1. Chapter 12 Urinary System Drugs Copyright © 2011 Delmar, Cengage Learning

2. 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 Copyright © 2011 Delmar, Cengage Learning

3. Basic Anatomy and Physiology Copyright © 2011 Delmar, Cengage Learning

4. Urinary System Disorders Include urinary tract infections, inflammation and irritation of the urinary tract, renal failure, urinary incontinence, and uroliths (urinary stones) Bacterial infections of the urinary system may lead to: – inflammation, pollakiuria (increased frequency of urination) –dysuria (painful urination) which may result in inappropriate urination for household pets These disorders affect the urinary tract resulting in clinical signs such as inappropriate urination, inability to urinate, frequent urination, increased urination, or pain Copyright © 2011 Delmar, Cengage Learning

5. 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 Copyright © 2011 Delmar, Cengage Learning

6. 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 Copyright © 2011 Delmar, Cengage Learning

7. 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 Copyright © 2011 Delmar, Cengage Learning

8. 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 Copyright © 2011 Delmar, Cengage Learning

9. 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 Copyright © 2011 Delmar, Cengage Learning

10. 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 Copyright © 2011 Delmar, Cengage Learning

11. 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 Copyright © 2011 Delmar, Cengage Learning

12. 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 Copyright © 2011 Delmar, Cengage Learning

13. 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 Copyright © 2011 Delmar, Cengage Learning

14. 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 Copyright © 2011 Delmar, Cengage Learning

15. 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 Copyright © 2011 Delmar, Cengage Learning

16. 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 Copyright © 2011 Delmar, Cengage Learning

17. 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 Copyright © 2011 Delmar, Cengage Learning

18. 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 Copyright © 2011 Delmar, Cengage Learning

19. 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 Copyright © 2011 Delmar, Cengage Learning

20. 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 Copyright © 2011 Delmar, Cengage Learning