Therapeutic Agents for the Renal System

Transcription

1 Therapeutic Agents for the Renal System Chapter 21 1 Anatomy and Physiology of the Renal and Urological Systems Kidneys: Located inside upper abdominal cavity on either side of vertebrae; bean shaped Renal fascia: Fibrous connective tissue that holds kidneys stationary Renal artery: Where blood enters kidney Blood is filtered in the kidney Sodium and chloride reabsorbed into body and circulatory system Renal vein and ureter leave kidney via hilus Renal vein returns blood to body after filtering process What is the function of the kidneys? (The kidneys filter the blood and send the waste to the bladder as urine.) Drugs are excreted through the renal system. The kidneys are important for the production of certain hormones, including the active form of vitamin D, renin, and erythropoietin. The kidneys are located inside the upper abdominal cavity, with one kidney positioned on each side of the vertebral column. 2 Anatomy of the Urinary Tract and Nephrons What are nephrons and where can they be seen on this diagram? (Nephrons are the elements in the kidneys that perform the actual filtering [separating out components of blood]. A magnified view of the internal structure of a nephron can be seen in the left circle on the diagram.) The ureters carry wastes removed from the blood to the bladder. Plasma is the liquid component of blood, which is mostly water. 3

2 Renal and Urological Systems What other organs excrete waste products from the body? (The intestines, lungs, and skin also excrete waste products from the body.) During urination, the sphincter muscles relax to open the bladder while the bladder (which is also a muscle) contracts to squeeze out the urine. Ureter carries waste removed from blood to bladder, where it is stored for excretion Bladder is a holding tank that can expand Urine eliminated through urethra: Tube leading from bladder to outside of body 4 Kidney Structure When was the first successful human kidney transplant performed? Was the donor living or deceased? (The first successful human kidney transplant was performed in Boston in 1954 using a living donor. The donor and the recipient were identical twin brothers. The recipient lived 8 years with the transplanted kidney.) From McCance KL: Pathophysiology: the biologic basis for disease in adults and children, ed 6, St Louis, 2010, Mosby. 5 Function of the Kidneys The four functions are essential to the function and balance of the body. The kidneys must maintain a balance of water and electrolytes. Kidneys filter out and reabsorb nutrients and chemicals Waste eliminated by excretion Four major functions of body: Absorption Distribution Metabolism Excretion 6

3 What is urea? (Urea is a by-product of protein metabolism in the liver.) Function of the Kidneys (Cont.) Bladder holds up to 1000 ml of urine Body excretes about 960 ml/day Urine contains urea, produced by liver; form of nitrogen that changes to ammonia Kidneys balance fluid content of body Fluids include water, blood, plasma, and ions 7 Function of the Kidneys (Cont.) Kidneys balance and eliminate ions within blood Acidosis and alkalosis: Imbalance of ions in blood Acidosis means too many free hydrogen ions Alkalosis means too many hydroxide ions Blood urea nitrogen (BUN) test determines levels of acid in patient s system Kidneys filter about 50 gallons of blood products daily People on a high-protein, low-carbohydrate diet can develop a condition known as ketosis. In this condition, the body produces ketones as it burns fat instead of producing carbohydrates for fuel. Such a diet is bad for the kidneys for two reasons: High levels of protein strain the kidneys, and the ketones themselves can cause kidney stones or kidney failure. What functions do the kidneys have besides filtering waste? (The kidneys produce erythropoietin, a stimulator of red blood cell formation; renin, a blood pressure regulator; and the active form of vitamin D.) Acidosis occurs when too many free H + are present in the fluids of the body, and alkalosis occurs when either retention of HCO 3 - occurs or the loss of H + is excessive. 8 Nephron Function Nephrons regulate fluids, solids, and waste for the body. The renal system is basically a filtering system. Nephrons do all work of regulation of fluids, solutes, and wastes in kidney Each kidney contains millions of nephrons Nephrons work 24 hours/day 9

