Pharmacology of CKD

Question 1

What are the different medications used for CKD?

Answer 1

-Statins
-Aspirin
-Trimethoprim
-Gentamicin
-Calcium channel blockers
-ACE inhibitors
-Angiotensin receptor blockers
-Dapaglifozin
-NSAIDs

Question 2

What is the primary mechanism of action of statins?

Answer 2

-Selective, competitive inhibitor of HMG-CoA reductase which is responsible for HMG-CoA → mevalonate in cholesterol synthesis
-Reduces hepatic cholesterol synthesis which up regulates 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 examples of statins? (2)

Answer 4

-Simvastatin
-Atorvastatin

Question 5

What are the main side effects of statins?

Answer 5

-Muscle toxicity (increased risk with increased dose)
-Constipation/diarrhoea and other GI symptoms

Question 6

What is the primary mechanism of action of aspirin?

Answer 6

-Irreversible inactivation of COX
-Prevents oxidation of arachnoid acid and prostaglandin production
-Reduction of thromboxane A2
-Reduction of PGE2 at sensory pain neurones reduces pain and sensation and decreases fever in brain

Question 7

What is the drug target for aspirin?

Answer 7

COX

Question 8

What are the main side effects of aspirin?

Answer 8

-Dyspepsia
-Haemorrhage
-Elderly avoid doses >160mg daily (increased bleeding risk)
-Coadminister PPI if history of peptic ulcer

Question 9

Why is there a peptic ulcer risk with aspirin?

Answer 9

COX1 blocks gastric mucosal cells which reduces mucus and bicarbonate production which exposes stomach lining to acid

Question 10

What is the primary mechanism of action of trimethoprim?

Answer 10

-Direct competitor of dihydrofolate reductase enzyme
-Inhibits reduction of dihydrofolic acid to tetrahydrofolic acid which is necessary for synthesising purines required for DNA and protein production

Question 11

What is the drug target for trimethoprim?

Answer 11

Dihydrofolate reductase

Question 12

What are the main side effects of trimethoprim?

Answer 12

-Diarrhoea
-Skin reactions

Question 13

What do you need to monitor in the long run with trimethoprim?

Answer 13

Blood count as can lead to folate deficiency
Serum electrocytes in patients at risk of hyperkalemia

Question 13

What is trimethoprim usually administered with?

Answer 13

Sulfamethoxazole (co trimoxazole) blocks 2 steps in bacterial biosynthesis of essential nucleic acids and proteins

Question 14

What is the primary mechanism of action of gentamicin?

Answer 14

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

Question 15

What is the drug target for gentamicin?

Answer 15

30s ribosome subunit

Question 16

What are the main side effects of gentamicin?

Answer 16

-Ototoxicity (hearing/balance problems)
-Nephrotoxicity