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

1. Water deprivation (this should stimulate normal ADH release in a normal person)
2. IM or intranasal dose of desmopression
3. If pt is able to produce concentrated urine and reduce urine output after water deprivation and admin of desmopression = cranial DI
4. Failure to respond (i.e. still producing dilute urine) = nephrogenic DI

Question 16

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

partial pituitary DI = subtype of cranial DI where the patient still produces some ADH but insufficient amounts.
complete pituitary DI = no production of ADH

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

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

less pressor activity = less effect on raising BP

Question 21

what is oxytocin

Answer 21

• Another posterior pituitary hormone
  Indicated in obstetrics

Question 22

name an ADH antagonist

hint - 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

in SIADH, too much ADH = more water reabsorbed = dilutes sodium in the blood = low sodium levels
demecleocycline blocks this and helps the kidneys get rid of excess water and thus allows sodium levels to increase to normal

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

Water reabsoption can result in dilution of sodium = hyponatraemia, even if levels in body are normal

Question 25

A patient has come into the out-patient clinic as they recently experienced urinary retention. They had their blood tests screened which showed an increase in antidiuretic hormone. Which electrolyte imbalance results would also be seen on the patient’s blood test results?

Answer 25

Increased antidiuretic hormone leads to more water being stored in the body. This then dilutes the salt concentration in the blood, resulting in hyponatraemia.

Question 26

pituitary DI aka

Answer 26

cranial

Question 27

partial diabetes inspidius is when…

Answer 27

cranial/pituitary
its when you have some ADH, but insufficient
so still have polydipsia and polyuria because there is not enough ADH to effectively control water levels in body

Question 28

If a patient has untreated DI, what electrolyte imbalance would you exepct?

Answer 28

HYPERnatraemia

This is because there is too much water loss from the body and not enough reabsorption

Body is dehydrated

Thus sodium in body rises

Question 29

How would you manage nephrogenic diabetes inspididus

Answer 29

Since nephrogenic diabetes insipidus does not respond to desmopressin, treatment typically involves using thiazide diuretics (despite the paradox of diuretic use) and managing electrolyte imbalances. It can also include increasing fluid intake to prevent dehydration.

Question 30

Desmopressin - what do you need to counsel pt on re water intake?

Answer 30

Have to ensure you are restricting fluid intake otherwise it can lead to fluid retention and/or hyponatraemia

Desmopressin increases water reabsorption in the kidneys, and without appropriate fluid restriction, this can lead to excessive water retention and dilution of sodium levels in the blood. Proper patient education about fluid intake and regular monitoring of electrolyte levels are essential components of safe desmopressin therapy.

Question 31

Desmopressin what do you need to counsel re nocturnal enuresis

Answer 31

Hyponatraemic convulsions
Patients being treated for primary nocturnal enuresis should be warned to avoid fluid overload (including during swimming) and to stop taking desmopressin during an episode of vomiting or diarrhoea (until fluid balance normal).