Renal Pharm: Diabetes Insipidus

Question 1

Define Diabetes Insipidus

Answer 1

Excretion of large volume of hypotonic, insipid (tasteless) urine

Question 2

What are some signs of Diabetes Insipidus ?

Answer 2

Polydypsia , Polyuria

ADH levels lower than what can be detected within the blood (No ADN –> increased urination)

Question 3

What does ADH bind to in the collecting duct ?

Answer 3

Vassopressin II Receptor (ADH receptor)

Question 4

The V2R, when activated, leads to the increase in what intracellular molecule ?

Answer 4

cAMP (By activating Adenyly Cyclase)

Question 5

What does the binding of ADH to V2R ultimately lead to ?

Answer 5

Insertion of Aquaporin (AQ2) into the membrane of the collecting duct–> reabsorption of H20

Question 6

What is the cause of Neurogenic (Central) Diabetes Insipidus ?

Answer 6

Damage to the structure (pituitary,hypothalamus) that secreted ADH in the body.

Question 7

What is the treatment for Neurogenic DI ?

Answer 7

Desmopressin (synthetic analogue of ADH (vasopressin))

Question 8

Selectivity for which receptor allows for desmopressins prolonged duration of action and decreased vasopressor effect ?

Answer 8

V2

Question 9

What is the overall cause of Nephrogenic DI ?

Answer 9

Inability of renal collecting duct cells to respond to ADH (Absence or damaged V2R, damaged or absent AQ2)

Question 10

What will be seen in the serum of someone with Nephrogenic DI as opposed to someone with Central DI ?

Answer 10

HIGH serum ADH (The body will continually produce this). Polydypsia and polyuria are still present.

Question 11

What are the FDA approved drugs for Nephrogenic DI ?

Answer 11

PSYCH ! There are none.

Question 12

Although, there are no FDA approved drugs for Neph. DI, Thiazide diuretics are often used. How do they work ?

Answer 12

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

Question 13

What drug is often associated with causing Nephrogenic Diabetes Insipidus ?

Answer 13

LITHIUM (Over-use)

Question 14

What drug is often given to limit the effects of Lithium induced Nephrogenic Diabetes Insipidus ?

Answer 14

Amiloride

Question 15

How does amiloride limit the effects of Lithium induced Nephrogenic Diabetes Insipidus ?

Answer 15

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.

Question 16

What are some side effects of Amiloride use ?

Answer 16

Hyperchloremia, hyperkalemia, metabolic acidosis

Question 17

What can be given to lessen the effects of hyperkalemia with concomitant use of Amiloride in treating Lithium induced Nephrogenic Diabetes Insipidus ?

Answer 17

Thiazide diuretic (K+ wasting diurectic)

Question 18

This drug is given to treat Nephrogenic Diabetes Insipidus. It works by inhibiting Cyclooxygenase II and thus reducing PGEII production. Less PGEII will lead to vasoconstriction of afferent arterioles leading to decreased GFR. This will lead to decreased Na and H20 filtration in the glomerulus leading to decreased urine flow. What is the name of this drug ?

Answer 18

Indomethacin