McKenna's Pharmacology for Nursing, 2e

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P A R T 9  Drugs acting on the renal system

sodium is reabsorbed. This action decreases the reab- sorption of sodium and chloride. The loop diuretics have a similar effect in the descending loop of Henle and in the distal convoluted tubule, resulting in the produc- tion of a copious amount of sodium-rich urine. These drugs work even in the presence of acid–base distur- bances, renal failure, electrolyte imbalances or nitrogen retention. Because they can produce a loss of fluid of up to 10 L/day, loop diuretics are the drugs of choice when a rapid and extensive diuresis is needed. In cases of severe oedema or acute pulmonary oedema, it is important to remember that these drugs can have an effect only on the blood that reaches the nephrons. A rapid diuresis occurs, producing a more hypertonic intravascular fluid. In pulmonary oedema, this fluid then circulates back to the lungs, pulls fluid out of the interstitial spaces by its oncotic pull, and delivers this fluid to the kidneys, where the water is filtered out, completing the cycle. In the treatment of pulmonary oedema, it can sometimes take hours to move all of the fluid out of the lungs because the fluid must be removed from the interstitial spaces in the lungs before it can be circulated to the kidneys for removal. Remembering how the drugs work and the way in which fluid moves in the vascular system will make it easier to understand the effects to anticipate. Loop diuretics are commonly indicated for the treat- ment of acute HF, acute pulmonary oedema, oedema associated with HF or with renal or liver disease and hypertension. See Table 51.1 for usual indications for each of these agents. Frusemide is less powerful than bumetanide and therefore has a larger margin of safety for home use. See the Critical thinking scenario for additional information about using frusemide in HF . Ethacrynic acid is used less frequently in the clinical setting because of the improved potency and reliability of the other drugs. Pharmacokinetics Loop diuretics are available for oral or IV use. Fruse- mide may also be given IM. They reach peak levels in 60 to 120 minutes (orally) or 30 minutes (parenterally) and are metabolised with a half-life of 30 to 60 minutes and excreted primarily through urine. Contraindications and cautions Among the contraindications to these drugs are allergy to a loop diuretic to prevent hypersensitivity reactions ; electrolyte depletion, which could be aggravated by the electrolyte effects of these drugs ; anuria—severe renal failure, which may prevent the diuretic from working or precipitate a crisis stage due to the blood flow changes brought about by the diuretic ; and hepatic coma, which could be exacerbated by the fluid shifts associated with drug use. Routine use during pregnancy is not

appropriate; these drugs should be reserved for situa- tions in which the mother has pathological reasons for use, not pregnancy manifestations or complications, and only if the benefit to the mother clearly outweighs the risk to the fetus. Caution should be used with the following condi- tions: SLE, which frequently causes glomerular changes and renal dysfunction that could precipitate renal failure in some cases ; glucose tolerance abnormalities or diabetes mellitus, which are worsened by the glucose- elevating effects of many diuretics ; and gout, which reflects an abnormality in normal tubule reabsorption and secretion . Safety for use in children younger than 18 years of age has not been established. If one of these drugs is used for a child, careful monitoring of the child’s fluid and electrolyte balance is needed, and emergency support measures should be on standby. Adverse effects Adverse effects are related to the imbalance in electro- lytes and fluid that these drugs cause. Hypokalaemia is a very common adverse effect because potassium is lost when the transport systems in the tubule try to save some of the sodium being lost. Alkalosis , or a drop in serum pH to an alkaline state, may occur as bicarbonate is lost in the urine. Calcium is also lost in the tubules along with the bicarbonate, which may result in hypo­ calcaemia and tetany. The rapid loss of fluid can result in hypotension and dizziness if it causes a rapid imbal- ance in fluid levels. Long-term use of these drugs may also result in hyperglycaemia because of the diuretic effect on blood glucose levels, so susceptible individu- als need to be monitored for this effect. Ototoxicity and even deafness have been reported with these drugs, but Prototype summary: Frusemide Indications: Treatment of oedema associated with HF, acute pulmonary oedema, hypertension. Actions: Inhibits the reabsorption of sodium and chloride from the distal renal tubules and the loop of Henle, leading to a sodium-rich diuresis. Pharmacokinetics: Route Onset Peak Duration Oral 60 mins 60–120 mins 6–8 hours IV, IM 5 mins 30 mins 2 hours T 1/2 : 120 minutes; metabolised in the liver and excreted in urine. Adverse effects: Dizziness, vertigo, paraesthesias, orthostatic hypotension, rash, urticaria, nausea, anorexia, vomiting, glycosuria, urinary bladder spasm.