Hyperlipidemia Flashcards
Are lipids hydrophobic/hydrophilic?
Hydrophobic
What are the 3 types of lipoproteins?
Very low-density chylomicrons, Low-density chylomicrons & high-density chylomicrons
Which is the good type of cholesterol?
HDL - want high marks
What causes primary hyperlipidemias?
Genetics
How is Type 1 Primary Hyperlipidemia identified & treated?
Familial Hyperchylomicronemia
Elevated TG & mildly elevated CHOL
Treated with low fat diet
How is type 2A primary hyperlipidemia identified & treated?
Familial Hypercholesterolemia
Elevated CHOL & LDL, normal TG
Treated with low cholesterol & low saturated fat diet. Drug treatment effective.
How is type 2B primary hyperlipidemia identified & treated?
Familial combined hyperlipidemia, like 2A but with elevated VLDL too
Elevated CHOL and TG caused by overproduction of VLDL by liver.
Treatment by low cholesterol & low saturated fat diet. Avoid alcohol
How is type 3 primary hyperlipidemia identified & treated?
Familial dysbetalipoproteinemia
Increased levels of LDL, TG & CHOL
Overproduction/underutilization of LDL, abnormal Apolipoprotein E
Accelerated CAD
Treatment like 2B
How is type 4 primary hyperlipidemia identified & treated?
Familial hypertriglyceridemia
Marked increase in VLDL, normal LDL, relatively common,
Often associated with hyperuricemia (high uric acid in urine), obesity, diabetes
Accelerated coronary disease noted
Treatment: low CHO diet, weight reduction, avoidance of alcohol
Features & treatment of type 5 primary hyperlipidemia?
Familial mixed hypertriglyceridemia
Type 1 & 4
Elevated VLDL & chylomicrons
Low fat & low CHO diet
What causes secondary hyperlipidemias?
Underlying medical conditions, lifestyle factors & certain medications that effect lipid metabolism
What diseases can cause secondary hyperlipidemias?
Diabetes mellitus, alcoholism, nephrotic syndrome, chronic renal failure, hypothyroidism & liver disease.
What medications can caused secondary hyperlipidemias?
Thiazides, estrogen, beta-blockers & isotretinoin
Treatment for hyperlipidemia is focused on reducing what?
LDL
Treatment for hyperlidemia?
Lifestyle modifications, low cholesterol diet, exercise, smoking cessation, low alcohol consumption
What are some major risk for ischaemic cardio- & cerebrovascular disease?
Diabetes mellitus, hypertension, central obesity, smoking, dyslipidemia (fasting levels- total cholesterol >5mmol/L or LDL>3mmol/L or HDL<1 in men & 1.2mmol/L in women; family history of early onset cardiovascular disease, age (men>55, women>65)
What drug category does cholestyramine fall into?
Bile acid resin
How do bile acid resins work?
Cause bile acid levels to drop so that the body is stimulated to produce more bile acid from cholesterol. It will initially use hepatic cholesterol until it’s depleted & then LDL levels in the blood will drop when more bile acid is needed.
What drug category do Simvastatin, Rosuvastatin & atorvastatin fall under?
Statins (HMG Co-A reductase inhibitor)
How do the statins work?
Inhibit HMG Co-A reductase which reduces cholesterol production & upregulate LDL receptors on hepatocytes, increasing clearance of LDL from the bloodstream.
They cause a reduction in total cholesterol, LDL, VLDL & TG with an increase in HDL.
What type of drug is Gemfibrozil?
Reduces synthesis of VLDL & apo protein B as well as removing TG-rich lipoproteins from the plasma
What type of drug is Ezetimibe?
Cholesterol absorption inhibitors
How does Ezetimibe work?
Prevents absorption of cholesterol from brush border of intestine & blocks cholesterol reabsorption from the GIT
How are statins administered & how long do they last?
Orally
Duration: 12-24hrs
The first line drug used is Simvastatin(40mg) but what is the draw back of this drug?
It has a major side effect of muscle cramps & therefore has poor patient adherence
Which statin is potent & reserved as a 2nd-line drug?
Rosuvastatin
Which statin is administered with protease inhibitors in HIV treatment?
Atorvastatin
What are the common side effects of statins?
GIT symptoms
Muscles cramps/aches
Less common: hepatitis, rashes, headache, insomnia, nightmares, difficulty concentrating, myopathy & rhabdomyolysis.
What are contraindications of statins?
Can have severe adverse effects on nursing infants. Women on treatment shouldn’t breastfeed.
What are interactions with statins?
-Gemfibrozil: inhibits metabolism of all statins causing their levels to get too high which increases risk of rhabdomyolysis.
-Warfarin: leads to increased anticoagulant effect
-Concurrent use of CYP3A4 inhibitors (Itraconazole,
ketoconazole, erythromycin, clarithromycin, teilithromycin, HIV antivirals, grapefruit juice, cyclosporine, amlodipine) increase levels
What are the effects of Ezetimibe - which is prescribed with statins, fibrates or nicotinic acid derivatives/ can be prescribed alone if pt. cannot tolerate statins
Decreases: total cholesterol, LDL-C (by 15-20% when added to diet) apolipoprotein B & TGs
Increases: HDL
Helps to reduce LDL more when combined with a statin
What type of drug is Gemfibrizol?
A fibrate- PPRA-alpha agonist which relates to genes that control lipid metabolism. Stimulates lipoprotein lipase. Results in hydrolysis of TG in chylomicrons and VLDL. Accelerates removal of VLDL & chylomicrons. Doesn’t alter secretion of VLDL from liver.
Also lowers fibrinogen levels (risk of bleeding). Increases HDL.
How is Gemfibrizol administered, how long does it last & what would toxicity lead to?
Orally, 3-24h
Toxicity leads to myopathy & hepatic dysfunction
What are adverse affects of Gemfibrizol?
GI effects, myositis syndrome (elevated CK & AST), hepatotoxicity, cholelithiasis (gall stones)
What are drug interactions with Gemfibrizol?
-Competes with highly protein bound drugs to albumin
-Warfarin (increase risk of bleeding?
What is Bezafibrate used for?
As an adjunctive therapy for adult patients with elevated serum TG at risk of pancreatitis with no response to dietary Mx. It inhibits TG synthesis & decreases VLDL by increasing VLDL metabolism. Administered once daily.
What type of drug is Cholestyramine?
A Bile Acid Sequestrant
(anion exchange resins)
How does Cholestyramine work?
It binds bile acids in the gut which prevents reabsorption & enterohepatic recirculation, increases cholesterol catabolism & upregulates LDL receptors. Work to decrease LDL levels.
How is Cholestyramine administered & what are affects of toxicity?
Orally- taken with meals
Constipation, bloating, interferes with absorption of some drugs & vitamins
what are the clinical uses of Cholestyramine?
-Heterozygous familiar hypercholesterolemia
-an addition to a stain if response has been inadequate
-hypercholesterolemia
-when a statin is CI
-pruritus in patients with partial biliary obstruction bile
acid diarrhea (diabetic neuropathy)
