PHARM CH6.pptx

CHAPTER 6 DRUGS USED IN RENAL AND URINARY TRACT DISORDERS Anatomy Introduction Basic functional unit of the kidney – the nephron Function of the kidneys      Filter waste products from the blood Acid-base balance Regulation of electrolyte concentrations Blood volume control Regulation...

CHAPTER 6 DRUGS USED IN RENAL AND URINARY TRACT DISORDERS Anatomy Introduction Basic functional unit of the kidney – the nephron Function of the kidneys      Filter waste products from the blood Acid-base balance Regulation of electrolyte concentrations Blood volume control Regulation of blood pressure Physiologic Principles Formation of urine  Glomerular filtration   Tubular reabsorption   Controlled by effective filtration pressure (EFP = arterial BP – [plasma osmotic pressure + capsule pressure]) H2O, glucose, amino acids, urea & ions (Na+, K+, Ca2+, HCO3-, etc) – “keepers” Tubular secretion  Potassium & hydrogen ions, ammonia, creatinine & some drugs – “excess and trash” Physiologic Principles Results of decreased function  Erythropoiesis may not occur correctly due to lack of erythropoietin  Uremia can increase sensitivity of some tissues to certain drugs (CNS depressants and tranquilizers)  Impaired excretion or biotransformation of drugs Renal Failure COMMON Causes – infectious disease, DM, toxins (antifreeze), neoplasia, congenital disorders, immunologic problems, amyloidosis & diets high in protein, phosphorus & sodium Prerenal, renal or postrenal Acute, chronic or end-stage Drugs Commonly Used for the Treatment of Renal Dysfunction & Associated Hypertension Diuretic drugs  Remove excess extracellular fluid by increasing urine flow & sodium excretion → reduced hypertension Diuretics Loop diuretics  Inhibit tubular reabsorption of sodium (& promote excretion of chloride, potassium & water)  Dosage forms – furosemide (Lasix)  Adverse side effects - hypokalemia Osmotic diuretics  Promote diuresis by exerting high osmotic pressure in the tubules & limiting tubular reabsorption  Uses – oliguric ARF & reduce intracranial pressure  Dosage forms – mannitol & glucose Diuretics Thiazide diuretics  Reduce edema by inhibiting reabsorption of sodium, chloride & water  Chlorothiazide & hydrochlorothiazide  Adverse side effects - hypokalemia Potassium-sparing diuretics  Weaker diuretic & antihypertensive effects but ability to conserve potassium  Aldosterone antagonists – increases the excretion of sodium & water  Dosage forms – spironolactone Drugs Commonly Used for the Treatment of Renal Dysfunction & Associated Hypertension Adrenergic blocking agents/Sympatholytic agents   Disrupt the SNS by blocking impulse transmission at adrenergic receptor sites Alpha-adrenergic antagonists     Relax vascular smooth m., enhance peripheral vasodilation & decrease BP Clinical uses – reduce internal urethral sphincter tone; used in the tx of detrusor areflexia or functional urethral obstruction Dosage forms – phenoxybenzamine and prazosin Adverse side effects – rapid hypotension w/ prazosin (selflimiting) Drugs Commonly Used for the Treatment of Renal Dysfunction & Associated Hypertension Adrenergic antagonists  Beta-adrenergic antagonists     Inhibits the action of catecholamines & other sympathomimetic agents Clinical uses – control of mild-moderate hypertension associated with CRF Dosage forms – propranolol Adverse side effects – decreased cardiac output & promotion of bronchospasm Drugs Commonly Used for the Treatment of Renal Dysfunction & Associated Hypertension Angiotensin-converting enzyme inhibitors  Block conversion of angiotensin I to angiotensin II resulting in decrease aldosterone secretion  Results in reduced pheripheral arterial resistance & alleviation of vasoconstriction  Clinical uses – mod-severe hypertension or nonresponding hypertension  Dosage forms – benazepril, captopril, enalapril (Enacard) Drugs Commonly Used for the Treatment