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Function:
12-Nov-16 1
Main function of kidneys is
• The excretion of waste products such as
urea, uric acid and creatinine.
• Also play an important role in acid-base
balance and regulation of salt and
electrolyte content and volume of
extracellular fluid.
• Production and release of different
hormones play a vital role in controlling
BP and red blood cell production.
12-Nov-16 2
Diuretics:
• Drugs that increase the amount of urine
produced by kidneys. OR
• Agents that promote a net loss of sodium
ions, and accompanying Cl- and HCO3
ions and water from body resulting in an
increase in flow of urine formation.
12-Nov-16 3
In vet. practice, diuretics are used to
increase urine flow when there is fluid
retention and oedema in case of heart
failure, hepatic disease, cerebral oedema etc.
12-Nov-16 4
• Most diuretics increase urine volume by
reducing the efficiency of sodium
resorbing processes and thereby
increasing the obligatory water loss.
• They alter not only the excretion of Na++
but also renal transport of other cations
like K, H, Ca and Mg, anions like Cl,
HCO3 and H2PO4 and uric acid.
12-Nov-16 5
12-Nov-16 6
An Overview of Diuretics:
• In strict sense, the term is applied to
drugs with a direct renal action.
• Predominant action of such agents is to
augment urine excretion by inhibiting
the reabsorption of NaCl and water
12-Nov-16 7
Indications of diuretics:
• Mobilization of edema: In edema there
is swelling of tissues owing to
accumulation of fluid, chiefly in the
extracellular (interstitial) space. When a
diuretic is given, increased renal
excretion of Na++ and water causes a
reduction in plasma volume with
hemoconcentration.
12-Nov-16 8
• Antihypertensive therapy: Diuretics
have been used as drugs of first choice
for lowering elevated blood pressure.
• Even at low dosage, they decrease
peripheral resistance and thereby
normalize blood pressure.
12-Nov-16 9
• Therapy of congestive heart failure: By
lowering peripheral resistance, diuretics
aid the heart in ejecting blood.
12-Nov-16 10
Classification:
Depending upon
• their major site of action
• mechanism of action
• chemical structure
• potency
• alteration of urinary pH
12-Nov-16 11
According to Potency:
• I. High Efficacy diuretics
12-Nov-16 12
• II. Moderate efficacy diuretics:
12-Nov-16 13
III. Low efficacy or adjunctive
diuretics:
• 1. Osmotic diuretics: Mannitol, sorbitol
etc.
12-Nov-16 14
• 3. Potassium sparing diuretics:
• a. Inhibitors of renal epithelial Na+
channels: Triamterene
12-Nov-16 15
IV. Miscellaneous Diuretics:
• 1. Acidifying or alkalinising salts:
• a. Acidifying salts: Ammonium chloride
and sodium chloride
• b. Alkalinising salts: Potassium acetate
and potassium citrate
• 2. Methylxanthines/Xanthine diuretics:
Aminophylline and theophylline
12-Nov-16 16
High ceiling diuretics/Loop
diuretics:
• Most potent group of diuretics
• Frusemide: structurally related to
sulphonamides so also called sulphonamide
loop diuretic.
• They inhibit sodium and chloride
reabsorption in nephrons producing rapid
diuretic effect by inhibiting Na, K and Cl
symporter.
12-Nov-16 17
• The sodium-chloride symporter (also
known as Na+-Cl− cotransporter) is
a cotransporter in the kidney which has
the function of
• reabsorbing sodium and chloride ions
from the tubular fluid into the cells of
the distal convoluted tubule of the nephron.
12-Nov-16 18
• Due to blockade of Na, K and Cl
symporter, frusemide causes a profound
increase in urinary excretion of Na and
Cl.
• Frusemide increases renal excretion of
Na, K, Cl, Ca, Mg, H, Ammonium and
Bicarbonate.
12-Nov-16 19
Clinical Use:
• Frusemide is used for its diuretic activity
in all species.
• Used in cardiovascular and pulmonary
oedema, hepatic and renal dysfunction,
hydrothorax, ascites and non-specific
oedema.
• During sporting event these diuretics are
banned with other drugs.
12-Nov-16 20
Mercurials:
• Used for many years where a prompt
and potent diuresis was indicated.
• In acidic pH, these drugs liberate
mercuric ion that combines with –SH
group of enzymes associated with
transport system in kidney tubule.
12-Nov-16 21
• These drugs depress mainly the
reabsorption of Na and Cl with less effect
on K and HCO3.
12-Nov-16 22
Thiazides diuretics:
• Thiazides are sulphonamide derivatives
and are related in structure to the
carbonic anhydrase inhibitors.
• They inhibit Na+-Cl cotransport and
have significantly greater diuretic
activity.
• Most of them are derived from
benzothiadiazine so called thiazide
diuretics.
12-Nov-16 23
• Thiazide diuretics act mainly in distal
tubule to decrease the reabsorption of
Na+ by inhibition of Na+- Cl co-
transporters.
• Also have a secondary effect in proximal
tubule.
