DIURETIC DRUGS

IHJAS HABEEB M
st
1 Year M.
Pharm
Dept. of
Pharmacology
Srinivas collage of
CONENTS:
• Introduction
• Classification of drugs
• Mechanism of action
• Pharmacokinetics
• Adverse drug reaction
• Uses
• References
DIURETICS:
• A diuretics is defined as a chemical that
increases the rate of urine formation.
• Diuretics are drugs which causes a net loss of
Na+ and water in urine.
• The primary action of most diuretics is the
direct inhibition of Na+ transport at one or
more of the four major anatomical sites along
the nephron where Na+ reabsorption takes
place.
• Diuretics are also known as water pills.
• Diuretics are used to treat heart failure, liver
cirrhosis, hypertension, edema, and certain
kidney diseases.
• The antihypertensive action of some diuretics
are independent of their diuretic effect.
•
CLASSIFICATION:

1.High ceiling (Loop) diuretics:

Mechanism of action
• Loop diuretics bind to the luminal side of
Na+/K+/2Cl- cotransporter and block its
function.
• There is an increased excretion of Na+ and Cl-.
• The tubular fluid reaching the DCT contains
large amount of Na+
• They also increase the excretion of Ca2+ and
mg2+ but excretion of uric acid is decreased.
PHARMACOKINETICS:
• Orally absorbed
• Bioavailability is about 60%
• Lipid solubility is low but highly bound with
plasma proteins.
• Conjugated with glucuronic acid
• Plasma half life is 1-2 Hrs
 USES
• Edema
• Acute pulmonary edema
• Cerebral edema
• Hypertension
• hyperkalaemia

Adverse effects
• Hypokalaemia
• hyponatraemia
• hyperglycaemia
• Hyperuricaemia
THIAZIDE AND RELATED
DIURETICS:
• Chlorothiazides was synthesized as a CAse
inhibitors variant which produces urine .
• Primary site of action is cortical diluting
segment of the early DT.
• They inhibit Na-Cl symport.
• They do not affect corticomedullary osmotic
gradient .
• They have some additional CAse inhibitory
activity.
Mechanism of action
Thiazides inhibit the Na+/Cl- symport in early
distal tubule and increase Na+ and Cl- excretion.
Some of the thiazides also have weak carbonic
anhydrase inhibitory action and increase HCO3
loss.
The tubular fluid in DCT contains more Na+.
Hence, there is increased exchange of Na+/K+
which results in K+ loss.
Therefore , there is net loss of Na+, K+, Cl-, HCO3-
in the urine.
Thiazides decrease Ca2+ excretion.

PHARMACOKINETICS:
• All thiazides and related drugs are well
absorbed orally.
• Their action starts within 1 hour, but the
duration varies from 6–48 hours.
• The more lipid-soluble agents have larger
volumes of distribution (some are also bound
in tissues), lower rates of renal clearance and
are longer acting.
 • The protein binding is also variable.
• Tubular reabsorption depends on
lipid solubility: the more lipid soluble
ones are highly reabsorbed—
prolonging duration of action.
• The elimination t½ of
hydrochlorothiazide is 3–6 hours, but
action persists longer (6–12 hours).
USES:
• Edema
• Hypertension
• Diabetes insipidus
• hypercalciuria
Adverse effects:
Hypokalaemia
Hypercalcaemia
Hyperglycaemia
Hyperlipidaemia
Hyperuricaemia
hypersensitivity
CARBONIC ANHYDRASE DIURETICS:
• Carbonic anhydrase (CAse) is an enzyme which
catalyses the reversible reaction H2O + CO2
H2CO3. Carbonic acid spontaneously ionizes
H2CO3 H+ + HCO3¯.
• Carbonic anhydrase thus functions in CO2 and
HCO3¯transport and in H+ ion secretion.
• The enzyme is present in renal tubular cell
(especially PT) gastric mucosa, exocrine pancreas,
ciliary body of eye, brain and RBC.

