Hyperlipidaemia drugs

Question 1

name 2 statins

Answer 1

Atorvastatin (t1/2 - 24hrs), Simvastatin (t1/2 - 2hrs)

Question 2

statin MoA

Answer 2

Competitive inhibition of HMG-CoA reductase which contributes to upregulation of hepatic LDL receptors and increased clearance of circulating LDL

First line - 20mg atorvastatin (primary prev.) and 80mg (secondary prev.) cos lower NNT

Simvastatin - taken at night cos LDL activity highest + short half life

Question 3

statin adverse effects

Answer 3

• GI disruption, nausea and vomiting
• Myalgia
• Rhabdomyolysis (very rare)
• Increased liver enzymes

Question 4

statin contradictions

Answer 4

• Renal/hepatic impairment

- Pregnancy and breastfeeding

Question 5

statin drug interactions

Answer 5

CYP 3A4 - macrolides, amiodarone, diltiazem - increase plasma [statin]

Question 6

non-lipid effects of statins

Answer 6

• Improved vascular endothelial function - ↑NO, VEGF, ↓endothelin
• Stabilisation of atherosclerotic plaque - ↓SMC proliferation ↑collagen
• Improved haemostasis - ↓plasma fibrinogen, platelet aggregation, ↑fibrinolysis
• Anti-inflammatory - ↓proliferation of inflammatory cells into plaque, plasma CRP, adhesion
  molecules and cytokines
• Antioxidant - ↓superoxide formation

Question 7

name a fibrate

Answer 7

fenofibrate

Question 8

fibrate MoA

Answer 8

Activates of nuclear transcription factor PPARα which regulates expression of genes that control lipoprotein metabolism – increase production of lipoprotein lipase causing: ↑triglycerides removal from lipoprotein in plasma, ↑fatty acid uptake by the liver, ↑levels of HDL and ↑LDL affinity for receptor

Question 9

fibrate adverse effects

Answer 9

• Cholelithiasis
• GI upset
• Myositis

Question 10

fibrate contradictions

Answer 10

• Photosensitivity

- Gallbladder disease

Question 11

fibrate drug interactions

Answer 11

Warfarin – increase anticoagulation

Question 12

name a cholesterol absorption inhibitor

Answer 12

ezetimibe

Question 13

CAI MoA

Answer 13

Inhibit NPC1L1 transporter at brush border in small intestines; reduces absorption of cholesterol by the gut

Pro-drug is metabolised by hepatic metabolism so it remains in enterohepatic circulation which limits systemic exposure

Given as an adjunct to statins or if statins aren’t tolerated

Question 14

CAI adverse effects

Answer 14

• Abdominal pain
• GI upset
• Angioedema

Question 15

CAI contradictions

Answer 15

hepatic failure

Question 16

CAI drug interactions

Answer 16

Statins - theoretical increased risk of rhabdomyolysis

Question 17

PCSK9 MoA

Answer 17

PCSK9 is the protein that binds to internalised LDL receptors so controls LDL homeostasis

Monoclonal antibody given by injections - secondline treatment

Question 18

name a siRNA used in the treatment of high cholesterol

Answer 18

inclisiran

Question 19

inclisiran MoA

Answer 19

Inhibits hepatic translation of PCSK9

Question 20

Natural options of lowering plasma cholesterol

Answer 20

• Plant sterols provide some LDL cholesterol lowering effects (↓~0.5 mmol/L), structurally similar to cholesterol so compete with it, work with statins but not with ezetimibe
• Fish oils/oily fish, fibre, whole grains, vitamin C/E
• Alcohol – increases HDL cholesterol BUT also increases triglycerides