4 Nephron Anatomy An afferent arteriole carries blood toward an organ or location; an efferent arteriole carries blood away from an organ or location. Cations are positively charged ions such as Na + and K +, and anions are negatively charged ions such as Cl - and HCO 3 - The functional unit of the kidney is called the nephron. 10 Tubular Reabsorption Two mechanisms affecting balance of ions: Ion exchange and active transport Ion exchange: Sodium/hydrogen ion exchange (osmosis) Result: Decrease in excreted water Active transport: One-way uptake of sodium and chloride from loop of Henle Result: Sodium returned to circulatory system What function does sodium perform for the nervous system? (Sodium helps to conduct nerve impulses, so it is important for it to be reabsorbed into the circulatory system.) Osmosis is the diffusion of water from low-solute concentrations to highsolute concentrations across a semipermeable membrane. HCO 3 - is a buffer. A buffer has the ability to bind H +, which creates a basic environment, or to release H +, which creates an acidic environment, balancing the ph of the blood. 11 Tubular Secretion What is ADH? Where is it produced? (ADH is the abbreviation for antidiuretic hormone; it causes an increased reabsorption of water from the collecting ducts of nephrons. ADH is produced by the pituitary gland.) How does dehydration affect ADH levels? (Dehydration causes an increase in ADH levels, resulting in more water being retained by the body.) Tubular secretion takes place throughout the nephron First, ions, toxins, and water are secreted into collecting duct Secretion and elimination of weak acids (aspirin and penicillin) and weak bases (narcotic analgesics, metformin, and antihistamines) takes place Second, secretion allows kidneys to regulate ph of body through urine acidification Acidification: Process of eliminating extra hydrogen ions through urine Urine ph 4 to 5; blood ph is

5 Tubular Secretion (Cont.) Hydrogen ions combine to form bicarbonate They are released into bloodstream to regulate overall ph of body, maintaining homeostasis Buffer can bind or release hydrogen to balance blood ph How does the bicarbonate molecule act as a ph-regulating buffer? (Bicarbonate molecules act as a buffer because they can either bind hydrogen ions [creating a basic environment by decreasing the hydrogen ion concentration] or release hydrogen ions [creating an acidic environment by increasing the hydrogen ion concentration]). 13 Importance of Electrolytes Electrolytes are required for the body. They are important on the cardiac cycle, the balance of water, the formation of teeth, and the growth of cells, for instance. Kidneys maintain balance through electrolytes in the body Specific cations and anions important Cations include calcium, potassium, magnesium, and sodium Anions include chloride, bicarbonate, and phosphate 14 Conditions Affecting the Renal and Urological Systems Many people can live with only one kidney or partial kidney function Dialysis and/or kidney transplant is sometimes necessary Other conditions include blockages, infections of kidney, ureter, bladder, and urethra How much can kidney function be reduced before health problems arise? (Having less than 25% of normal kidney function causes health problems. A patient with less than about 15% of normal kidney function requires either dialysis or a transplant for survival. [When both kidneys are working normally, kidney function is 100%.]) 15

6 Chronic Kidney Disease Progressive loss of renal function Causes: Diabetes mellitus and uncontrolled hypertension, glomerulonephritis, pyelonephritis, and vascular disorders Five stages based on glomerular filtration rate Early symptoms: Fatigue, headache, shortness of breath, weight changes, and edema Dietary changes are important; protein restriction 16 Kidney function, in general, decreases with age; older individuals have chronic kidney disease (CKD) more often than younger adults. The progression of CKD is thought to be associated with a series of common changes in the kidneys, including glomerular hypertension and hyperfiltration, glomerulosclerosis, and inflammation of the tubules. Anemia is a common symptom of more advanced CKD because the kidneys produce the hormone erythropoietin. Ferrous sulfate and erythropoietin increase iron concentration within the blood to help increase the production of red blood cells. Iron supplements also increase the oxygen-carrying capacity of the hemoglobin in red blood cells. Stage 5 is considered ESRD, during which the patient may experience severe hypertension, hyperphosphatemia*, and anemia. (*Hyperphosphatemia, a major issue with renal failure, can be treated with calcium acetate (PhosLo), sevelamer (Renagel), sevelamer (Renagel). Diabetes mellitus and uncontrolled hypertension are the most common causes of CKD in adults in the United States. Other potential causes of CKD include kidney diseases such as glomerulonephritis, pyelonephritis, and vascular disorders. Kidney function, in general, decreases with age, with older adults being diagnosed with CKD more often than younger adults. Dietary management is extremely important in the treatment of CKD. The intake of foods high in phosphates (e.g., colas) and dairy products (e.g., milk, cheese) are often limited in this patient population. For those with significant edema and/or hypertension, moderation of sodium intake is important. Treatment of Chronic Kidney Disease: Dialysis Waste products removed from blood Compensates for lack of filtration Two types: Hemodialysis and peritoneal dialysis Hemodialysis: Patient must visit clinic or hospital Peritoneal dialysis: Alternative to hemodialysis Nocturnal dialysis: Treatment received while sleeping Negative aspects of dialysis include the additional medications that patients must take to further balance ph and fluids, the inconvenience of having to be stationary for a length of time during a dialysis session, and the fact that even sophisticated machinery cannot perform as efficiently as the body s own kidneys. Dialysis is the procedure used to remove waste products from the blood of patients with end-stage renal disease (ESRD). Dialysis is used to compensate for a lack of filtration by the kidneys to remove waste products from the blood and to balance electrolytes and fluid volume. 17 Drug Treatment for Chronic Kidney Disease Nutrients lost during hemodialysis must be replaced by supplements Vitamin supplements Antihypertensives Phosphorus-lowering medications Vitamin D supplements Vitamin D supplements are often used because the kidneys are important in the synthesis of the active form of vitamin D, which places people with CKD at risk of having weak bones. 18

