Module 3 Drugs Acting on Urinary System PDF

MODULE 3 DRUGS ACTING ON URINARY SYSTEM Clinical Pharmacology ANNALIE B. PARAGAS, DVM ,MPH ASSOCIATE PROFESSOR 1 COLLEGE OF VETERINARY MEDICINE TARLAC AGRICULTURAL UNIVERSITY  DRUGS ACTING ON URINARY SYSTEM Introduction The urinary sy...

MODULE 3 DRUGS ACTING ON URINARY SYSTEM Clinical Pharmacology ANNALIE B. PARAGAS, DVM ,MPH ASSOCIATE PROFESSOR 1 COLLEGE OF VETERINARY MEDICINE TARLAC AGRICULTURAL UNIVERSITY  DRUGS ACTING ON URINARY SYSTEM Introduction The urinary system (the renal system) is composed of two kidneys, tow ureters, a urinary bladder, and a urethra. The medical study of the renal system is known as nephrology, because the basic functional unit of the kidney is the nephron. The kidneys act in the body the way a filter acts in a fish aquarium. All water in the aquarium is sent through the filter to capture waste products in the water to keep it clean. Thus the kidneys filter all waste products out of the blood stream but allow those elements needed by the body to stay in the blood stream.  The job of the nephron is to regulate water and soluble matter (especially electrolytes) in the body. Nephrons filter the blood under pressure and then reabsorb necessary fluid and molecules back into the blood, while secreting other unneeded molecules. The kidneys thus excrete a variety of waste products produced by metabolism usch as urea, uric acid, and water. The kidneys are involved in factors of homeostasis such as acid-base balance, regulation of electrolyte concentrations, blood volume control, and regulation of blood pressure. The kidneys communicate with other organs in the body through hormones that are secreted into the blood stream.  Physiologic Principles The formation of urine is a rather three complex process that involves glomerular filtration, tubular reabsorption, and tubular secretion. The glomerular filtrate is composed of water and dissolved substance, which pass from the plasma into the glomerular capsule. The formation of glomerular filtrate is controlled by effective filtration pressure (EFP = arterial blood pressure – [plasma osmotic pressure + capsule pressure]). The amount of glomerular filtrate is directly proportional to the effective filtration pressure. Changes in blood flow through the glomerulus, glomerular blood pressure, plasma osmotic pressure, and capsule pressure affect glomerular filtration.  The kidney tubules are responsible for the reabsorption, or the secretion, of specific substances. Substances needed by the body are reabsorbed from the filtrate, pass through the tubular cell wall, and reenter the plasma. This process filters needed substances and returns them to the body. reabsorbed materials include water, glucose, amino acids, urea, and ions such as Na+, K+, Ca2+, Cl-, HCO3-, and HPO4-. Any excess of these substances or of substances that are not useful remains in the filtrate and is excreted in the urine.  Tubular secretion occurs when substances are carried to the tubular lumen. This involves the active transport of certain endogenous substances and may exogenous substances. These secreted substances include potassium and hydrogen ions, ammonia, creatinine and some drugs. The main effects of tubular secretion are to rid the body of certain materials and to help control blood pH. The kidneys are very important to remember that these actions may be inhibited in cases of renal failure or dysfunction has increased risks. Renal failure can impair a drug’s absorption from an administration site or can affect a drug’s distribution in the body.  RENAL FAILURE It is among the major causes of nonaccidental death in dogs and cats. Although the disease is most common on in older animals, it may be diagnosed in younger animals. Renal damage may stem from many causes, including infectious diseases, diabetes mellitus, toxins, neoplasia, congenital disorders, immunologic problems, and amyloidosis, Diets with excessive protein, phosphorus and sodium are other factors that may cause renal damage. Renal damage may categorized as prerenal, renal or posterenal. Renal failure may be differentiated as acute, chronic or end-stage, according to parameters common to each stage. DRUGS COMMONLY USED FOR THE TREATMENT OF RENAL DYSFUNCTION AND ASSOCIATED HYPERTENSION DIURETIC DRUGS I. LOOP DIURETICS These are highly potent diuretics that inhibit the tubular reabsorption of sodium. Once administered, their actions are generally rapid. Additionally, loop diuretics promote the excretion of chloride, potassium, and water. Some patients in long term loop diuretic therapy have to be placed on potassium supplementation. Dosage Forms 1. Furosemide (Lasix, Disal, Diuride) 2. Ethacrynic acid (edectin – human label) Adverse Side Effects These include hypokalemia because of the increase excretion of potassium.  