ACETAZOLAMIDE:
• It is a sulphonamide derivative which
noncompetitively but reversibly inhibits
CAse (type II) resulting in slowing of
hydration of CO2 decreased availability of
H+ to exchange with luminal Na+ through
the Na+-H+ antiporter.
• Inhibition of brush border CAse (type IV)
retards dehydration of H2CO3 in the tubular
fluid so that less CO2 diffuses back into the
cells.
• The net effect is inhibition of
HCO3¯reabsorption in PT.
PHARMACOKINETICS:
• Acetazolamide is well absorbed orally and
excreted unchanged in urine.
• Action of a single dose lasts 8–12 hours.
 USES:
• Because of self-limiting action, production of
acidosis and hypokalaemia, acetazolamide is
not used as diuretic. Its current clinical uses
are:
• 1. Glaucoma: as adjuvant to other ocular
hypotensives.
• 2. To alkalinise urine: for urinary tract
infection or to promote excretion of certain
acidic drugs.
• 3. Epilepsy: as adjuvant in absence seizures
when primary drugs are not fully effective.
ADVERSE EFFECTS:
• Acidosis, hypokalaemia, drowsiness, fatigue,
abdominal discomfort.
• Hypersensitivity reactions—fever, rashes.
• Bone marrow depression is rare but serious.
• Acidosis is more likely to occur in patients of
COPD.
POTASSIUM SPARING
DIURETICS:
 Aldosterone antagonist:
 Spironolactone:
• It is a steroid, chemically related to the
mineralocorticoid aldosterone.
• The AIPs(aldosterone-induced proteins)
promote Na+ reabsorption by a number of
mechanisms and K+ secretion.
• Spironolactone acts from the interstitial side of
the tubular cell, combines with MR and
inhibits the formation of AIPs in a competitive
manner.
 • It has no effect on Na+ and K+
transport in the absence of
aldosterone, while under normal
circumstances, it increases Na+ and
decreases K+ excretion.

PHARMACOKINETICS:
• The oral bioavailability of spironolactone
from micro fine powder tablet is 75%.
• It is highly bound to plasma proteins and
completely metabolized in liver.
• The half life of spironolactone is 1-2 hours.
USES:
Spironolactone is a weak diuretic in its own r
combination with other more efficacious diuretics.
1. To counteract K+ loss due to thiazide and loop
2. Edema
3. Hypertension
4. CHF

ADVERSE EFFECTS:
• The side effects are drowsiness, ataxia, mental
confusion, epigastric distress and loose
motions.
• Spironolactone interacts with progestin and
androgen receptors as well.
Osmotic diuretics
• Osmotic diuretics are pharmacologically
inert substances (e.g. mannitol) that
are filtered in the glomerulus but
not reabsorbed by the nephron.
• To cause a diuresis, they must
constitute an appreciable fraction of
the osmolarity of tubular fluid.
• These include
 Mannitol
 Isosorbide

Pharmacokinetics :
• Administered i.v(mannitol)
• It is neither metabolised in the body
nor reabsorbed from the renal tubules.
Mechanism of action:
• Osmotic diuretics draw water from
tissues by osmotic action.
• This results in excretion of water and
electrolyes.
Therapeutic uses:
• Used to increase water excretion in
preference to sodium excretion (acute sodium
retention)
• Maintain urine volume and to prevent anuria
that might result from large pigment load to
the kidney
• Reduction of Intracranial pressure in
neurologic conditions
• Reduction of Intraocular pressure before
ophthalmologic procedures

Adverse effects:
Extra cellular volume expansion ---- complicate
heart failure / pulmonary edema
Headache, nausea, vomiting – common complaint
Dehydration hyperkalemia
Osmotic extraction of water from cells, leading to
Hyponatremia
REFERENCE:
• Tripathi KD ; Essentials of Medical
Pharmacology; 7th Edition; JAYPEE BROTHERS
MEDICAL PUBLISHERS (P) LTD; New Delhi,
London, Philadelphia, Panama.pp:(579-590).