Cholesterol Drugs Flashcards
What are some examples of Statin drugs?
- Simvastatin
* Atorvastatin
What is the effect of statin on the cholesterol synthesis and lipoproteins?
- Inhibit cholesterol synthesis
- Increase clearance of IDL and LDL
- Decrease production of VLDL and LDL so less in serum
What is the mechanism of action demonstrated by Statins?
- Antagonising HMG-CoA reductase
- Increase in synthesis of LDL receptor
What are the uses of Statins?
- Cardiovascular risk prevention
* Familial hypercholesterolemia
What are the side effects of Statins?
- Increased transaminase levels (reversible)
- Myopathy resulting in muscle pain.
- Increase in creatinine phosphokinase levels with higher dose
- GI complaints
- Arthralgia
- Headaches
What are some examples of cholesterol lipase inhibitors?
•Ezetimibe
What are the effects of ezetimibe on cholesterol?
Selectively inhibits intestinal cholesterol absorption
- Decreased intestinal delivery of cholesterol to the liver
- Increased expression of hepatic LDL receptor
- Decreased cholesterol content of atherogenic particles
What are the uses of cholesterol lipase inhibitors?
-Cardiovascular risk prevention
What are the side effects of Ezetimibe?
- Headache
- Abdominal pain
- Diarrhoea
What are the classes of cholesterol drugs?
- Statin
- Cholesterol lipase inhibitors
- Nicotinic Acid
- Fibrates
What are the effect of nicotinic acids on cholesterol?
- Reduce VLDL
* Increases HDL at high doses. Best agent to raise HDL-C
What is the mechanism of action of nicotinic acids?
•Lipid lowering by inhibition of lipoprotein synthesis
What are the uses of Nicotinic acid?
-Reduces coronary events
What are the side effects of Nicotinic acids?
- Flushing, Itching, Headache
- Hepatoxicity, GI
- Activation of peptic ulcer
- Hyperglycaemia and reduced insulin sensitivity
What are the contraindications of nicotinic acids?
- Peptic ulcer disease
- Active liver disease or unexplained LFT elevations
What are effects of fibrates on cholesterol?
PPAR-alpha agonist which increases production of lipoprotein lipase
- Reduces triglyceride production
- Some reduction in LDL but variable
What is the mechanism of action of Fibrates?
- Increase in fatty acid uptake and oxidation
- Increase LDL particle size and HDL-C levels
- Direct vascular effects
What are some key messages about combination therapies to lower cholesterol?
Statins are used in combination with:
- Fibrate
- Nicotinic Acid
- Ezetimibe
- Omega-3 Fatty acids
- Resins
What are some risk of using fibrates and statins?
- Increased risk of myopathy and rhabdomyolysis
- Gemfibrozil in particular may impair glucorinidation of statins.
- Fenofibrate appears to have less potential for impairment of statin metabolism and thus this may account for the reduced reports
What are examples of fibrates?
- Fenofibrate
- Bezafibrate
- Gemfibrozil
How is Ezetimibe delivered?
Ezetimibe and its active glucuronide circulate entero-hepatically
- Delivers agents back to the site of action
- Limited systemic exposure
When are fibrates used?
- Adjunctive therapy to diet
- Hypertriglyceridemia
- Combined hyperlipidaemia with low HDL who do not respond to NA
What are some side effects of fibrates?
- GI upset
- Cholelithiasis
- Myositis
- Abnormal LFTs
What are some contraindications to consider when using fibrates?
- Hepatic or renal dysfunction
* Pre-existing gallbladder disease
What are secondary benefits of statin?
- Anti-inflammatory
- Plaque reduction
- Improved endothelial cell function
- Reduced thrombotic risk
