Hyperlipidaemias Flashcards
Statin examples
Atorvastatin - 24hr half life
Simvastatin - Short half life 2hrs
Statin mechanism
Competitive HMG COA reductase inhibitor (rate controlling enzyme in production of cholesterol)
Unregulated hepatic LDL receptors - increases clearance of circ. LDL
Additional benefits of statin therapy
Decreases platelet aggregation
Ant inflammatory
Stabilises atherosclerosit plaque
ADRS of statins
GI disruption
Myopathy (diffuse muscle pain)
Rarely rhabdimyolyisus
Increased liver enzymes!
Contras of statins
Do not give to renally/heaptically impaired (first pass metabolism)
Do not give in pregnancy
CYP enzyme interactions with statins
CYP 3A4
Amlodipine CCb, diltiazem, clarithyromycin (macrolide) increases plasma conc. statin
Explain Statin interaction with grapefruit juice
Grapefruit juice
CYP 3A4 inhibition
So plasma conc. statin increases past therapeutic window
Doses of statins for primary and secondary prevention of CVD
Primary - high risk patient intervention. 20mg
Secondary - patients already had CVD. 80mg
What to give instead of/in combination with statin?
Ezetimibe (cholesterol absorption inhibitor)
Ezetimibe mechanism
Inhibits NPC 1L1 transporter
At brush border in SI
Reduces cholesterol absorption by gut
Ezetimibe ADRS
GI upset
Abdominal pain
Angioedema
Ezetimibe contraindications and DDI
Do not give to hepatic failure pts (pro drug so requires hepatic metabolism and secreted by bile)
Do not give with fibrates - causes gall stones
Fenofibrate mechanism & condition used
Coprescribed with statins in familial hypercholesterolaemia
Activation of nuclear transcription factor PPAR
Increases production of lipoprotein lipase
Increases triglyceride removal from plasma
Increases fatty acid uptake in liver
Fenofibrate ADRS
GI upset
Gall stones (cholelithiasis)
Fenofibrate contras and DDIS
Do not give with gall bladder disease (causes stones)
Do not give with warfarin. Anticoagulation increases