• They don’t cause significant alteration
in acid-base balance.
12-Nov-16 24
Thiazide like diuretics:
• Recently discovered group of
sulphonamide diuretic drugs
• Pharmacological properties similar to
thiazide diuretic.
• Primary target of all non-thiazide
diuretics is the distal convoluted tubule,
where they inhibit the sodium-chloride
symporter.
12-Nov-16 25
Osmotic diuretics
• Pharmacologically inert substances,
freely filtered at the glomerulus but not
significantly reabsorbed from tubules.
• Administered in large doses to increase
the osmolality of plasma and tubular
fluid.
12-Nov-16 26
MoA:
• Appear to limit tubular reabsorption of
water and electrolyte in a variety of
ways.
• a. Inhibit passive reabsorption of water
in those segments of nephron which are
freely permeable to water i-e proximal
tubule, descending limb of loop of Henle
and also distal tubule.
12-Nov-16 27
• b. They extract water from intracellular
compartments and expand extracellular
fluid volume.
• This decreases blood tonicity, increases
renal blood flow and glomerular
filtration rate and reduces renin and
aldosterone secretion.
12-Nov-16 28
• c. The increase in renal medullary blood
flow removes excess of Na+, Cl- and
urea from renal medulla
• d. Also inhibit transport processes in
thick ascending limb of loop of Henle by
an unknown mechanism.
12-Nov-16 29
Osmotic diuretics:
• Mannitol: Pharmacologically inert.
Its presence in renal tubule prevents
reabsorption of water by osmotic action.
It increase urine volume and excretion of all
cations and anions.
12-Nov-16 30
• In general, it increases urinary excretion
of Na, K, Ca, Mg, Cl, HCO3 and
phosphate
• Like other osmotic diuretics, mannitol
may increase renal blood flow and
glomerular filtration
12-Nov-16 31
Treatment:
• Mannitol toxicity may be treated by
correcting electrolyte and fluid
imbalance.
• Haemodialysis is effective in clearing
mannitol.
12-Nov-16 32
Carbonic anhydrase (CA)
inhibitors:
• They block the carbonic anhydrase
enzyme that catalyses the first part of
reversible reaction in which CO2 and
water are converted to carbonic acid
and vice-versa.
• Thus they function on CO2 and HCO3
transport and in H+ ion secretion.
12-Nov-16 33
• They block the functioning of CA
enzyme predominantly at proximal
convoluted tubule, reducing the number
of hydrogen ions available for Na+-H+
exchange.
12-Nov-16 34
Potassium sparing diuretics:
• Interfere with sodium reabsorption at the
distal segments of nephron and promote
sodium excretion without potassium loss.
• these diuretics are mild diuretics and are
usually used in conjunction with loop or
thiazide diuretics.
12-Nov-16 35
Methylxanthines/ Xanthine
derivatives:
• Long been used as weak diuretics.
• They act by increasing the renal blood
flow by cardiac stimulation and increase
in glomerular filtration rate.
• They also act directly by inhibiting
reabsorption of Na+ and water in
proximal convoluted tubule.
12-Nov-16 36
Drugs affecting urinary pH :
• The kidneys control acid-base balance
by excreting either acidic or basic urine.
• Unlike blood, the pH of urine can range
from 4.5 to 8.0 depending on the acid-
base status of extracellular fluid.
12-Nov-16 37
• Changes in urine pH are therapeutically
achieved by use of either urinary
acidifier or alkalizer.
12-Nov-16 38
Urinary Acidifiers:
• Cause acidification of urine
• They enhance excretion of basic
substances by increasing their ionisation
in the filtrate that diminishes their
passive reabsorption across the tubular
wall.
12-Nov-16 39
• Ammonium chloride, ascorbic acid,
sodium acid phosphate, methionine,
sodium chloride, ethylenediamine
dihydro-chloride and ammonium
sulphate are clinically used to acidify the
urine.
12-Nov-16 40
Acidifying or alkalinising salts/
Saline diuretics:
• Some salts used primarily for
acidification of urine also provide a
diuretic effect and are known as saline
diuretics.
• Rarely used clinically for their diuretic
effect.
12-Nov-16 41
• Ammonium Chloride: Acidifying salt
that possesses some diuretic effect. It has
limited and short term effect. It causes
metabolic acidosis which is an adverse
effect.
12-Nov-16 42
Alkalinising Salt:
• Potassium citrate and Potassium
acetate: In the past they are used as
diuretics. They are potentially
dangerous and mostly used to change
the pH of urine, rather than as diuretics.
12-Nov-16 43
Urinary Alkalinizers:
• Cause alkalinisation of the urine.
• They increase the antibacterial activity
of some antimicrobials like
aminoglycosides, erythromycin and
fluoroquinolones.
• They increase the solubility of
sulphonamides so decrease chances of
crystalluria and kidney damage.
12-Nov-16 44
• Alkalinisation of urine decreases
formation of uric acid and stones.
• Sodium bicarbonate and sodium citrate
are commonly used urinary alkalizers.
12-Nov-16 45
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