DRUGS ACTING ON THE RENAL SYSTEM (SUMMARY)

I. Introduction to the Renal System

A. The Kidneys
 Kidneys are two small, bean-shaped organs that receive about 25%
of the cardiac output.
a. Structure
 Nephron is the functional unit of the kidneys and is involved in
three processes: Glomerular filtration, tubular secretion, and
tubular reabsorption
 Nephron is composed of Bowman’s capsule, the proximal
convoluted tubule, the loop of Henle, the distal convoluted
tubule and the collecting duct.
 The blood flow to the nephron is unique, allowing auto-
regulation of blood flow through the glomerulus.
 Other structures include juxtaglomerular apparatus which
connects the afferent arteriole to the distal convoluted tubule and
macula densa which consists of immune system cells and
chemicals that can respond quickly to any cellular damage pr
injury.
b.1 Nephron Function
 Glomerular Filtration is the passage of fluid and small
components of the blood through the glomerulus into the
nephron tubule.
 Tubular Secretion is the active movement of substances from the
blood into the renal tubule.
 Tubular Reabsorption is the movement of substances from the
renal tubule back into the vascular system.
c. 1 Maintenance of Volume and Composition of Body Fluids
 Sodium regulation takes place throughout the tubule by active
and passive movement and is fine-tuned by the presence of
aldosterone in the distal tubule.
 The countercurrent mechanism in the medullary nephrons
allows for the concentration or dilution of urine under the
influence of ADH secreted by the hypothalamus.
 Potassium concentration is regulated throughout the tubule with
aldosterone being the strongest influence for potassium loss.
 Calcium regulation takes place by activating Vitamin D to allow
GI calcium reabsorption and by reabsorbing or excreting
calcium from the tubule under the influence of PTH.
d.1 Blood Pressure Control
 Blood pressure control releases renin to activate the renin-
angiotensin system which leads to increased blood pressure and
volume and a resultant increased blood flow to the kidney.
e.1 Regulation of RBC Production
 RBC production is controlled by erythropoietin released from
the juxtaglomerular apparatus when oxygen delivery to the
nephron is decreased.
B. The Urinary Tract
a. Ureters
 Ureters have a smooth endothelial lining and circular muscular
layers, draining the filtrate from the collecting ducts.
b. Urinary Bladder
 Urinary bladder is a muscular pouch that stretches and holds the
urine until it is excreted from the body.

c. Urethra
  (Female) Urethra is a very short tube that leads from the bladder
to an area populated by normal flora which can cause frequent
bladder infections or cystitis.

