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RENAL SYSTEM
DIURETIC AGENTS
DIURETICS Thiazide- Like Diuretics Carbonic Anhydrase Osmotic Diuretics
chlorthalidone Inhibitors glycerin
Thiazide Diuretics and
indapamide acetazolamide isosorbide
Thiazide- Like Diuretics
metolazone methazolamide mannitol
Thiazide Diuretics urea
bendroflumethiazide Loop Diuretics Potassium- Sparing
chlorothiazide bumetanide Diuretics
hydrochlorothiazide ethacrynic acid amiloride
hydroflumethiazide furosemide spironolactone
methyclothiazide torsemide triamterene
Diuretic agents are commonly thought of simply as drugs that increase the amount of urine produced
by the kidneys. Most diuretics do increase the volume of urine produced to some extent, but the
greater clinical significance of diuretics is their ability to increase sodium excretion.
Therapeutic Actions
Thiazide and thiazide-like diuretics act to block the chloride pump. Chloride is actively pumped out
of the tubule by cells lining the ascending limb of the loop of Henle and the distal tubule. Sodium
passively moves with the chloride to maintain electrical neutrality. (Chloride is a negative ion, and
sodium is a positive ion.) Thiazides are considered to be mild diuretics compared with the more
potent loop diuretics.
Indications
Treatment of edema of HF
Treatment of liver and renal disease
Adjunct for hypertension
Adverse Effects
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can result in gout. If these drugs are used over a prolonged period, blood glucose levels may
increase.
Loop Diuretics
Loop diuretics are so named because they work in the loop of Henle. Loop diuretics are also
referred to as high-ceiling diuretics because they cause a greater degree of diuresis than other
diuretics do.
Therapeutic Actions
Loop diuretics block the chloride pump in the ascending loop of Henle, where normally 30% of all
filtered sodium is reabsorbed. This action decreases the reabsorption of sodium and chloride.
Indications
Adverse Effects
Hypokalemia is a very common adverse effect because potassium is lost when the transport
systems in the tubule try to save some of the sodium being lost. Alkalosis, or a drop in serum pH to
an alkaline state, may occur as bicarbonate is lost in the urine. Calcium is also lost in the tubules
along with the bicarbonate, which may result in hypocalcemia and tetany. The rapid loss of fluid can
result in hypotension and dizziness if it causes a rapid imbalance in fluid levels. Long-term use of
these drugs may also result in hyperglycemia because of the diuretic effect on blood glucose levels,
so susceptible patients need to be monitored for this effect. Ototoxicity and even deafness have
been reported with these drugs, but the loss of hearing is usually reversible after the drug is
stopped.
Therapeutic Actions
Diuretics that block the effects of carbonic anhydrase slow down the movement of hydrogen ions;
as a result, more sodium and bicarbonate are lost in the urine.
Indications
Inducing diuresis in HF
Treatment of glaucoma
Treatment of mountain sickness
Treatment of epilepsy
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Adverse Effects
Metabolic acidosis is a relatively common and potentially dangerous effect that occurs when
bicarbonate is lost. Hypokalemia is also common because potassium excretion is increased as the
tubule loses potassium in an attempt to retain some of the sodium that is being excreted. Patients
also complain of paresthesias (tingling) of the extremities, confusion, and drowsiness, all of which
are probably related to the neural effect of the electrolyte changes.
Potassium-Sparing Diuretics
The potassium-sparing diuretics are not as powerful as the loop diuretics, but they retain
potassium instead of wasting it.
Therapeutic Actions
Potassium-sparring diuretics cause a loss of sodium while promoting the retention of potassium.
Spironolactone acts as an aldosterone antagonist, blocking the actions of aldosterone in the
distal tubule. Amiloride and triamterene block potassium secretion through the tubule. The
diuretic effect of these drugs comes from the balance achieved in losing sodium to offset the
potassium retained.
Indications
Adverse Effects
The most common adverse effect of potassium-sparing diuretics is hyperkalemia, which can cause
lethargy, confusion, ataxia, muscle cramps, and cardiac arrhythmias. They also should be advised to
avoid foods that are high in potassium. Because these drugs work much like aldosterone, they are
associated with various androgen (another similar hormone) effects such as hirsutism,
gynecomastia, deepening of the voice, and irregular menses.
Osmotic Diuretics
Osmotic diuretics pull water into the renal tubule without sodium loss.
Therapeutic Actions
They act to pull large amounts of fluid into the urine due to the osmotic pull exerted by the large
sugar molecule. Because the tubule is not able to reabsorb all of the osmotic diuretics pulled into it,
large amounts of fluid are lost in the urine.
Indications
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Reduction of intraocular pressure
Renal clearance of toxic substances
Adverse Effects
The most common and potentially dangerous adverse effect related to osmotic diuretics is the
sudden drop in fluid levels. Nausea, vomiting, hypotension, light-headedness, confusion, and
headache can be accompanied by cardiac decompensation and even shock. Patients receiving
these drugs should be closely monitored for fluid and electrolyte imbalance.
