2: Drugs acting on the kidney 3

Question 1

Which diuretic acts on the proximal tubule to inhibit water reabsorption?

Answer 1

Mannitol

Increases osmolarity of filtrate, so less water enters interstitium by osmosis

Question 2

How is mannitol administered?

Answer 2

IV

Question 3

How does mannitol enter the filtrate?

Answer 3

Filtered by glomeruli

Question 4

How does mannitol decrease

a) water
b) sodium reabsorption?

Answer 4

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

Question 5

What is mannitol used to treat?

Answer 5

Increased intracranial pressure (cerebral oedema, papilloedema)

Increased intraocular pressure (glaucoma)

Question 6

What are two side effects of mannitol?

Answer 6

Hyponatraemia (inc. blood volume, so diluted)

Hypervolaemia

Question 7

What complication of diabetes causes osmotic diuresis?

Why?

Answer 7

Hyperglycaemia

All the SGLT2 channels are saturated

So less Na+ reabsorbed

So less H₂O reabsorbed

Osmotic diuresis

Question 8

What is an example of a carbonic anhydrase inhibitor?

Answer 8

Acetazolamide

Question 9

What is a renal effect of carbonic anhydrase inhibitors?

Answer 9

Stop carbonic anhydrase from converting H+ and HCO3- to carbonic acid

So BICARBONATE is excreted

Causing metabolic acidosis

Question 10

Which eye condition is carbonic anhydrase inhibitors used to treat?

Answer 10

Glaucoma

Inhibits secretion of aqueous humour, reducing intraocular pressure

Question 11

Where is aldosterone secreted from?

What does it do?

Answer 11

Adrenal cortex

Increases Na+ reabsorption and K+ secretion from the distal tubules and collecting ducts

Question 12

Where is ADH secreted from?

What does it do?

Answer 12

Posterior pituitary gland

Increases water reabsorption from collecting ducts

Question 13

Which receptor does ADH bind to?

Answer 13

V2 receptors

Question 14

What is the problem in

a) neurogenic
b) nephrogenic

diabetes insipidus?

Answer 14

a) Lack of ADH secretion from posterior pituitary

b) Resistance of V2 receptors to ADH

Question 15

What causes nephrogenic diabetes insipidus?

Answer 15

Resistance of V2 receptor to ADH binding

Question 16

Which gene mutates to cause nephrogenic diabetes insipidus?

Answer 16

AVPR2

Question 17

How is neurogenic diabetes insipidus treated?

Answer 17

Desmopressin

Question 18

Why does ethanol cause increased diuresis?

Answer 18

Alcohol inhibits ADH

Question 19

Why does smoking cause reduced diuresis?

Answer 19

Nicotine stimulates ADH

Question 20

What type of receptor is V2?

Answer 20

G-protein coupled receptor

activates adenyl cyclase, then cAMP etc.

Question 21

What change in the apical membrane does activation of V2 receptors cause?

Answer 21

Increased expression of aquaporins

Question 22

Which drugs block V2 receptors?

How do they affect

a) water reabsorption
b) Na+ reabsorption?

Answer 22

Vaptans

Block V2 receptors, so less water is reabsorbed

Same amount of Na+ is reabsorbed, but smaller BV, so HYPERNATRAEMIA

Question 23

What is an example of a vaptan which is used to treat SIADH and ADPKD?

Answer 23

Tolvaptan

Question 24

Which transporters are found in the proximal tubules and can be targeted by -flozins?

Answer 24

SGLT2

Question 25

Which sodium-glucose transporters are found in the a) early proximal b) late proximal tubules?

Answer 25

**a) SGLT2** **b) SGLT1**

Question 26

How does SGLT work?

Answer 26

**Transports glucose INTO cells, against a concentration gradient, by coupling it to Na**+ **transport down a concentration gradient**

Question 27

Which SGLT channels have a) a **low affinity** and **high capacity** b) a **high affinity** and **low capacity**? Why is this useful?

Answer 27

**a) SGLT2 (proximal)** **b) SGLT1 (distal)** If SGLT2 is overloaded with glucose, SGLT1 picks up the rest

Question 28

What renal symptom do **SGLT2 inhibitors** cause?

Answer 28

**Glycosuria** sugary urine

Question 29

Which drugs are used to inhibit SGLT2 inhibitors in the treatment of diabetes?

Answer 29

**-flozins** e.g empagliflozin

Question 30

What are the effects on SGLT2 inhibitors?

Answer 30

**Reduces HbA1c** **Weight loss**

Question 31

Given that they cause glycosuria, what is a side effect of SGLT2 inhibitors?

Answer 31

**UTI**

Question 32

Which **acid** is metabolised by enzymes to form **prostaglandins**?

Answer 32

**Arachidonic acid**

Question 33

Which enzymes metabolise arachidonic acid to form prostaglandins?

Answer 33

**COX1 and COX2**

Question 34

What do **prostaglandins** cause in the kidney?

Answer 34

**1. Vasodilation of the afferent arteriole (directly)** **2. Vasoconstriction of the efferent arteriole (by stimulating RENIN release)** Help to maintain vascular tone of kidneys

Question 35

What property of the kidney do prostaglandins have a large effect on?

Answer 35

**GFR**

Question 36

How do **prostaglandins** increase **GFR**?

Answer 36

**1. Prostaglandins DILATE afferent arteriole**, increasing RBF **2. Also stimulate secretion of renin, causing Angiotensin II to CONSTRICT efferent arteriole**, increasing filtration pressure

Question 37

What may **NSAIDs** cause in patients with kidney problems? Why? Which other drugs may contribute to this?

Answer 37

**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