Substances that inhibit water excretion without affecting salt excretion Reduce urine output More precise term anti aquaretics Primary indication diabetes insipidus Drug classification ID: 914574
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Slide1
Anti-diuretics
Slide2What are Anti-diuretics?
Substances that inhibit water excretion without affecting salt excretion.
Reduce urine output
.
More precise term
anti-
aquaretics
Primary indication - diabetes
insipidus
Slide3Drug classification
• Anti-diuretic hormone: ADH/Vasopressin,
Desmopressin
,
Lypressin
,
Terlipressin
• Thiazide Diuretics:
amiloride
.
Miscellaneous
: indomethacin,
chlorpropamide
, carbamazepine
Slide4ADH
Synthesis: posterior pituitary secretes both ADH and oxytocin.
•
Regulation:
osmoreceptors
in hypothalamus volume receptors in left atrium, ventricles, pulmonary veins.
•
Stimulus: rise in plasma
osmolarity
contraction of ECF volume
.
Human form: 8-arginine-vasopressin.
Slide5ADH receptors
G protein coupled cell membrane receptors • Types: V1 and V2
•
V1 receptors: all except on renal CD cells,
AscLH
cells and vascular endothelium
.
• Subtypes: V1a and V1b
•
V1a: vascular, uterine, visceral smooth muscle, adipose tissue, brain • V1b: anterior pituitary, brain and pancreas.
Slide6ADH receptors
V2 receptor: more sensitive
.
location:
collecting duct in kidney: regulate water permeability
•
AscLH
cells: activate Na/K/2Cl transporter
. vascular
endothelium: vasodilator
Slide7Actions
Kidney: Acts on CD cells
,
increase the
permeability.
Water gets absorbed concentrated urine (hyperosmolar urine with same
osmolarity
of the medulla
)
Blood vessels: i. Constriction of blood vessels via v1 receptors
Raises BP
,
Prolonged exposure causes smooth muscle hypertrophy.
Slide8Actions
GIT: Increased peristalsis Evacuation and expulsion of gases • Uterus: i. Contraction due AVP acting on oxytocin receptors. ii. Increases sensitivity to oxytocin
.
CNS:
AVP doesn’t penetrate blood brain barrier
.
Acts as a peptide neurotransmitter
.
Regulation of temperature
.
Systemic circulation
.
Task learning
.
ACTH release
Slide9Other uses:
Platelet aggregation
•
Hepatic
glycogenolysis
•
Coagulation factor VIII
release
• Von
willebrand’s
factor release
Slide10Mechanism of action
V2R:
Principal cells of collecting duct: increased
aquaporins
expression leading to increased water absorption decreased urine formed
.
Increased vasopressin regulated urea transporter expression in terminal CD cells
,
increased medullary
hypertonicity
,increased
water absorption
,
decreased urine formed.
Slide11V1R:
Constricts vasa recta: diminished blood flow to inner medulla; reduces washing off effect and helps in maintaining high
osmolarity
; contributing to
antidiuresis
Slide12AVP interactions
Lithium,
demelocycline
; partially antagonise AVP action (limit CAMP formation
)
NSAIDS
(indomethacin): augments AVP {increased renal PG synthesis}
Carbamazepine,
chlorpropamide
: potentiates AVP action on kidney.
Slide13AVP uses
Based on V2 actions: i. Diabetes
insipidus
ii. Bedwetting in children iii.
Nocturia
in adults
iv
. Renal concentration test v.
Hemophilia
, von
willebrand’s
disease
Based on V1 actions: i. Bleeding
esophageal
varices
Before abdominal radiography
Slide14Adverse effects
Transient
headache
Flushing
Nasal irritation • Congestion • Belching • Nausea
Hyponatremia
and fluid retention
Slide15Thiazides
Paradoxical anti-diuretic effect in DI • Short and brisk action • Low efficacy
Valuable in renal DI as AVP is ineffective • Induce state of sustained electrolyte depletion.
Reduce GFR and fluid load
Hydrochlorothiazide 25-50mg TDS
Slide16Other antidiuretics
Amiloride
: indomethacin i. Drug of choice, reduce
polyurea
in renal DI. ii. Reduces renal PG synthesis
Chlorpropamide
: i. long acting
sulphonylurea
oral
hypoglycemic
ii. Sensitizes the kidney to ADH action.
Carbamazepine: anti-epileptic
Slide17Thank you
Slide18