drugs and the kidney

Question 1

what is the relationship between glomerular filtration rate and serum creatinine

Answer 1

inverse (hyperbolic, y = 1/x)
there is a big drop in GFR with a modest creatnine rise

Question 2

how does GFR change with age

Answer 2

it declines

Question 4

what drug can be removed by dialysis

Answer 4

lithium

Question 5

what drugs need to have doses adjusted due to renal failure

Answer 5

those w narrow theraputic windows e.g. phenytoin, digoxin -> protein binding is affected leading to more free drug in the system and also change in excretion leading to increased half lives

Question 6

are cationic or anionic drugs more toxic to kidneys and why

Answer 6

anionic -> anions have many ways to enter tubular cells (e.g. Na/anion transporters) but only 1 way to be removed from the cell and into the urine, leading to a build up in the cell

cations have 1 channel in and 1 channel out of the cells

Question 7

why should trimethoprim not be given to kidney transplant patients

Answer 7

trimethoprim moves into tubular cells due to low protein binding (i.e. more free trimethoprim) and competitively inhibits excretion of creatinin -> increased creatinin in the blood

Question 8

what kind of distribution do protein bound drugs normally have in the body and what needs to be done to the dose in renal failure

Answer 8

high protein bound drugs are usually in the vascular space and so have a low volume of distribution -> less protein binding in renal failure leads to higher volume of distribution in the body => a lower dose should be prescribed

Question 9

what enzyme is used by the kidney to metabolise certain drugs

Answer 9

cyt P450

Question 10

examples of drugs that can cause toxicity due to renal impairment (6)

Answer 10

1. digoxin
2. glibenclamide (prolonged hypoglycaemia)
3. gliclazide (prolonged hypoglycaemia)
4. codeine, dihydrocodeine (metabolised to morphine)
5. antibiotics e.g. gentamicin
6. lithium (filtered and reabsorbed)

Question 11

what drugs can interfere with renal function tests and how

Answer 11

1. cimetidine + trimethoprim -> interfere w tubular secretion of creatnine
2. methyldopa -> interferes w drug assay leading to elevated creatinine
3. refampicin -> makes urine red
4. nitrofurantoin, amitriptyline -> makes urine green
5. cephalospoprins, penicillins ->false +ve protein dipstick

Question 12

why can NSAID use lead to renal failure

Answer 12

NSAIDs block the production of prostoglandins and of Ang II -> both are key players in autoregulation -> lack of autoregulation leads to renal damage and to failure

Question 13

what are the 2 main types of Acute tubular necrosis

Answer 13

1. ischaemic tubular necrosis
2. nephrotoxic tubular necrosis

Question 14

5 exogenous causes for nephrotxoic Acute tubular necrosis

Answer 14

1. radiocontrast
2. aminoglycosides e.g. gentamicin (cause mitochondrial damage)
3. cisplatin
4. lithium
5. ethylene glycol (antifreeze)

Question 15

3 endogenous causes for nephrotxoic Acute tubular necrosis

Answer 15

1. rhabdomylolysis
2. myeloma
3. hypercalcaemia

Question 16

what white cell is typically high in tubular interstitial nephritis

Answer 16

eosinophils -> seen in the urine as well