II. OSMOTIC DIURETICS These can be administered IV to promote dieresis by exerting high osmotic pressure in the kidney tubules and limiting tubular reabsorption. Water is drawn into the glomerular filtrate, reducing its reabsorption and increasing the excretion of water. These drugs may be used to treat oliguric acute renal failure and to reduce intracranial pressure. Dosage forms 1. mannitol 20% 2. Glucose Adverse side Effects These are uncommon Notes: These drugs are administered over a 10 to 15 minute period. III. THIAZIDE DIURETICS These drugs reduce edema by inhibiting reabsorpiton of Na, Cl, and water. Their duration of action is longer than that of loop diuretics. Dosage forms 1. Chlorothiazide (Diuril – human label) 2. Hydrochlorothiazide (HydroDIURIL – human label) Adverse Side Effects These include hypokalemia if therapy is prolonged Notes: Similar to loop diuretics, thiazide diuretics cause an increase in potassium excretion. A potassium supplement may be necessary to prevent hypokalemia These drugs cross the placental border. IV. POTASSIUM-SPARING DIURETICS These have weaker diuretic and antihypertensive effects than other diuretics, but they have the ability to conserve potassium. These agents are also referred to as ALDOSTERONE ANTAGONISTS. They work by antagonizing aldosterone, and adrenal mineralocorticoid. This action enhances the excretion of sodium and water and reduces the excretion of potassium. Aldosterone secretions may be a factor in edema associated with heart failure. Dosage Forms 1. Spironolactone (Aldactone – human label) 2. Triamterene (Diazide, Dyrenium – human label) Adverse Side Effects These are uncommon, but hyperkalemia may result if these drugs are administered concurrently with potassium supplements or angiotension- converting ezyme (ACE) inhibitors, such as captopril or enalapril. Notes: these drugs may be used alone or with other diuretics V. CARBONIC ANHYDRASE INHIBITORS A carbonic anhydrase inhibitor is a substance that decreases the rate of carbonic acid and H+ production in the kidney, thereby promoting the excretion of solutes and increasing the rate of urinary output (Mosby, 1988). These drugs also reduce intraocular pressure by reducing the production of aqueous humor and may be used in the treatment of glaucoma. Dosage Forms 1. Acetozolamide (Diamox – human label) 2. Dichlorphenamide (Daranide – human label) Adverse Side Effects These include the ability to cause hypokalemia Note: these are not commonly used to treat edema. VI. CHOLINERGIC AGONISTS These drugs act directly or indirectly to promote the function acetylcholine (ACH). These agents may also be referred to as PARASYMPATHOMIMETIC AGENTS because their effects mimic stimulation of the parasympathetic nervous system. Cholinergic agonists mimic the action of natural ACH by directly stimulating the cholinergic receptors. Once the cholinergic agonists bind with the receptors on the cell membrane of smooth muscles, the permeability of the cell membrane changes, permitting calcium and sodium to enter into the cells. Depolarization of the cell membrane occurs, and muscle contraction is achieved. Clinical Uses Cholinergic agents are used to help void the urinary bladder. Their action increases the tone of the detrusor muscle of the bladder and decreases bladder capacity. Dosage form Bethanecol (Urecholine- human lable) Adverse Side Effects These include the potential cholinergic toxicity. Notes: 1. Observe the patient for signs of cholinergic toxicity (e.g. vomiting, defecation, dyspnea, tremors). 