Pharmacology of CKD

Question 1

Which drugs are used to treat CKD?

Answer 1

• Statins
• Aspirin
• Trimethoprim
• Gentamicin
• CCBs (covered before)
• ACEis (covered before)
• ARBs (covered before)
• Dapaglifozin (covered before)
• NSAIDs (covered before)

Question 2

What are examples of statins?

Answer 2

Simvastatin, artorvastatin

Question 3

What is the primary mechanism of action of statins?

Answer 3

selective, competitive inhibitor of HMG-CoA reductase,

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

By reducing hepatic cholesterol synthesis, an upregulation of LDL-receptors and increased hepatic uptake of LDL-cholesterol from the circulation occurs.

Question 4

What is the drug target of statins?

Answer 4

Hydroxymethylglutaryl-CoA (HMG-CoA) reductase

Question 5

What are the main side effects of statins?

Answer 5

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 6

What else do statins do?

Answer 6

Effective at reducing the risk of adverse cardiac events in people.

Question 7

What follow ups should occur for statins?

Answer 7

All patients should be regularly followed up to monitor for hyperkalaemia and acute renal failure.

Question 8

What is the effect of coadministration of statins with 34A inhibitors?

Answer 8

Increased statin serum concentrations

Question 9

What is the drug target of aspirin?

Answer 9

COX

Question 10

What is the primary mechanism of action of aspirin?

Answer 10

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 (ii) in the brain decreases fever.



Question 11

What are the side effects of aspirin?

Answer 11

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 12

What is the effect of aspirin on COX1?

Answer 12

Blockade of COX1 in gastric mucosal cells reduces mucus/bicarbonate production which can expose the stomach lining to acid.

Question 13

What is the drug target of trimethoprim?

Answer 13

Dihydrofolate reductase

Question 14

What is the primary mechanism of action of trimethoprim?

Answer 14

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

Question 15

What are the side effects of trimethoprim?

Answer 15

Diarrhoea

Skin reactions

Question 16

What is trimethoprim often administered with?

Answer 16

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

Question 17

What needs to be monitored in long term use of trimethoprim?

Answer 17

blood counts with long term use or in those at risk of folate deficiency
serum electrolytes in patients at risk of developing hyperkalaemia

Question 18

What is the drug target for gentamicin?

Answer 18

30s ribosomal subunit

Question 19

What is the mechanism of action of gentamicin?

Answer 19

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

Question 20

What are the side effects of gentamicin?

Answer 20

Ototoxicity and nephrotoxicity are important side effects to consider.

Question 21

What are statins effective at reducing?

Answer 21

risk of adverse cardiac events in people

Question 22

What can aspirin blocking COX1 cause?

Answer 22

In gastric mucosal cells reduces mucus/bicarbonate production which can expose the stomach lining to acid

Question 23

What is trimethoprim often administered with?

Answer 23

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

Question 24

What type of antibiotic is gentamicin?

Answer 24

Aminoglycoside antibiotic

Question 25

What type of bacteria can gentamicin pass through?

Answer 25

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

Question 26

When is gentamicin likely to be administered?

Answer 26

More likely to be administered intravenously (in hospital) for endocarditis, septicaemia, meningitis, pneumonia or surgical prophylaxis.