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2 Classification
Types of diuretics
Mechanism of action
Table of 3
Diuretics
4 Clinical use
Contents Veterinary importance
5 Pharmacokinetics
How drugs works
6 Adverse effects
Dosage and side effect ,drug interaction
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DIURETICS & URINARY ALKALIZES
A drugs that used against blood pressure, glaucoma and oedema
History:
The remarkable German-Swiss
physician Paracelsus (1493-1521)
described inorganic mercury-
containing compounds as having
diuretic properties in 1520. He used
Calomel, mercurous chloride, Hg2Cl2.
It was more of a laxative than a
diuretic, and notably toxic.
illustration about Site of action of loop diuretics, thiazides and potassium sparing drugs, showing details of the
kidney nephron. Illustration of loop, action, drawing -
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Diuretics Definition .
A diuretic is any substance
that promotes diuresis, the
increased production of urine.
Classification of diuretics
All diuretics increase the excretion of water from bodies, although each
class does so in a distinct way.
2 Ethacrynic acid 50 mg
(Edecrin)
3 Furosemide 40 mg
High ceiling/loop (Lasix)
diuretic
4 Torsemide 20 mg
Example
Which Loop diuretic is most potent? 5 Loop diuretics are diuretics that act at the
ascending limb of the loop of Henle in the
6 kidney.
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Veterinary Clinical use Furosemide is primarily used for the treatment of edema, but
also in some cases of hypertension (where there is also
kidney or heart impairment).
Furosemide is also used for liver cirrhosis, kidney
impairment, nephrotic syndrome, in adjunct therapy
for swelling of the brain or lungs where rapid diuresis is
required (IV injection), and in the management of
severe hypercalcemia in combination with adequate
rehydration.
The neuromuscular symptoms of hypercalcaemia are caused
by a negative bathmotropic effect due to the increased
interaction of calcium with sodium channels.
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Adverse effects
Furosemide may result in these side effects
In specially cat
Tilting of the head in cats, Reduced ability to hear in cats
.
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Pharmacokinetics
Loop diuretics are highly protein bound and therefore have a low volume of distribution. The protein bound nature of the loop
diuretic molecules causes it to be secreted via several transporter molecules along luminal wall of the proximal convoluted
tubules to be able to exert its function.
The availability of furosemide is high variable from 10% to 90%. The biological half-life of furosemide is limited
by absorption from gastrointestinal tract into the bloodstream. The apparent half-life of its excretion is higher than the apparent
half-life of absorption via oral route. Therefore, intravenous dose of furosemide is twice as potent as the oral route.
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Drug interaction
Furosemide may react with these drugs:
Corticosteroids, Other diuretics, Muscle relaxants, Drugs that may be toxic to the
kidneys, Drugs that may be toxic to the ears, Aminophylline, Corticotropin, Digoxin,
Insulin, Succinycholine chloride, Theophylline
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Dose of furosemide
4–6 mg/kg IV, IM, or SC, as needed for acute therapy
0.5–1 mg/kg/day, IV or IM
0.5–1 mg/kg/day, IV or IM
1 mL/20 kg of b.w
Furosemide should be used with caution in animals that are dehydrated. Furosemide
should not be used in animals that are unable to produce urine (anuric), or those with serious electrolyte imbalances or electrolyte depletion.
Furosemide should be used with caution in animals that are dehydrated, have decreased liver function or diabetes mellitus.
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How do loop diuretics cause alkalosis?
Loop diuretics act in the ascending limb of the loop of henle. They inhibit the Na-K-2Cl contransporter to
inhibit sodium and chloride reabsorption.
Loop and thiazide diuretics can cause metabolic alkalosis due to increased excretion of chloride in
proportion to bicarbonate.
Cotransporter
An integral membrane protein that actively transports molecules by using the concentration gradient of one
molecule or ion concentration to force the other molecule or ion against its gradient.
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How do loop diuretics cause ototoxicity?
The most likely mechanism responsible for the potentiation of ototoxicity by loop diuretics is damage
to the tight cell junctions in the blood vessels in the stria vascularis resulting in temporary disruption of
the blood-cochlear barrier which increases the permeability of the lateral wall to ototoxic drugs
Drug Interaction
Drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen(Motrin), naproxen (Naprosyn), and nabumetone (Relafen) can reduce
the effectiveness of thiazide diuretics in lowering blood pressure because they may reduce the ability of the kidneys to make urine, particularly in
patients who have reduced kidney function.
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Side effects of thiazide diuretics
Side effects of thiazide diuretics are dose related and include:
Dose
Dogs and cats: 20–40 mg/kg, PO, once or twice daily
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3.Carbonic anhydrase inhibitors
Acetazolamide and methazolamide are carbonic anhydrase inhibitors used as diuretics and in the therapy of glaucoma.
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Mechanism of action
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5.Osmotic diuretics
Mannitol and Isosorbide are available for therapeutic use
Indication
Used for the promotion of diuresis before irreversible
renal failure becomes established, the reduction of
intracranial pressure, the treatment of cerebral
edema, and the promotion of urinary excretion of toxic
substances..
Mechanism of action
Mannitol is a six-carbon, linear, simple sugar which is
only mildly metabolized by the body and largely
excreted rapidly by the kidneys when given
intravenously and poorly absorbed when taken orally.
Administration
Mannitol can be found in varying concentrations from 5% mannitol (5
gm mannitol dissolved in 100 mL of fluid) up to 25% mannitol (25 gm
of mannitol dissolved in 100 mL of fluid). A
commonly encountered solution is 20% mannitol (20 grams of
mannitol dissolved in 100 mL of fluid).
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OTHER DIURETICS
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Urinary alkalizers
Alkalinizing agents are drugs used to manage disorders associated with low pH. For example, they may
be used to treat acidosis due to renal failure.
Sodium bicarbonate is an antacid that Citric acid and sodium citrate are
neutralizes stomach acid. alkalinizing agents that make the urine less
acidic.
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Thank You
Any Questions?