Drugs and the Kidneys

Question 1

What is excreted more readily by the kidney?

Answer 1

→polar compounds more than non polar compounds

→non polar compounds can be reabsorbed by the kidney

Question 2

What are the three methods of drug excretion by the kidney?

Answer 2

→ Glomerular filtration
→ Tubular reabsorption
→ Tubular secretion

Question 3

What size do drugs have to be to be freely filtered?

Answer 3

→Smaller than 20 kDA it is freely filtered

Question 4

What are drugs bound to that doesn’t allow them to be filtered?

Answer 4

→ when bound to albumin

Question 5

What is the clinical importance of whether a drug is bound to albumin or not and give an example?

Answer 5

→ Warfarin
→ 98% bound to albumin
→ long half life - stays in the body for long

Question 6

How are drugs that are not bound removed?

Answer 6

→ removed by secretion

→ non specific cation and anion transporters for charged drugs

Question 7

How is morphine removed?

Answer 7

→ Cation transporter

Question 8

How is penicillin removed?

Answer 8

→ Anion transporter

Question 9

What does the degree of drug ionization depend on?

Answer 9

→ pKa and pH of environment

Question 10

What do diuretics cause?

Answer 10

→ Increase in urine output (diuresis)

Question 11

What do diuretics increase?

Answer 11

→ Na+ (natriuresis)

→ K+ excretion (hypokalaemia)

Question 12

What conditions are diuretics used for?

Answer 12

→hypertension
→acute pulmonary oedema
→ heart failure

Question 13

What are the two major groups of diuretics?

Answer 13

→ affecting H2O excretion

→ increasing electrolyte excretion

Question 14

What are the diuretics that affect water excretion?

Answer 14

→ water
→ ethanol (decreases ADH release)
→ osmotic diuretics

Question 15

What are the diuretics that increase electrolyte excretion?

Answer 15

→ Carbonic anhydrase inhibitors
→ loop diuretics
→ Thiazides
→ K+ sparing diuretics

Question 16

What is reabsorbed at the PCT and how (site 1 +2) ?

Answer 16

→ 65% of Na+ is reabsorbed
→ by the Na+ and glucose symporter
→ Na+/H+ antiport

Question 17

What is reabsorbed at the descending loop?

Answer 17

→ Pure water

Question 18

What is reabsorbed at the ascending loop ( site 3) ?

Answer 18

→ NaCl
→ K+
→ Cl-

Question 19

What is reabsorbed at the DCT and how (site 4-6) ?

Answer 19

→ NaCl and H2O 4
→ Na+ through the eNAC channels in exchange for K+ - stimulated by aldosterone - 5
→ Na+/H+ exchanger - stimulated by aldosterone -6

Question 20

How is mannitol usually administered?

Answer 20

→ I.V

→Does not cross blood-brain barrier

Question 21

What is mannitol and how does it pass through the kidney?

Answer 21

→ Inert substance

→ Freely filtered but not reabsorbed

Question 22

What do high concentrations of mannitol do?

Answer 22

→ Increase osmolarity in the tubules

→decrease reabsorption of H2O

Question 23

Where does mannitol act?

Answer 23

→ PCT
→ DCT
→ Collecting duct

Question 24

What are the uses of mannitol?

Answer 24

→ reduce intracranial and intraocular pressure

Question 25

How does mannitol reduce intracranial pressure?

Answer 25

→ Does not enter CNS
→ creates an osmotic gradient
→ H2O leaves the CNS into the plasma

Question 26

How does mannitol prevent acute renal failure?

Answer 26

→ if GFR drops very low
→ distal nephron can dry up
→ osmotic pressure in the tubule increases
→ water reabsorption decreases

Question 27

How do diuretics that affect electrolyte excretion work?

Answer 27

→ Increase urine flow by increasing excretion of Na+

→ Where Na+ goes H2O follow

Question 28

What is the major determinant of ECFV?

Answer 28

→ Na+

Question 29

What happens with increased NaCl excretion?

Answer 29

decreased ECF (RAAS activated)
↓
decreased blood volume
↓
decreased cardiac output
↓
oedema

Question 30

What is an example of a carbonic anhydrase inhibitor?

Answer 30

→ acetazolamidee

Question 31

How do carbonic anhydrase inhibitors increase urine output?

