Pharmacology Of Ckd

Question 1

Statins
Examples:
Simvastatin, artorvastatin

Mechanism of action

Answer 1

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 2

Statins drug target

Answer 2

Hydroxymethylglutaryl-CoA (HMG-CoA) reductase

Question 3

Main side effects of statin

Answer 3

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 4

Extra info on statins

Answer 4

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.

used for primary and secondary prevention

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 5

Aspirin mechanism of action

Answer 5

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 6

Aspirin drug target

Answer 6

Cyclo oxygenase

Question 7

Aspirin side effects

Answer 7

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 8

Aspirin extra info

Answer 8

Low dose aspirin is the most cost effective medicine for the prevention of secondary events of thrombosis.
used for cvd risk prevention although benefit doesn’t outweigh harm

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 9

Trimethoprim mechanism of action

Answer 9

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 10

Trimethoprim drug target

Answer 10

Dihydrofolate reductase

Question 11

Trimethoprim side effects

Answer 11

Diarrhoea
Skin reactions

Question 12

Trimethoprim extra info

Answer 12

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.

trimethoprim increases active secretion of creatinine thus gives false reduction in creatinine this egfr calculation becomes invalid

Question 13

Gentamicin mechanism of action.

Answer 13

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

Question 14

Gentamicin drug target

Answer 14

Binds to the bacterial 30s ribosomal subunit

Question 15

Gentamicin side effects

Answer 15

Ototoxicity and nephrotoxicity are important side effects to consider.

Question 16

Gentamicin extra info

Answer 16

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

worsens Renal function

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

Question 17

Calcium channel blockers

Examples:
Amlodipine
Felodipine

Mechanism of action

Answer 17

Block L-type calcium channels – predominantly on vascular smooth muscle. This results in a decrease in calcium influx, with downstream inhibition of myosin light chain kinase and prevention of cross-bridge formation. The resultant vasodilation reduces peripheral resistance.

Question 18

Calcium channel blocker target

Answer 18

L type calcium channel

Question 19

Calcium channel blocker side effects gs

Answer 19

Ankle oedema
Constipation
Palpitations
Flushing/Headaches

Question 20

Calcium channel blocker extra info

Answer 20

Dihydropyridine type calcium channel blockers demonstrate a higher degree of vascular selectivity

increasw gfr and can worsen ckd?

In 2020, amlodipine was the 2nd and felodipine the 98th most commonly prescribed drugs in the West London area

Question 21

Angiotensin converting
enzyme inhibitors

Examples:
Ramipril
Lisinopril
Perindopril

Mechanism of action

Answer 21

Inhibit the angiotensin converting
enzyme.
Prevent the conversion of
angiotensin I to angiotensin II
by ACE.

Dilate efferent arteriole

Question 22

Ace inhibitors target

Answer 22

Angiotensin converting enzyme

Question 23

ACEi side effects

Answer 23

Cough

Hypotension

Hyperkalaemia (care with K+ supplements or K+-sparing diuretics)

Foetal Injury (AVOID IN PREGNANT WOMEN)

Renal failure (in patients with renal artery stenosis)-

Urticaria/Angioedema

Question 24

Ace inhibitor extra info

Answer 24

Most ACE inhibitors (not lisinopril) are pro-drugs. They require hepatic activation to generate the active metabolites required for therapeutic effects.

eGFR and serum potassium must be regularly monitored when prescribing ACE inhibitors.

