2. The Renal System and Drug Therapy
Chapter 19
The Renal System and
Drug Therapy
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Topics
Anatomy and Physiology of the Renal System
Nephrotoxicity and Renal Dosing
Urinary Tract Infections
Spastic or Overactive Bladder
Benign Prostatic Hyperplasia
Kidney Failure
Herbal and Alternative Therapies
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4. Anatomy and Physiology of the Renal System
The renal system clears waste products from the blood and maintains proper fluid and electrolyte balance
Kidneys, the primary filter, have several main functions
Clear blood flowing through them of metabolic by- products and waste substances (toxic if not eliminated)
Balance fluids and electrolytes, such as sodium, potassium, calcium
Affect acidity (blood pH) and BP
Produce erythropoietin, which stimulates RBC production
blood pressure (BP)
red blood cell (RBC)
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5. Anatomy and Physiology of the Renal System
The Renal System (continued)
The ureters transport the waste products and excess fluid to the urinary bladder
The bladder holds the substances until voiding (urination)
Urine exists the body through the urethra
The Kidneys
The renal cortex (outer layer) produces hormones
The renal medulla (body of the kidney) is made up of many triangle-shaped sections, or nephrons, that perform filtration
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6. Anatomy and Physiology of the Renal System
Anatomy of Renal System
The proximity of the kidneys to the abdominal aorta makes these organs sensitive to changes in BP.
High BP damages kidneys’ filtration; low BP can cause acute renal failure
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7. Anatomy and Physiology of the Renal System
The Nephron and Urine Production
Each triangular section of the kidney contains thousands of microscopic-sized nephrons
Nephrons are the functional filtering units
Three steps in urine production process: glomerular filtration, tubular reabsorption, and tubular secretion
Glomerular filtration
Blood with fluid and waste products enters the nephron into the Bowman’s capsule, which holds the glomerulus
Inside the glomerulus, high pressure forces fluid and small substances (filtrates) out of the blood
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8. Anatomy and Physiology of the Renal System
The Nephron and Urine Production (continued)
The filtered blood leaves glomerulus and continues on
Tubular Reabsorption and Secretion
As filtrate passes through tubules and loop of Henle, molecules selectively reenter blood via 3 mechanisms
Reabsorption: simple diffusion
Active transport process: exchange between blood and urine via secretion
Filtration: move across membranes from pressure
Substances filtered out or secreted into the urine (but do not reenter the blood) are eliminated
Tubular Reabsorption
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9. Anatomy and Physiology of the Renal System
The Nephron and Urine Production
Each part of the nephron performs specific functions: filtration, reabsorption, and secretion of select electrolytes, fluids, and other substances
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10. Anatomy and Physiology of the Renal System
Urine Production and Elimination
Urine production and maintenance of fluid balance rely on the tubular reabsorption and secretion processes
Hormones such as aldosterone and ADH regulate the rate and volume of urine production
The urinary bladder collects and holds urine until urination
External urinary sphincter is a voluntary muscle that holds urine in the bladder before it exits the body
Urinary retention: when the urinary process does not function properly and urine accumulates in the bladder
Incontinence: inability to control external urinary sphincter
antidiuretic hormone (ADH)
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11. Anatomy and Physiology of the Renal System
The Bladder
Stretch receptors sense pressure when the bladder distends
They cause detrusor muscles in the bladder to contract and the external sphincter to relax
Urine is pushed out; bladder empties
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12. Nephrotoxicity and Renal Dosing
Drug Accumulation in the Blood
Many drugs are eliminated through the kidneys
Some drugs can directly damage kidney tissue (nephrotoxicity), including NSAIDs, amphotericin B, aminoglycosides, and vancomycin
Conditions are usually reversible but can cause kidney failure if not addressed quickly