II. Diuretic Agents

 Diuretic agents increase the excretion of sodium.
 Most diuretics prevent the cells lining the renal tubules from reabsorbing
an excessive, proportion of the sodium ions in the glomerular filtrate.
A. Thiazide and Thiazide-like Diuretics
 Thiazide diuretics belong to a chemical class of drugs called the
sulfonamides.
 Thiazide-like diuretics have a slightly different chemical structure
but work in the same way as thiazide diuretics.
a. Therapeutic Actions and Indications
 Act to block the chloride pump
b. Pharmacokinetics
 These drugs are well absorbed from the GI tract after oral
administration with onset of action ranging from 1 to 3 hours.
 They are metabolized in the liver and excreted in the urine
 They cross the placenta and enter breast milk.
c. Contraindications
 Contraindicated with allergy to thiazides to prevent
hypersensitivity reactions, fluid and electrolyte imbalances, and
severe renal disease
d. Cautions
 Systemic lupus erythematosus (SLE)
 Glucose tolerance abnormalities or diabetes mellitus
 Gout
 Liver disease
 Hyperparathyroidism
 Bipolar disorder
e. Adverse Effects
 GI upset
 Fluid and electrolyte imbalances
 Hypotension
 Electrolyte disturbances
f. Clinically Important Drug-Drug Interactions
 Increase risk of digoxin toxicity
 Increase risk of quinidine toxicity
 Decrease effectiveness of antidiabetic agebts
 Increase risk of lithium toxicity
B. Loop Diuretics
 They work in the loop of Henle.
 They are referred to as high ceiling diuretics because they cause
a greater degree of diuretics than other diuretics.
a. Therapeutic Actions and Indications
 Block the chloride pump in the ascending loop of Henle where
normally 30% of all filtered sodium is reabsorbed
 Indicated for the treatment of acute HF, acute pulmonary edema,
edema associated with HF or with renal or liver disease and
hypertension
b. Pharmacokinetics
 Available for oral or IV use
 May also be given IM
c. Contraindications
 Contraindicated with allergy to prevent hypersensitivity
reactions, electrolyte depletion anuria, hepatic coma
 d. Cautions
 Systemic lupus erythematosus (SLE)
 Glucose tolerance abnormalities or diabetes mellitus
 Gout
e. Adverse Effects
 Fluid and electrolyte imbalances
 Hypokalemia
 Alkalosis
 Lost of calcium
 Rapid loss of fluid
 Hyperglycemia
 Ototoxicity
 Deafness
f. Clinically Important Drug-Drug Interactions
 Increase risk of ototoxicity
 Increase anticoagulation effects
 Decrease loss of sodium
 Decrease antihypertensive effects
Carbonic Anhydrase Inhibitors
 relatively mild diuretics
 agents include acetazolamide (Diamox) and methazolamide (generic)
A) Therapeutic Actions and Indications
 enzyme carbonic anhydrase is a catalyst for formation of sodium
bicarbonate, which is stored as the alkaline reserve in the renal tubule,
and for the excretion of hydrogen, which results in slightly acidic urine
 diuretics that block the effects of carbonic anhydrase slow down the
movement of hydrogen ions resulting in more sodium and bicarbonate
loss in urine
B) Pharmacokinetics
 these drugs are rapidly absorbed and widely distributed
 acetazolamide is available orally and for IV use
 they peak in 2-4 hours and 6-12 hour duration
 excreted in urine
 some agents are associated with fetal abnormalities therefore should
not be used during pregnancy
C) Contraindications and Cautions
 contraindicated in px with allergy to drugs or to antibacterial
sulfonamides or thiazides, or in px with chronic noncongestive angle-
closur glaucoma
 routine use during pregnancy is inappropriate
 caution in px who have fluid or electrolyte imbalances, renal or
hepatic disease, adrenocortical insufficiency, respiratory acidosis, or
COPD
D) Adverse Effects
 disturbances in acid-base and electrolyte balances
 metabolic acidosis is a relatively common and potentially dangerous
effect that occurs when bicarbonate is lost
 hypokalemia is also common
 px also complain of paresthesias of extremities, confusion, and
drowsiness
E) Clinically Important Drug-Drug Interaction
 increased excretion of salicylates and lithium if they are combined
with these drugs
Potassium-Sparing Diuretics
 not as powerful as loop diuretics, but retains K instead of wasting them
 drugs include amiloride (Midamor), spironolactone (Aldactone), and
 triamterene (Dyrenium)
A) Therapeutic Actions and Indications
 cause loss of sodium while promoting the retention of K
 spironolactone acts as an aldosterone antagonist, blocking the actions
of aldosterone in distal tubule
 amiloride and triamterene block K secretion through the tubule
 the diuretic effect of these drugs comes from the balance achieved in
losing sodium to offet the K retained
B) Pharmacokinetics
 well absorbed after oral administration, protein bound and widely
distributed
 metabolized in liver and excreted in urine
C) Contraindications and Cautions
 contraindicated for use in px with allergy to the drug, and
hyperkalemia, renal diseas, or anuria
 routine use during pregnncy is not appropriate
D) Adverse Effects
 most common: hyperkalemia, which can cause lethargy, confusion,
ataxia, muscle cramps, and cardiac arrhytmias
 px should be evaluated regularly for signs of increased potassium
 hirsutism, gynecomastia, deepening of voice, and irregular menses
E) Clinically Important Drug-Drug Interaction
 diuretic effect decreases if ptassium-sparing diuretics are combined
with salicylates
Osmotic Diuretics
 pull water into the renal tubule without sodium loss
 only available is mannitol (Osmitrol)
A) Therapeutic Actions and Indications
 some nonelectrolytes are used IV to increase the volume of fluid
produced by the kidneys
 mannitol is a sugar that is not well absorbed by the tubules; it acts to
pull large amounts of fluid into urine due to osmotic pull exerted by
the large sugar molecule
 because the tubules is not able to reabsorb all of the sugar pulled into
it, large amount of fluid are lost in the urine
B) Pharmacokinetics
 only available for IV use
 freely filtered at the renal glomerulus, poorly reabsorbed by the renal
tubule, not secreted by the tubule, and resistant to metabolism
 action depends on concentration of osmotic activity in the solution
 not known if it causes fetal harm
C) Contraindications and Cautions
 contraindicated in px with renal disease and anuria from severe renal
disease, pulmonary congestion, intracranial bleeding, dehydration, and
HF
 routine use for pregnancy is not appropriate
D) Adverse Effects
 most common: sudden drop in fluid levels
 nausea, vomiting, hypotension, light-headedness, confusion, and
headache can be accompanied by cardiac decompensation and even
shock