In 2020, ramipril was the 7th, lisinopril the 42nd and perindopril the 51st most commonly prescribed drugs in the West London area

Question 25

Angiotensin receptor blockers Examples: Losartan Irbesartan Candesartan Mechanism of action

Answer 25

These agents act as insurmountable (i.e. non-competitive) antagonists at AT1 receptor (found on kidneys and on the vasculature)

Question 26

Angiotensin receptor blocker target

Answer 26

Angiotensin enzyme

Question 27

Side effects of ARB

Answer 27

Hypotension Hyperkalaemia (care with K+ supplements or K+-sparing diuretics) Foetal Injury (AVOID IN PREGNANT WOMEN) Renal failure (in patients with renal artery stenosis)-

Question 28

Arb extra info

Answer 28

Most trials indicate that angiotensin receptor blockers are not as effective anti-hypertensive agents as ACE inhibitors. Losartan and candesartan are pro-drugs. They require hepatic activation to generate the active metabolites required for therapeutic effects. In 2020, losartan was the 13th, irbesartan the 57th and candesartan the 80th most commonly prescribed drugs in the West London area

Question 29

Dapaglifozin mechanism of action

Answer 29

Reversibly inhibits sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.

Question 30

Dapaglifozin target

Answer 30

SGLT2 IN PCT

Question 31

Side effects of Dapaglifozin

Answer 31

Uro-genital infections due to increased glucose load (5% of patients) Slight decrease in bone formation Can worsen diabetic ketoacidosis (stop immediately)

Question 32

Extra info for Dapaglifozin

Answer 32

SGLT2 inhibitors cause weight loss and a reduction in BP SGLT2i action depends on normal renal fucntion so they are less effective in patients with renal impairment In 2020 – Dapaglifozin was the 127th most commonly prescribed drug in West London area

Question 33

NSAIDS ibuprofen naproxen diclofenac

Answer 33

NSAIDS inhibit the enzyme cyclo-oxygenase (COX) which is the rate-limiting step for the production of all prostanoids (prostaglandins & thromboxanes) from the parent arachidonic acid. Prostanoids act through a large number of prostanoid receptors to produce a highly complex array of actions. It is thought that the anti-inflammatory actions, and probably most of the analgesic & antipyretic actions, of the NSAIDs are related to inhibition of COX-2, while their unwanted effects are largely a result of inhibition of COX-1.

Question 34

NSAIDs drug target

Answer 34

COX

Question 35

Side effects if NSAIDS

Answer 35

Common unwanted effects include gastric irritation, ulceration and bleeding and, in extreme cases, perforation; reduced creatinine clearance and possible nephritis; and bronchoconstriction in susceptible individuals (contraindicated in asthma). Skin rashes & other allergies, dizziness, tinnitus. Adverse cardiovascular effects (hypertension, stroke, MI) may occur following prolonged use or in patients with pre-existing CV risk. Prolonged analgesic abuse over a period of years is associated with chronic renal failure. Aspirin has been linked with a rare but serious post-viral encephalitis (Reye’s syndrome) in children. Common unwanted effects include gastric irritation, ulceration and bleeding and, in extreme cases, perforation; reduced creatinine clearance and possible nephritis; and bronchoconstriction in susceptible individuals (contraindicated in asthma). Skin rashes & other allergies, dizziness, tinnitus. Adverse cardiovascular effects (hypertension, stroke, MI) may occur following prolonged use or in patients with pre-existing CV risk. Prolonged analgesic abuse over a period of years is associated with chronic renal failure. Aspirin has been linked with a rare but serious post-viral encephalitis (Reye’s syndrome) in children.

Question 36

Extra info NSAIDs

Answer 36

The main uses of NSAIDs are as analgesics for the relief of mild to moderate pain (e.g. musculoskeletal pain, headache, dysmenorrhoea); as antipyretics to reduce fever; as anti-inflammatory drugs for chronic control of inflammatory diseases (e.g. rheumatoid arthritis, osteoarthritis); and (aspirin only) as an anti-aggregatory agent to inhibit platelet aggregation in patients who are at risk of stroke or myocardial infarction. In 2020, ibuprofen was the 48th, naproxen the 45th and diclofenac the 92nd most commonly prescribed drugs in the West London area.

Question 37

To slow progression

Answer 37

Control bp us sing ACE ARB Glycaemic control using SGLT2 Lifestyle

Question 38

For CVD prevention

Answer 38

Low dose aspirin usually usually avoided as can cause harm but dies have antiplatelet action Stats is for primary and secondary orevention