Cholesterol lowering drugs Flashcards
Describe an atheroma
Fatty deposits in the tunica intima covered by a fibrous cap
What effects of oxidised LDLs have?
Inhibits macrophage motilityInduces T-cell activation Induces vascular smooth muscle cells divisions and differentiationIt is toxic to endothelial cellsEnhances platelet aggregation
Describe the effects of different types of lipids
HDLs - reduces CHD riskLDLs - links to coronary atherosclerosis
What are the different types of drugs which can be used to lower levels of lipids?
StatinsCholesterol absorption inhibtorsFibratesNiacinBile acid sequestrants
Describe the transport function of chylomicrons
Dietary TAGs from intestine to the tissues (adipose)
Describe the transport function of VLDLs
Dietary TAGs synthesised in the liver to adipose for storage
Describe the transport function of LDLs
Cholesterol synthesised in the liver to the tissues
Describe the transport function of HDLs
Excess tissue cholesterol to the liver so its can be disposed as biles salts
Which of the lipoproteins causes the worst clinical effects?
LDLs
Which is the most commonly used lipid lowering drug and why/
Statins- cheap- best tolerated for lowering LDLs- is very effective
What is the primary physiological action of statins?
Inhibits hepatic HMG CoA Reductase- involved in cholesterol synthesis
What happens when the hepatic cholesterol concentration decreases?
This stimulates LDL receptor production which increase the rate of removal of LDLs from the plasma
Describe simvastatin
Has a short half lifeMost commonly used statinGiven at night so have highest conc at time when cholesterol production is greatest
Describe atorvastatin
Half life = 20 hoursHas a superior efficacy to simvastatin
Describe rostuvastatin
Contains sulphurIs more potent than simvastatinHalf life = 20 hours
What is the indication for prescription for statins?
Hyperlipidaemia which has not responded to changes in diet or exercise
When would you not give a statin?
Pregnant womenBreastfeeding womenPt with liver disease
Give some adverse drug reactions which occur with statins
Increase transaminase levelsMyopathyGI disturbancesArthralgiaHeadaches
Describe myopathy and when would you get it
Diffuse muscle pain- when combining statin use with cyclosporin, erythromycin, niacin- can test levels of creatinine kinase to confirm presence of myopathy
What is the mechanism of action of fibrates?
Act as agonists on the Peroxisome Proliferator-Activated Receptor-α (PPAR-α).
What actions do fibrates have?
- LDL lowering (variable amount)- HDL increases of 15-25% in hypertriglyceridemia- Decreases Triglycerides 25-50%
When would you prescribe fibrates?
Used as first line choice in hypertriglyceridemia
Give some examples of fibrates
BezafibrateCiprofibrateGemfibrozil
When would you not use fibrates?
PregnancyBreast feedingGall bladder diseaseSevere renal of hepatic impairmentHypoalbuminaemia
What are some ADRs which occur with fibrates?
GI disturbancesDermatitisPruritisRashImpotenceHeadacheDizzinessBlurred vision
Describe cholesterol absorption inhibitors
Inhibit cholesterol uptake by blocking NPC1L1 (cholesterol transport uptake protein) in the brush border. This decrease the hepatic cholesterol concentration.
Give an example of a cholesterol uptake inhibitor
Ezetimibe
What kind of effect does a dose of ezetimibe have?
A single 10mg dose reduces LDL levels by 15-20%.
When would you use ezetimibe?
In statin intolerant patients- can give with a statin to reduce LDL levels by 40% and to reduce the side effects of statins
What are some adverse drug reactions for cholesterol uptake inhibitors?
GI disturbances- diarrhoea- painHeadache
Describe the mechanism of action of bile acid sequestrants
Bind to bile acids in the intestine and prevent their reabsorption which means that there will be lower cholesterol levels as bile acids are produced from cholesterol.
Give some ADRs for bile acids sequestrants
GI disturbances- nausea- vomiting- constipation- abdominal pain- flatulence- heart burn
When would you not use bile acid sequestrants?
Biliary obstruction
Give the mechanism of action of niacin
Inhibits lipoprotein-a synthesis
What are the effects of niacin?
Increases HDL levels- decreases risk of cardiovascular events
Give some side effects of niacin
Skin flushingItchingDry skinEczema exacerbationsAcanthosis nigricans
