Fundamentals of Pharmacology for Veterinary Technicians

Chapter 12

Urinary System Drugs

Basic Anatomy and Physiology

• The structures of the urinary system include paired kidneys, paired ureters, a single urinary bladder, and a single urethra

• Within each kidney are millions of individual structures, called nephrons, that do the actual work of the kidney– A nephron consists of a glomerulus,

Bowman’s capsule, proximal convoluted tubule, loop of Henle, distal convoluted tubule, and a collecting duct

Basic Anatomy and Physiology

Drugs Affecting the Urinary System

• Diuretics– Increase the volume of urine excreted by the

kidneys and promote release of water from tissues

– Lower the fluid volume in tissues; are used to decrease edema and lower blood pressure

– May also be used to reduce udder edema in cattle and promote voiding to enhance removal of toxins from the body

– Types of diuretics include thiazides, loop diuretics, potassium-sparing diuretics, carbonic anhydrase inhibitors, and osmotics

Drugs Affecting the Urinary System

• Diuretics (cont.)– Thiazides

• Act directly on the renal tubules to block sodium reabsorption and promote chloride ion excretion

• Side effects include hypokalemia and cardiac dysfunction

• Examples include hydrochlorothiazide, chlorothiazide, hydroflumethiazide, and bendroflumethiazide

Drugs Affecting the Urinary System

• Diuretics (cont.)– Loop diuretics

• Influence the reabsorption action at the loop of Henle, resulting in tremendous diuresis

• Side effects include electrolyte imbalances, especially hypokalemia

• An example is furosemide

Drugs Affecting the Urinary System

• Diuretics (cont.)– Potassium-sparing diuretics

• Act on the distal convoluted tubules to promote sodium and water excretion and potassium retention (interfere with the sodium-potassium pump that is controlled by aldosterone)

• Main side effect is hyperkalemia• Examples include spironolactone,

triamterene, and amiloride

Drugs Affecting the Urinary System

• Diuretics (cont.)– Carbonic anhydrase inhibitors

• Block the action of the enzyme carbonic anhydrase, which is used by the body to maintain acid-base balance

• Used to decrease intraocular pressure with open-angle glaucoma

• Main side effect is metabolic acidosis• Examples include acetazolamide and

dichlorphenamide

Drugs Affecting the Urinary System

• Diuretics (cont.)– Osmotic diuretics

• Increase the osmolality (concentration) of the urine filtrate in the renal tubules, resulting in the excretion of chloride, potassium, and water

• Used to prevent kidney failure and to decrease intracranial and intraocular pressure

• Side effects include fluid and electrolyte imbalance and vomiting

• Examples include mannitol and glycerin

Drugs Affecting the Urinary System

• Antihypertensive drugs– Drugs that decrease hypertension (lower

blood pressure)– Types of antihypertensive drugs include:

• Diuretics: promote sodium and water loss, which decreases fluid volume and blood pressure (covered previously in this chapter and Chapter 8)

• Angiotensin-converting enzyme inhibitors (ACE inhibitors): block the conversion of angiotensin I to angiotensin II, which results in decreased aldosterone secretion. Examples include enalapril, captopril, lisinopril, and benazepril

Drugs Affecting the Urinary System

• Antihypertensive drugs (cont.)– Types of antihypertensive drugs

include:• Calcium-channel blockers: block the influx

of calcium ions into the myocardial cells, resulting in an inhibition of cardiac and smooth muscle contractility; examples include diltiazem, verapamil, and nifedipine

• Direct-acting arteriole vasodilators: relax smooth muscles of blood vessels causing vasodilation; examples include hydralazine and minoxidil

Drugs Affecting the Urinary System

• Antihypertensive drugs (cont.)– Types of antihypertensive drugs

include:• Beta-adrenergic antagonists (also known

as beta-blockers): has side effect of decreasing blood pressure; an example of a nonselective beta-blocker is propranolol

• Alpha-adrenergic antagonists: block alpha-1 adrenergic receptors, resulting in vasodilation; examples include phenoxybenzamine, prazosin, and nicergoline

Drugs Affecting the Urinary System

• Urolith treatment– Uroliths are abnormal mineral masses in the

urinary system– Types of uroliths include: struvite, calcium

oxalate, calcium phosphate, urate, cystine, and mixed

– Each type of urolith may be treated differently and may include dietary management as well as drug treatment

– Drug categories used to treat uroliths include urinary acidifiers, urinary alkalinizers, and xanthine oxidase inhibitors

Drugs Affecting the Urinary System

• Urolith treatment (cont.)– Urinary acidifiers are used clinically to produce

acid urine, which dissolves and helps prevent formation of struvite uroliths. Their use has declined with the use of urinary acidifying diets. Examples include methionine and ammonium chloride

– Urinary alkalinizers are used clinically to treat calcium oxalate, cystine, and ammonium urate uroliths. An example is potassium citrate

– Xanthine oxidase inhibitors decrease the production of uric acid, which helps decrease the formation of ammonium urate uroliths. An example is allopurinol

Drugs Affecting the Urinary System

• Urinary incontinence drugs– Urinary incontinence is the loss of

voluntary control of micturition– Urinary incontinence may be due to:

• Neurologic disorders resulting from trauma to the spinal cord, tumors of the nervous system, or degeneration of the nervous system tracts

• Nonneurologic disorders, which include hormone-responsive, stress, urge, ectopic ureter formation, or urinary bladder overdistention

Drugs Affecting the Urinary System

• Drugs used to treat neurologically caused urinary incontinence:– Cholinergic agonists treat animals with

damage to the nerves that control relaxation of the urinary bladder

• Promote voiding of urine from the urinary bladder• An example is bethanechol

– Anticholinergics treat urinary incontinence by promoting urine retention in the urinary bladder

• Block binding of ACh to its receptor site, causing muscle relaxation

• Examples include propantheline, dicyclomine, and butylhyoscine

Drugs Affecting the Urinary System

• Drugs used to treat neurologically caused urinary incontinence (cont.):– Alpha-adrenergic antagonists decrease the

tone of internal urethral sphincters and are used to treat urinary incontinence due to decreased urinary tone as a result of overdistention of the urinary bladder

• Examples include phenoxybenzamine, prazosin, and nicergoline

Drugs Affecting the Urinary System

• Drugs used to treat nonneurologically caused urinary incontinence:– Estrogen treats hormone-responsive urinary

incontinence seen mainly in F/S dogs. An example is diethylstilbestrol (DES)

– Testosterone treats hormone-responsive urinary incontinence seen mainly in M/C dogs. Examples include testosterone cypionate and testosterone propionate

Drugs Affecting the Urinary System

• Drugs used to treat nonneurologically caused urinary incontinence (cont.):– Alpha- and beta-adrenergic agonists stimulate

these receptors, which increases urethral tone; examples include phenylpropanolamine and ephedrine

– Skeletal muscle relaxants treat urge incontinence or urethral obstructions due to increased external urethral sphincter tone; examples include dantrolene, aminopropazine, and diazepam