of Renal Dysfunction & Associated Hypertension Vasodilators & calcium channel blockers  Clinical uses – used in combination with other drugs or in place of other drugs when previous therapy has failed to control hypertension  Dosage forms    Vasodilators – hydralazine, dopamine Calcium channel blockers – ditiazem, verapamil, amlodipine Adverse side effects  Hypotension, edema, conduction disturbances, heart failure & bradycardia Pharmacotherapy of Renal Failure Complications Anemia  Dosage forms     Parenteral androgens – nandrolone & testosterone enanthate Recombinant human erythropoietin (Epogen, Procrit) Supplemental iron Adverse side effects – local or systemic allergic rxns & pain at injection site with Epogen & Procrit Renal secondary hyperparathyroidism  Dosage forms  Vitamin D supplements - calcitriol (Rocaltrol) & dihydrotachysterol Pharmacotherapy of Diabetes Insipidus Antidiuretic hormones  ADH is secreted by the posterior pituitary gland & regulates fluid balance  Synthesis failure results in PU/PD  Dosage form – desmopressin (DDAVP)* Pharmacotherapy of Urolithiasis Urinary acidifiers  Used to produce acidic urine which assists in dissolving & preventing formation of struvite uroliths  Rarely used today due to acidifying diets available Xanthine oxidase inhibitors    Decrease the production of uric acid Clinical uses – used in combination w/ a urate calculolytic diet for the dissolution of ammonium acid urate uroliths Dosage form – allopurinol Urinary alkalizers  Clinical uses – used in the management of ammonium acid urate, calcium oxalate & cystine urolithiasis  Adverse side effect – fluid & electrolyte imbalances w/ the use of sodium bicarbonate Pharmocotherapy of Urinary Incontinence Neurogenic disorder vs nonneurogenic disorder Upper motor neuron lesions → spastic neuropathic bladder  Bladder & urethral function is abnormal   Bladder is hypercontractile Relaxation of the urethral sphincter not coordinated w/ detrusor m. → interrupted, incomplete & involuntary urination Lower motor neuron lesions → atonic neuropathic bladder  Detrusor m. contractions are abnormal  Sensation of fullness is absent → bladder capacity increases → damage to tight junctions b/w smooth m. fibers → urination occurs when pressure inside bladder exceeds outlet resistance Pharmocotherapy of Urinary Incontinence Nonneurogenic disorders – result of some type of anatomic anomaly of the lower urinary tract  Congenital anomalies   Acquired anomalies   Ectopic ureter Chronic cystitis, chronic urethritis, neoplasia, urolithiasis & postsurgical adhesions Functional anomalies  Urethral incompetence & partial urethral obstruction Medical management or surgical correction Pharmocotherapy of Urinary Incontinence  Cholinergic agonists/Parasympathomimetic agents      Promote the function of acetylcholine by stimulating cholinergic receptors Results in permeability changes of the cell membrane of smooth mm. → calcium & sodium enter cell → depolarization of cell membrane → m. contraction Clinical uses – used to help void the urinary bladder by increasing tone of the detrusor m. of the bladder Dosage forms – bethanecol Adverse side effects – potential for cholinergic toxicity Pharmocotherapy of Urinary Incontinence Anticholinergic drugs/Parasympatholytic agents      Block action of acetylcholine at the receptor sites in the PNS Results in muscle relaxation Clinical uses – used for treating urge incontinence by promoting retention of urine Dosage forms – propantheline, butyl hyoscine Adverse side effects – decreased gastric motility & delayed gastric emptying → decreased absorption of other drugs Miscellaneous Renal Drugs Tricyclic antidepressants  Amitriptyline (Elavil) – tx of interstitial cystitis & idiopathic FLUTD Glycosaminoglycans  Cosequin Other agents  Epakitin – used to reduce phosphorus associated w/ RF  Azodyl – reduce azotemia associated w/ RF  Rx diets