2. Atropine is antidotal. VII. ANTICHOLINERGIC DRUGS The action of these drugs is opposite to cholinergic agonist. They block the action of ACH at the receptor sites in the parasympathetic nervous system. These drugs may also be described as PARASYMPATHOLYTIC because of their ability to block the passage of impulses through the parasympathetic nerves. Their action produces muscle relaxation. Clinical Uses These can be used for treating urge incontinence by promoting the retention of urine in the urinary bladder. Dosage Forms 1. Propantheline (Pro-Banthine- human label) 2. Butyl hyoscine (Buscupan) Adverse side Effects Decrease gastric motility and delayed gastric emptying, which may decrease the absorption of other medications VIII. ADRENERGIC ANTAGONISTS These agents disrupt the sympathetic nervous system by blocking impulse transmission at adrenergic neurons, adrenergic receptors sites, or adrenergic ganglia. These agents may also be described as SYMPATHOLYTIC AGENTS because of their ability to block the sympathetic n.s. stimulation. The classification of adrenergic antagonists is based on their site of action (ie. Alpha blockers, beta blockers or autonomic ganglionic blockers). A. Alpha-adrenergic Antagonists It relax the vascular smooth muscle, enhance peripheral vasodilation, and decrease blood pressure by interrupting the actions of sympathomimetic agents at alpha-adrenergic receptors sites. Clinical Uses These drugs reduce internal sphincter tone when the urethral sphincter is in hypertonus. This action is useful in the treatment of urinary retention because of detrusor areflexia or functional urethral obstruction. Prazosin is effective in controlling moderate to severe hypertension, which may be a complicating factor in chronic renal failure. Dosage Forms 1. Phenoxybenzamine (Dibenzyline – human label) 2. Nicergoline (Sermion) 3. Moxisylyte (Carlytene) 4. Prazosin (Minipress – human label) Adverse side Effects These include rapid decrease in blood pressure, resulting in weakness or syncope after the first dose of prazosin. This is usually self-limiting. Notes: Prazosin may be used along or combine with a diuretic to produce the desired effect Because alpha-adrenergic antagonists are metabolized by the liver, dosage modification is not necessary in patients with renal dysfunction. B. Beta – Adrenergic Antagonists It inhibits the action of catecholamines and other sympthomimetic agents at beta-aderenergic receptos sites and thereby inhibit stimulation of the sympathetic n.s. Clinical uses Control of mild to moderate hypertension associated with chronic renal failure. Dosage form Propanolol (inderal-human label) Adverse Side effects Decreased cardiac output and the promotion of bronchospasm. Therefore, caution should be exercise with their use in patients with cardiac or pulmonary disease (Cowgill 1991). Notes: Combination with a diuretic is common because of the tendency of beta- adrenergic antagonists to cause salt and fluid retention. IX. ANGIOTENSIN-CONVERTING ENZYME INHIBITORS It blocks the conversion of angiotensin I to angiotensin II, decrease aldosterone secretion, reduce peripheral arterial resistance, and alleviate vasoconstriction. Clinical Uses Used to treat nonresponding hypertension or moderate to severe hypertension. Dosage Forms Benazepril Fortekor (vet.label) Benazepril Lotension (human label) captopril (capoten –human label) enalapril (enacard) Adverse Side Effects Complications in patients with renal insufficiency caused by excretion by the kidneys. X. VASODILATORS AND CALCIUM CHANNEL BLOCKERS May be substituted for or used in combination with other medications if previous drug therapy to control hypertension fails. Clinical Uses Used to treat nonresponding hypertension. Dopamine may be used to promote dieresis in patients unresponsive to loop or osmotic diuretics Dosage forms Vasodilators hydralazine (apresoline – human label) dopamine (Intropin – human label) calcium channel blockers diltiazem (Cardizem- human label) verapamil (Isoptin – human label) amlodipine (Norvasc and Besylate – human label) Adverse Side Effects Hypotension, edema, conduction disturbances, heart failure, and bradycardia (Cowgill, 1991). Hydralazine is excreted by the kidneys and requires modification when used to treat hypertentison in patients with renal failure. XI. ANTIDIURETIC HORMONE This is normally secreted by the posterior pituitary gland. This secretion regulates fluid balance in the body. in some conditions, such as pituitary diabetes insipidus, this hormone fails to be synthesized or excreted properly, and polyuria and polydipsia (PUPD) occur. Clinical uses Treatment of diabetes insipidus Dosage form Vasopressin (Pitressin – human label) Adverse Side Effects Uncommon Notes: Chlorpropamide (Diabinese, Glucamide) is a human product that is used to control