Doses are kept low to avoid negative effects
nonsteroidal anti-inflammatory drugs (NSAIDs)
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13. Nephrotoxicity and Renal Dosing
Renal Dosing Calculations
Dosing calculations must take into account the reduced renal function in patients with kidney problems
Doses for such patients must be adjusted because drugs require good renal function for elimination
Adjustment depends on degree of renal dysfunction
Technicians may help in gathering kidney function laboratory tests
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14. Urinary Tract Infections
UTIs and Drug Therapy
UTIs usually occur in the bladder
Cystitis: lower UTI involving the bladder; pyelonephritis: upper UTI affecting the kidneys
Prostatitis is a prostate infection in men; bladder infections in men are rare and difficult to treat
UTIs occur most often in sexually active women
Symptoms: pain or burning during urination, frequent urge to urinate, abdominal pain, fever, chills, cloudy urine
Treatment: antibiotics (penicillins, nitrofurantoin, sulfamethoxazole-trimethoprim, ciprofloxacin)
urinary tract infections (UTIs)
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15. Spastic or Overactive Bladder
Spastic or Overactive Bladder and Drug Therapy
Malfunction of the detrusor muscles in the bladder; causes contraction and frequent urination
Drug Therapy: urinary antispasmodics; mostly oral
Mechanism of Action: inhibit ACh in the autonomic nerves that control involuntary bladder contraction and emptying
Side Effects (common): dry mouth, constipation, blurred vision, urine retention; (other): drowsiness, stomach upset
Side Effects (rare): allergic reactions
Cautions: phenazopyridine can turn urine orange and stain clothing; methenamine can turn urine blue
acetylcholine (ACh)
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Your Turn
Question 1: What is the function of the bladder? Answer: The bladder collects and holds urine until urination. Question 2: A patient feels the urge to urinate often. She jokingly tells the physician that she knows where all the restrooms are when she runs errands or is out with family or friends. This is also causing problems for her at work. What drug therapy is the physician likely to prescribe? Answer: The physician will likely prescribe an urinary antispasmodic.
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17. Benign Prostatic Hyperplasia (BPH)
About BPH
Chronic condition that occurs in men as prostate gland enlarges with age (common from ages 60 to 85)
Condition itself is not harmful, but the enlarged gland can impinge on the urethra and obstruct urine flow
Symptoms: weak or slow urine stream, delayed start of urination, straining to urinate
Feel need to urinate often, but void only small amounts
PSA is a lab test to screen for BPH and other prostate problems, such as prostate cancer
Some drugs cause urine retention; do not use with BPH
benign prostatic hyperplasia (BPH)
prostate-specific antigen (PSA)
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18. Benign Prostatic Hyperplasia (BPH)
Agents to Avoid for Patients with BPH
Avoid
Instead Try…
Anticholinergics
H2 blockers, sucralfate, antacids
Oral bronchodilators
Inhaled bronchodilators
Tricyclic antidepressants (TCAs)
Selective serotonin reuptake inhibitors (SSRIs)
Calcium-channel blockers
Alpha blockers
Disopyramide
Quinidine
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19. Benign Prostatic Hyperplasia (BPH)
Male Urinary System
Unvoided urine can promote infection
Men with BPH may have bladder infections frequently
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20. Benign Prostatic Hyperplasia (BPH)
Prostate Cancer
Prostate tissue growth can become a malignant process
Prostate cancer is the second most common type of cancer in men (just behind skin cancer)
Approximately 1 in 6 men will be diagnosed with prostate cancer
Prostate cancer is highly treatable, especially when caught early
Symptoms: difficulty starting or stopping urination, frequent urination, painful urination, blood in the urine
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21. Benign Prostatic Hyperplasia (BPH)
Drugs for BPH: Alpha Blockers
Indication: BPH, especially if accompanied by high BP
Indication (other): passage of kidney stones
Mechanism of Action: inhibit alpha-1 receptors that relax smooth muscle in the prostate and bladder
Side Effects (common): dizziness, drowsiness, fatigue, headache, fainting, orthostatic hypotension
Side Effects (rare, severe): priapism