Answer 31

→ Inhibit CA activity
→ decrease formation of protons in luminal PCT cells ( site 2)
→ Loss of Na+ HCO3- into lumen
→ loss of H2O

Question 32

What non-renal things are dependent on carbonic anhydrase activity?

Answer 32

→ glaucoma

→ aqueous humor formation

Question 33

What are the most powerful diuretics called?

Answer 33

→ Loop diuretics (furosemide)

Question 34

What do loop diuretics do?

Answer 34

→ Inhibit Na/K/Cl co-transporter at thick ascending LoH
→ decreases reabsorption of Na, K and 2 Cl-
→ prevents concentration of interstitial fluid and reduces the effect of ADH on collecting duct

Question 35

What do loop diuretics do in chronic heart failure?

Answer 35

→ decrease ECFV
→ decrease pressure
→ decrease cardiac output

Question 36

What do loop diuretics do in acute renal failure?

Answer 36

→ Increased renal blood flow

Question 37

What do loop diuretics do in acute pulmonary oedema?

Answer 37

→ Decrease capillary pressure

Question 38

How do loop diuretics cause vasodilation?

Answer 38

→ Increasing PGs in blood vessels

Question 39

What are side effects of loop diuretics?

Answer 39

→ loss of K+

→ metabolic alkalosis (compensatory)

Question 40

What do thiazide diuretics do?

Answer 40

→ Inhibits Na/Cl uptake via co-transporter at DCT

Question 41

What are the uses of thiazide diuretics?

Answer 41

→ Low doses effective for Hypertension
→ Decreased blood volume
→ decreased cardiac output

Question 42

What is the effect of thiazide diuretics?

Answer 42

→ compensation mechanisms
→ Less Na+ reabsorbed so more Na+ inside tubule
→ More Na+ in the eNAC
→ balanced by further outflow of K+
→ more Na+ so further loss of H+
→ hypokalemia occurs
No longer first line in NHS (see NICE guidelines) but may be 2nd or 3rd

Question 43

Flowchart for what happens if blood volume drops

Answer 43

BV decreases
↓
increased RAAS
↓
increased aldosterone
↓
Increased Na+ reabsorption
↓
Increased K+/H+ loss

Question 44

What are the side effects of loop diuretics?

Answer 44

Hypokalaemia ( loss of K+)
→ Metabolic alkalosis (loss of H+)
→ Hypercalcaemia ( increased Ca/Na exchanger)
→ Hypotension (too much vasodilation)

Question 45

Why are K+ sparing diuretics important?

Answer 45

→ cause K+ retention

→ counter powerful electrolyte secretions of diuretics such as furosemide

Question 46

Where do K+ sparing diuretics act?

Answer 46

→ End of DCT and collecting duct

Question 47

What is spironolactone?

Answer 47

→ competitive antagonist of aldosterone at sites 5&6

block the epithelial sodium channel (expression increased by aldosterone),

Question 48

What does amiloride do?

Answer 48

→ Blocks eNAC at site 5

→ reduces Na+ reabsorption and K+ loss

Question 49

What does captopril do?

Answer 49

→ Inhibits angiotensin converting enzyme
→ decreased angiotensin II formation
→ Decreased aldosterone

Question 50

What are nephrotoxic slides?

Answer 50

→ NSAIDs
→ prevent formation of prostaglandins by inhibiting COX
→ COX and PG formation is important for renal blood flow and GFR

Question 51

Describe the movement of HCO3 with carbonic anhydrase inhibitors

Answer 51

→HCO3 already in the filtrate combines (catalysed by CA) with the extruded protons to form CO2 and water, which diffuse back in.
→In the cell CA catalyses the reaction the other way, producing protons to drive the Na/H exchange.
→The HCO3 diffuses out to ECF via membrane channels.
→Net result is reabsorption of NaHCO3. Inhibition of CA impedes this process

Question 52

Recent drugs with mild diuretic action…

Answer 52

SGLT-2 inhibitors used to treat hyperglycaemia
Impair glucose reabsorption
→More remains in tubular fluid, lowers plasma concentration

SGLT1: glucose absorption from gut
SGLT1, SGLT2: glucose reabsorption from kidney (PCT)