Cholesterol drugs

Question 1

functions of cholesterol

Answer 1

membrane integrity,

precursor in production of steroid hormones, bile acids and vitamin D

Question 2

steps for atheromatous plaques

Answer 2

LDL susceptible to oxidation at damaged endothelium,
ROS contributes to endothelial dysfunction
increasing adherence of lipid rich deposits and foam cells formed –
precursor to atheromatous plaques

Question 3

statins mechanism

Answer 3

Competitive inhibition of HMG-CoA reductase
upregulation of hepatic LDL receptors
Increased clearance of circulating LDL

Question 4

benefits of statins

Answer 4

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 5

statin examples

Answer 5

atorvastatin (first pass metabolism, long T1/2) and

simvastatin (prodrug, short T1/2, take at night)

Question 6

statins

Answer 6

GI disruption, nausea and headache
myalgia – diffuse muscle pain - dose related
Rarely – rhabdomyolysis –
Increased liver enzymes

Question 7

x statins

Answer 7

renal or hepatic impairment

pregnancy! and breastfeeding

Question 8

^ statins

Answer 8

CYP 3A4 important – amiodarone, diltiazem, macrolides - increases [plasma] statin
amlodipine (CCB) also increases [plasma] statin
Grapefruit/juice

Question 9

fibric acid derivates mechanism

Answer 9

↑ lipoprotein lipase 
↑triglycerides removal from lipoprotein in plasma 
↑fatty acid uptake by the liver
 ↑levels of HDL 
↑LDL affinity for receptor 
co prescribed

Question 10

fibrates example

Answer 10

fenofibrate

Question 11

fibrates

Answer 11

cholelithiasis (gall stones), GI upset, myositis

Question 12

x fibrates

Answer 12

photosensitivity, gall bladder disease

Question 13

^ fibrates

Answer 13

warfarin – increase anticoagulation

Question 14

Cholesterol absorption inhibitors mechanism

Answer 14

• Inhibit NPC1L1 transporter at brush border in small intestines
• Reduces absorption of cholesterol by the gut ~50%
• Hepatic LDL receptor expression increases
• Pro-drug - hepatic metabolism - enterohepatic circulation limits systemic exposure secreted by bile
• co prescribed statin

Question 15

Cholesterol absorption inhibitors example

Answer 15

ezetimibe

Question 16

Cholesterol absorption inhibitors

Answer 16

abdominal pain, GI upset, angioedema

Question 17

xCholesterol absorption inhibitors

Answer 17

hepatic failure

Question 18

^Cholesterol absorption inhibitors

Answer 18

mindful with statin – theoretical increased risk of rhabdomyolysis,
ciclosporin

Question 19

PCSK9 inhibitors mechanism

Answer 19

binds internalised LDL-R – directing for degradation

causes reduction in LDL cholesterol

Question 20

PCSK9 inhibitors example

Answer 20

alirocumab

evolocumab Requires lifetime injections

Question 21

siRNA mechanism

Answer 21

siRNA- inhibits hepatic translation of PCSK9 – less produced

Question 22

siRNA example

Answer 22

inclisiran