Cautions: interact with several prescription medications; should be used with caution in patients with GI disorders, liver disease, kidney impairment
gastrointestinal (GI)
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22. Benign Prostatic Hyperplasia (BPH)
Drugs for BPH: 5-Alpha Reductase Inhibitors
Indications: BPH; male-pattern hair loss
Mechanism of Action: inhibit conversion of testosterone into DHT
Restricting this active form of testosterone reduces the size of the prostate
Side Effects (common): decreased libido, erectile dysfunction, ejaculation disorders, breast enlargement
Cautions: could be harmful to a developing fetus in utero
Women of childbearing age must not handle these agents with bare skin
dihydrotestosterone (DHT)
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Kidney Failure
Acute and Chronic Kidney Failure
Acute renal failure is due to physical or chemical damage or to lack of blood supply to the kidneys
Temporary or short-lived; can return to normal status
Life threatening if severe; possible permanent damage
CKD is progressive damage or results in the death of kidney tissue over time
Irreversible condition
chronic kidney disease (CKD)
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Kidney Failure
Renal Function Tests
BUN and SCr are lab blood tests used to diagnose and monitor renal function
When renal function is impaired, the elimination of urea, nitrogen, and creatinine is also impaired; elements accumulate in blood
Normal range for SCr is 0.5–1.5 mg/dL
SCr is used to calculate CrCl which estimates GFR
CrCl and GFR estimate the level of kidney function while taking into account such factors as age and gender
blood urea nitrogen (BUN)
serum creatinine (SCr)
creatinine clearance (CrCl)
glomerular filtration rate (GFR)
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25. Kidney Failure Renal Function Tests (continued)
Most common formula to calculate CrCl is the Cockcroft and Gault equation
Example: if CrCl drops below 30 or 60 mL/min, the dose is decreased or the interval between doses is increased
Technician: retrieve lab results and perform calculations
CrCl (mL/min) = [(140 – age) × IBW]
SCr x 72
For females, multiply the result of right side by 0.85
Where IBW is ideal body weight in kg and SCr is in mg/dL
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Kidney Failure
Stages of CKD
CKD is more common than acute renal failure; common cases for CKD include diabetes and untreated hypertension
As it worsens, CKD is categorized into four stages that guide treatment (see Table 19.5)
Diuretics and other renal-protective medications can help slow the progression of the disease in early stages
Eventually, dialysis and kidney transplant are the only means of treatment (Stage IV)
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Kidney Failure
Dialysis
Artificial method of filtering blood and correcting the electrolyte imbalances caused by renal failure
Two common methods are hemodialysis and peritoneal dialysis
Hemodialysis: a machine mechanically filters the blood and returns it to the body; occurs every 2 to 4 days
Peritoneal dialysis: dialysate is put into the abdominal cavity and left for a few days, then drained
The dialysate fluid is changed at home
Risk of infection and other complications is greater
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Kidney Failure
Hemodialysis
Peritoneal Dialysis
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Kidney Failure
Drugs for Renal Failure
Acute renal failure improves or reverses; drug treatment is limited and short term
CKD is more frequently treated with medication
Diuretics are used to improve urine output
In advanced stages of CKD
Dialysis and various drugs are needed
Imbalances of various micronutrients and vitamin D become problematic
Anemia occurs, requiring hemopoietic therapy and iron supplementation
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Kidney Failure
Drugs for Renal Failure: Diuretics
Thiazides and potassium-sparing diuretics are used for hypertension
Loop diuretics are used for renal failure or reducing edema
See Table 19.6 for commonly used diuretics by class
Routes: all are oral; some are IV; bumetanide is also IM
intravenous (IV)
intramuscular (IM)
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Kidney Failure
Diuretic Sites of Action
Thiazide diuretics work in the distal convoluted tubule
Loop diuretics work in the loop of Henle
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Kidney Failure
Drugs for Renal Failure: Thiazide Diuretics
