Hyperlipidaemia

Question 1

Atorvastatin

Answer 1

• competitive inhibitor of HMG-CoA reductase (rate controlling enzyme in mevalonate pathway)
• upregulation of hepatic LDL receptors
• increased clearance of circulating LDL
• first line therapy for cholesterol
• has a long half life and goes through first pass metabolism (active derivatives)
• side effects: GI disruption, nausea, headache, muscle pain (will see increased CPK), rhabdomyolysis (very rare)
• contraindication: renal impairment, pregnancy, breastfeeding, using antibiotics (macrolides) or amlodipine, amiodarone, diltiazem,
• primary prevention: 20mg once daily
• secondary prevention: 80mg once daily
• taken orally

Question 2

Simvastatin

Answer 2

• first line statin
• prodrug activated by first pass metabolism
• short half-life so should take just before bedtime because of circadian rhythm and cholesterol cycle as well
• side effects: GI disruption, nausea, headache, myalgia
• contraindications: renal impairment, pregnancy, breastfeeding, antibiotics, (same as atorvastatin)
• oral
• check liver function, CK, and diabetes before treatment

Question 3

Fluvastatin

Answer 3

• used to treat high cholesterol in adults and children of at least 10
• same side effects and contraindications as other statins
• Dont take: liver problems, pregnant, breastfeeding
• hydrophilic so will cause less insomnia
• does not require dosage adjustment in patients with renal impairment
• is metabolised by the CYP2C9

Question 4

Pravastatin

Answer 4

• first pass metabolism doesnt occur with this one
• least protein-bound of the statins
• hydrophilic so will cause less insomnia
• greater renal elimination

Question 5

Rosuvastatin

Answer 5

• better at lowering LDLs (right after atorvastatin)
• very few negative interactions with other drugs
• hydrophilic
• may have diabetic side effects

Question 6

Lovastatin

Answer 6

-food increases the bioavailability of this statin

Question 7

Cerivastatin

Answer 7

• withdrawn
• is a fibrates
• caused some deaths through rhabdomyolysis and renal failure

Question 8

Fenofibrate

Answer 8

• is a fabric acid derivative (fibrates)
• oral
• activates nuclear transcription factor (PPARa)
• promotes gene expression in nucleus to increase lipoprotein lipase
• usually used as an adjunct with statins when the statins are contraindicated
• increases triglyceride metabolism, fatty acid uptake by liver, HDL levels, and LDL affinity for receptor
• side effects: gallstones, flatulence, myositis
• contraindication: warfarin as it will increase bleeding risk
• do not give to patients with hypothyroidism

Question 9

Ezetimibe

Answer 9

• cholesterol absorption inhibitor
• inhibits NPC1L1 transporter at the brush border of the intestines
• usually co-prescribed with statins
• reduces absorption of cholesterol in the gut
• hepatic LDL receptor expression increases
• decreases total cholesterol by 15% and LDL by 20%
• is a prodrug which means it needs hepatic metabolism and it limits systemic exposure
• side effect: abd pain, GI upset, diarrhoea
• contraindication: hepatic failure

Question 10

Alirocumab

Answer 10

• monoclonal antibodies
• PCSK9 inhibitors
• PCSK9 usually internalizes LDL with receptor for degradation
• inhibitor allows more LDL recruitment without the receptor
• subcutaneous injection
• side effects: nasal, pulmonary, skin reactions

Question 11

Evolocumab

Answer 11

• PCSK9 inhibitor
• for hypercholesterolaemia
• subcutaneous injection
• side effects: back pain, nausea, arthralgia
• contraindication: renal impairment

Question 12

What food options are there to lower cholesterol?

Answer 12

• plant sterols
• fish oils
• fibre
• vitamin C/E
• NO to alcohol even though it increases HDL, it also increases triglycerides

Question 13

What are the benefits of statin therapy?

Answer 13

• main: reduce CVD risk
• improves vascular endothelial function
• stabilization of atherosclerotic plaque
• improved haemostasis
• anti-inflammatory: decrease in proliferation of inflammatory cells into plaque
• antioxidant: superoxide formation