Hyperlipidemia

Question 1

Are lipids hydrophobic/hydrophilic?

Answer 1

Hydrophobic

Question 2

What are the 3 types of lipoproteins?

Answer 2

Very low-density chylomicrons, Low-density chylomicrons & high-density chylomicrons

Question 3

Which is the good type of cholesterol?

Answer 3

HDL - want high marks

Question 4

What causes primary hyperlipidemias?

Answer 4

Genetics

Question 5

How is Type 1 Primary Hyperlipidemia identified & treated?

Answer 5

Familial Hyperchylomicronemia
Elevated TG & mildly elevated CHOL
Treated with low fat diet

Question 6

How is type 2A primary hyperlipidemia identified & treated?

Answer 6

Familial Hypercholesterolemia
Elevated CHOL & LDL, normal TG
Treated with low cholesterol & low saturated fat diet. Drug treatment effective.

Question 7

How is type 2B primary hyperlipidemia identified & treated?

Answer 7

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

Question 8

How is type 3 primary hyperlipidemia identified & treated?

Answer 8

Familial dysbetalipoproteinemia
Increased levels of LDL, TG & CHOL
Overproduction/underutilization of LDL, abnormal Apolipoprotein E
Accelerated CAD
Treatment like 2B

Question 9

How is type 4 primary hyperlipidemia identified & treated?

Answer 9

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

Question 10

Features & treatment of type 5 primary hyperlipidemia?

Answer 10

Familial mixed hypertriglyceridemia
Type 1 & 4
Elevated VLDL & chylomicrons
Low fat & low CHO diet

Question 11

What causes secondary hyperlipidemias?

Answer 11

Underlying medical conditions, lifestyle factors & certain medications that effect lipid metabolism

Question 12

What diseases can cause secondary hyperlipidemias?

Answer 12

Diabetes mellitus, alcoholism, nephrotic syndrome, chronic renal failure, hypothyroidism & liver disease.

Question 13

What medications can caused secondary hyperlipidemias?

Answer 13

Thiazides, estrogen, beta-blockers & isotretinoin

Question 14

Treatment for hyperlipidemia is focused on reducing what?

Answer 14

LDL

Question 15

Treatment for hyperlidemia?

Answer 15

Lifestyle modifications, low cholesterol diet, exercise, smoking cessation, low alcohol consumption

Question 16

What are some major risk for ischaemic cardio- & cerebrovascular disease?

Answer 16

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)

Question 17

What drug category does cholestyramine fall into?

Answer 17

Bile acid resin

Question 18

How do bile acid resins work?

Answer 18

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.

Question 19

What drug category do Simvastatin, Rosuvastatin & atorvastatin fall under?

Answer 19

Statins (HMG Co-A reductase inhibitor)

Question 20

How do the statins work?

Answer 20

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.

Question 21

What type of drug is Gemfibrozil?

Answer 21

Reduces synthesis of VLDL & apo protein B as well as removing TG-rich lipoproteins from the plasma

Question 22

What type of drug is Ezetimibe?

Answer 22

Cholesterol absorption inhibitors

Question 23

How does Ezetimibe work?

Answer 23

Prevents absorption of cholesterol from brush border of intestine & blocks cholesterol reabsorption from the GIT

Question 24

How are statins administered & how long do they last?

Answer 24

Orally
Duration: 12-24hrs

Question 25

The first line drug used is Simvastatin(40mg) but what is the draw back of this drug?

Answer 25

It has a major side effect of muscle cramps & therefore has poor patient adherence

Question 26

Which statin is potent & reserved as a 2nd-line drug?

Answer 26

Rosuvastatin

Question 27

Which statin is administered with protease inhibitors in HIV treatment?

Answer 27

Atorvastatin

Question 28

What are the common side effects of statins?

Answer 28

GIT symptoms Muscles cramps/aches Less common: hepatitis, rashes, headache, insomnia, nightmares, difficulty concentrating, myopathy & rhabdomyolysis.

Question 29

What are contraindications of statins?

Answer 29

Can have severe adverse effects on nursing infants. Women on treatment shouldn't breastfeed.

Question 30

What are interactions with statins?

Answer 30

-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

Question 31

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

Answer 31

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

Question 32

What type of drug is Gemfibrizol?

Answer 32

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.

Question 33

How is Gemfibrizol administered, how long does it last & what would toxicity lead to?

Answer 33

Orally, 3-24h Toxicity leads to myopathy & hepatic dysfunction

Question 34

What are adverse affects of Gemfibrizol?

Answer 34

GI effects, myositis syndrome (elevated CK & AST), hepatotoxicity, cholelithiasis (gall stones)

Question 35

What are drug interactions with Gemfibrizol?

Answer 35

-Competes with highly protein bound drugs to albumin -Warfarin (increase risk of bleeding?

Question 36

What is Bezafibrate used for?

Answer 36

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.

Question 37

What type of drug is Cholestyramine?

Answer 37

A Bile Acid Sequestrant (anion exchange resins)

Question 38

How does Cholestyramine work?

Answer 38

It binds bile acids in the gut which prevents reabsorption & enterohepatic recirculation, increases cholesterol catabolism & upregulates LDL receptors. Work to decrease LDL levels.

Question 39

How is Cholestyramine administered & what are affects of toxicity?

Answer 39

Orally- taken with meals Constipation, bloating, interferes with absorption of some drugs & vitamins

Question 40

what are the clinical uses of Cholestyramine?

Answer 40

-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)