Diuretics

Drug
Thiazides
Chlorothiazide
Hydrochlorothiazide

Thiazide-like Analogs
Chlorthalidone
Indapamide
Metolazone

Loop Diuretics
Bumetanide
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Actions

Therapeutic Uses

Pharmacokinetics

Adverse Effects

Others

-Act mainly in distal tubule

to decrease the reabsorption
of Na+ by inhibiting the
Na+/Cl- cotransport
-Increase the concentration
of Na+ and Cl- in tubular fluid
diuresis with increased
Na+ and Cl- excretion
(hyperosmolar urine)
-K+ is exchanged for Na+,
causing continual loss of K+
from the body with
prolonged use of the drug
-Decrease the Ca2+ content
of urine by promoting
reabsorption
-Initial reduction in BP, but
with continued use, volume
recovery occurs

-Hypertension :reduce
systolic and diastolic BP
for extended periods of
time; after 3-7 days of tx
BP stabilizes and can be
maintained by dailydosage of the drugs
-DOC: reducing ECF
volume in mild to
moderate HF
-Idiopathic hypercalciuria
-Diabetes insipidus

-These drugs must be

excreted into the
tubular lumen to be
effective
-Effective orally
-Take 1-3 weeks to
produce stable
reduction in BP
-1/2 life: 40 hours
-Secreted by the organic
acid secretory system of
kidney

-Hypokalemia
-Predisposes pts taking
DIGITALIS to ventricular
arrhythmias
-Hyponatremia: due to
elevation of ADH as a result
of hypovolemia
-Hyperuricemia: decrease
the amount of acid excreted
by organic acid secretory
system
-Orthostatic hTN, lightheadedness
-Hypercalcemia
-Hyperglycemia: due to
impaired release of insulin
and tissue uptake of glucose
-Hyperlipidemia: increased
cholesterol, LDL
-Hypersensitivity: BM
suppression, dermatitis,
necrotizing vasculitis,
interstitial nephritis

-Lose efficiency in pts with

decreased renal function
-Diuretic action isnt
affected by acid-base
status of body
-Periodic blood tests for
potassium and uric acid
levels should be done
-Ceiling diuretics

-Metolazone: causes Na+

excretion in advanced renal
failure
-Indapamide: at low doses it
shows antihypertensive
action

-Chlorthalidone: HTN
-Indapamide: useful in
treatment of pts with
renal failure

-Major action of the

ascending limb of loop of

-DOC: reducing acute

pulmonary edema of HF

-Chlorthalidone: very
long duration of action,
given once per day
-Indapamide: long
duration of action,
metabolized and
excreted by GIT and
kidneys
-Highest efficacy to
mobilize Na+ and Cl-

-Metolazone more potent

than THIAZIDES
-Indapamide: lipid-soluble

-Hypomagnesemia
-Ototoxicity (especially

-High-ceiling diuretics
-Bumetanide and

Diuretics
Furosemide
Torsemide
Ethacrynic acid

Aldosterone
Antagonists
Spironolactone
Eplerenone

Triamterene
Amiloride
(K+- Sparing)
Acetazolamide
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Henle
-Inhibit the cotransport of
Na+/K+/2Cl- in luminal
membrane Reabsorption
of ions is decreased
-Increase the Ca2+ content of
urine
-Decreased renal vascular
resistance, increased renal
blood flow
-Increase PG synthesis
-Act in collecting tubules to
inhibit Na+ reabsorption and
K+ excretion
-Spironolactone: antagonizes
aldosterone at intracellular
cytoplasmic receptor sites
Prevents translocation of
complex into nucleus, so
cant bind to DNA Failure
to produce proteins which
stimulate Na+/K+-exchange
in CT Prevention of Na+
absorption and K+ and H+
secretion
-Canrenone:
mineralocorticoid- blocking
activity
-Block Na+ transport
channels Decrease in
Na+/K+ exchange

-Useful in emergency
situations
-Hypercalcemia
-Hyperkalemia

from the body

-Bumetanide is more
potent than Furosemide
-Administered orally or
parenterally
-Duration of action: 2-4
hours
-Secreted into the urine

when used w/
aminoglycoside antibiotics)
-Hyperuricemia: compete
with uric acid for renal and
biliary secretory systems
-Acute hypovolemia, may
lead to hTN, shock, cardiac
arrhythmias
-Hypokalemic alkalosis

Furosemide are
sulfonamide derivatives

-Spironolactone given
with THIAZIDES or LOOP
DIURETICS to prevent K+
excretion
-DOC: pts with hepatic
cirrhosis
-Spironolactone:
Secondary
hyperaldosteronism
-Spironolactone prevents
remodling of heart in
progressive HF

-Spironolactone:
completely absorbed
after orally and strongly
bound to proteins
-Spironolactone gets
converted to active
metabolite: canrenone
-Spironolactone:
induces hepatic CYP450

-Spironolactone: gastric
upsets that can cause peptic
ulcers
-Gynecomastia in males
-Menstrual irregularities in
females
-Hyperkalemia
-Nausea
-Lethargy
-Mental confusion

-Used alone primarily

when aldosterone is
present in access
-Effects of Spironolactone
depend on renal PG
synthesis
-Eplerenone: actions
comparable to
Spironolactone, with less
endocrine effects
-Spironolactone shouldnt
be given at high doses on
chronic basis

-Triamterene: leg cramps,

increased BUN, uric acid
and K+ retention

-Inhibits CA located

-Chronic tx of glaucoma:

-Because their exchange

ability doesnt depend on
levels of aldosterone, they
are effective diuretics in
pts with Addisons disease
-Should be avoided in pts

-Used in combination
with other diuretics for
potassium-sparing
abilities
-Given orally 1-4 times

-Hyperchloremic metabolic

Diuretics

Osmotic Diuretics
Mannitol
Urea

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intracellularly on apical
membrane of PCT epithelium
-Decreased ability to
exchange Na+ and H+ leads
to mild diuresis
-HCO3- retained in lumen,
causing increase in urinary
pH
-Phosphate excretion in
increased
-Hydrophilic substances
which have the ability to
carry water with them into
the tubular fluid

decreased production of
aqueous humor
-Prophylaxis of mountain
sickness: given nightly for
5 days before ascent
prevents weakness,
breathlessness, dizziness,
nausea, cerebral and
pulmonary edema

daily
-Secreted by PCT

acidosis
-Potassium depletion
-Renal stone formation
-Drowsiness
-Paresthesia (tingling)

with hepatic cirrhosis

because it can lead to
decreased excretion of
NH4+

-Used to maintain urine

flow following acute toxic
ingestion of substances
capable of producing
acute renal failure
-Tx of pts w/: increased
ICP, acute renal failure,
drug toxicity, trauma

-Only given via IV

-Extracellular water
expansion
-Dehydration
-Hypo- or hypernatremia

-Maintaining urine flow

preserves long-term
kidney function

Diuretics

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