Pharmacology of diuretics, presented by us in 5th semester. Lippincot and Adams Pharma books are reference.

1. DIURETICS
PRESENTED TO
MAM TEHREEM
FAYYAZ

2.  PRESENTED BY
 GROUP NO. 1
1. IRFAN ADIL 24
2. HAMZA JAWAD 32
3. MUHAMMAD FAISAL 26
4. HAFIZ M. YOUSAF 06

3. DIURETICS

4. Inhibitors of renal ion transporters
that decrease the reabsorption of
Na+ at different sites in the nephron
Na+ , Cl− etc, enter the urine in
greater than normal amounts along
with water
Maintain osmotic equilibrium
Increase the volume of urine

5. CONT…
Effect varies
potassium-sparing
diuretics
2%
loop diuretics
20% the increase
in Na+ secretion
USE
Management of
abnormal fluid
retention (edema)
Treatment of
hypertension.

6. URINE FORMATION

8. Summary of Diuretic Drugs

9. Major locations of ion and water exchange in the
nephron, showing sites of action of the diuretic drugs

10. DRUGS
1. LOOP DIURETICS
2. THIAZIDES DIURETICS
3. CARBONIC ANHYDRASE INHIBITORS
4. POTASSIUM SPARING DIURETICS
5. OSMOTIC DIURETICS

11. 1- LOOP, OR HIGH-
CEILING DIURETICS

12. MECHANISM OF ACTION OF
LOOP DIURETICS
Peak diuresis much
greater than other by
inhibiting the
luminal Na/K/2Cl
symporter
The concentrations
of Na+, K+ and Cl- in
the distal tubule are
increased,
This inhibits the
water reabsorption
from the distal
tubule to give a
diuretic effect

13. Furosemide, Bumetanide and Ethacrynic
acid

14. Veterinary formulations of
Furosemide
• Oral tablets approved for use in
dogs and cats(12.5mg,50mg)
• Oral solution approved for use in
dogs(10mg/ml)
• Large animal boluses approved
for use in cattle(2g/bolus).
• Milk & slaughter with drawl
time for both oral & Injectable
fomulation for cattle is 48
hours

15. 77% bio available in dogs
Elimination half life of about 1h following
an IV dose of 5mg/kg in dogs
Due to variable oral bio availability and
rapid elimination in the dog
Absorption & Elimination of
Furosemide

16. THERAPEUTIC USE
In Small Animals
Treatment of
edema of
cardiac,
hepatic or
renal origin.
In dogs
(1-3mg/kg
every 8-24h
PO)
for chronic
use 2-5mg/kg
every 6h
IV,IM,SC)
In cats
1-2mg/kg
every 12h
Use to
establish
diuresis in
renal failure
and to promote
secretion of
other
substances,
included
elevated
electrolytes
(Ca2+ and K+)

17. Furosemide in Large
Animals
In cattle
Edema
In horses 
Edema and
exercise-
induced
pulmonary
hemorrhages
0.5-
1mg/kg
twice is
used to
treat

18. ADVERSE EFFECT AND
DRUG INTERACTION
Abnormalities
of fluid and
electrolyte
balance
Extracellular
volume depletion
and
hyponatremia 
reduced blood
pressure and
diminished organ
perfusion.
volume
depletion
in patients
with renal,
cardiac
and
hepatic
disease.

19. 2. Thiazide Diuretics
Inhibitors of Na+,Cl- Symport

20. MECHANISM OF ACTION

21. Act
mainly in
the
cortical
region of
the
ascendin-
g loop of
Henle
and the
distal
convolute
-d tubule
To decrease
the
reabsorption
of Na+,
apparently
by inhibition
of a Na+/Cl−
cotransporte
r on the
luminal
membrane
of the
tubules
They have a
lesser effect
in the
proximal
tubule ,
these drugs
increase the
concentration
of Na+ and
Cl− in the
tubular fluid

22. • Because the site of action of the thiazide
derivatives is on the luminal membrane
• These drugs must be excreted into the tubular
lumen to be effective.
• Therefore, with decreased renal function,
thiazide diuretics lose efficacy.
• The efficacy of these agents may be
diminished with concomitant use of NSAIDs,
such as indomethacin, which inhibit production
of renal prostaglandins, thereby reducing renal
blood flow.