7 Kidney Stones (Urolithiasis) Kidney stones are small clumps of material that form in the kidney from substances that pass through the renal system Cystine Uric acid Struvite Calcium phosphate Calcium oxalate Kidney stones often do not cause any symptoms unless they block the flow of urine. When blockage does occur, it usually results in extreme pain. The most commonly used surgical procedure for kidney stone removal is extracorporeal shockwave lithotripsy (ESWL). This procedure uses external shock waves to break the stone into small particles, which can be passed in the urine. Urolithiasis is the medical term for kidney stones. In severe cases, kidney stones can actually cause a blockage within the urinary tract, which is a serious medical situation. Lithotripsy is the use of shock waves to break up kidney stones. Kidney stones can be caused by urinary tract infections (UTIs), hyperparathyroidism, gout, idiopathic hypercalciuria, and genetics. Although dairy intake can increase the size of kidney stones, it does not cause the formation of kidney stones. 19 Drug Treatment for Kidney Stones Stones may pass on their own. For larger stones, lithotripsy, ureteroscopes, and/or surgery may be necessary. Drink water and limit caffeine intake. Agents to prevent the formation of uric acid stones are allopurinol and potassium citrate. Zyloprim is also used to prevent gout. Calcium channel blockers and alpha blockers to help speed up stone passing and reduce pain To prevent stones: Calcium: Thiazides and potassium citrate Uric acid: Allopurinol* and potassium citrate Cystine: Captopril, tiopronin, and potassium citrate 20 Edema What are dyspnea and orthopnea? (Dyspnea is difficulty breathing. Orthopnea is difficulty breathing while lying down.) Causes: Congestive heart failure (CHF), hypertension CHF: Heart muscle weakened by disease; decreases efficiency; blood pumped less throughout body Signs and symptoms include edema, chest pain, fatigue, dyspnea, and orthopnea 21

8 Edema (Cont.) HF must be treated, and several of the medications discussed in Chapter 18 are used (the ABCDs). Heart failure (HF): Kidneys retain fluid, puts more work on heart, creating vicious cycle There is no cure for HF Hypertension can damage heart muscle/veins, leads to HF Avoid salt and sitting for long periods of time 22 Drug Treatment for Edema Depends on underlying cause of the edema Main drugs are: Diuretic thiazides and thiazide-like agents Loop diuretics and potassium-sparing* diuretics (Lasix is a loop diuretic but is not potassium sparing) Carbonic anhydrase inhibitors Osmotics What are two common beverage ingredients that are diuretics? (Caffeine and alcohol are both diuretics.) *Aldactone is classified as a potassium-sparing diuretic agent. (The generic name for Aldactone is spironolactone.) Although diuretics are frequently used to decrease blood pressure, all diuretics have the potential for causing low blood pressure. Potassiumsparing diuretics do not cause hypokalemia. Hydrochlorothiazide (HCTZ) may cause photosensitivity, and aldosterone antagonists may cause nausea, vomiting, and diarrhea. 23 Thiazides and Thiazide-like Agents Drug action: Increase urinary excretion of sodium and chloride ions equally Inhibit normal process of reabsorption with ascending tubule following loop of Henle and distal tubules Increased loss of potassium and bicarbonate Rapid onset of action Side effect is frequent urination Taken early in day to avoid nocturia* The most common of these agents are Dyazide/Maxzide and hydrochlorothiazide (HCTZ), and there are also combinations of these together. What other potential side effects do thiazides and thiazide-like agents have? (Indapamide can cause headaches, dizziness, and upset stomach. Hydrochlorothiazide [HCTZ] can cause gastrointestinal (GI) upset and photosensitivity. Chlorthalidone and metolazone can also cause photosensitivity.) *Nocturia is urination at night. Diuretic agents are normally taken early in the day to avoid nocturia. For most causes of edema, the primary drugs prescribed are diuretics. Thiazide medications can also be used to treat hypertension and to prevent the formation of kidney stones. They are commonly used for the treatment of chronic hypertension because they lower blood pressure by reducing blood volume, cardiac output, and systemic vascular resistance. A common side effect for all diuretics is frequent urination. Diuretics are often used to treat hypertension. Some diuretics are potassium-depleting medications, whereas others have potassium-sparing actions. 24

