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Lecture 6-1
Lecture 6-1
Tentishev
Department of Interprofessional discipline
Subject - Basic and clinical Pharmacology
Teacher - Temirbekovа Gulnura
Lecture:№6
Theme: Diuretics
Diuretics are drugs that increase the
volume of urine excreted.
1- THIAZID DIURETICS
Thiazides are the most widely used diuretics.
They are sulfonamide derivatives.
Chlorothiazide [klor-oh-THYE-ah-zide] was
the first orally active diuretic that was able to act
on the severe edema often seen in cirrhosis of the
liver and heart failure with minimal side effects.
Antagonists of Aldosterone:
Spironolactone and eplerenone
1. Mechanism of action: Spironolactone [spear-
oh-no-LAK-tone] is a synthetic steroid that
counteracts aldosterone at intracellular receptor
sites, making the spironolactone receptor complex
inactive. It prevents the translocation of the
receptor complex into the nucleus of the target
cell, which ultimately leads to the inability to
produce mediator proteins that normally stimulate
N +/K+-exchange sections of the collecting
tubule.
Thus, the lack of mediator proteins prevents
the reabsorption of Na+ and, consequently,
the secretion of K+ and H+. Eplerenone [eh-
PLEH-reh-none] is another aldosterone
receptor antagonist that has actions
comparable to those of spironolactone,
although it may have fewer endocrine effects
than spironolactone.
2. Actions: In most edematous conditions,
the level of aldosterone in the blood is high,
causing a delay in Na+. Spironolactone
counteracts the activity of aldosterone, which
leads to a delay in K+ and the excretion of
Na+ (Figure 18.8). Like thiazides and loop
diuretics, the effect of these agents can be
reduced with the introduction of NSAIDs.
3. Therapeutic use:
Diuretic: Although aldosterone antagonists are
low in mobilizing Na+ from the body compared to
other diuretics, they have the beneficial property
of inducing an increase in K+. These agents are
often prescribed alongside thiazide or loop
diuretics to prevent the excretion of K+ that would
otherwise occur with these drugs.
Secondary hyperaldosteronism: Spironolactone
is particularly effective in clinical situations
involving secondary hyperaldosteronism, such as
cirrhosis of the liver and nephrotic syndrome.
4 Pharmacokinetics: Both spironolactone and
eplerenone are absorbed after oral administration
and are reliably bound to plasma proteins.
5. Side effects: Spironolactone can cause
indigestion. Hyperkalemia, nausea, and confusion
may occur.
Triamterene and amyloride [trye-AM-ter-een]
and amiloride [a-MIL-oh-ride] block the
Transport Channels+, resulting in a decrease in
Na+/K+ exchange. Although they have a K+-
sparing diuretic effect similar to those of
aldosterone antagonists, their ability to block
Na+/K+-exchanges in the collecting tubule is
independent of the presence of aldosterone.
Like aldosterone antagonists, these agents are not
very effective diuretics. Like triamterene, both
amiloride are commonly used in combination with
other diuretics, usually because of their potassium
properties. Like aldosterone antagonists, they
prevent the loss of K+, which occurs with thiazide
and loop diuretics. Side effects of triamterene
include increased uric acid, kidney stones, and K+
retention.
Carbonic anhydrase inhibitor
acetazolamide [ah-set-a-ZOLE-a-mide] and other
carbonic an hydrazine hesitators are more often
used for their other pharmacological actions than
for their diuretic effect, since they are much less
effective than the thiazide or loop diuretics.
Acetazolamide
1. Mechanism of action:
Acetazolamide inhibits
carbonic anhydrase
located intracellularly
(cytoplasm) and on the
apical membrane of the
proximal tubular
epithelium (Figure 18.9)
Carbonic anhydrase catalyzes the reaction of CO2 and
H2O, which leads to H2CO3, which spontaneously
ionizes into H+ and HCO3- (bicarbonate).] A decrease
in the ability to exchange Na+ for H+ in the presence
of acetazolamide leads to mild diuresis.
Additionally, HCO3- persists in the lumen, with a
pronounced deletion in the pH of urine. Loss of
HCO3- causes hyperchloremic metabolic acidosis and
a decrease in diuretic efficacy after several days of
therapy.
2. Therapeutic use:
Glaucoma: Acetazolamide reduces the production of
aqueous humor and reduces intraocular pressure in
patients with chronic open-angle glaucoma, likely by
blocking carbonic anhydrase in the ciliary body of the
eye.
Altitude sickness: Acetazolamide can be used in the
prevention of acute mountain sickness.
Acetazolamide prevents weakness, shortness of breath,
dizziness, nausea and brain, as well as pulmonary
edema characteristic of the syndrome.
3. Pharmacokinetics: Acetazolamide can be
administered orally or intravenously.