23. ABSORPTION & ELIMINATION
Absorb
slowly and
incompletely
from the GIT.
High protein bound
are excreted renally
(Chlorothiazide &
Hydrochlorothiazide)
• Or by a
combination of
renal and biliary
routes
All drugs in this
class gain access
to the lumen of
the renal tubule
via an organic
acid secretary
pathway.

24. Toxicity, Adverse Effects,
Contraindication
K+ wasting, especially with concurrent use of
digitalis, increases the risk of cardiac arrhythmias.
Low K+ may secondary affect
conversion of pro-insulin to insulin
Enhanced Ca
reabsorption can
lead to
hypercalcemia
mild magnesuria
may cause Mg
deficiency
leading to
hyperglycemia.
Fluid and
electrolyte
disturbances.

25. CONT..
Increase in the
risk of
hyponatremia
under conditions
of increased
consumption of
hypotonic fluids.
Sensitivity to
sulfonamides
limits use of
thiazide diuretics
because of the
structural
similarity b/w
these two classes
of drugs
Patient with
severe renal
disease,
hypovolemia, or
electrolyte
disturbances are
poor candidates
for thiazide
therapy.

26. Drugs Interaction
Include decreased effects of anti-coagulatns
and insulin and increased effects of some
anesthetics, diazoxide, and vit.D
Diabetic patients are at
risk for thiazide induced
derangements of glucose
and insulin
Thiazides prolong the half
life of quinidine.
Impaired hepatic function

27. CONT…
• NSAIDs may reduce the effectiveness of
thiazide and loop diuretics by increasing
solute reabsorption at the TAL of the loop
of henle

28. Therapeutic Uses
To treat edema of cardiac, hepatic, or renal origin
Typically dosage in the dog and cats are 20-40
mg/kg every 12h (chlorothiazide) and 2-4 mg/kg
every 12h (hydrochlorothiazide)
Effects of these two drugs peak at 4h and last up
to 12h, with hydrochlorothiazide typically having
a longer duration (12h) than chlorothiazide (6-
12h)

29. Therapeutic Uses
Cattle may be treated for udder edema with
hydrochlorothiazide (125-250 mg IV or IM once
or twice daily)
Thiazides are used effectively to reduce the volume of
urine in patients with nephrogenic diabetes insipidus
Oral chlorothiazide
(not a veterinary approved
product)

30. Loop diuretics Thiazide diuretics
They inhibit Na/K/2Cl symporetr.
Acts at thick ascending loop of
henle.
These are Ca wasting drugs.
They cause heavy diuresis.
Para thyroid hormone independent
Ca absorption.
It can reabsorb 25%to 30% of Na.
They act by inhibiting Na/Cl
symporter.
Acts at distal convoluted tubule.
These are Ca retaining drugs.
They cause mild diuresis.
Para thyroid hormone dependent
Ca absorption.
It can reabsorb 8% of Na.

31. 3.CARBONIC
ANHYDRASE
INHIBITORS

32. MECHANISM OF ACTION
Inhibits carbonic anhydrase
located intracellularly and on the
apical
membrane of the proximal tubular
epithelium
The decreased ability to exchange
Na+
for H+ in the presence of
acetazolamide results in a mild
diuresis.
• [Note: Carbonic anhydrase
catalyzes the reaction of CO2
and H2O, leading to H2CO3,
which spontaneously ionizes
to H+ and HCO3 −
(bicarbonate).]

33. CONT..
The decreased ability to
exchange Na+
for H+ in the presence of
acetazolamide results in a mild
diuresis.
Additionally, HCO3
− is retained in the lumen, with marked
elevation in urinary pH.
The loss of HCO3
− causes a hyperchloremic
metabolic acidosis and decreased
diuretic efficacy
following several days of therapy.

34. Relative changes in the composition
of urine induced by Acetazolamide.

35. Pharmacokinetic:
• Limited information is available regarding
pharmacokinetics
• Acetazolamide is eliminated by kidneys.
• A dose of 22mg/kg is reported for onset
of action of 30 minutes, maximal effects
in 2-4 hours, & duration is 4-6 hours.

