2: Drugs acting on the kidney 3 Flashcards
Which diuretic acts on the proximal tubule to inhibit water reabsorption?
Mannitol
Increases osmolarity of filtrate, so less water enters interstitium by osmosis
How is mannitol administered?
IV
How does mannitol enter the filtrate?
Filtered by glomeruli
How does mannitol decrease
a) water
b) sodium reabsorption?
a) Increases omsolarity of filtrate, so less water wants to pass into the interstitium of the proximal tubules
b) Filtrate is more dilute because there’s more water, so Na+ reabsorption decreases
What is mannitol used to treat?
Increased intracranial pressure (cerebral oedema, papilloedema)
Increased intraocular pressure (glaucoma)
What are two side effects of mannitol?
Hyponatraemia (inc. blood volume, so diluted)
Hypervolaemia
What complication of diabetes causes osmotic diuresis?
Why?
Hyperglycaemia
All the SGLT2 channels are saturated
So less Na+ reabsorbed
So less H2O reabsorbed
Osmotic diuresis
What is an example of a carbonic anhydrase inhibitor?
Acetazolamide
What is a renal effect of carbonic anhydrase inhibitors?
Stop carbonic anhydrase from converting H+ and HCO3- to carbonic acid
So BICARBONATE is excreted
Causing metabolic acidosis
Which eye condition is carbonic anhydrase inhibitors used to treat?
Glaucoma
Inhibits secretion of aqueous humour, reducing intraocular pressure
Where is aldosterone secreted from?
What does it do?
Adrenal cortex
Increases Na+ reabsorption and K+ secretion from the distal tubules and collecting ducts
Where is ADH secreted from?
What does it do?
Posterior pituitary gland
Increases water reabsorption from collecting ducts
Which receptor does ADH bind to?
V2 receptors
What is the problem in
a) neurogenic
b) nephrogenic
diabetes insipidus?
a) Lack of ADH secretion from posterior pituitary
b) Resistance of V2 receptors to ADH
What causes nephrogenic diabetes insipidus?
Resistance of V2 receptor to ADH binding
Which gene mutates to cause nephrogenic diabetes insipidus?
AVPR2
How is neurogenic diabetes insipidus treated?
Desmopressin
Why does ethanol cause increased diuresis?
Alcohol inhibits ADH
Why does smoking cause reduced diuresis?
Nicotine stimulates ADH
What type of receptor is V2?
G-protein coupled receptor
activates adenyl cyclase, then cAMP etc.
What change in the apical membrane does activation of V2 receptors cause?
Increased expression of aquaporins
Which drugs block V2 receptors?
How do they affect
a) water reabsorption
b) Na+ reabsorption?
Vaptans
Block V2 receptors, so less water is reabsorbed
Same amount of Na+ is reabsorbed, but smaller BV, so HYPERNATRAEMIA
What is an example of a vaptan which is used to treat SIADH and ADPKD?
Tolvaptan
Which transporters are found in the proximal tubules and can be targeted by -flozins?
SGLT2
Which sodium-glucose transporters are found in the
a) early proximal
b) late proximal
tubules?
a) SGLT2
b) SGLT1
How does SGLT work?
Transports glucose INTO cells, against a concentration gradient, by coupling it to Na+ transport down a concentration gradient
Which SGLT channels have
a) a low affinity and high capacity
b) a high affinity and low capacity?
Why is this useful?
a) SGLT2 (proximal)
b) SGLT1 (distal)
If SGLT2 is overloaded with glucose, SGLT1 picks up the rest
What renal symptom do SGLT2 inhibitors cause?
Glycosuria
sugary urine
Which drugs are used to inhibit SGLT2 inhibitors in the treatment of diabetes?
-flozins
e.g empagliflozin
What are the effects on SGLT2 inhibitors?
Reduces HbA1c
Weight loss
Given that they cause glycosuria, what is a side effect of SGLT2 inhibitors?
UTI
Which acid is metabolised by enzymes to form prostaglandins?
Arachidonic acid
Which enzymes metabolise arachidonic acid to form prostaglandins?
COX1 and COX2
What do prostaglandins cause in the kidney?
1. Vasodilation of the afferent arteriole (directly)
2. Vasoconstriction of the efferent arteriole (by stimulating RENIN release)
Help to maintain vascular tone of kidneys
What property of the kidney do prostaglandins have a large effect on?
GFR
How do prostaglandins increase GFR?
1. Prostaglandins DILATE afferent arteriole, increasing RBF
2. Also stimulate secretion of renin, causing Angiotensin II to CONSTRICT efferent arteriole, increasing filtration pressure
What may NSAIDs cause in patients with kidney problems?
Why?
Which other drugs may contribute to this?
Acute renal failure
Inhibit COX1 and COX2, inhibiting prostaglandin production
Renal vascular tone disrupted, decreased renal blood flow causes ischaemic nephropathy > AKI
ACE inhibitors, ARBs, diuretics
