Diuretics indications

Bumetanide is a loop diuretic indicated in oedema. Common side-effects of loop diuretics include hypokalaemia, hyponatraemia, hypotension and gout. 

Table 12.4 Loop diuretics indications and side effects...

Oedema states associated with sodium overload, e.g. cardiac, renal or hepatic disease, and also without sodium overload, e.g. acute pulmonary oedema following myocardial infarction. Note that oedema may also be localised, e.g. angioedema over the face and neck or aroimd the ankles following some calcium channel blockers, or due to low plasma albumin, or immobility in the elderly in none of these circumstances are diuretics indicated. 

Furosemide is a widely used loop diuretic indicated for the treatment of different pathological conditions such as congestive heart failure, hepatic cirrhosis, and chronic renal failure. It has a narrow absorption window and mainly absorbed from the stomach and the upper part of the small intestine. Following administration of furosemide, the natriuretic effect rapidly disperses and is concealed before the next administration. This problematic aspect in furosemide therapy is mostly attributed to the natural homeostatic compensatory mechanisms. Lately, it has been demonstrated that the diuretic and natriuretic effects of furosemide can be significantly improved, following a continuous input (intravenous infusion) compared to immediate release DFs. Beside the narrow absorption window, this pharmacodynamic feature of the drug provides another rationale for the development of a GRDF for furosemide. 

Figure 15-2. Tubule transport systems and sites of action of diuretics. Circles with arrows denote known ion cotransporters that are targets of the diuretics indicated by the numerals. Question marks denote preliminary or incompletely documented suggestions for the location of certain drug effects. (Reproduced, with permission, from Katzung BG [editor] Basic Clinical Pharmacology, 8th ed. McGraw-Hill. 2001.)...

ACE inhibitors can be administered with diuretics (qv), cardiac glycosides, -adrenoceptor blockers, and calcium channel blockers. Clinical trials indicate they are generally free from serious side effects. The effectiveness of enalapril, another ACE inhibitor, in preventing patient mortaUty in severe (Class IV) heart failure was investigated. In combination with conventional dmgs such as vasodilators and diuretics, a 40% reduction in mortaUty was observed after six months of treatment using 2.5—40 mg/d of enalapril (141). However, patients complain of cough, and occasionally rash and taste disturbances can occur. 

Diuretics are needed to return to normal the expanded extracellular volume that other antihypertensive agents produce, such as fluid retention and blood volume expansion, via compensatory mechanisms of the body. The loss of efficacy of antihypertensive agents can be restored if a diuretic is used concomitandy. In the treatment of hypertension, high ceiling or loop diuretics, such as furosemide, ethacrynic acid, and bumetanide, are no more efficacious than the thiazide-type of diuretics. In fact, these agents cause more side effects, such as dehydration, metaboHc alkalosis, etc, and therefore, should not be used except in situations where rapid elimination of duid volume is cleady indicated. 

Kidney and bladder disorders Herbal drugs with this indication arc usually only for supportive treatment, since their effects as urinary disinfectants and as diuretics are mostly slight, a point which is mentioned under the individual drugs. 

The efficacy of these diuretics led to their extensive use in the clinic, particularly in treatment of hypertension. In theory at least, reduction of the blood volume by diuresis should lead to a lowering of pressure (PV=RT). This expectation was in fact met in actual practice. Recent research does, however, seem to indicate that the thiazides have an antihypertensive effect beyond that explainable by a simple lowering of blood volume. 

Diuretics promote the urinary excretion of sodium and water by inhibiting the absorption of filtered fluid across the renal tubular epithelium. The ensuing reduction in Na reabsorption reduces the Na content of the body, the critical determinant of extracellular and plasma fluid volumes. Thus, the use of diuretics is primarily indicated in the treatment of edematous diseases and of arterial hypertension. 

The use of CA inhibitors as diuretics is limited by their propensity to cause metabolic acidosis and hypokalemia. Their use can be indicated in patients with metabolic alkalosis and secondary hyperaldosteronism resulting for example from aggressive use of loop diuretics. Furthermore, CA inhibitors are effective dtugs to produce a relatively alkaline urine for the treatment of cysteine and uric acid stones as well as for the accelerated excretion of salicylates. Perhaps the most common use of CA inhibitors is in the treatment of glaucoma. 

The use of V2 antagonists is promising in the treatment of the hyponatremia that usually accompanies congestive heart failure and cirrhosis, two edematous conditions in which the use of diuretics is indicated. In addition, V2 antagonists may be beneficial in the treatment of polycystic kidney disease. 

Diuretics This indicates the unique property of capsaicin-sensitive primary afferent neurons to release mediators (neuropeptides and others) from both peripheral and central nervous system terminals upon adequate stimulation. Capsaicin and other chemical (protons) or physical (heat) stimuli release mediators from both peripheral and... 

When a diuretic is being administered for heart failure, which of die following would be most indicative of an effective response of diuretic tiierapy ... 

Combination therapy with an ARB and ACE inhibitor offers a theoretical advantage over either agent alone through more complete blockade of the deleterious effects of angiotensin II. However, clinical trial results indicate that the addition of an ARB to optimal HF therapy (e.g., ACE inhibitors, /3-blockers, diuretics) offers marginal benefits at best with increased risk of adverse effects. Addition of an ARB may be considered in patients who remain symptomatic despite receiving optimal conventional therapy. 

Diuretics, ACE inhibitors, ARBs, and CCBs are primary agents acceptable as first-line options based on outcome data demonstrating CV risk reduction benefits (Table 10-2). /TBIockers may be used either to treat a specific compelling indication or as combination therapy with a primary antihypertensive agent for patients without a compelling indication. 

This is not the only example. Recently, polymorphisms in the G protein p3-subunit gene have been shown to predict response to hydrochlorothiazide (Turner et al., 2001). Psaty et al. identified a subset of patients with a variant of the a-adducin gene that were associated with a lower risk of myocardial infarction and cerebral hemorrhage with diuretic therapy (Psaty et al., 2002). In addition, Genaissance has indicated that it has identified markers that predict the response to the statins, a class of drugs used to lower cholesterol. 

Clinical reports on minoxidil indicate that the drug is effective, particularly in cases which are refractory to other drugs (21. 22). It has the typical side-effects of a vasodilator and co-administration of a diuretic and a p-adrenergic blocker is recommended in many of the reported studies (21-28). 

Amlodipine and nifedipine are dihydropyridine calcium-channel blockers. Amlodipine differs from nifedipine in that it has a longer duration of action and can therefore be given once daily, unlike nifedipine. Both are indicated in hypertension and angina and tend to cause ankle oedema that does not respond to diuretic therapy. Neither amlodipine nor nifedipine are available as spray formulations. 

Thiazide diuretics act on the beginning of the distal convoluted tubule by inhibiting sodium re-absorption. Thiazide diuretics are indicated in hypertension, and at higher doses to relieve oedema caused by heart failure. Thiazide diuretics lead to hyponatraemia and hypokalaemia. They may cause hypercalcaemia and are therefore avoided in patients with this condition. 

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