Drugs Acting on the Kidney 2 Flashcards
Give an example of an osmotic diuretic
Mannitol
Which properties of osmotic diuretics allow them to initiate a diuresis?
Small molecular size - Easily filtered
Not reabsorbed - Increase filtrate osmolarity
How do osmotic diuretics affect electrolyte reabsorption?
Decrease it
(filtrate is more diluted)
What are the side effects of osmotic diuretics?
Transient expansion of blood volume
Hyponatraemia
Why are carbonic anhydrase inhibitors redundant as diuretics?
Weak and self limiting effect
Why do carbonic anhydrase inhibitors cause a metabolic acidosis?
The is an increase in the excretion of bicarbonate (along with sodium, potassium and water)
What is the main direct action of vasopressin?
Insertion of aquaporins into the apical membrane of the collecting tubule
What are the two type of diabetes insipidus?
Neurogenic
Nephrogenic
What causes neurogenic diabetes insipidus?
Lack of vasopressin excretion from the posterior pituitary
How can neurogenic DI be treated?
Demopressin (synthetic vasopressin with only V2 selectivity)
What does activation of the V1 vasopressin receptor do?
Vasoconstriction of circulation and in the kidneys
What does activation of the V2 vasopressin receptor do?
Insertion of aquaporins into the apical membrane of the collecting duct cells
How do the following substances affect vasopressin?
a) Ethanol
b) Nicotine
a) Ethanol - Inhibits (so more water is lost)
b) Nicotine - Enhances (so less water is lost)
What causes nephrogenic DI?
Usually recessive and X-linked mutations in V2 receptor gene (AVPR2)
Why are the Vaptans called “aquaretics”?
They do not cause loss of electrolytes - only water
How do the Vaptans function?
Competitive antagonists of all/some vasopressin receptors
By blocking V1, vasoconstriction occurs
By blocking V2 aquaporin 2 channels are not recruited into the apical membrane
Give an example of a Vaptan
Tolvaptan
Where does the reabsorption of glucose take place in the kidneys?
Proximal tubule
Which receptors are responsible for glucose reabsorption?
SGLT2
SGLT1
At which blood glucose level will glucose begin appearing in the urine and what is the cause of this?
>11mmol/l
Reabsorptive mechanisms are overloaded
Under normal conditions, what percentage of glucos eis each of the following channel types responsible for reabsorbing?
SGLT2 - 90% (occurs first in the tubule)
SGLT1 - 10% (occurs second when most of the work is done)
How do both SGLT channels transport glucose into the luminal cells?
Coupled with sodium against a concentration gradient
For which reason can sodium be continually pumped into the luminal cells with glucose?
Na+/K+ATPase on the basolateral membrane pumps sodium out of the cell maintain a sodium gradient into the cell at the apical membrane
How do the two SGLT transporters differ in stoichiometry and also affinity for glucose?
SGLT2 - 1:1 (Na:glucose), high absorptive capacity and low affinity for glucose
SGLT1 - 2:1 (Na:glucose), low absorptive capacity and high affinity for glucose
What is Familial Renal Glucosuria?
A familial condition in which there is an inherited mutation in the SGLT2 gene resulting in a dysfunctional protein
Patients usually have no symptoms, yet a persistant glucosuria
Which SGLT receptor is targeted for therapeutic blockade and why?
SGLT2
It is responsible for reabsorbing more glucose so its blockade results in higher glucose loss
Give examples of SGLT2 inhibitors
Empagliflozin
Dapagliflozin
How are prostaglandins formed?
From arachidonic acid by cyclo-oxygenase enzymes (COX1 and 2)
What are the major prostaglandins synthesised in the kidney?
PGE2 - medullary formation
PGI2 (prostacylin) - glomerular formation
What do prostaglandins do?
Vasodilators
Natriuretic (causes sodium excretion at kidneys)
Synthesised in response to ischaemia
Upregulate angiotensin II, ADH and bradykinin
How do prostaglandins inpact GFR?
Direct vasodilator effect on afferent arteriole
Releasing renin and indirectly increasing angiotensin II which vasoconstricts the efferent arteriole
Both factors increase filtration pressure
Why should NSAIDs be avoided in renal failure?
They inhibit COX activity and lower prostaglandin concentration
This lowers GFR due to lack of prostaglandins
What is the action of allopurinol?
Inhibition of urate synthesis
