CKD Pharamacology Flashcards by rachael a

What are the drugs for CKD? (4 main)

Statins
aspirin
trimethoprim
gentamicin

previously mentioned…
calcium channel blockers
ACEi
angiotensin receptor blockers
dapagliflozin
NSAIDs

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What are examples of statins?

Simvastatin, artorvastatin

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What are the drug targets of statins?

Hydroxymethylglutaryl-CoA (HMG-CoA) reductase

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What is the mechanism of action of statins?

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.

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What are the side effects of statins?

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

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What adverse effect are statins good at reducing?

cardiac events

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Should patients be followed up if using statins?

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

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Statins co-administered with what may increase statin serum conc?

potent 3A4 inhibitors

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What is the drug target of aspirin?

Cyclo-oxygenase

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What is the mechanism of aspirin?

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.

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What are the main side effects of aspirin?

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

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What is the most cost effective medicine for the prevention of secondary events of thrombosis?

Low dose aspirin

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How can aspirin expose the stomach lining to acid?

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

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What is the drug target of trimethroprim?

Dihydrofolate reductase

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What is the mechanism of trimethoprim?

Direct 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 in bacteria (it is an antibiotic)

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What are the side effects of trimethoprim?

Diarrhoea
Skin reactions

What is trimethoprim often administered with?

sulfamethoxazole – known as co-trimoxazole.

In combination, they block two steps in bacterial biosynthesis of essential nucleic acids and proteins.

What do you need to monitor if prescribing trimethoprim?

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.

What are the drug targets of gentamicin?

30s ribosomal subunit

What is the mechanism of action for gentamicin?

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

What are the side effects of gentamicin?

Ototoxicity and nephrotoxicity are important side effects to consider.

What is gentamicin?

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

How is gentamicin more likely to be administered?

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

What treatment would the GP initiate at this point?

For HTN: Aged > 55 = Amlodipine (L-type calcium channel blocker) Target should be lower than normal due to CKD (eg 130/70) For CKD: Tight blood pressure control (to slow CKD progression – regardless of cause) For cardiovascular risk: Conservative measures (smoking, salt, exercise) Atorvastatin as risk >10% (13%-31% depending on ethnicity) Statins reduce cholesterol – you will learn about them later

The patient is referred to nephrology services and diagnosed with chronic kidney disease secondary to hypertension, with no other causes identified. The amlodipine is controlling his BP well (125/70) but he now has significant proteinuria (ACR >30). What treatments should the nephrologist initiate for the proteinuria and what treatment might need to be stopped?

- Proteinuria is a marker of glomerular dysfunction AND damaging in its own right - Drugs/interventions which improve proteinuria: Ø Angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) Ø Sodium-glucose co-transporter-2 (SGLT-2) inhibitors (e.g. dapagliflozin) Ø Salt restriction (to normal recommended levels!) - Stop Amlodipine if the ACEi reduces his BP too low

His use of trimethoprim invalidates the GFR calculators. Why is this, and do you think his GFR has in fact changed?

GFR probably hasn’t changed (but impossible to say without formally measuring it) Trimethoprim inhibits the active secretion of creatinine so the equation to calculate GFR is now invalid. Trimethoprim breaks the link between creatinine and GFR

Both answers are justified NICE guidelines in CKD: * Consider prescribing aspirin in people with a high risk of stroke or myocardial infarction * There is limited evidence of benefit even in people with multiple risk factors and there is a risk of harm In general, we tend to avoid aspirin for primary prevention

What is his GFR now and which of his drugs are contributing to the worsening GFR and how?

GFR – 12mls/min (15mls/min if black) Ibuprofen Inhibits PG synthesis and reduces renal blood flow ACEi Reduces perfusion pressure in glomerulus, exacerbated by sepsis Note sepsis will also be contributing to his acute injury

You are the admitting doctor on the medical ward and making a plan for his medication. What would you do about the ibuprofen, ACEi, and gentamicin?

Ibuprofen STOP. Use alternatives (e.g., paracetamol) ACEi Pause whilst he is acutely unwell. Gentamicin Can continue but reduce frequency and be guided by blood gentamicin levels. (Or choose alternative!)

What are 2 things to consider when prescribing for a patient with reduced renal function?

1) Might the drug damage the kidney and hence worsen the kidney injury (eg ibuprofen) 2) Is the drug eliminated by the kidney, and hence will it accumulate in the blood if kidney function is impaired, and hence lead to side effects? (eg morphine, metformin)