Drugs Affecting the Urinary Tract and Bladder

Conditions affecting the Urinary Tract and Bladder

  UTI
 bladder spasm
 bladder pain
 benign prostatic hyperplasia
Urinary Tract Anti-Infectives
 has two types
1. The antibiotics which particularly effective against the gram negative
bacteria that cause the most UTIs. These include fosfomycin
(Monurol), and nitrofurantoin (Furadantin).
2. The other types works to acidify the urine, killing bacteria that might
be in the bladder. This includes methenamine (Hiprex) and methylene
blue (Urolene Blue).
A) Therapeutic Actions and Indications
 act specifically within the urinary tract to destroy bacteria, either
through direct antibiotic effect (drugs interfere with reproduction of
gram negative bacteria and cause bacterial cell death) or through
acidification of urine (produce an environment that is not conducive to
bacterial survival, leading to bacterial cell death)
 they are used to treat chronic UTIs, as adjunctive therapy in acute
cystitis and pyelonephritis, and as prophylaxis with urinary tract
anatomical abnormalities and residual urine disorders
B) Pharmacokinetics
 Fosfomycin – taken orally, one-time dose, not recommended for
children under 18, rapidly absorbed, undergoes slow hepatic
metabolism, excreted in urine and feces, drug of choice for cystitis
during pregnancy or lactation
 Nitrofurantoin – old drug, very short half-life (20-60mins), not as
effective as new ones, successfully used for suppression therapy for
children and adults with chronic UTIs, well absorbed orally,
metabolized in liver, and excreted in urine
 Methenamine – taken orally, well absorbed, metabolized in liver,
excreted in urine
 Methylene blue – well absorbed orally, widely distributed,
metabolized in tissues, and excreted in urine, bile, and feces
C) Contraindications and Cautions
 contraindicated in presence of any known allergy to any of these drugs
to prevent hypersensitivity reactions
 should be used with caution in the presence of renal dysfunction,
pregnancy and lactation
D) Adverse Effects
 nausea, vomiting, diarrhea, anorexia, bladder irritation, and dysuria
 infrequent symptoms include pruritus, urticaria, headache, dizziness,
nervousness, and confusion
E) Clinically Important Drug-Drug Interaction
 consult a nursing drug guide for specific interactions since these drugs
are from several different chemical classes
Urinary Tract Antispasmodics
 they block the spasm of urinary tract muscles caused by various conditions
A) Therapeutic Actions and Indications
 the urinary tract antispasmodics relieve the spasms by blocking
parasympathetic activity, thus suppressing overactivity, which leads to
relaxation of the detrusor and other urinary tract muscles
 because parasympathetic system uses acetylcholine to cause its effects,
these drugs are called anticholinergic drugs
 Trospium – specifically blocks muscarinic receptors and reduces the
muscle tone of bladder, specifically indicated for treatment of
 overactive bladder with symptoms of urinary incontinence, urgency,
and urinary frequency
 Mirabegron – treats overactive bladder, beta-agonist and stimulates
sympathetic nerves in bladder which leads to detrusor muscle
relaxation
B) Pharmacokinetics
 all agents are administered orally except oxybutynin (orally, dermal
patch, topical gel)
 rapidly absorbed, slow onset of action (6-12hrs), metabolized in liver,
excreted in urine
 Oxybutynin when given transdermally lasts 96 hours
C) Contraindications and Cautions
 contraindicated in presence of any known allergy to any of these
drugs, with pyloric or duodenal obstruction or recent surgery, with
obstructive urinary tract problems, and with glaucoma, myasthenia
gravis or acute hemorrhage
 caution in patients with acute renal or hepatic dysfuntion, and in
pregnantand lactating mothers
 Mirabegron must be used with caution in presence of hypertension
D) Adverse Effects
 nausea, vomiting, dry mouth, nervousness, tachycardia, and vision
changes
 Flaxovate – associated with CNS effects
 Oxybutynin – has anticholinergic effects
 Mirabregon – stimulates sympathetic system and may cause
hypertension and urinary retention
E) Clinically Important Drug-Drug Interaction
 Oxybutynin + phenothiazines and haloperidol = decreased
effectiveness
 Darifenacin or fesoterodine + antifungals or antiviral agents = toxic
effects
 Solifenacin + antihistamines or antipsychotics = risk of increased QT
intervals and serious cardiac arrythmias
 Solifenacin + ketoconazole or other cytochrome P-450 (CYP) 3A4
inhibitors = risk of increased serum levels and toxic effects
 Tolterodine + CYP2D6 inhibitors = increased toxicity
 Trospium can interfere with excretion of drugs by tubular secretion,
