McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 5 1 Diuretic agents

the loss of hearing is usually reversible after the drug is stopped. This may be an effect of electrolyte changes on the conduction of fragile nerves in the central nervous system. Clinically important drug–drug interactions The risk of ototoxicity increases if loop diuretics are combined with aminoglycosides or cisplatin. Antico- agulation effects may increase if these drugs are given with anticoagulants. There may also be a decreased loss of sodium and decreased antihypertensive effects if these drugs are combined with indomethacin, ibupro- fen, salicylates or other non-steroidal anti-inflammatory agents; a person receiving this combination should be monitored closely, and appropriate dose adjustments should be made. C arbonic anhydrase inhibitors The carbonic anhydrase inhibitors are relatively mild diuretics. Available agents include acetazolamide ( Diamox ) and brinzolamide ( Azopt ). Therapeutic actions and indications The enzyme carbonic anhydrase is a catalyst for the for- mation of sodium bicarbonate, which is stored as the alkaline reserve in the renal tubule, and for the excre- tion of hydrogen, which results in a slightly acidic urine. Diuretics that block the effects of carbonic anhydrase slow down the movement of hydrogen ions; as a result, more sodium and bicarbonate are lost in the urine. These drugs are used as adjuncts to other diuretics when a more intense diuresis is needed. Most often, carbonic anhydrase inhibitors are used to treat glaucoma because the inhibition of carbonic anhydrase results in decreased secretion of aqueous humour of the eye. See Table 51.2 for usual indications for each of these agents. Pharmacokinetics These drugs are rapidly absorbed and widely distrib- uted. Acetazolamide is available orally and for IV use. These drugs peak in 2 to 4 hours (15 minutes if given IV) and have a 6- to 12-hour duration. They are excreted in urine. Some of these agents have been associated with fetal abnormalities and they should not be used during pregnancy. Because of the potential for adverse effects on the baby, another method of feeding should be used if one of these drugs is needed during breastfeeding. Contraindications and cautions Carbonic anhydrase inhibitors are contraindicated in individuals with allergy to the drug, to antibacterial sulfonamides or thiazides to prevent hypersensitivity reactions , or in individuals with chronic non-congestive

angle-closure glaucoma, which would not be effectively treated by these drugs . Routine use during pregnancy is not appropriate; these drugs should be reserved for situations 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. Cautious use is recommended in people who have fluid or electrolyte imbalances, renal or hepatic disease, adrenocortical insufficiency, respiratory acidosis or chronic obstructive pulmonary disease, which could be exacerbated by the fluid and electrolyte changes caused by these drugs. Adverse effects Adverse effects of carbonic anhydrase inhibitors are related to the disturbances in acid–base and electrolyte balances. Metabolic acidosis is a relatively common and potentially dangerous effect that occurs when bicar- bonate is lost. Hypokalaemia is also common because potassium excretion is increased as the tubule loses potassium in an attempt to retain some of the sodium that is being excreted. People also complain of par- aesthesias (tingling) of the extremities, confusion and drowsiness, all of which are probably related to the neural effect of the electrolyte changes. Clinically important drug–drug interactions There may be an increased excretion of salicylates and lithium if they are combined with these drugs. Caution Prototype summary: Acetazolamide Indications: Adjunctive treatment of open-angle glaucoma, secondary glaucoma; preoperative use in acute angle-closure glaucoma when delay of surgery is indicated; oedema caused by HF; drug-induced oedema. Actions: Inhibits carbonic anhydrase, which decreases aqueous humour formation in the eye, intraocular pressure and hydrogen secretion by the renal tubules. Pharmacokinetics: Route Onset Peak Duration Oral 1 hour 2–4 hours 6–12 hours Sustained- release oral 2 hours 8–12 hours 18–24 hours IV 1–2 mins 15–18 mins 4–5 hours T 1/2 : 5 to 6 hours; excreted unchanged in urine. Adverse effects: Weakness, fatigue, rash, anorexia, nausea, urinary frequency, renal calculi, bone marrow suppression, weight loss.