Pharmacology of CKD

Question 1

What are examples of statins?

Answer 1

• simvastatin

- artorvastatin

Question 2

What is the primary mechanism of action of statins?

Answer 2

selective, competitive inhibitors of hydroxy-methylglutaryl-CoA (HMG-CoA) reductase
(responsible for converting HMG-CoA into mevalonate in the cholesterol synthesis pathway)
- reducing cholesterol synthesis, there is an up-regulation of LDL receptors and increased hepatic uptake of LDL- cholesterol from circulation occurs

Question 3

What is the drug target of statins?

Answer 3

Hydroxy-methyglutaryl-CoA (HMG-CoA) reductase

Question 4

What are the main side effects of statins?

Answer 4

• muscle toxicity (increased possibility at higher doses and in certain patients)
• GI symptoms: constipation and diarrhoea

Question 5

Are statins effective?

Answer 5

effective at reducing the risk of adverse cardiac events in people

Question 6

What follow up should there be with statins?

Answer 6

followed up to monitor:

• hyperkalaemia
• acute renal failure

Question 7

Is co-administration recommended with statins?

Answer 7

co-administration with potent 3A4 inhibitors may result in increase statin serum concentrations

Question 8

What is the primary mechanism of action of aspirin?

Answer 8

• irreversible inactivation of the COX enzyme
• prevents the oxidation of arachidonic acid to produce prostaglandins
• reduction in thromboxane A2 in platelets reduces aggregation
• reduction of PGE2 at sensory pain neurones reduces pain and sensation
• in the brain, decreases fever

Question 9

What is the drug target of aspirin?

Answer 9

Cyclo-oxygenase

Question 10

What are the main side effects associated with aspirin?

Answer 10

• dyspepsia

- haemorrhage

Question 11

What should be done when administering aspirin to the elderly?

Answer 11

• avoid doses higher than 160mg daily (increased bleeding risk) and co-administer PPI with a history of PUD.

Question 12

What is a possible unintended side effect of aspirin?

Answer 12

blockade of COX1 (in gastric mucosal cells) reduces mucus/bicarbonate production which exposes the stomach lining to acid

Question 13

Why is low dose aspirin often prescribed?

Answer 13

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

Question 14

What is the primary mechanism of action of Trimethoprim?

Answer 14

direct competitor of the enzyme dihydrofolate reductase
(inhibits the reduction of dihyrofolic acid to tetrahydrofolic acid (active form))
which is necessary for synthesising purines involved in DNA and protein production

Question 15

What is the drug target of Trimethoprim?

Answer 15

dihydro-folate reductase

Question 16

What are the main side effects of Trimethoprim?

Answer 16

• diarrhoea

- skin reactions

Question 17

What is often co-administered with Trimethoprim?

Answer 17

with sulfamethoxazole, in combination: block 2 steps in bacterial biosynthesis of essential nucleic acids and proteins

Question 18

What follow up is required after administration of Trimethoprim?

Answer 18

need to monitor blood counts with long term use, or in those with folate deficiency
monitor serum electrolytes in patients with hyperkalaemia risk.

Question 19

What is the main mechanism of action of Gentamicin?

Answer 19

binds to the bacterial 30s ribosomal subunit disturbing mRNA translation and leading to the formation of dysfunctional proteins

Question 20

What is the drug target of Gentamicin?

Answer 20

30s ribosomal subunit

Question 21

What are the main side effects of Gentamicin?

Answer 21

• Ototoxicity

- Nephro-toxicity

Question 22

Why is Gentamicin ineffective against anaerobic bacteria?

Answer 22

• aminogylcoside antibiotic

- passes through gram negative cell membranes in an oxygen dependent manner

Question 23

When is Gentamicin most likely to be administered and how?

Answer 23

- intravenously 
for:
- endocarditis
- septicaemia
- meningitis
- pneumonia
- surgical prophylaxis

Question 24

What other drugs can also be used in the treatment of CKD?

Answer 24

• Calcium Channel Blockers
• ACEi
• ARB
• Dapaglifozin
• NSAIDs

Question 25

What conservative measures should be used to reduce CVD risk?

Answer 25

• reduce smoking
• restrict salt consumption
• increase risk

Question 26

When should statins be used to treat high CVD risk?

Answer 26

when risk is >10% (13-30% dependent on ethnicity)

Question 27

What is indicated by proteinuria?

Answer 27

• marker of glomerular dysfunction

- damaging in it’s own right

Question 28

What drugs/interventions reduce proteinuria?

Answer 28

• ACEi
• ARB
• SGLT-2 inhibitors
• salt restriction (to normal recommended levels)

Question 29

When should aspirin be considered in those with CKD?

Answer 29

when high risk of`:
- stroke
- MI
limited evidence of benefit even in those with multiple risk factors and harm risk is present

Question 30

When is aspirin used?

Answer 30

Avoided in primary prevention

Question 31

Why does the use of Trimethoprim invalidate GFR?

Answer 31

Trimethoprim inhibits the active secretion of creatinine and therefore the equation is invalid
- inhibits tubular secretion, leading to a rapid but reversible increase in serum creatinine irrelevant of GFR
(breaks the link between creatinine and GFR)

Question 32

What is the relationship between creatinine and GFR?

Answer 32

(inverse relationship)

if creatinine levels go up, it must be because GFR has decreased

Question 33

What drugs can worsen GFR and how?

Answer 33

• ibuprofen, inhibits PG synthesis and reduces renal blood flow
• ACEi, reduces perfusion pressure in glomerulus, exacerbated by sepsis

Question 34

What 2 things should be considered when prescribing for a patient with reduced renal function?

Answer 34

• will the drug damage the kidney?

- is the drug eliminated by the kidney?

Question 35

What is the target for blood pressure in those with CKD

Answer 35

slightly lower than normal