Hyperlipidaemias Flashcards
What is the mechanism of action for statins?
Competitive inhibition of HMG-CoA reductase
Statins cause an upregulation of what type of receptor?
Hepatic LDL receptor to increase clearance of circulating LDL
Name the two statins we have covered
Atorvastatin
Simvastatin
What is the half life of the active derivatives of Atorvastatin?
> 30hrs
Which statin is a prodrug activated by first pass metabolism?
Simvastatin
What is the half life of simvastatin?
2 hrs
What are the side effects associated with statins?
GI disruption Nausea Headache Myalgia Rhabdomyolysis
When are statins contraindicated?
Renal impairment
Breast feeding
Pregnant
Which CYP450 is important when considering statins?
CYP3A4
If the patient required other drugs that interacted with the CYP450, then the statins would have to be temporarily withheld. What drugs does this apply to?
Amiodarone
Diltiazem
Macrolides
Amlodipine
How do statins improve vascular endothelial function?
Increase NO and VEGF
Decrease endothelin
How do statins improve plaque stability?
Increased collagen
Decreased smooth muscle cell proliferation
Statins have antioxidant effects, they prevent the formation of what?
Superoxide
When in the day should statins be taken?
At night due to the circadian rhythm of the LDL receptor synthesis and activity.
What is fenofibrate?
A fibric acid derivative
Fenofibrate activates which nuclear transcription factor?
PPARa
PPARa regulates the expression of genes that control lipoprotein metabolism, the production of which enzyme gets upregulated as a result?
Lipoprotein lipase
What are the warnings and contraindications associated with fenofibrate?
Gallbladder disease
Pancreatitis
Cholilithiasis
Myositis
Fenofibrate does what to warfarin?
Potentiates it so there is an increased chance of bleeding.
What is Alirocumab?
PCSK9 inhibitor
What is the mechanism of action for Alirocumab?
PCSK9 normally binds internalised LDL receptors.
So the drug prevents the internalisation of the receptor.
What is Ezetimibe?
Cholesterol absorption inhibitor
Ezetimibe inhibits what?
NPC1L1 transporter in the small intestine, reducing gut absorption of cholesterol by 50%
And hepatic LDL receptor expression increases
Is Ezetimibe a pro drug?
Yes
In familial hypercholesterolaemia, what would be prescribed?
Statins and Ezetimibe as an adjunct.
What is the dose of Ezetimibe?
10mg
It has no dose escalation