ADH disorders

Question 1

what is diabetes inspidius

Answer 1

○ Rare condition
○ Characterised by excessive urination and often feeling thirsty
○ Not related to diabetes mellitus

Question 2

main symptoms of diabetes insidious

Answer 2

§ extreme thirst (polydipsia)
§ excessive urination and at night (polyuria)

Question 3

cause of diabetes insipidus

Answer 3

○ Problems with a hormone called vasopressin (AVP), aka ADH

Question 4

what is role of ADH

Answer 4

○ Plays a key role in regulating the amount of fluid in the body
○ Produced by nerve cells in the hypothalamus
○ AVP from the hypothalamus travels to pituitary gland, where it is stored until needed
○ Pituitary gland releases AVP when fluid in the body is low
○ Helps retain water in the body by reducing amount of water lost through kidneys, making the kidneys produce more concentrated urine

Question 5

what happens in diabetes insipidus re ADH

Answer 5

lack of ADH = kidneys cannot make enough concentrated urine = too much water passes from the body

Question 6

nephrogenic diabetes inspipidus

Answer 6

○ Rare cases: kidneys do not respond to ADH, causing nephrogenic diabetes insipidus

Question 7

2 types of diabetes insipidious

Answer 7

cranial
nephrogenic

Question 8

what is cranial DI

Answer 8

not enough ADH in body to regulate urine production
§ Most common type
§ May be caused by damage to hypothalamus or pituitary gland e.g. post infection, post op, brain tumour, head injury

Question 9

what is nephrogenic DI

Answer 9

§ Sufficient ADH in body but kidneys do not respond to it
§ May be caused by kidney damage or may be inherited
May be caused by some medications - particularly lithium

Question 10

which medicine is known to cause nephrogenic DI

Answer 10

lithium

Question 11

use of the drug desmopressin

Answer 11

analogue of vasopressin = desmopressin

used in the treatment of cranial DI

dose tailored to produce slight diuresis every 24h to avoid water intoxication

Question 12

when may desmopressin only be required for short period

Answer 12

only in diabetes insipidus following trauma or pituitary surgery

Question 13

which one has longer duration of action and potency - desmipressin or vasopressin

Answer 13

desmopressin

Question 14

compare desmopressin and vasopressin

Answer 14

• Desmopressin is more potent and has longer duration of action than vasopressin
• Also has no vasoconstrictor effect, unlike vasopressin - this means it will not increase BP
• Given PO or intranasally for maintenance therapy
• Given by injection in postop period or in unconscious pt

Question 15

explain use of desmopressin in differential diagnosis of DI - e.g. is it cranial or nephrogenic??

Answer 15

○ Following an IM or intranasal dose, restoration of the ability to concentrate urine after water deprivation = confirmed diagnosis of cranial diabetes insipidus
○ Failure to respond occurs in nephrogenic diabetes insipidus

Question 16

In nephrogenic and partial pituitary diabetes insipidus, benefit may be gain from the paradoxical antidiuretic effect of which drugs

Answer 16

thiazides e.g. bendro

Question 17

this AED drug may be useful sometimes in partial pituitary diabetes insidious (unlicensed)

discuss its use

Answer 17

Carbamazepine

	○ May act by sensitising the renal tubules to the action of remaining endogenous vasopressin Important safety information on the use of anti epileptic drugs and the risk of suicidal thoughts and behaviour

Question 18

Other uses of desmopressin - 3

Answer 18

• Also used to boost factor VIII conc in mild to moderate haemophilia and inn von Willebrand’s disease
  
  • Also used to test fibrinolytic response
  • May also have a role in nocturnal enuresis (bed wetting)

Question 19

other use of vasopressin infusion

Answer 19

used to control variceal bleeding in portal hypertension, before more definitive treatment and with variable results

Question 20

what is terlipressin

Answer 20

• Derivative of vasopressin with less pressor and antidiuretic activity
  Also used in a similar way to vasopressin infusion i.e. for variceal bleeding

Question 21

what is oxytocin

Answer 21

• Another posterior pituitary hormone
  Indicated in obstetrics

Question 22

name an ADH antagonist

hint it is an abx

Answer 22

• Demeclocycline HCl: can be used in treatment of hyponatraemia resulting from inappropriate secretion of ADH, if fluid restriction alone doesn’t restore sodium concentration or is not tolerable
  
  • Thought to act by directly blocking renal tubular effect of ADH

Question 23

name the other ADH antagonist (hint not the abx)

and discuss its use

Answer 23

• Tolvaptan
  ○ Vasopressin V2-receptro antagonist
  ○ Licensed for treatment of hyponatraemia secondary to syndrome of inappropriate ADH secretion
  ○ Treatment duration with tolvaptan is determined by the underlying disease and its treatment
  ○ Rapid correction of hyponatraemia during tolvaptan therapy can cause osmotic demyelination
  § Leads to serious neurological events
  § Close monitoring of serum sodium conc and fluid balance essential!!

Question 24

interactions with desmopressin are to do with this electrolyte imbalance

Answer 24

hyponatreaemia

e..g diuretics antipsychotics antidepressants NSAIDs AEDs