Pharmacology of CKD

Question 1

give 2 statins

Answer 1

simvastatin, atorvastatin

Question 2

what is the primary mechanism of statins

Answer 2

selective competitive inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase used in cholesterol synthesis, reducing this leads to upregulation of LDL receptors and increased hepatic uptake of LDL cholesterol from circulation

Question 3

what does HMG CoA reductase do

Answer 3

enzyme responsible for converting HMG-CoA to mevalonate in cholesterol synthesis

Question 4

what is the drug target for statins

Answer 4

Hydroxymethylglutaryl-CoA (HMG-CoA) reductase

Question 5

what are main side effects of statins

Answer 5

muscle toxicity, likelihood of this increases with higher doses and for patients at increased risk
constipation or diarrhoea, other GI symptoms

Question 6

statins are effective at reducing what risk

Answer 6

risk of adverse cardiac events

Question 7

patients on statins should be followed up how

Answer 7

regularly to monitor for hyperkalaemia and acute renal failure

Question 8

what increased statin serum concentrations

Answer 8

co administration with potent 3A4 inhibitors

Question 9

what is aspirins mechanism of action

Answer 9

irreversible inactivation of COX enzyme, prevents oxidation of arachidonic acid to produce prostaglandins
this means less thromboxane A2 in platelets so reduces aggregation, reduction of PGE2 at sensory pain neurones which reduces pain sensation, reduction of PGE2 in the brain decreases fever

Question 10

what is the drug target for aspirin

Answer 10

cyclo oxygenase

Question 11

what is the most cost effective med for prevention of secondary events of thrombosis

Answer 11

low dose aspirin

Question 11

side effects of aspirin

Answer 11

dyspepsia, haemorrhage
in elderly avoid doses larger than 160mg daily (increased risk of bleeding) and co administer PPI if past history of peptic ulcer

Question 12

blockade of COX1 by aspirin can do what

Answer 12

in the gastric mucosal cells it reduces mucus, bicarbonate production which can expose stomach lining to acid

Question 13

what is trimethoprim mechanism of action

Answer 13

direct competitor of dihydrofolate reductase, inhibits reduction of dihydrofolic acid to tetrahydrofolic acid (active form), this is needed for synthesising purines requried for DNA and protein production

Question 14

what is trimethoprim prescribed for

Answer 14

is an antibiotic

Question 15

what is the drug target for trimethoprim

Answer 15

dihydrofolate reductase

Question 16

side effects of trimethoprim

Answer 16

diarrhoea, skin reactions

Question 17

what is trimethoprim often administered with

Answer 17

sulfamethoxazole known as co trimoxazole, in this combo they block 2 steps in bacterial biosynthesis of essential nucleic acids and proteins

Question 18

what do u need to monitor for those taking trimethoprim

Answer 18

monitor blood count in long term use or in those at risk of folate deficiency
also monitor serum electrolytes in those at risk of hyperkalaemia

Question 19

what is gentamicins mechanism of action

Answer 19

binds to bacterial 30S ribosomal subunit disturbing the translation of mRNA leading to formation of dysfunctional proteins

Question 20

what is the drug target for gentamicin

Answer 20

30S ribosomal unit

Question 21

side effects of gentamicin

Answer 21

ototoxicity (hearing and balance issues) and nephrotoxicity (deterioration in kidney function)

Question 22

what class is gentamicin

Answer 22

aminoglycoside, can pass through gram negative cell membrane in oxygen dependent manner

Question 23

why is gentamicin ineffective against anaerobic bactera

Answer 23

bc it can only pass through gram negative cell membrane in O2 dependent manner

Question 24

what is gentamicin administered for and how

Answer 24

IV (in hosp)
for endocarditis, septicaemia, meningitis, pneumonia or surgical prophylaxis

Question 25

what is the mechanism of action for dapaglifozin

Answer 25

reversible inhibits sodium glucose co transporter 2 to the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion

Question 26

what is the drug target for dapaglifozin

Answer 26

SGLT2 (in PCT)

Question 27

side effects of dapaglifozin

Answer 27

uro genital infections due to increased glucose load (5% of patients)
slight decrease in bone formation
can worsen DKA (stop immediately)

Question 28

what are other effects of SGLT2 inhibitors

Answer 28

causes weight loss and reduction in BP

Question 29

in which patients are SGLT2 inhibitors less effective

Answer 29

patients with renal impairment as their action depends on normal renal function

Question 30

what is the procedure for getting an ambulatory blood pressure monitor and what happens once u get it

Answer 30

if clinical BP above 140/90 then offer ABPM
if this says under 135/85 then monitor at least every 5y
if 135/85 - 149/94 then start drug treatment if there is also target organ damage, CVD, renal disease, diabetes, 10y CVD risk >=10%
if 150/90 or more then start drug treatment

Question 31

how does target BP change for those with HTN and CKD

Answer 31

target should be lower, tight BP control is needed to slow CKD progression regardless of its cause

Question 32

proteinuria is a marker of

Answer 32

glomerular dysfunction and is damaging in its own right

Question 33

what can u do to improve proteinuria

Answer 33

ACE inhibitors or angiotensin receptor blockers
SGLT2 inhibitors (eg dapaglifozin)
salt restriction
(stop amlodipine if ACEi reduces BP too low)

Question 34

do u tend to go for aspiring for primary prevention

Answer 34

no we tend to avoid as there is limited evidence of benefit even in those with multiple risk factors and there is also a risk of harm

Question 35

why does trimethoprim invalidate GFR calculators

Answer 35

GFR might not have necessarily changed but trimethoprim inhibits the atcive secretion of creatinine so the equation to calculate GFR is now invalid
trimethoprim breaks the link between creatinine and GFR

Question 36

how does GFR relate to creatinine

Answer 36

the rate at which muscles leak creatinine tends not to change so only factor which determines creatinine in blood is GFR
if creatinine goes up must be bc GFR has decreased (GFR leaks the creatinine out of the plasma) and vice versa

Question 37

how does ibuprofen and ACEi affect GFR

Answer 37

ibuprofen inhibits PG synthesis and reduces renal blood flow, ACEi reduce perfusion pressure in glomerulus which is exacerbated by sepsis
this causes GFR to keep decreasing

Question 38

what do u need to consider when prescribing for a patient with reduced renal function

Answer 38

might the drug damage the kidney (and hence worsen kidney injury like ibuprofen)
is the drug eliminated by the kidney and so will it accumulate in the blood if kidney function is impaired and hence lead to side effects (eg morphine, metformin)