Treatment of lipid disorders Flashcards
What is dislipidemia
A disorder of lipoprotein metabolism, including
lipoprotein overproduction or deficiency
Increased: total cholesterol/LDL/TG
Decreased: HDL
What are the sources of cholesterol
Diet (exogenous)
Liver (endogenous)
Hepatobilliary circulation
Examples of bile acid binding resins
colestyramine
colestipol
What is the action of bile acid binding resins
Cholesterol is converted into bile acids in the liver and enters the bile ducts
resins bind to the BA and allow excretion as faeces instead of returning to the liver
How do bile acid binding resins reduce lipids
decrease cholesterol absorption and enterohepatic circulation of BA/cholesterol in hepatocytes
increases LDLr expression and removal of LDL
What are the adverse drug reactions of bile acid binding resins
- Constipation
- Reduced absorption of other medicines
- Fat-soluble vitamin deficiency
- Increased triglyceride levels
- Avoid in bowel or biliary obstruction
What is the action of ezetimibe
Blocks transport protein NPC1L1 in brush border of n enterocytes
inhibits chylomicron (dietary and billiary cholesterol)
Why are ezetimibes better than bile acid binding resins
-does not affect transport of fat-soluble vitamins /TGs/bile acids
-more potent
How does ezetimibe reduce lipids
-decrease cholesterol absorption
-increase LDL r expression
-decreases LDL in circulation/small HDL increase
Ezetimibe and its active metabolite circulate enterohepatically - Delivers agent back to the site of action - Limits
systemic exposure
What are the adverse drug reactions of ezetimibe
- GI disturbance
- Headache
- Hepato-biliary disorders (rare)
- Increased risk of rhabdomyolysis if used with a statin
What is an example of fibrates
fenofibrate
What is the action of fibrates
agonists at PPARa receptor
increases LPL expression in muscle
increases fatty acid uptake and oxidation in muscle cells
decreases TG
Increases apoAI/apoAII synthesis in hepatocytes
increases plasma HDL
What are the adverse drug reactions of fibrates
- GI side-effects most common
- Myositis-like syndrome
- Rhabdomyolysis (with statin)
Avoid: hepato-biliary disorders
Give examples of statins
simvastatin
atorvastatin
pravastatin
What is the action of statins
Inhibit HMG-CoA reductase
How do statins reduce lipids
-decreased cholesterol synthesis
-decreased synthesis and secretion of lipoproteins
-increased LDL r expression
-decreased LDL in circulation
-small increase in HDL
What are the adverse drug reactions of statins
- GI disturbances, insomnia, rashes
- Hepato-biliary effects
- Monitor LFT’s (baseline, within 3 months and at 12 months)
- Transaminases
- Myopathy / rhabdomyolysis
- Advise patients to seek medical advice if develop muscle pain,
tenderness or weakness
Contra-indications
* Active liver disease
* Pregnancy, breast-feeding
What is rhabdomyolysis
breakdown of myoglobin in muscle and kidney
causes kidney toxicity
What to avoid when taking simvastatin (CYP450 metabolised)
Avoid:
– Antibacterials (Clarithromycin, erythromycin)
– Antifungals (Azoles – ketoconazole, itraconazole)
– Grapefruit juice
Do not exceed simvastatin 20mg/day:
– Amiodarone
– Anticoagulants
– Calcium-channel blockers
* Amlodipine
* Diltiazem
* Verapamil
Do not exceed simvastatin 10mg/day:
– Fibrates (bezafibrate or ciprofibrate)
What drug is taken by those who cannot tolerate statins/ezetimibe
PCSK9 inhibitors
alirocumab (monoclonal antibody for PCSK9)
What is the action of PCSK9 inhibitors
PCSK9 normally decreases LDL receptor
alirocumab increases LDL receptors
How is alirocumab administered
subcutaneously every 2 weeks
