An antidiuretic is a substance that helps to control fluid balance in a living body by reducing urination, opposing diuresis.
Antidiuretics: Drug List
Table of Contents
Antidiuretic Hormone (ADH, Vasopressin)
Desmopressin, Lypressin, Terlipressin
Indomethacin, Chlorpropamide, Carbamazepine
Antidiuretic Hormone (ADH)
ADH is a hormone (protein) secreted by the posterior pituitary (neurohypophysis). Rate of ADH Release controlled by:
- Osmoreceptors present in the hypothalamus.
- Volume receptors present in the left atrium, ventricles, and pulmonary veins.
- ADH and Desmopressin are ADH Agonists.
- Secretion of ADH increase in response to:
- Plasma osmolarity
- Hypovolemia, hypotension (bleeding, dehydration)
- Demeclocycline and conivaptan are ADH antagonists
- Lithium has an ADH antagonist effect but is never used for this purpose.
- At all sites except for sites of V2 (i.e. Collecting Duct cells).
- Further classified as V1a and V1b.
V1 (a) Vascular smooth muscles (including that of vasa recta in the renal medulla), uterine, visceral smooth muscles, interstitial cells in the renal medulla, cortical CD cells, adipose tissue, brain, platelets, liver, etc.
V1 (b) Anterior pituitary, certain areas in the brain and pancreas.
V2 Receptors: More sensitive:
- Collecting Duct Principal cells in Kidney: Regulates their water permeability.
- Also present in AscLH cells: Activates Na+ K + 2Cl cotransporter.
- Endothelium: Vasodilator.
ADH: Action on Various Organs
- Kidneys: Acts on CD principal cells—- renders them water-permeable — water absorbed—- concentrated urine (equilibrating with hyperosmolar medulla) passed.
- Blood Vessels: Constricts through V1 receptors: raises blood pressure.
Dilates through V2 receptors: endothelium-dependent NO production.
- GIT: Increased peristalsis: evacuation and expulsion of gases.
- Uterus: Contracted by acting on oxytocin receptors.
- Central Nervous System: Endogenous AVP may be involved in the regulation of temperature, learning of tasks.
- Others: Induces platelet aggregation, hepatic glycogenolysis. Release of factor VIII and von Willebrand’s factor from vascular endothelium: V2 mediated.
Mechanism of Action:
- Works in ascending limb of Henle’s loop and collecting ducts.
- Two kinds of receptors:
- V1: Vascular smooth muscle − vasoconstriction.
- V2: Kidney − increase water permeability of tubular epithelium − water reabsorption.
- ADH facilitates water reabsorption from the collecting tubule by activation of V2 receptors (coupled to GS, stimulate AC) to increase cAMP.
- Cause insertion of additional aquaporin AQP2 water channels into the luminal membrane in this part of the tubule.
Clinical uses of ADH Agonists:
- ADH and desmopressin reduce urine volume and concentrate it, which are useful in Pituitary Diabetes Insipidus (DI).
- Gastrointestinal bleeding due to portal hypertension.
- Conivaptan is an ADH inhibitor at V1a and V2 receptors.
- Demeclocycline and Li inhibit the action of ADH at some point distal to the generation of cAMP and presumably the insertion of water channels into the membrane.
Clinical uses of ADH Antagonists:
- Oppose the actions of ADH and other naturally occurring peptides (certain tumors; small cell carcinoma of the lung) that act on the same V2 receptors, leads to significant water retention and dangerous hyponatremia.
- Syndrome of inappropriate ADH secretion.
- (SIADH) can be treated with demeclocycline and conivaptan.
AVP (Arginine vasopressin) Interactions:
- Lithium, demeclocycline: Partially antagonize AVP action (limiting cAMP formation).
- Used in patients with inappropriate ADH secretion.
- NSAIDs (Indomethacin): Augments AVP (increased renal PG synthesis).
- Carbamazepine, chlorpropamide: potentiates AVP action on kidney.
Based on V2 Actions:
- Diabetes Insipidus (Neurogenic).
- Bedwetting in children and nocturia in adults.
- Renal Concentration Test.
- Hemophilia, von Willebrand’s Disease.
Based on V1 Actions:
- Bleeding Esophageal Varices.
- Before abdominal radiography.
Vasopressin: Adverse Effects
- Selective drugs produce lesser side effects.
- Transient headache and flushing: frequent.
- Local Application: Nasal irritation, congestion, rhinitis, ulceration, epistaxis.
- Systemic Side effects: belching, nausea, vomiting, abdominal cramps, pallor, urge to defecate, backache. In females (uterine contraction) Fluid retention, hyponatremia.
- Paradoxical Effect.
- Furosemide: effective but less desirable: short and brisk action.
- Effective in both neurogenic as well as nephrogenic DI.
Mechanism of Action:
1. Similar to Salt Restriction:
- State of sustained electrolyte depletion.
- Glomerular filtrate completely reabsorbed iso-osmotically in PT.
- Urine passing has low solutes − presented to cortical DT − salt reabsorption decreases − less dilute urine presented to CD − same is passed out.
2. Reduces glomerular filtration rate − reduced fluid load on tubules.
- Decreases renal prostaglandin synthesis reduced polyuria in nephrogenic DI.
- Combined with thiazide +/- amiloride.
- Long-acting sulfonylurea oral hypoglycaemics.
- Effective in neurogenic DI: sensitizes kidney to ADH.
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