Hyperlipidaemia Flashcards
Name the 3 major enzymes involved in lipoprotein metabolism
- Lipoprotein lipase: in muscle and adipose. Hydrolyse chylomicron and vLDL triglyceride
- Lecithin - cholesterol acetyltransferase: In plasma. Esterify free cholesterol on HDL
- triglyceride lipase: liver. Hydrolyse TG within IDL and HDL particles
Describe type 1 primary hyperlipidaemia
- Familial hyperchylomicronemia
- elevated tg, mildly elevated cholesterol
- treat with low fat diet
Describe type 2 primary hyperlipidaemia (2)
Type a: familial hypercholesterolaemia. Elevated cholesterol (LDL), normal tg. Treat with low cholesterol and low saturated fat diet, drugs effective.
Type B: familial combined hyperlipidaemia. Similar to 2a but also elevated VLDL, Tg. Caused by overproduction VLDL in liver. Diet as above with avoidance alcohol and low carbs.
Describe type 3 primary hyperlipidaemia
- Familial dysbetalipoproteinemia
- increased IDL: increased tg and cholesterol. Overproduce or underutilise IDL, abnormal ApoE. Accelerated coronary artery disease.
- treat low cholesterol, saturated fat, carbs diet and avoid alcohol
Describe type 4 primary hyperlipidaemia (6)
- Familial hypertriglyceridemia
- marked increase VLDL, normal LDL
- common
- associated with hyperuricemia, obesity, diabetes
- accelerated coronary artery disease
- treat with low carb diet, lose weight, avoid alcohol
Describe type 5 primary hyperlipidaemia (4)
- Familial mixed hypertriglyceridemia
- type 1 and 4 combined
- elevated vLDL and chylomicrons
- diet should be low fat and low carbs
Name 4 drugs that may cause secondary hyperlipidaemia
- Thiazides
- estrogens
- B blockers
- isotretinoin (roaccutane)
Name 3 examples 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
Aka statins • atorvastatin • simvastatin • pravastatin • lovastatin • rosuvastatin
Moa statins?
Reversible inhibit enzyme HMG - coA reductase which catalyse rate limiting step in cholesterol synthesis.
This also increases amount of LDL receptors, so decrease LDL!
Name 3 side effects statins
- increase liver enzymes (hepatitis)
- myopathy (myalgia, myosotis, rhabdomyolysis)
- git
Name a cholesterol absorption inhibitor
Ezetimibe
Nicotinic acid/ niacin moa? (5)
Vit b3
• Inhibit cholesterol synthesis , decreasing VLDL and thus LDL production
• stimulate lipoprotein lipase to reduce triglyceride content! of VLDL and chylomicrons
• increase HDL! By decrease catabolism
• increase tissue plasminogen activator! TPA
. Decrease plasma fibrinogen! Reverse endothelial cell dysfunction contributing to thrombosis and atherosclerosis
• decrease esterification tg in liver by increased HDL, change LDL to large buoyant particles
Name side effects nicotinic acid/niacin (3)
Anticholesterol • flushing • gi distress • hepatotoxic • hyperglycaemia •Hyperuricemia
Name 2 fibric acid /fibrates
- gemfibrozil
* bezafibrate
Moa fibrates? (4)
• Stimulate lipoprotein lipase, thus reducing triglyceride content ! vLDL and chylomicrons
. Stimulate hepatic LDL clearance by increasing hepatic uptake
• reduce plasma triglyceride, LDL and vLDL concentrations
Activate nuclear transcription factor peroxisome proliferator activated receptor alpha (ppar-alpha) which relates genes that control lipid metabolism
Lower fibrinogen levels
Gemfibrozil increase HDL, decrease lipolysis, may decrease VLDL secretion
Name 2 bile acid sequestrants / binding resins
- Cholestyramine
* Colestipol
Name 2 pcsk9 inhibitors
New class anticholesterol
• alirocumab
• evolocumab
Name 4 treatment options for hypercholesterolaemia and examples
• HMG -coa reductase inhibitors (statins): simvastatin, atorvastatin, pravastatin
. Bile acid binding resin: colestyramine, colestipol
• ezetimibe (cholesterol absorption inhibitor)
• pcsk9 inhibitors: alirocumab, evolocumab
Name 3 treatment options to reduce triglycerides and raise HDL and examples
- Fibric acid derivatives: bezafibrate, gemfibrozil
- Niacin
- omega 3 PUFA (dha/epa)
Name 3 drug interactions with statins
• Gemfibrozil (fibrate) inhibit metabolism all statins so don’t use together. Increased risk rhabdomyolysis.
• warfarin: increased anticoagulant effect
Simvastatin and clarithromyCIN = myositis (cyp3a4)
Indication Statins?
Effective in all hyperlipoproteinemias but less so in familial homozygous type 2a (lack LDL receptors )
When are statins taken in day?
Evening once daily
Atorvastatin longer acting so give in morning
Name 2 statins that may be used in children
- Pravastatin
* atorvastatin
Indication gemfibrozil?
Fibric acid derivative
Hypertriglyceridemia, especially type 3 and 4