36. Therapeutic effects
• Inhibit production of aqueous humor.
• Reduce intraocular pressure.
• For acute glaucoma IV dose of 50mg/kg.
• Have least CVS & pulmonary side
effects.

37. CONT..
Mountain sickness:
• Acetazolamide can be used in the
prophylaxis of acute mountain sickness.
• Acetazolamide prevents weakness,
breathlessness, dizziness, nausea, and
cerebral as well as pulmonary edema
characteristic of the syndrome.

38. ➢Adverse effects :
• Disorientation & drowsiness.
• CNS depression.
• Hepatic encephalopathy.
• Respiratory acidosis.
• Metabolic acidosis.

39. 4- POTASSIUM SPARING
DIURETICS

40. MECHANISM OF ACTION
These antagonizes
aldosterone at intracellular
cytoplasmic receptor sites
rendering the spironolactone–
receptor complex inactive.
It prevents translocation of the receptor
complex into the nucleus of the target
cell,
ultimately resulting in a
failure to produce mediator
proteins that normally
stimulate the Na+/K+-
exchange sites of the
collecting tubule

41. CONT…
. Thus, a lack of mediator proteins
prevents Na+ reabsorption and,
therefore, K+ and H+ secretion
In most edematous states, blood
levels of aldosterone are high,
causing retention of Na+.
These antagonizes the activity of
aldosterone, resulting in retention
of K+ and excretion of Na+

42. Absorption and Elimination
• Administered orally
• Triamterene is 70 percent bioavailable
• Amiloride is renaly excreted
• Triamterene is converted in liver to an
active metabolite 4 hydroxy
triamterene sulphate ,which is actively
secreted into renal tubule.
• Peak onset of action of triamterene is
6-8 hour with effects persisting up to
the 12-16 hours

43. Therapeutic uses
Clinically important because of their k sparing
property in combination with with thiazide or loop
diuretics.
Both used for treatment of edema associated
with CHF , liver cirrhosis ,nephrotic syndrome ,
steroid induced edema and idiopathic edema
Relatively weak
diuretics
Dose:2-4mgkgday

44. Toxicity
CNS, gastro intestinal and hematological
side effects have also been reported
Most important side effects is
hyperkalemia
Interstitial
nephritis
Renal
stones
Hypersen-
sitivity
reactions

45. OSMOTIC DIURETICS

46. ACTION
• Hydrophilic chemical substances that are filtered
through the glomerulus, such as mannitol and urea
result in some degree of diuresis.
• Filtered substances that undergo little or no
reabsorption will cause an increase in urinary output.
• Results in a higher osmolarity of the tubular fluid and
prevents further water reabsorption, resulting in osmotic
diuresis.
• Only a small amount of additional salt may also be
excreted.

47. CONT…
• Only a small amount of additional salt may also
be excreted.
• Because osmotic diuretics are used to increase
water excretion rather than Na+ excretion, they
are not useful for treating conditions in which
Na+ retention occurs.
• They are used to maintain urine flow following
acute toxic ingestion of substances capable of
producing acute renal failure

48. USES
• They are used to maintain urine flow following
acute toxic ingestion of substances capable of
producing acute renal failure.
• Osmotic diuretics are a mainstay of treatment
for patients with increased intracranial pressure
or acute renal failure due to shock, drug
toxicities, and trauma.
• Maintaining urine flow preserves long-term
kidney function and may save the patient from
dialysis.

49. Adverse effects
• [Note: Mannitol is not absorbed when given
orally and should be given intravenously.]
• Adverse effects include extracellular water
expansion and dehydration, as well as hypo- or
hypernatremia.
• The expansion of extracellular water results because
the presence of mannitol in the extracellular fluid
extracts water from the cells and causes
hyponatremia until diuresis occurs.

50. Mannitol
• Mannitol is commonly used in small
animals but is expensive for use in adult
large animals
• Mannitol acts as a protectant against
further renal tubular damage and initiates
an osmotic diuresis
• The initial dosage is 0.25–0.5 g/kg, given
IV over 3–5 min.
• A response should be noted within 20–30
min

51. Summary of relative changes in
urinary composition induced by
diuretic drugs.