Drugs and the kidney

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 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

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

→ 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 ```

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

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