Diuretics are widely used in the clinical application of kidney disease and are commonly used in the treatment of hypertension, glomerulonephritis, nephrotic syndrome, renal insufficiency and other diseases. Because of their ease of use and exact efficacy, they have been used for many years without fail. Since there are many varieties of diuretics with different chemical structures, pharmacokinetics and clinical pharmacological mechanisms of action, the clinical applications for different renal diseases also differ greatly, and the use of diuretics should be adjusted according to different diseases to achieve individualized medication. Only when diuretics are used rationally can their clinical therapeutic effects be given full play.
(A) Diuretic classification and mechanism of action.
The mechanism of action of different diuretics varies, and can be divided into five major categories according to the diuretic mechanism.
1, carbonic anhydrase inhibitors (acetazolamide, vinpocetine).
2, osmotic diuretics (mannitol, sorbitol).
3, collaterals diuretics (furosemide, torasemide).
4, thiazide diuretics (hydroflumethiazide, indapamide).
5. potassium-protective diuretics (spironolactone, aminoglutethimide). The mechanism of action of tab diuretics is to block the Na+ -K+-2Cl-transport system, thiazide diuretics block the electroneutral Na+-Cl-transport system, and spironolactone and amiloride block the sodium channel. Both tab diuretics and thiazide diuretics increase urinary potassium excretion and can cause hypokalemia. The diuretic effect is strongest with tab diuretics.
(B) Clinical application of diuretics.
1, for patients with renal insufficiency preferred tab diuretics, there are patients with mild renal insufficiency using high-dose thiazide diuretics can also produce diuretic effect. However, if the endogenous creatinine clearance (Ccr) <50ml/min, the diuretic effect of the drug is very poor. When Ccr<15ml/min, the dose of tab diuretics must be increased to produce diuretic effect.
2. Acute glomerulonephritis has a good prognosis, but serious complications and life-threatening effects can occur if not treated promptly. For those with mild to moderate edema, in principle, water and salt intake should be restricted and rest should be paid attention to, without the use of diuretics.
The indications for the use of diuretics are.
(i) Those with high edema and no other complications.
(ii) In acute glomerulonephritis complicated by heart failure, water and sodium intake should be strictly limited and rapid diuresis should be performed, and tab diuretics are preferred.
③ For those with mild hypertension (diastolic blood pressure <100mmhg), >100mmH, adult diastolic blood pressure >110mmHg, diuretics (tachyphylaxis or dihydrocortisone) should be used
together with the use of insulin or the vasodilator hydrazinepyridazine.
④ herbal diuretic drugs can also achieve good results. Such as corn husk can improve microcirculation, diuretic and antihypertensive effect. Zedoary can increase the discharge of urea and sodium, with diuretic and hypotensive, hypoglycemic and cholesterol-lowering effect.
3, nephrotic syndrome (NS) due to the loss of large amounts of urine protein, plasma colloid permeability pressure drop, intravascular fluid infiltration into the tissue interstitial, reduced circulating blood volume, aldosterone hypersecretion, can lead to water and sodium retention. Therefore, diuretic therapy plays a very important role in nephrotic syndrome.
In nephrotic syndrome, hypoalbuminemia and proteinuria have an inhibitory effect on diuretics, and patients with active sodium reabsorption in the distal tubules show diuretic resistance. In urine albumin > 4g/L, the dose of collateral diuretics should be increased by 2-3 times in order to have sufficient amount of free type drugs to work. The combination with albumin can enhance the diuretic effect.
②The combination of thiazides can increase the efficacy. Diuresis should not be too fast, otherwise blood volume will decrease too fast and blood concentration will induce complications such as acute renal failure and thromboembolism. For nephrotic syndrome with azotemia, in principle, thiazide diuretics are not used because they can lead to further damage to renal function.
③Tachyphylaxis, a tab diuretic, can still be used when renal function is impaired, but the degree of renal function impairment seriously affects the diuretic effect.
All diuretics can lead to electrolyte disorders and hyperuricemia, while thiazide and tab diuretics often induce hyperglycemia, so diuretics should be gradually increased in renal insufficiency.
⑤ For patients with high edema accompanied by pleural or ascites and good renal function, often accompanied by increased aldosterone, more than two diuretics such as tachyphylaxis and amnestic acid can often be used. At the same time, to reduce proteinuria, hormones or immunosuppressants (such as primaquine) can be used according to the clinical type or pathological typing.
(6) In nephrotic syndrome with hypertension, after the edema subsides but the blood pressure still cannot return to normal, hydrazinopyridazine, tretinoin and diuretics are usually used, which is the so-called standard triple therapy.
4. Mild and moderate idiopathic hypertension can be treated according to the following principles.
① limiting sodium intake (NaCl 4-5g/d).
② change lifestyle, quit smoking and alcohol, low-fat diet, weight loss, exercise.
③ antihypertensive drugs,β-blockers are appropriate for those with myocardial infarction; angiotensin-converting enzyme inhibitors (ACEI) are preferred for those with heart failure or diabetic nephropathy; calcium channel antagonists should be chosen for angina pectoris and idiopathic hypertension.
④ In recent years, the anti-hypertensive efficacy of diuretics has received renewed attention, advocating the initial use of small doses of diuretics and the desirability of short- and medium-acting thiazides.
The 2010 Guidelines for the Prevention and Treatment of Hypertension in China propose that diuretics should be preferred for the treatment of simple systolic hypertension in the elderly; diuretics or ACEIs must be used for hypertension combined with heart failure. it is beneficial to treat hypertensive patients with type II diabetes or osteoporosis with low-dose diuretics. In contrast, diuretics are not used for hypertension with gout, as they can produce adverse effects.
(iii) Side effects of diuretics.
1.Decrease in blood volume.
2, electrolyte disorders: can cause hypokalemia, hyperkalemia, hyponatremia, hypomagnesemia, hypochlorhydria.
3, acid-base balance disorders.
4, hyperuricemia.
5, ototoxicity.
6, renal calculi and renal calcium deposits.
7, other side effects: less common, including cardiac arrhythmias, hyperlipidemia, abnormal glucose metabolism, acute interstitial nephritis, pancreatitis, pulmonary edema, musculoskeletal pain, hypogonadism, etc.