leading to increased serum levels f those drugs
 Mirabegron should not be combined with drugs that are metabolized
by CYP2D6 system as it inhibits that system
Other Drugs Affecting the Urinary Tract and Bladder
 Urinary Tract Analgesics – a dye used to decrease pain
A) Therapeutic Actions and Indications
 Phenazopyridine exerts a direct, topical analgesic effect on the
urinary tract mucosa
 it is used to relieve symptoms related to urinary tract irritation
from infection, surgery, or trauma
B) Pharmacokinetics
 Phenazopyridine – available for oral use, rapid onset of action,
widely distributed, crossing placenta and entering breastmilk,
metabolized in liver, and excreted in urine
C) Contraindications and Cautions
 contraindicated in presence of known allergy to drug, and with
serious renal dysfunction
 should be avoided during pregnancy and lactation
 D) Adverse Effects
 GI upset, headache, rash, and reddish-orange coloring of urine
 potential for renal or hepatic toxicity
 using drugs for longer than 2 days increases risk of toxic effects
E) Clinically Important Drug-Drug Interaction
 risk of toxic effects increases when combined with antibacterial
agents
 Bladder Protectant – used to coat or adhere to bladder mucosal wall to
prevent irritation
A) Therapeutic Actions and Indications
 has anticoagulant and fibrinolytic effects
 the drug adheres to the bladder wall to act a buffer to control cell
permeability, preventing irritating solutes in urine from reaching
the bladder wall cells
 used specifically to decrease pain and discomfort
B) Pharmacokinetics
 administered orally and only 3% is absorbed
 distributed to GI tract, liver, spleen, kin, bone marrow, and
periosteum
 undergoes metabolism in liver and spleen and is excreted in urine
 has a half-life of 4.8 hours
C) Contraindications and Cautions
 should not be used with any condition that involved increased risk
of bleeding
 contraindicated in presence of a history of heparin-induced
thrombocytopenia
 caution in patients with hepatic or splenic dysfunction
D) Adverse Effects
 bleeding that may progress to hemorrhage, headache, alopecia, and
GI disturbances
E) Clinically Important Drug-Drug Interaction
 potential of increased bleeding risks if combined with
anticoagulants, aspirin, or nonsteroidal anti-inflammatory drugs
Drugs for Treating Benign Prostatic Hyperplasia
 also called benign prostatic hypertrophy or enlarged prostate
 common problem in men and increases in incidence with age
 the prostate completely encircles the urethra
 two types of drugs are used to relieve the symptoms of BPH: the alpha-
adrenergic blockers doxazosin (Cardura), tamsulosin (Flomax), alfuzosin
(Uroxatral), silodosin (Rapaflo), and terazosin (generic) and drugs that
block testosterone production like finasteride (Proscar) and dutasteride
(Avodart)
A) Therapeutic Actions and Indications
 prostate enlargement must be benign and not caused by cancer,
infection, stricture, or hypotonic bladder
 patients receiving long-term therapy must be reassessed periodically
 alpha-adrenergic blockers block postsynaptic alpha-adrenergic
receptors, which results in a dilation of arterioles and veins and a
relaxation of sympathetic effects of bladder and urinary tract
 drugs that block testosterone production inhibit the intracellular
enzyme that converts testosterone to potent androgen dihydrotes-
testosterone, which the prostate gland depends for its development and
maintenance
B) Pharmacokinetics
 alpha, selective adrenergic blocking agents are well absorbed after oral
administration, reaching peak levels in 2-8 hours and undergo
 extensive hepatic metabolism
 excreted in urine
 finasteride and dutasteride are rapidly absorbed from GI tract after oral
administration, undergo hepatic metabolism, and are excreted in feces
and urine
C) Contraindications and Cautions
 contraindicated in patient who are allergic to drugs
 caution should be used in patients with hepatic or renal dysfunction
 adrenergic blockers should be used with caution in px with heart
failure or known coronary disease
 finasteride and dutasteride have no indications for women and are
rated pregnancy X
 women must not touch finasteride or dutasteride tablets
D) Adverse Effects
 headache, fatigue, dizziness, postural dizziness, lethargy, tachycardia,
hypotension, GI upset, and sexual dysfunction
 finasteride and dutasteride are associated with decreased libido,
impotence, and sexual dysfunction
 px using finasteride or dutasteride can’t donate blood for 6months after
last dose
E) Clinically Important Drug-Drug Interaction
 alpha-adrenergic blockers + antihypertensives, nitrates, or
erectile dysfunction drugs = increased anti hypertensive effects