-release preparations can maintain blood pressure control for 24 hours. (3) Lacidipine and Lercanidipine have long-lasting antihypertensive effects (though their half-lives are not long).
7. Main side effects (1) Facial flushing, headache, dizziness, palpitations, gastrointestinal discomfort, and orthostatic hypotension.