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
Name 3 adverse effects fibrates
- Myositis-like syndrome, especially if renal impairment
- cholelithiasis
- hepatotoxic
Drug interactions with fibric acid derivatives?
Competes with highly bound drugs to albumin
Major problem with warfarin
Indications niacin for hyperlipidaemia? (2)
Type 2b and 4 primary hyperlipidemia
Raises HDL most effectively
Used with bile acid resins in type 2b
Indications bile acid binding resins? (2)
Heterozygous familial hyper cholesterolaemia (with statin as additive if not respond on only statin)
Hypercholesterolaemia (when statin contraindicated)
Pruritis in pts with partial biliary obstruction, bile acid diarrhoea (diabetic neuropathy)
Management patients with Framingham risk score <3%? (3)
- life style changes
- consider statin if LDL persistently >4.9
- aim LDL <3
Management patients with Framingham risk score 3-15%? (3)
- lifestyle changes
- consider statin if LDL >3 persistently
- keep LDL<3
Management patients with Framingham risk score 15-30%? (3)
- lifestyle
- consider statin if LDL <2.5, start immediately if more
- keep LDL <2.5
Management patients with Framingham risk score >30%? (3)
- lifestyle
- start statin immediately
- keep LDL <1.8
Which statin best for heart disease?
Pravastatin
