Dr.Jibachha Sah,M.V.Sc (Veterinary pharmacology),Lecture,College of Veterinary science,NPI,Bhojard,Chitwan,Nepal.This is part of lecture note on veterinary pharmacologyAUTONOMIC AND SYSTEMIC PHARMACOLOGY, Sixth Semester, B.V.Sc & A.H 6th semester. Dr.Jibachha sah,Email: jibachhashah@gmail.com,Mobile:00977-9845024121

1. Welcome to My Lecture Notes
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AUTONOMIC AND SYSTEMIC PHARMACOLOGY, Sixth Semester, B.V.Sc & A.H
Diuretics, Urinary alkalizes
Dr. Jibachha Sah, Lecture, M.V.Sc ( Veterinary Pharmacology)
College of Veterinary Science, NPI, Bhojard, Chitwan, Nepal
Email: jibachhashah@gmail.com;00977-9845024121

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Table of
Contents
History/Definition
Diuretics and alkanizers
Adverse effects
Dosage and side effect ,drug interaction
Classification
Types of diuretics
Mechanism of action
Diuretics
Clinical use
Veterinary importance
Pharmacokinetics
How drugs works
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3. DIURETICS & URINARY ALKALIZES
A drugs that used against blood pressure, glaucoma and oedema
illustration about Site of action of loop diuretics, thiazides and potassium sparing drugs, showing details of the
kidney nephron. Illustration of loop, action, drawing -
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.
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4. Diuretics Definition .
A diuretic is any substance
that promotes diuresis, the
increased production of urine.

5. Classification of diuretics
All diuretics increase the excretion of water from bodies, although each
class does so in a distinct way.
1.High ceiling/loop
diuretic
2.Thiazides 3.Carbonic
anhydrase
inhibitors
Alternatively, an antidiuretics such as vasopressin (antidiuretic hormone), is an agent
or drug which reduces the excretion of water in urine..
4.Potassium-sparing diuretics 5.Osmotic diuretics

6. 1.High ceiling/loop diuretic
Mechanisms and Sites of Action
High ceiling diuretics may cause a substantial diuresis – up to 20% of the
filtered load of NaCl (salt) and water. This is large in comparison to
normal renal sodium reabsorption which leaves only about 0.4% of filtered
sodium in the urine. Loop diuretics have this ability, and are therefore often
synonymous with high ceiling diuretics.
Loop diuretics, such as furosemide, inhibit the body's ability to
reabsorb sodium at the ascending loop in the nephron, which leads to
an excretion of water in the urine, whereas water normally follows
sodium back into the extracellular fluid.
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High ceiling/loop
diuretic
Example
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Bumetanide 1 mg
(Bumex)
Loop diuretics are diuretics that act at the
ascending limb of the loop of Henle in the
kidney.
Ethacrynic acid 50 mg
(Edecrin)
Furosemide 40 mg
(Lasix)
Torsemide 20 mg
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Which Loop diuretic is most potent?

8. 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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9. Adverse effects
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Furosemide may result in these side effects
In dog & cat
Increased water intake, Increased sensitivity to light, Lethargy, Restlessness,
Increased heart rate
In dog & cat
Vomiting, Diarrhea, Seizures, Loss of appetite
In specially cat
Tilting of the head in cats, Reduced ability to hear in cats
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10. Pharmacokinetics
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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.
A dose of 40 mg of furosemide is equivalent to 20 mg of torsemide and 1 mg bumetamide.

11. Drug interaction
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
Furosemide may react with these drugs:
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12. Dose of furosemide
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4–6 mg/kg IV, IM, or SC, as needed for acute therapy
1–2 mg/kg, PO, once or
twice daily
0.5–1 mg/kg/day, IV or IM
2–4 mg/kg, PO, once to
three times daily
1 mL/20 kg of b.w
0.5–1 mg/kg/day, IV or IM
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.

14. How do loop diuretics cause ototoxicity?
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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

15. Mechanism of action of Thiazide diuretics
Thiazide diuretics can lower potassium and magnesium blood levels
since they are both eliminated in urine. Low levels of potassium and
magnesium in the blood can result in abnormal heart rhythms,
particularly in those who are also taking digoxin(Lanoxin) in addition
to a thiazide. Thiazide diuretics can increase the risk
of lithium(Eskalith, Lithobid) toxicity by reducing the kidney's ability
to eliminate lithium in the urine..
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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16. Side effects of thiazide diuretics
Side effects of thiazide diuretics are dose related and include:
dizziness and lightheaded
ness
blurred vision loss of appetite,
itching, stomach upset weakness.
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Dose
Dogs and cats: 20–40 mg/kg, PO, once or twice daily

17. 3.Carbonic anhydrase inhibitors
Acetazolamide and methazolamide are carbonic anhydrase inhibitors used as diuretics and in the therapy of glaucoma.
Off label drug/ Extra
label drug
Mechanism of action
Acetazolamide and methazolamide are inhibitors of
carbonic anhydrase, an enzyme that converts
carbon dioxide and water to carbonic
acid. Inhibition of this enzyme in the kidney causes
an alkalization of the urine and diuresis. In the eye,
inhibition of carbonic anhydrase causes a decrease
in intraocular pressure making these agents
valuable in the treatment of glaucoma.
dogs, the usual dose is 7 to 10 mg/kg
every 6 hourswitter.com
Cat7 mg/kg every 8 hours.
Common Side effect
change in taste, polyuria, nausea
numbness and tingling in fingers and toes
blurred vision, tinnitus, dizziness,
diarrhea, fatigue, and headache
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18. Mechanism of action
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The potassium-sparing diuretics are competitive
antagonists that either compete with aldosterone for
intracellular cytoplasmic receptor sites, or directly block
sodium channels (specifically epithelial sodium
channels (ENaC) by amiloride). The former prevents the
production of proteins that are normally synthesized in
reaction to aldosterone.
These mediator proteins are not produced, and so stimulation of
sodium-potassium exchange sites in the collection tubule does not
occur. This prevents sodium re-absorption and potassium and
hydrogen ion secretion in the late distal tubule and collecting duct of
a nephron in the kidneys

19. 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.

20. 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).
For increased intracranial pressure dosages typically range
0.25 g/kg to 2 g/kg administered intravenously over 30 to 60 minutes
with effect within 5 to 10 minutes and effect lasting up to approximately
6 hours.
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21. OTHER DIURETICS
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Spironolactone Dogs: 2–4 mg/kg, PO, bid
Mannitol 0.25–0.5 g/kg, IV
Dimethyl sulfoxide
Large animals: 1 g/kg, IV or via nasogastric
tube

22. 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
neutralizes stomach acid.
sodium bicarbonate
Sodium bicarbonate is used to
relieve heartburn and indigestion.
Citric acid and sodium citrate are
alkalinizing agents that make the urine less
acidic.
citric acid, potassium citrate,
and sodium citrate
The combination of citric acid, potassium
citrate, and sodium citrate is used to prevent
gout or kidney stones, or metabolic acidosis
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23. Thank You
Any Questions?