CKD

Question 1

Give two examples of statins

Answer 1

• Simvastatin
• Atorvastatin

Question 2

What is the primary mechanism of action of statins?

Answer 2

• Selective, competitive inhibitor of HMG-CoA reductase responsible for converting HMG-CoA to mevalonate in cholesterol synthesis
• Reduces hepatic cholesterol synthesis which upregulates LDL receptors and increases hepatic uptake of LDL-cholesterol from circulation

Question 3

What is the drug target of statins?

Answer 3

HMG-CoA reductase

Question 4

What are the main side effects of statins?

Answer 4

• Muscle toxicity- likelihood increases with higher doses and in patients at increased risk of muscle toxicity
• Constipation/diarrhoea and other GI symptoms

Question 5

What are statins useful for?

Answer 5

Effective at reducing risk of adverse cardiac events in people

Question 6

Why do patients with statins need to be regularly followed up?

Answer 6

To monitor for hyperkalaemia and acute renal failure

Question 7

Why may a patient have increased statin serum concentrations?

Answer 7

Coadministration with potent 3A4 inhibitors may result in increased statin serum concs

Question 8

What is the primary mechanism of action of aspirin?

Answer 8

• Irreversible inactivation of COX
• Prevents oxidation of arachidonic acid for prostaglandin production
• Reduction of thromboxane A2 in platelets reduces aggregation
• Reduction of PGE2 at sensory pain neurones reduces pain and sensation and decreases fever in brain

Question 9

What is the drug target of aspirin?

Answer 9

COX

Question 10

What are the main side effects of aspirin?

Answer 10

• Dyspepsia
• Haemorrhage
• In elderly, avoid doses >160mg daily (increased bleeding risk)
• Coadminister PPI if past history of peptic ulcer

Question 11

Why is aspirin good prevention?

Answer 11

Low dose aspirin is most cost effective medicine for prevention of secondary events of thrombosis

Question 12

Why does aspirin cause side effects such as dyspepsia?

Answer 12

COX1 blockade in gastric mucosal cells reduces mucus/bicarbonate production which can expose stomach lining to acid

Question 13

What is the primary mechanism of action of trimethoprim?

Answer 13

• Direct competitor of dihydrofolate reductase enzyme
• Inhibits reduction of dihydrofolic acid to tetrahydrofolic acid (active form)- necessary part for synthesising purines required for DNA and protein production

Question 14

What is the drug target of trimethoprim?

Answer 14

Dihydrofolate reductase

Question 15

What are the main side effects of trimethoprim?

Answer 15

• Diarrhoea
• Skin reactions

Question 16

What is trimethoprim often administered with?

Answer 16

Often administered with sulfamethoxazole aka co-trimoxazole → in combo they block 2 steps in bacterial biosynthesis of essential nucleic acids and proteins

Question 17

What needs monitoring after administration of trimethoprim?

Answer 17

• Need to monitor blood counts in long term use or in those at risk of folate deficiency
• Also monitor serum electrolytes in patients at risk of developing hyperkalaemia

Question 18

What is the primary mechanism of action of gentamicin?

Answer 18

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

Question 19

What is the drug target of gentamicin?

Answer 19

30s ribosomal subunit

Question 20

What are the main side effects of gentamicin?

Answer 20

• Ototoxicity (hearing or balance problems)
• Nephrotoxicity

Question 21

Why is gentamicin ineffective against anaerobic bacteria?

Answer 21

It’s an aminoglycoside antibiotic and can pass through gram -ve cell membrane in an oxygen dependent manner

Question 22

How is gentamicin administered?

Answer 22

More likely to be IV administered for endocarditis, septicaemia, meningitis, pneumonia or surgical prophylaxis

Question 23

What other drugs may be used for CKD?

Answer 23

• Calcium channel blockers
• ACE inhibitors
• Angiotensin receptor blockers
• Dapaglifozin
• NSAIDs