Mechanism of Action: inhibit reabsorption of sodium and chloride ions in the distal tubule of the nephron; water is pulled into urine and eliminated, thus reducing blood volume and pressure
Indication: first-line therapy for newly diagnosed patients with hypertension
Side Effects (common): hypotension, dizziness, headache, rash, hair loss, stomach upset, diarrhea, constipation
Caution: often must take with potassium supplements; several drug interactions including corticosteroids, lithium, and drugs for diabetes; avoid alcohol
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Kidney Failure
Drugs for Renal Failure: Loop Diuretics
Mechanism of Action: inhibit reabsorption of sodium, chloride, and water in the ascending loop of Henle
Pulls fluid out of the body rapidly
Indication: swelling and fluid accumulation due to heart or kidney failure
Side Effects (common): hypotension, dizziness, headache, rash, hair loss, stomach upset, diarrhea, constipation
Caution: often must take with potassium supplements
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Kidney Failure
Drugs for Renal Failure: Potassium-sparing Diuretics
Mechanism of Action: block the exchange of potassium for sodium that takes place in the distal tubule; more sodium and water are excreted while potassium is preserved in body
Indication: hypertension
Side Effects (common): gynecomastia
Side Effects (other): stomach upset, headache, confusion, drowsiness
Caution: possible hyperkalemia; monitor potassium levels
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Kidney Failure
Drugs for Renal Failure: Aldosterone Antagonists
Mechanism of Action: Work by inhibiting a hormone that promotes fluid retention
Spironolactone, in particular, inhibits aldosterone, which promotes sodium and water reabsorption in the distal tubule and collecting duct of the nephron
Indication (spironolactone): hypertension; sometimes, hyperaldosteronism
Caution (spironolactone): hyperkalemia; monitor potassium levels
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Kidney Failure
Drugs for Renal Failure: Carbonic Anhydrase Inhibitors
Mechanism of Action: work in the nephron by increasing excretion of bicarbonate ions, which carry sodium, potassium, and water into the urine
Indication: open-angle glaucoma, diuresis in CHF
Side Effects (common): tinnitus, nausea, vomiting, diarrhea, drowsiness, tingling, changes in taste
Side Effects (severe): sulfa allergy, Stevens-Johnson syndrome
Caution: do not take with aspirin
congestive heart failure (CHF)
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Your Turn
Question 1: What is the purpose of calculating a patient’s GFR? Answer: The GFR is used as a guide for estimating renal function and dosing for drug therapy. Question 2: A patient has edema due to kidney failure. The physician needs a medication to quickly pull a large amount of fluid out of the patient’s body. What drug therapy is the physician likely to order? Answer: The physician will likely order a loop diuretic.
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Kidney Failure
Drugs for Renal Failure: Potassium Supplements
Indication: potassium deficiency caused by diuretics
Route: oral; taken daily
Side Effects: nausea, vomiting, diarrhea, stomach upset
Caution: do not use salt substitutes
Drugs for Renal Failure: Osmotic Diuretics
Indication: severe trauma, cardiac operations, elevated intracranial pressure
Mechanism of Action: increases concentration of filtrate, hindering reabsorption of water; mannitol used most
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39. Herbal and Alternative Therapies
Saw palmetto is taken for BPH symptoms such as frequent or painful urination and urination hesitancy and urgency
Works by reducing thickness of inner layer of prostate and inhibiting 5-alpha reductase
Causes dizziness, headache, nausea, vomiting, constipation, diarrhea
Has possible interactions with anticoagulants and some hormone therapies
Cranberry juice is taken for prevention of recurrent UTIs
Adheres to bacteria, preventing the cells from attaching to the inner walls of the bladder
Can interact with warfarin
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Summary
Antispasmodics are used for spastic or overactive bladder
Alpha blockers and 5-alpha reductase inhibitors are used for BPH
Diuretics are used to improve kidney function and urine production
Thiazides and potassium-sparing diuretics are used most for high blood pressure
Loop diuretics are used to pull large amounts of fluid from the body in patients with heart or kidney failure
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