Drugs Acting on the Kidney 2 Flashcards

(33 cards)

1
Q

Give an example of an osmotic diuretic

A

Mannitol

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2
Q

Which properties of osmotic diuretics allow them to initiate a diuresis?

A

Small molecular size - Easily filtered

Not reabsorbed - Increase filtrate osmolarity

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3
Q

How do osmotic diuretics affect electrolyte reabsorption?

A

Decrease it

(filtrate is more diluted)

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4
Q

What are the side effects of osmotic diuretics?

A

Transient expansion of blood volume

Hyponatraemia

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5
Q

Why are carbonic anhydrase inhibitors redundant as diuretics?

A

Weak and self limiting effect

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6
Q

Why do carbonic anhydrase inhibitors cause a metabolic acidosis?

A

The is an increase in the excretion of bicarbonate (along with sodium, potassium and water)

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7
Q

What is the main direct action of vasopressin?

A

Insertion of aquaporins into the apical membrane of the collecting tubule

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8
Q

What are the two type of diabetes insipidus?

A

Neurogenic

Nephrogenic

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9
Q

What causes neurogenic diabetes insipidus?

A

Lack of vasopressin excretion from the posterior pituitary

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10
Q

How can neurogenic DI be treated?

A

Demopressin (synthetic vasopressin with only V2 selectivity)

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11
Q

What does activation of the V1 vasopressin receptor do?

A

Vasoconstriction of circulation and in the kidneys

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12
Q

What does activation of the V2 vasopressin receptor do?

A

Insertion of aquaporins into the apical membrane of the collecting duct cells

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13
Q

How do the following substances affect vasopressin?

a) Ethanol
b) Nicotine

A

a) Ethanol - Inhibits (so more water is lost)
b) Nicotine - Enhances (so less water is lost)

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14
Q

What causes nephrogenic DI?

A

Usually recessive and X-linked mutations in V2 receptor gene (AVPR2)

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15
Q

Why are the Vaptans called “aquaretics”?

A

They do not cause loss of electrolytes - only water

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16
Q

How do the Vaptans function?

A

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

17
Q

Give an example of a Vaptan

18
Q

Where does the reabsorption of glucose take place in the kidneys?

A

Proximal tubule

19
Q

Which receptors are responsible for glucose reabsorption?

20
Q

At which blood glucose level will glucose begin appearing in the urine and what is the cause of this?

A

>11mmol/l

Reabsorptive mechanisms are overloaded

21
Q

Under normal conditions, what percentage of glucos eis each of the following channel types responsible for reabsorbing?

A

SGLT2 - 90% (occurs first in the tubule)

SGLT1 - 10% (occurs second when most of the work is done)

22
Q

How do both SGLT channels transport glucose into the luminal cells?

A

Coupled with sodium against a concentration gradient

23
Q

For which reason can sodium be continually pumped into the luminal cells with glucose?

A

Na+/K+ATPase on the basolateral membrane pumps sodium out of the cell maintain a sodium gradient into the cell at the apical membrane

24
Q

How do the two SGLT transporters differ in stoichiometry and also affinity for glucose?

A

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

25
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
26
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
27
Give examples of SGLT2 inhibitors
Empagliflozin Dapagliflozin
28
How are prostaglandins formed?
From arachidonic acid by cyclo-oxygenase enzymes (COX1 and 2)
29
What are the major prostaglandins synthesised in the kidney?
PGE2 - medullary formation PGI2 (prostacylin) - glomerular formation
30
What do prostaglandins do?
Vasodilators Natriuretic (causes sodium excretion at kidneys) Synthesised in response to ischaemia Upregulate angiotensin II, ADH and bradykinin
31
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
32
Why should NSAIDs be avoided in renal failure?
They inhibit COX activity and lower prostaglandin concentration This lowers GFR due to lack of prostaglandins
33
What is the action of allopurinol?
Inhibition of urate synthesis