Frusemide is the only loop diuretic which is licensed for veterinary use. By inhibiting the co-transport of sodium, potassium and chloride ions in the loop of Henle, loop diuretics are the most efficacious diuretics available, being capable of stimulating the loss of up to 20% of the filtered load of sodium ions. Loop diuretics also promote loss of potassium, magnesium and calcium in the urine. Excessive loss of potassium and magnesium may have detrimental consequences for other drug therapies, for example cardiac glycosides and certain antidysrhythmic drugs. Frusemide can be administered orally or parenterally. In cases of severe pulmonary oedema due to left-sided heart failure, the intravenous administration of frusemide (up to 4 mg kg-1) is indicated. Frusemide is thought to have venodilator actions on the pulmonary vasculature which occur more rapidly than its natriuretic effects and these contribute to its therapeutic action in the management of cardio genie pulmonary oedema. Following intravenous administration, the onset of action of frusemide peaks at 30 min and returns to baseline within 2-3 h. When administered orally, the absorption of frusemide from the intestine can be variable in terms of rate and extent. This may be affected by the formulation of the preparation, the individual animal and the degree of congestion in the intestinal circulation. It is important to recognize that the dose required varies for each individual patient according to its physiological state and to the pharmacological effects of concurrent therapies (vasodilators, dietary salt restriction and other diuretics) which may be employed. In general, cats are more sensitive to frusemide than are dogs and unless lower dosages are used in the cat serious side effects may result.
Hydrochlorothiazide is a thiazide diuretic which works by interfering with sodium transport in the early distal tubule and is capable of causing excretion of up to 10% of the filtered load of sodium in the urine. Excessive loss of both potassium and magnesium in the urine will occur with thiazide diuretics but they reduce urinary loss of calcium. Hydrochlorothiazide can be administered by intramuscular injection or orally (2-4 mg kg-1). The absorption of orally administered drug will be affected by the state of the intestinal circulation and in cases of refractory right-sided heart failure, parenteral administration may be more successful The duration of action of hydrochlorothiazide is longer than frusemide with effects being evident for up to 12 hours after administration.
Adverse effects of potassium-losing diuretics
Overzealous use of diuretic drugs will lead to a fall in cardiac output and arterial blood pressure due to excessive reduction in cardiac filling pressure. This will lead to clinical signs of dehydration, weakness due to poor muscle perfusion, and azotaemia due to reduced renal blood flow and a consequent decrease in glomerular filtration rate. In addition, particularly in animals which are anorectic, excessive potassium loss in the urine can result in hypokalaemia. This may contribute to the state of muscle weakness, cause gastrointestinal and renal problems, predispose to the development of cardiac arrhythmias and enhance the toxicity of cardiac glycosides. Monitoring plasma potassium and urea concentrations in animals on diuretic therapy is good clinical practice as it allows early correction of hypokalaemia and prerenal azotaemia. Hypo-magnesaemia may contribute to the adverse effects of loop and thiazide diuretics although less information is available from veterinary patients. The animals most susceptible to these problems are cats which are often anorectic and azotaemic on presentation and become dehydrated very rapidly when challenged with potent diuretics (particularly frusemide). Provided appetite remains reasonably good, diuretic-induced hypokalaemia is less likely to be significant.