type II diabetes mellitus. It potentiates the action of ADH and may be used to treat mild diabetes insipidus. XII. URINARY ACIDIFIERS These are used to produce acid urine, which assists in dissolving and preventing formation of struvite uroliths. Since the introduction of urinary acidifying diets, urinary acidifiers have not been routinely prescribed. Dosage forms Methionine (Methigel, Methio-Tabs) Ammonium chloride (Uroeze) Adverse Side Effects GIT disturbances. These products should not be administered to patient with severe liver, kidney, or pancreatic disease or to those who exhibit acidosis. Notes: It is very important to inform clients who may change from using an acidifier to one of the available acidifying diets that while the diet is being administered, no acidifiers, salt, vitamins or mineral supplements, or any other food items- other than what is allowed in the diet- should be given to the patient. XIII. XANTHINE OXIDASE INHIBITORS These agents decrease the production of uric acid and are used in combination with a urate calculolytic diets for the dissolution of ammonium acid urate uroliths. Once dissolution occurs, a urine alkalizing, low-protein, low-purine, low- oxalate diet is usually prescribed to prevent recurrence of uroliths. Dosage forms Allopurinol (zyloprim – human label) Adverse side effects These are uncommon, but because excretion occurs via the kidneys, the doage may be altered in patients with renal insufficiency. Notes: In cases of recurrence, allopurinol may once again be prescribed. XIV. URINARY ALKALIZERS It may be used in the management of ammonium acid urate, calcium oxalate, and cystine urolithiasis. Dosage forms Potassium citrate (Urocit-K – human label) Sodium bicarbonate, administered orally Tiopronin tabs (Thiola – human label) Adverse side effects Possible fluid and electrolyte imbalance with the use of sodium bicarbonate  MISCELLANEOUS RENAL DRUGS URINARY TRACT ANALGESICS Phenazopyridine This is used in human as a urinary tract analgesic. It can be bought OTC. It can be used alone or with sulfa drugs. Its use is contraindicated in felines because they are quite susceptible to dose related methemoglobinemia, and oxidative changes in hemoglobin may be irreversible, causing formation of Heinz bodies and anemia (Osborne, 2001).  TRICYCLIC ANTIDEPRESSANTS Amitriptyline Dosage Form Amitriptyline (Elavil) It is used to treat interstitial cystitis in humans. ins mechanism is not fully understood. Amitriptyline is a tricyclic antidepressant and anxiolytic drug with anticholinergic, antihistaminic, anti-alpha-adrenergic, anti-inflammatory, and analgesic properties.  It has been used extensively for the treatment of interstitial cystitis in humans. Although it is a popular drug, its exact mechanism of action and therapeutics value in managing patients with interstitial cystitis remain unknown. This has been used recently for symptomatic treatment of idiopathic feline lower urinary tract disease (LUTD) (Osborne, 2001). Adverse side effects Dry mouth, rapid heart rate and sedation (i.e. antihistamine effects) are associated with this drug. High doses can cause heart toxicity. Sometimes it may cause cats to be less interested in grooming themselves. Additionally, weight gain may occur (Papich, 2002).  Glycosaminoglycans (GAGs) This substances are found covering the transitional epithelium of the urinary tract, these urothelial GAGs have the ability to keep microorganisms and crystals from adhering to the bladder wall and limit the transepithelial movement of urine proteins and solutes ionic or nonionic), Defects in surface GAGs and subsequent urothelial permeability are believed to be a factor in pathogenesis of feline idiopathic LUTD (Osborne, 2001). Pentosan Polysulfate Sodium (Elmiron) Clinical Uses Often used to manage human interstitial cystitis. Used to reinforce urothelial GAGs and to reduce transitional cell injury.  OTHER AGENTS Epakitin Is a chitosen-based nutritional supplement made from a polysaccharide extracted from crab and shrimp shells. Clinical uses It binds phosphorus in the intestine, causing phosphorus to be eliminated through the intestinal tract. Reducing the amount of phosphorus absorbed then helps to lower the elevated levels of phosphorus noted in renal failure. Azodyl It has potential to reduce the azotemia of renal failure through “enteric dialysis”. THANK YOU FOR LISTENING… QUESTIONS???