pharmacology of CKD

Question 1

Mechanism of action of statins

Answer 1

selective competitive inhibitor of HMG-CoA reductase. Preventing conversion of HMG-CoA to mevalonate in the cholesterol synthesis pathway.
By decreasing cholesterol synthesis, there is an upregulation of LDL receptors and increased hepatic uptake of LDL cholesterol from the circulation occurs

Question 2

target of statin

Answer 2

HMG CoA reductase

Question 3

Side effects of statins

Answer 3

Muscle toxicity can occur with all statins, however the likelihood increases with higher doses and in certain patients at increased risk of muscle toxicity.

Constipation or diarrhoea. Other gastrointestinal symptoms.

Question 4

What should pts taking statins be followed up for

Answer 4

hyperkalaemia and acute renal failure

Question 5

statins with what other drug can increase statin serum conc

Answer 5

potent 3A4 inhibitors

Question 6

Aspirin primary mech of action

Answer 6

Irreversible inactivation of COX enzyme. Prevents oxidation of arachidonic acid to produce prostaglandins.

Reduction of thromboxane A2 in platelets reduces aggregation.

Reduction of PGE2 (i) at sensory pain neurones reduces pain and sensation and (ii) in the brain decreases fever.

Question 7

Side effects of aspirin

Answer 7

Dyspepsia

Haemorrhage

In the elderly, avoid doses greater than 160mg daily (increased risk of bleeding) and coadminister PPI if past history of peptic ulcer.

Question 8

Mech of action of trimethroprim

Answer 8

Direct competitor of the enzyme dihydrofolate reductase. Inhibits the reduction of dihydrofolic cid to tetrahydrofolic acid (active form) – a necessary component for synthesising purines required for DNA and protein production.

Question 9

side effects of trimethroprim

Answer 9

Diarrhoea

Skin reactions

Question 10

What is trimethroprim co administered with

Answer 10

Often administered with sulfamethoxazole – known as co-trimoxazole. In combination, they block two steps in bacterial biosynthesis of essential nucleic acids and proteins.

Question 11

mech of action of gentamicin

Answer 11

Binds to the bacterial 30s ribosomal subunit disturbing the translation of mRNA leading to the formation of dysfunctional proteins.

Question 12

target of gentamicin

Answer 12

30S ribosomal sub unit

Question 13

Gentamicin side effects

Answer 13

1) ototoxicity

2) nephrotoxicity

Question 14

What type of antibiotic is gentamicin

Answer 14

aminoglycaside

Question 15

Why are aminoglycasides ineffective against gram negative bacteria

Answer 15

Gentamicin is an aminoglycoside antibiotic. Can pass through gram negative cell membrane in an oxygen dependent manner (why they are ineffective against anaerobic bacteria).

Question 16

Exs of drugs that improve proteinuria

Answer 16

a) ACEi
b) ARBs
c) SGLT-2 inhibitors

Question 17

What do you need to consider with trimethoprim and eGFR calculations

Answer 17

trimethoprim invalidates eGFR calculations with creatinine as it prevents active secretion of creatinine leading to it building up and giving an usually low eGFR

Question 18

What and why effect NSAIDs have on kidneys

Answer 18

Inhibits PG synthesis and reduces renal blood flow

Question 19

effect of ACEi on kidneys. What would you do in sepsis

Answer 19

Reduces perfusion pressure in glomerulus, exacerbated by sepsis

Question 20

What 2 key things do you need to consider about drugs in reduced renal failure

Answer 20

1) might the drug damage the kidneys

2) would there be reduced clearance by the kidney and so accumulate in the blood causing side effects