Diuretics

diuretics, antidiuretics

1. DIURETICS

2. •Diuretics are the drugs that increase the rate
of urine flow. Clinically useful diuretics also
increase the rate of excretion of Na
+
(Natriuresis)
and accompanying ion Cl
-
.
•NaCl in the body is the major determinant of
extracellular fluid (ECF) volume, and most clinical
applications of diuretics are directed toward
reducing extracellular fluid volume by decreasing
total body NaCl content.
•Increase in sodium excretion by diuretics are
used to adjust volume of body fluids in clinical
conditions like hypertension, heart failure, renal
failure, nephrotic syndrome & cirrhosis.

3. OVERVIEW OF NEPHRON FUNCTION
The basic urine forming unit of kidney is nephron.
Each human kidney is composed of approximately one
million nephrons.
The kidney filters large quantities of plasma, reabsorb
substances that the body must conserve, and leave behind
substances that must be eliminated.
The two kidneys in humans produce together
approximately 120 ml of fluid, yet only 1 ml/min of urine is
produced per day.
 Greater than 99% of the glomerular ultrafiltrate is
reabsorbed: Just 1% decrease in tubular reabsorption can
double urine formation.
The kidneys consume 7% of total-body oxygen intake &
kidneys make up only 0.5% of body weight.

5. Classification of Diuretics
1. High efficacy diuretics/Loop Diuretics (Inhibitors of Na
+
K
+
2Cl
-

cotransport): Frusemide, Bumetanide, Torasemide,
Ethacrynic acid
2. Medium efficacy diuretics (Inhibitors of Na
+
Cl
-
symport)
a. Thiazides: Chlorthiazide, Hydrochlorthiazide, Benzthiazide
b. Thiazide like: Chlorthalidone, Metolazone, Xipamide
3. Weak or adjunct diuretics
a. Carbonic anhydrase inhibitors: Acetazolamide
b. K
+
sparing diuretics
i. Inhibitors of renal epithelial Na+ channel: Triamtrene,
Amiloride
ii. Aldosterone antagonist: Spironolactone
c. Osmotic diuretics: Mannitol, Glycerol, Isosorbide

7. •High ceiling (Loop) Diuretics: Frusemide,
Bumetanide, Torsemide, Ethacrynic acid
•MOA: Inhibits the NA
+
K
+
2CL
-
COTRANSPORT in thick ascending
loop of Henle. It also inhibits Ca
++
& Mg
++
reabsorption. It
increases the urinary excretion of K
+
& uric acid.
•Indications:
Edema (Cardiac, Hepatic, Renal)
Acute Pulmonary edema
Cerebral edema
Hypertension
Chronic congestive heart failure
Along with blood transfusion to avoid volume overload
Hypercalcemia

10. •Adverse effects:
#Hypotension #Hypokalemia #Hyponatremia
#Hypomagnesemia #Hypocalcemia #Circulatory
collapse #Hepatic encephalopathy #GI
disturbances
•Contraindications:
•anuria, liver cirrhosis, together with lithium
Nursing Care:
•Check for dehydration & electrolyte imbalance to
avoid circulatory collapse.
•Administer drug in morning & afternoon to avoid
nocturia
•Encourage potassium containing diet

11. •Medium efficacy diuretics
•Thiazides: Chlorthiazide, Hydrochlorthiazide,
Benzthiazide, Hydroflumethiazide
•MOA: Inhibits NaCl reabsorption in Distal tubule by
binding & blocking NA
+
CL
-
SYMPORTER from
luminal side.
•It increases excretion of NaCl, water & other
electrolytes.
•Thiazide like diuretics have same pharmacological
activity like thiazides but are not thiazides. E.g:
Chlorthalidone, Metolazone, Xipamide,
Indapamide

14. •Indications:
•Edema associated with heart
•Hypertension
•Diabetes insipidus
•Hypercalciuria
•Adverse effects:
#Hypotension #Hypokalemia #Hyponatremia
#Hypochloremia #Hypomagnesemia
#Hypercalcemia #Hyperuricemia
•Contraindications:
•Renal impairment, anuria, hyperuricemia,
hypercalcemia

15. •Carbonic Anhydrase Inhibitors: ACETAZOLAMIDE
•MOA: Inhibits the formation of H2CO3 &
decomposition of H2CO3 to H
+
& HCO3
-
. Hence
there is decrease in ability to exchange H
+
for Na
+

& diuresis occurs.
•Inhibits the reabsorption of Na
+
, NaHCO3 & causes
metabolic acidosis.
•Carbonic anhydrase is present in renal tubular
cell, ciliary of eye and other parts.
•In ciliary of eye acetazolamide causes decreased
formation of aqueous humor and lowers
intraocular pressure (iop). It is indicated for
glaucoma.