9 Loop Diuretics These medications should be taken a minimum of a few hours before bedtime to keep the patient from getting up all night to urinate. Loop diuretics inhibit reabsorption of sodium and chloride in proximal convoluted tubule, distal convoluted tubule, and loop of Henle Great deal of potassium is lost with urination They are taken early to avoid nocturia 25 Potassium-Sparing Agents These work primarily in distal convoluted tubule They inhibit sodium reabsorption and decrease potassium loss in urine Large quantities of potassium-rich foods must be avoided What foods are naturally high in potassium? (Bananas, orange juice, and potatoes are all high in potassium.) Potassium-sparing diuretics are generally weaker than the other two types; this is why they are often used in combination. Refer to Table 21-3 (p. 541). 26 Osmotic Diuretics Osmotic diuretics inhibit tubular reabsorption of water by increasing osmolarity of glomerular filtrate Used for prophylaxis of acute renal failure when glomerular filtration is reduced Agents include: Urea, glycerin, and isosorbide (also used for glaucoma) What is osmolarity? (Osmolarity is the concentration of an osmotic solution, often measured in osmols per liter of solution. So, basically, increasing osmolarity of glomerular filtrate means that the osmotics increase the concentration of particles found in the filtrate.) Mannitol is Osmotic Diuretics and must be stored at a temperature from 15 to 30 C (59 to 86 F). It has a tendency to crystallize at lower temperatures because of its high sugar content. If mannitol crystallizes, then it can be placed for short periods in 70 C water with periodic vigorous shaking. 27

10 Urinary Tract Infection Urinary tract infections (UTIs) are a common cause of bacterial infections Women more susceptible because of a shorter urethra Catheterization is another cause Kidney infection: Glomerulonephritis and pyelonephritis Bladder infection: Cystitis Most UTIs are caused by E. coli bacteria from the digestive tract. A few are caused by chlamydia and Mycoplasma spp. Cranberry juice contains compounds called proanthocyanidins that prevent bacteria from adhering to the lining of the urinary tract. The most common cause of UTIs is the bacterium E. coli from the colon. For bacterial infections, medications such as Septra or a type of cephalosporin or fluoroquinolone may be prescribed. For symptomatic fungal UTIs, fluconazole (Diflucan) or other antifungal agents may be ordered. If the infection is caused by Chlamydia or is an uncomplicated gonorrheal infection, then a tetracycline may be indicated, although a tetracycline antibiotic is not effective for the treatment of all types of sexually transmitted diseases (STDs). Zyloprim is a medication for gout. 28 Symptoms of Urinary Tract Infections Symptoms of upper UTI: Lower back pain, stomach pain, nausea, vomiting, and headache Symptoms of lower UTI: Frequent but small amounts of urine, dysuria, and sometimes incontinence* Most UTIs start in the urethra and then move to the bladder. If not treated, the infection can spread upward to the kidneys. What is dysuria? (Dysuria is painful or difficult urination.) * Urge incontinence has several causes including decreased bladder capacity, infection, or irritation. Stress incontinence is when a force is placed on the bladder and causes the release of a small amount of urine, such as when coughing or sneezing. Weight gain can intensify this type of incontinence. 29 Drug Treatment for Urinary Tract Infections Bacterial infections: Cephalosporin and fluoroquinolone Fungal infections: Fluconazole (Diflucan) Tetracycline for infections caused by some sexually transmitted diseases (STDs) Patients often treat these infections with over-the-counter (OTC) medications. A nosocomial infection is an infection that originates in the hospital or institutional setting. The medication phenazopyridine is a urinary analgesic frequently recommended to treat pain associated with UTIs. It is available OTC and by prescription under a number of different brand names. One side effect is its tendency to turn urine orange or reddish in color, which should be noted with an auxiliary label on the prescription formulation. 30

11 Urinary Incontinence Common urinary condition Older adults, females, and women with multiple pregnancies Stress continence: Coughing, sneezing; force placed on bladder; urine released Urge incontinence has several causes: Decreased bladder capacity, infection, and irritation Risk increased by alcohol and caffeine ingestion Common non-drug therapy treatment: Kegel exercises (involve tightening of pelvic floor muscles) This condition affects millions of people. Overactive bladder is a common term used today. (Oxybutynin is available as Ditropan, Ditropan XL, Oxytrol (patch), Gelnique (topical gel), and Oxytrol for Women (OTC patch) In addition to treating urinary incontinence, Kegel exercises can also improve the tone of a woman s vaginal muscles in preparation for childbirth. 31