PROBLEMS OF DIURETIC THERAPY

PROBLEMS OF DIURETIC THERAPY

            The adverse effect of high ceiling and thiazide type of drugs are related to fluid and electrolyte changes caused by them. They are remarkable safe in low dose used over short period on long term use as antihypertensive and high doses cause metabolic disturbances.

1. Hypokalemia : The most significant  problem. Degree of hypokelemia related to length of action of diuretics the usual manifestations are weakness, fatigue, muscle cramps, cardiac arrythmias are serious complication. Hypokelemia can be prevented and treated by
1. High dietary potassium intake
2. Supplement of potassium chloride (24-72 m-Eq/day)
3. Concurrent use of potassium sparing diuretics

            Hypokelemia in special situation eg. Cirrhosis, cardiac patients à post MI, those receiving digitalis, or tricyclic antidepressants and elderly patient. Maintain serum potassium at or above 3.5 mEq/l. Potassium sparing diuretics are more efficious and more convenient in correcting hypokelemia than potassium supplement. Eg. Captorpri + Thiazide Alkalosis may occur with hypokalemia because more H⁺ exchange Na in distal tabule when less potassium is available for exchange.

2. Acute saline depletion: Over enthusiastic use of diuretic particularly high ceiling one, cause dehydration and fall in BP (especially in erect posture) treat with saline.
3. Dilutional hyponatremia: In congestive cardiac failure, virgorous diuresis is induced with high ceiling agents. Kidney tends to retain water through it is unable to retain salt due to diuretic, extra cellular fluids gets diluted.  Hyponatremia occur and edema persists despite nitriuresis patients feels very thirsty. Withhold diuretics, restrict water intake, give glucocorticoids with enhance excretion of water load. If hypokalemia is present, its correction helps.
4. GIT and CNS disturbance: Nausea, vomiting and diarrhea occur with erthacrynic acid. Headache, giddiness, weakness, parasthesia, impotence are complaints with thiazides as well as loop diuretics.
5. Hearing loss: Only with high ceiling diuretics specially ethacrynic acid in presence of renal insufficiency. Increased salt content of endolymph and a direct toxic action on the hair cells in internal ear.
6. Allergic manifestation, rashes, photosensitivity in patient hypersensitive to sulfonamide.
7. Thiazide aggravated renal insufficiency by reducing glomerular filtration rate.
8. Brisk diuresis induced in cirrhotics precipitate mental disturbances and hepatic coma. It may be due to hypokalemia, alkalosis and increased blood ammonia level.
9. Diurectics contra indicated in toxemia of pregnancy in which blood volume is low despite edema. Diuretics reduce blood volume and compromise placental circulation – miscarriage, fetal death thus; diuretics are contra indicated in PIH.
10. Hyperuricaemia – Long term use of thiazide in hypertension has caused rise in blood urate level. 2% develop clinical gout. This effect can be contracted by allopurinol.
11. Hyperglycemia and hyperlipidimia
12. Hypercalcemia occurs with thiazides while hypocalcemia occur with high ceiling diuretics.
13. Magnesium depletion after prolonged use of thiazide as well as loop diuretics. This may increase risk of ventricular arrythmia, after MI, digitalized patient potassium sparing diuretic minimize magnesium loss.

Interactions

            Hypokalemia induced by diuretics, enhances digitalis toxicity, increased incidence of polymorphic VT due to quinidine, potentiates competitive neuromuscular blockers and reduces sulfonylurea action. Hypoceiling diuretics and aminoglycoside both ototoxicity produce additive toxicity. High ceiling diuretics enhance neprotoxity of aminoglycosides and I generation cephalosporins. Cotrimoxazole given with diuretics has higher incidence of thrombocytopenia. Indomethacin and most NSAIDS diminish action of high ceiling diuretics. Antihypertensive action of thiazide and furosenamide is also diminished by NSAID. Probenecid inhibits tubular secretion of furosenamide and thiazide, diuretics diminish uricosuric action of probhincid. Serum lithium level rises with diuretics due to enhance reabsorption of lithium in proximaltubule.

Carbonic Anhydrase Inhibitors

Acetazolamide side effects acidosis, hypokalemia, drowsiness, parasthesia, fatigue, abdominal discomfort. Hypersensitive reaction; Fever rash; Contra indicated in liver diseases, precipitate hepatic coma by interfering with urinary elimination of ammonia. Acidosis in patient with COPD.

Adverse Effect of Spironolactone

            Drowsiness, confusion, abdominal upset, hirsutism, gynaecomastia, impotence, menstrual irregularities, hyperkalemia if renal function is inadequate. Acidosis occurs specially in cirrhotics.

Interactions

            Given together with potassium supplement dangerous hyperkalemia aspirin blocks spironolactone action by inhibiting tabular secretion of can renone. Spironalactone blocks carbenoxolone sodium induced water retention. Spironolcatone increases plasma digoxin concentration.

            Both triametrine and amloride (biduret) used in conjunction with thiazide type or high ceiling diuretic prevent hypokalemia and slightly angment natriuretic  and antihypertensive response. They should not be given with potassium supplements, dangerous hypokalemia may develop. Hyperkalemia is also more likely in patient with ACE inhibitor and with renal impairment. Both drugs elevate plasma digoxin levels. Triamterine side effect nausea, dizziness, muscle cramps and rise in blood urea, IGT and photosensitivity. Amiloride 10 times more potent than triamtrine decrease calcium excretion, increased urate excretion. Side effects of amiloride are nausea, diarrhea, and headache as aeronsal symptomatic improvement in cystic fibrosis by increasing fluidity and respiratory secretion.

            Mannitol contra indicated in acute renal failure since kidney is incapable of forming urine even after an osmotic load. It will expand plasma volume – pulmonary edema and heart failure may develop. Mannitol is contra indicated in acute tabular necrosis, anuria, pulmonary edema, acute LVF, cerebral hemorrhage. Headache is common, nausea and vomiting may occur.

NOTE:

            Diuretics in high doses cause fluid and electrolyte imbalance and metabolic disturbances. But remarkable safe in low dose used over short period and on long term use as antihypertensive.

REFERENCE: Essential of Medical Pharmacology, Tripati