Flashcards in Renal Pharm: Diabetes Insipidus Deck (18)
Define Diabetes Insipidus
Excretion of large volume of hypotonic, insipid (tasteless) urine
What are some signs of Diabetes Insipidus ?
Polydypsia , Polyuria
ADH levels lower than what can be detected within the blood (No ADN --> increased urination)
What does ADH bind to in the collecting duct ?
Vassopressin II Receptor (ADH receptor)
The V2R, when activated, leads to the increase in what intracellular molecule ?
cAMP (By activating Adenyly Cyclase)
What does the binding of ADH to V2R ultimately lead to ?
Insertion of Aquaporin (AQ2) into the membrane of the collecting duct--> reabsorption of H20
What is the cause of Neurogenic (Central) Diabetes Insipidus ?
Damage to the structure (pituitary,hypothalamus) that secreted ADH in the body.
What is the treatment for Neurogenic DI ?
Desmopressin (synthetic analogue of ADH (vasopressin))
Selectivity for which receptor allows for desmopressins prolonged duration of action and decreased vasopressor effect ?
What is the overall cause of Nephrogenic DI ?
Inability of renal collecting duct cells to respond to ADH (Absence or damaged V2R, damaged or absent AQ2)
What will be seen in the serum of someone with Nephrogenic DI as opposed to someone with Central DI ?
HIGH serum ADH (The body will continually produce this). Polydypsia and polyuria are still present.
What are the FDA approved drugs for Nephrogenic DI ?
PSYCH ! There are none.
Although, there are no FDA approved drugs for Neph. DI, Thiazide diuretics are often used. How do they work ?
Hypovolemia increases proximal tubular reabsorption of NaCl and H2O
Reduces delivery of fluid to downstream segments
Reduces urine flow
The downstream effect of Thiazide causes and up-stream regulation of Na/H20 reabsorption
What drug is often associated with causing Nephrogenic Diabetes Insipidus ?
What drug is often given to limit the effects of Lithium induced Nephrogenic Diabetes Insipidus ?
How does amiloride limit the effects of Lithium induced Nephrogenic Diabetes Insipidus ?
Li+ is structurally similar to Na+ and thus often comes in to the cell by processes often meant for transport of Na+
Amiloride blocks the ENaC channel on the lumenal surface of Principal cells in the collecting duct.
This will stop the influx of Li+ into the cells.
What are some side effects of Amiloride use ?
Hyperchloremia, hyperkalemia, metabolic acidosis
What can be given to lessen the effects of hyperkalemia with concomitant use of Amiloride in treating Lithium induced Nephrogenic Diabetes Insipidus ?
Thiazide diuretic (K+ wasting diurectic)