Chapter 19
The Renal System and
Drug Therapy
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Chapter 19
Topics
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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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Anatomy and Physiology of the Renal System
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 byproducts 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
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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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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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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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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
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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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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
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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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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
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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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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)
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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
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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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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
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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)
Calcium-channel blockers
Selective serotonin reuptake
inhibitors (SSRIs)
Alpha blockers
Disopyramide
Quinidine
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Benign Prostatic Hyperplasia (BPH)
Male Urinary
System
•Unvoided urine
can promote
infection
•Men with BPH
may have
bladder
infections
frequently
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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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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
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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
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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
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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
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Kidney Failure
Renal Function Tests (continued)
• Most common formula to calculate CrCl is the Cockcroft
and Gault equation
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
• 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
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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
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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
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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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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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