Urinary tract anti-infectives are of two types: 1) antibiotics, which are particularly effective against
the gram-negative bacteria that cause most UTIs and 2) agents work to acidify the urine, killing
bacteria that might be in the bladder.
Therapeutic Actions
Urinary tract anti-infectives act specifically within the urinary tract to destroy bacteria, either
through a direct antibiotic effect or through acidification of the urine.
Indications
Adverse Effects
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Reduction of intraocular pressure
Renal clearance of toxic substances
Adverse Effects
The most common and potentially dangerous adverse effect related to osmotic diuretics is the
sudden drop in fluid levels. Nausea, vomiting, hypotension, light-headedness, confusion, and
headache can be accompanied by cardiac decompensation and even shock. Patients receiving
these drugs should be closely monitored for fluid and electrolyte imbalance.
Urinary tract anti-infectives are of two types: 1) antibiotics, which are particularly effective against
the gram-negative bacteria that cause most UTIs and 2) agents work to acidify the urine, killing
bacteria that might be in the bladder.
Therapeutic Actions
Urinary tract anti-infectives act specifically within the urinary tract to destroy bacteria, either
through a direct antibiotic effect or through acidification of the urine.
Indications
Adverse Effects
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Nausea, vomiting, diarrhea, anorexia, bladder irritation, and dysuria. Infrequent symptoms include
pruritus, urticaria, headache, dizziness, nervousness, and confusion. These effects may result from
GI irritation caused by the agent, which may be somewhat alleviated if the drug is taken with food,
or from a systemic reaction to the urinary tract irritation. Fosfomycin is associated with unpleasant
GI effects, which limit its usefulness in some patients. Methylene blue can stain the skin if it comes
in contact with it.
Therapeutic Actions
The urinary tract antispasmodics relieve spasms by blocking parasympathetic activity, thus
suppressing overactivity, which leads to relaxation of the detrusor and other urinary tract muscles.
Because the parasympathetic system uses acetylcholine to cause its effects, these drugs are called
anticholinergic drugs.
Indications
Adverse Effects
Adverse effects of urinary tract antispasmodics are related to the blocking of the
parasympathetic system and include nausea, vomiting, dry mouth, nervousness, tachycardia,
and vision changes. Flavoxate is associated with CNS effects (blurred vision, dizziness, confusion)
that make it less desirable to use in certain patients, such as the elderly or patients with
neurological problems.
Oxybutynin has numerous anticholinergic effects, making it undesirable in certain conditions or
situations that might be aggravated by decreased sweating, urinary retention, tachycardia, and
changes in GI activity.
Urinary tract analgesics are used to decrease pain, and the bladder protectant pentosan is used to
prevent irritation to the bladder wall.
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Urinary Tract Analgesic
Pain involving the urinary tract can be very uncomfortable and lead to urinary retention and
increased risk of infection.
Therapeutic Actions
Phenazopyridine exerts a direct, topical analgesic effect on the urinary tract mucosa.
Indications
Adverse Effects
GI upset, headache, rash, and a reddish-orange coloring of the urine, all of which are related to
the drug’s chemical actions in the system. There also is a potential for renal or hepatic toxicity.
Bladder Protectant
The bladder protectant pentosan polysulfate sodium is used to coat or adhere to the bladder
mucosal wall and protect it from irritation related to solutes in urine.
Therapeutic Actions
This drug adheres to the bladder wall mucosal membrane and acts as a buffer to control cell
permeability, preventing irritating solutes in the urine from reaching the bladder wall cells.
Indications
Used to decrease the pain and discomfort associated with interstitial cystitis, a chronic
inflammation of the interstitial connective tissue of the bladder that may extend into deeper
tissue.
Adverse Effects
Bleeding that may progress to hemorrhage (related to the drug’s heparin effects), headache,
alopecia (seen with heparin-type drugs), and GI disturbances related to local irritation of the GI
tract with administration.
Benign prostatic hyperplasia (BPH), also called benign prostatic hypertrophy or enlarged prostate,
is a common problem in men, and it increases in incidence with age. The prostate completely
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encircles the urethra. The enlargement of the gland surrounding the urethra leads to discomfort,
difficulty in initiating a stream of urine, feelings of bloating, and an increased incidence of cystitis.
Alpha-adrenergic blockers
Refer to the alpha-adrenergic blockers in previous chapters
They inhibit the intracellular enzyme that converts testosterone to the potent androgen
dihydrotestosterone (DHT), which the prostate gland depends on for its development and
maintenance.
Indications
Long-term treatment of symptomatic BPH to shrink the prostate and relieve symptoms of
hyperplasia
Prevention of male-pattern baldness in patients with strong family history
Adverse Effects
Decreased libido, impotence, and sexual dysfunction, all of which are related to decreased levels of
DHT. Patients using either finasteride or dutasteride cannot donate blood for 6 months after the
last dose to protect potential blood recipients from exposure to the testosterone-blocking effects.
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