2
09
Thiazides
–
chlorothiazide, hydrochlorothiazide,
Pharmacodynamics
benzthiazide, chlorthalidone,
+
Furosum- ide’s mechanism of action is by inhibiting Na /
+
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+
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•
•
Exert their diuretic effect by inhibiting the Na /Cl
co-transport in the early distal convoluted tubules.
K /2Cl transporter in the thick ascending loop of Henle.
This inhibits the reabsorption of NaCl leading to in-
They elicit a weaker diuretic response compared to
the loop diuretics.
2+
Increase the loss of K and Mg , but reduce Ca
excretion
2
creased NaCl and H O excretion.
+
2+
Pharmacokinetics
Furosemide is available for both oral and parenteral ad-
ministration. Its onset of action is rapid, usually within
0 minutes after oral and five minutes after intravenous
administration. It produces peak diuresis in about two
hours, with a total duration of diuretic action of approxi-
mately six to eight hours.
Na channel blockers – Amiloride, triamterene
3
+
•
They act by blocking the Na channels in the lu-
minal membrane of the principal cells of the cortical
+
collecting ducts. This reduces the Na entry through
the luminal membrane and hence the net reabsorp-
tion of NaCl. Action is independent of aldosterone.
They have weak diuretic effect.
Furosemide is extensively bound to plasma proteins and
is eliminated in the urine by both glomerular filtration
and tubular secretion. Approximately a third of an ad-
ministered dose is excreted by the liver into the bile,
from where it may be eliminated in the feces.
•
Aldosterone antagonists - spironolactone
•
•
Act at the late distal tubule and the cortical collect-
ing tubule and competes with aldosterone for recep-
tor sites in DCT and the collecting tubule.
Dosage
+
Conventional: 1- 2mg/kg/dose, maximum of 6mg/kg/
day. Higher dose may be given in certain situations – up
to 600mg/day
Results in decreased Na reabsorption in DCT and
+
the collecting tubule and promotes Na and wate+r
+
loss. Decreased Na reabsorption balanced by K
+
retention at this site (and H ) – K sparing.
Formulations
Furosemide (Frusemide)
Furosemide is available in tablets for oral administration
and injectable for I.V. administration.The tablets are a
white to off-white odorless crystalline powder. They are
available in dosage strengths of 20, 40 and 80 mg. The
injection comes as 20mg/2ml; clear colourless solution.
•
•
The most efficacious agent available for inducing
marked water and electrolyte excretion.
It can increase diuresis even in patients who are
already responding maximally to other diuretics. It
has no significant pharmacological effects other
than on renal function.
5
00mg tablet and 250mg injection also available for use
in selected patients who do not respond to conventional
doses.
Chemical properties
Clinical use of diuretics
•
•
•
•
It is an anthranilic acid derivative
It is practically insoluble in water
Sparingly soluble in alcohol
Freely soluble in dilute alkali solutions and insolu-
ble in dilute acids.
Diuretics interfere with sodium reabsorption and lower
extracellular fluid volume. Therefore useful in the fol-
lowing conditions:
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•
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•
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Heart failure and pulmonary oedema.
Chronic kidney disease
Acute renal failure
Hypertension
Liver cirrhosis
Poisoning.
Diabetes insipidus.
Glaucoma
Prevent cardiovascular complications of chronic
kidney disease.
•
Chemically, it is 4chloro-N-furfuryl-5-
sulfamoylanthranilic acid
•
Potentiate the effect of antihypertansive and for
resistant hypertension.
Adverse effects of diuretics
The structural formula of furosemide
•
•
Hypovolaemia (Loop and thiazides)
Hypokalaemia (Loop, thiazides, carbonic anhy
drase)