CKD

Question 1

Drugs

Answer 1

Statins Examples: Simvastatin, artorvastatin

Aspirin

Trimethoprim

Gentamicin

Calcium channel blocker 
ACEi
Angiotensin receptor blocker
Dapaglifozin
NSAIDS

Question 2

Statin action

Answer 2

Statins are a selective, competitive inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase, which is 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 3

Statin target

Answer 3

Hydroxymethylglutaryl-CoA (HMG-CoA) reductase

Question 4

Statin side effects

Answer 4

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 5

Statin other

Answer 5

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

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

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

In 2020, artorvastatin was the 1st and simvastatin the 11th most commonly prescribed drugs in the West London area

Question 6

Aspirin 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

Aspirin target

Answer 7

Cyclo-oxygenase

Question 8

Aspirin side effects

Answer 8

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 9

Aspirin other

Answer 9

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

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

In 2020, aspirin was the 8th most commonly prescribed drugs in the West London area

Question 10

Trimethoprim action

Answer 10

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 11

Trimethoprim target

Answer 11

Dihydrofolate reductase

Question 12

Trimethoprim side effects

Answer 12

Diarrhoea

Skin reactions

Question 13

Trimethoprim other

Answer 13

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

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

Question 14

Gentamicin action

Answer 14

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

Question 15

Gentamicin target

Answer 15

30s ribosomal subunit

Question 16

Gentamicin side effects

Answer 16

Ototoxicity and nephrotoxicity are important side effects to consider.

Question 17

Gentamicin other

Answer 17

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

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