Lipid drugs Flashcards
At what LDL level is seen as high?
> 200mg/dL
Below what level of HDL is considered low?
< 45mg/dL
- Little evidence that raising low levels reduces risk
What is a normal TG level?
< 150mg/dL
What is the main risk associated with elevated triglycerides?
Pancreatitis
What are statins used to treat specifically?
Elevated LDL-C
- Rarely used to treat elevated TG or low HDL-C
What is usually used as a guidline for whether to start a patient on statins?
QRISK score (>5%) - Old guidelines mainly based on LDL and risk factors
When would high TG or low HDL be treated?
Triglycerides
- > 500
- High non-HDL cholesterol (TC-HDL)
Low HDL
- Patients w. established CAD
What are all the lipid lowering drugs?
- Statins
- Niacin
- Fibrates
- Absorption blockers
- Bile acid resins
- Omega-3 fatty acids
What are the effects of statins?
HMG-CoA reductase inhibitors
- Decrease cholesterol synthesis in liver
- Increase LDL receptors in liver
- Decrease LDL (to a lesser degree TG and increase HDL)
What is thought to be the mechanism behind muscle aches with statins?
Low levels of coenzyme Q in muscles
- People can take supplements
How can you differentiate muscle conditions as a side-effect of statin therapy?
Myalgias
- Normal CK levels
- Weakness, soreness
Myositis
- Increased CK
Rhabdomyolysis
- Weakness, pain, dark urine
- CKs in 1000s
What can statins cause which may result in death?
Rhabdomyolysis
- Acute renal failure, leading to death
What drugs may increase the risk of Rhabdomyolysis in combination with statin therapy?
- Cyclosporine
- Gemfibrozil (fibrate)
What are the hydrophilic statins?
- Pravastatin
- Fluvastatin
- Rosuvastatin
What are the lipophilic statins?
- Atorvastatin
- Simvastatin
- Lovastatin
What is an advantage of hydrophilic statins?
Cause less myalgias (e.g rosuvastatin)
What are statins metabolised by?
Liver P450 system
What do P450 inhibitors (e.g grapefruit juice) increase the chances of with statins?
- LFTs
- Myalgias
What is the overall effect of niacin on lipid levels?
Lower LDL and increase HDL
- Main effect increasing HDL (decreased HDL breakdown)
- Decreased VLDL
- Decreased FA mobilization (decreased TG)
What are the side-effects of niacin?
- FLushing
(aspirin can inhibit PGs) - Hyperglycemia
- Huperuricemia (gout)
Give examples of fibrates
- Gemfibrozil
- Clofibrate
- Bezafibrate
- Fenofibrate
What do fibrates activate?
PPAR-a
- Modifies gene transcription
- Increase activity lipoprotein lipase
- Increase FA oxidation -> decreased VLDL
- Increase TG breakdown
What patients are given fibrates?
High triglycerides
What are the side-effects of fibrates? (e.g Gemfibrozil, Clofibrate)
- Myositis (rhabdo w. gemfibrozil)
- Increased LFTs
- Cholesterol gallstones
What is an example of an absoption blocker?
Ezetimibe
How does Ezetimibe work?
Intestinal brush border
- Highly selective for cholesterol
- Increased LDL receptors on liver
- Does not affect vits ADEK, triglycerides
What are side-effects of absorption blockers (e.g Ezetimibe)?
- Increased LFTs
- Diarrhea
What are examples of bile acid resins (less used now)?
- Cholestyramine
- Colestipol
- Colesevelam
Describe how bile acid resins work?
- More bile excretion in stool
- Liver converts cholesterol -> bile to makeup losses
- Modest lowering LDL
What are some of the ~side-effects of bile acid resins?
- Bloating
- Bad taste
- ADEK vits not absorbed
- Cholesterol gallstones
What are the effects of omega-3 fatty acids on lipid levels?
Incorporated into cell membranes
- Reduce VLDL production
- Lowers triglycerides
- Modest increase in HDL
What is the mechanism behind PCSK9?
Degrade LDL receptors
- Bind to LDL receptors
- LDL receptor transported to lysosome
Give examples of PCSK9 inhibitors
- Alirocumab
- Evolocumab
Monoclonal antiBs
What is the mechanism of action behind PCSK9 inhibitors?
- Decrease LDL-receptor degrasation
- Increased LDL receptors on hepatocytes
- Decrease LDL cholesterol in plasma (>60%)
How are PCSK9 inhibitors administered?
SC injection
What are side-effects of PCSK9 inhibitors?
- Administration - injection site reaction
- Memory problems
