Lipid Lowering Drugs Flashcards
Where specifically in the blood vessels to atherosclerotic plaques develop?
In the intima [of large and medium sized arteries).
What is the first clinical appearance of a plaque?
Stable (exertional angina).
What biochemical increases with plaque development?
C-reactive protein (not very specific)
What BMI does the WHO consider overweight?
20
What three things are in the outer coat of lipoproteins?
cholesterol, phospholipids, apolipoproteins
What two things are in the core of lipoproteins?
cholesterol esters, triglycerides.
Because lipid-lowering drugs are expensive, they have the most benefit to patients with…
…high risk of CV events, or high cholesterol.
ALWAYS treated in conjunction with reduction of modifiable risk factors.
List eight modifiable risk factors for plaques
as always just say diabetes at least
lipid profile, diabetes, weight, tobacco intake, alcohol intake, diet (salt/fat), exercise, hypertension.
List four non-modifiable risk factors
ethnicity
age
sex (male)
family history
In what way do fibrates sorta influence reverse cholesterol transport?
Lower VLDL secretion, meaning lower future CETP-mediated redistribution of cholesterol via ApoB-48 lipoproteins to the periphery. More delivered straight back to the liver.
What are the first-line lipid-lowering drugs?
Statins
What does HMG-CoA reductase catalyse?
HMG-CoA → mevalonic acid
What is the hepatic cholesterol synthesis rate-limiting enzyme that statins competitively, reversibly inhibit?
HMG-CoA reductase.
What is the net effect of statins?
20-50% reduction in LDL.
Statins, resins and fibrates’ mechanisms aren’t related to LDLr, but as the diagram points out, they increase LRLr-mediated uptake of LDLs. Explain.
Same resins.
It’s a net effect brought on by cholesterol starvation in the liver. Hepatocytes avoid cholesterol starvation by increasing LDLr expression, promoting accumulation in the hepatic compartment by uptake of LDLs (and chylomicron remnants). IOW they promote clearance of LDL from circulation.
Same with resins.
What are the second-in-line drugs when LDL is elevated?
Bile-acid-binding resins.
Cholestyramine, colestipol.
What are the two resins?
Both have the fat in their name. What should mum have used on the floor? What do MAOIs increase that we with they wouldn’t?
Colestipol, cholestyramine
What are the two resins? (no prompts)
Colestipol, cholestyramine
Why isn’t the reduction in circulating cholesterol as low as we’d predict in resin therapy?
Reduction in cholesterol form bile reabsorption results in increased cholesterol synthesis.
The net reduction is due to reduction in the overall cholesterol economy and increased LRLr expression.
What are the two downsides to resins?
GI complaints (indigestion, bloating, constipation). Can bind other drugs in the GI tract. But avoidable if taken in 3-4 hours isolation.
Fibrates are a first-line therapy to control cholesterol. T or F?
FALSE - they are a first line therapy, but for triglycerides (not cholesterol).
What four things do we need to know about the mechanism of fibrates?
- Involves fatty acid oxidation
- Involves PPARs
- Increases LRLr LDL uptake
- Inhibits cholesterol and bile synthesis - enhances cholesterol secretion in the bile.
What are two big risks of fibrate therapy?
Gallstones (increase bile cholesterol content)
Myopathy (with CPK elevation)
What are the poorly tolerated (not unsafe) effects of fibrates?
The bald man made a rash decision to get out of bed too quickly with a tummy upset.
Mainly tummy upset, also rash fatigue and hair loss.
What are the poorly tolerated (not unsafe) effects of fibrates?
No prompts
Mainly tummy upset, also rash fatigue and hair loss.
In the liver, niacin inhibits X. In adipose tissue, it inhibits Y.
It can even Z if very low.
Liver: triglyceride synthesis.
Adipose: lipolysis.
It can even elevate HDL if it’s very low.
Niacin is cheap and effective but patient compliance is poor. Aside from myopathy and hepatotoxicity (same as fibrates), what four things are overtly bothersome?
Gastric irritation, gout, flushing, impaired glucose tolerance.
Eww there’s a zit in my bowl.
What’s that cholesterol absorption inhibitor called?
Ezitimibe.
Where does ezitimibe block cholesterol absorption?
Enterocytes in the duodenum.
What are the adverse effects of ezitimibe?
Imagine shitting uncontrollably for hours on the toilet. How would that feel?
Abdominal pain, diarrhoea, headache
How can you decrease LDL cholesterol with plant sterols? What can you expect?
Eat about 2-3g a day, leading to around a 10% decrease in LDL cholesterol.
You may need to compensate for carotenoids.