17. •Indications:
•Glaucoma
•To alkalinize Urine
•Epilepsy
•Acute mountain sickness
•Premenstrual edema
•Adverse Effects:
#Acidosis # Hypokalemia #Paresthesia #Renal stone
# Drowsiness #Fatigue # Hypersensitivity
•Contraindications: In Liver disease may lead to
hepatic coma, In COPD may cause acidosis

18. •K+ Sparing Diuretics
•Inhibitors of Renal Epithelium Na+ Channel:
Triamtrene, Amiloride
•MOA: Causes NaCl excretion without loss of
Potassium by inhibiting sodium channel.
•Aldosterone Antagonist: Spironolactone
•MOA: Binds with mineralocorticoid receptor (MR)
& inhibits action of aldosterone.
•It causes increase in excretion of salt & water
without loss of Potassium.

20. •Indications:
•Edema
•Hypertension
•CHF (Congestive Heart Failure)
•Together with other diuretics to counter K
+
loss
•Adverse Effects:
#Hyperkalemia #Acidosis #Epigastric distress
#Gynecomastia #Menstrual irregularities
•Contraindication: renal failure, anuria,
Addison’s disease, Pregnancy, Lactation

21. •Osmotic diuretics: Mannitol, Glycerol, Isosorbide
•MOA: Increases the osmolarity of the renal tubular
fluid and prevents reabsorption of water &
electrolytes.
•Osmotic effect of mannitol causes water to be
drawn from cells to extracellular space, increases
flow to kidney & increases urine output.
•Indications:
•Oliguria
•Acute renal failure
•Cerebral edema
•Reduction of intraocular pressure (iop)

22. •Mannitol is given i.v only as 10-20% solution.
•Glycerol & Isosorbide can be given orally.
•Adverse effects:
#hyponatremia #acidosis #thirst #chest pain
#expansion of ECF volume #inflammation &
thrombophlebitis if extravasation occurs
•Contraindications: anuria, cranial bleeding,
congestive heart failure, dehydration

23. Classification of diuretics
According to the site of Action
1) Site –I ( Proximal convoluted tubule) acting drugs :
–Osmotic diuretics: mannitol, isosorbide, glycerol
–Carbonic anhydrase inhibitors : acetazolamide
2) Site-II (Ascending limb of loop of Henle) acting drugs:
–Furosemide , bumetanide, ethacrynic acid
3) Site –III ( Distal convoluted tubule )acting drugs :
–Thiazides: chlorothiazide, hydrochlorthiazide,
benzthiazide
–Thiazide like: chlorthalidone , metolazone ,
Xipamide , Indapamide
4) Site –IV ( Collecting Duct) :
–K
+
sparing diuretics: spironolactone, triamterene,
amiloride

24. Drug Dose
Frusemide 40mg 0ral; 10mg/ml inj
Hydrochlorthiazide50mg oral
Spironolactone25mg, 100mg oral
Mannitol 10% 20% inj

25. •Urinary antiseptics
•Urinary antiseptics are the drugs that have
antibacterial activity in the urine but have little or
no systemic antibacterial effects
•Their usefulness is limited to lower urinary tract
infections
•Nitrofuranoin
•Nalidixic acid
•Methenamine
•Trimethoprim

26. •NALIDIXIC ACID
•Bactericidal to most of the Gram –ve bacteria that
causes UTI such as E.Coli, Proteus, Kliebsella.
•MOA: Inhibit the replication of bacterial by
interfering with the action of DNA gyrase during
bacterial growth and development.
•Indications:
•Against Gram –ve bacteria causing UTI
•Recurrent cases
Dose 1g QID for 7 days

27. •Adverse effects: GI upset, rashes, headache ,
drowsiness , vertigo , visual disturbances ,
seizures (children), hemolysis in G-6DP deficient
patient
•Contraindications: infants, should not be used
concurrently with nitrofurantoin, G-6PD deficient
patients

28. •NITROFURANTOIN
•Bacteriostatic against Gram +ve & Gram –ve
bacteria such as E.coli, Kliebsella.
•MOA: The drug works by damaging bacterial DNA,
since its reduced form is highly reactive.
•Dose: 50-100mg QID oral
•Indications:
•Uncomplicated Lower urinary tract infection
•Supportive long term therapy
•Long term prophylaxis
•Following catheterization, instrumentation, in
women with recurrent cystitis

29. •Adverse Effects
•Gastrointestinal Intolerance: Nausea, epigastric
pain, diarrhea, discoloration of urine (brown)
•-Hypersensitivity: fever, chills
•Peripheral neuritis, other neurological effects
with long term use
•-Hematologic disorders: leukopenia,
granulocytopenia, Hemolytic anemia in G6PD
deficient patients
•-Liver damage, pulmonary reaction with fibrosis
on chronic use
•Contraindication
•Renal impairment, pregnancy and neonates.

30. •Antidiuretics are the drugs that reduce urine
volume without affecting salt excretion.
•Used in Diabetes insipidus
1. Antidiuretic hormones (Vasopressin), Desmopressin,
Lypressin, Terlipressin
2. Thiazides, Amilorides
3. Chlorpropamide, Carbamazepine
•MOA: Increases water permeability & constrict blood
vessels
•Indications:
•Neurogenic Diabetes Insipidus
•Bedwetting in children & nocturia in adults
•Haemoplilia
•Bleeding Oesophageal varices