58 - Drug Regulation of Serum Lipids

Question 1

Treatment for dyslipidaemia
1)
2)
3)
4)

Answer 1

1) Establish baseline fasting plasma lipid profile
2) Consider cardiovascular status and risk factors
3) Treat secondary causes (EG: obesity, diabetes)
4) Manage modifiable risk factors

Question 2

Sources of cholesterol
1)
2)

Answer 2

1) Diet (animal fats)

2) De novo synthesis in liver (probably sufficient for body’s cholesterol needs)

Question 3

Where do statins originally come from?

Answer 3

Fungi

Mevastatin from Penicillium citrinum

Question 4

Effects of statins 
1)
2)
3)
4)
5)

Answer 4

1) Decrease mevalonic acid, therefore cholesterol synthesis
2) Compensatory increase in hepatic LDL receptors
3) Increased clearance of LDL from blood
4) Decreased plasma total cholesterol as well as LDL
5) Increased plasma HDL:LDL ratio

Question 5

Effect of increasing statin dose

Answer 5

Doubling dose leads to significantly lesser percentage decreases in serum LDL

Question 6

Pharmacological action of statins

Answer 6

HMG-CoA inhibitors

Question 7

How long does it take for statin therapy to reach maximum effectiveness?

Answer 7

1-2 years

Question 8

Precautions to take with statin therapy
1)
2)
3)

Answer 8

1) Grapefruit juice involves cytochrome P450 metabolism in liver. So does statin, so increases toxicity of statins
2) Some antibiotics, antifungals also use P450
3) Barbituates decrease statin levels
4) Minor increases in creatine kinase (from muscle breakdown, can lead to muscle pain and tenderness)

Question 9

Common contraindications of statins 
1)
2)
3)
4)

Answer 9

1) Mild GI symptoms
2) Headaches
3) Insomnia
4) Dizziness

Question 10

Rare, serious side effects of statins 
1)
2)
3)
4)

Answer 10

1) Myopathy (minimised with coenzymeQ10 therapy)
2) Rhabdomyolysis
3) Renal failure
4) Hepatitis, liver failure (~2% of patients have mild increase in serum aminotransferase)

Question 11

Effect of statins on foeti

Answer 11

Impair myelination

Question 12

When are statins not to be prescribed?

Answer 12

Pregnancy, pre-surgery, post-trauma

Question 13

Treatment options for hypercholesterolaemia
1)
2)
3)
4)
5)

Answer 13

1) Statins
2) Bile acid sequestrants/resins
3) Nicotinic acid (niacin)
4) Fibrates
5) Fish oils

Question 14

Examples of bile acid sequestrants

Answer 14

1) Cholestyramine

2) Cholestipol

Question 15

How do bile acid sequestrants work?
1)
2)
3)
4)

Answer 15

1) Non-absorbable macromolecules, ingested as a granular preparation.
2) Bind bile acids, preventing gut absorption of lipids
3) This results in an up-to-10-times increase in bile acid secretion
4) As bile acid requires cholesterol to synthesise, this causes upregulation of hepatic LDL receptors, removal of LDL from plasma, more cholesterol metabolism

Question 16

Common adverse effects of bile acid sequestrants 
1)
2)
3)
4)

Answer 16

1) Abdominal discomfort
2) Bloating
3) Constipation
4) Flatulence

Question 17

What are bile acid sequestrants used to treat?

Answer 17

Hypercholesterolaemia, mixed hyperlipidaemia

Question 18

Rare adverse events of bile acid sequestrants 
1)
2)
3)
4)

Answer 18

1) Increased TGs
2) Faecal impaction
3) Decreased absorption of fat soluble viamins
4) Steatorrhoea

Question 19

Effect of resins on absorption of other drugs

Answer 19

Decreases absorption of anionoic, cationic, neutrally-charged drugs.

Question 20

When should resins be taken?

Answer 20

Hours before or after other drugs taken, as decrease absorption of other drugs

Question 21

Drug that lowers LDL by binding to a sterol transporter

Answer 21

Ezetimibe

Question 22

Ezetimibe effect

Answer 22

Binds to a sterol transporter in the intestine. This inhibits cholesterol absorption, lowers LDL.

Question 23

Possible ezetimibe side effects

Answer 23

Diarrhoea, tiredness, headache,allergic reactions, joint, stomach pain

Question 24

How is ezetimibe used?
1)
2)

Answer 24

1) Alone in statin-intolerant patients

2) Used together with statins to lower statin dose

Question 25

Other names for niacin

Answer 25

Nicotinic acid, vitamin B3

Question 26

Mechanism by which niacin decreases LDL

Answer 26

Unclear.

Question 27

Effects of niacin 
1)
2)
3)
4)

Answer 27

1) Decrease secretion of VLDL particles from liver
2) Reduces plasma LDL and triglycerides (so also for mixed hyperlipidaemia)
3) Increases HDL
4) Lowers potentially atherogenic lipoprotein (a) -
Lp(a) formed from LDL is found in plaques, inhibits thrombolysis

Question 28

Common adverse effects of niacin

Answer 28

–vasosodilation, flushing, hypotension
–nausea, vomiting
–tolerance develops to flushing as gastric upsets

Question 29

Rare adverse effects of niacin

Answer 29

–itching
–glucose intolerance
–uric acid retention
–may increase hepatic impairment

Question 30

When is niacin used?

Answer 30

Rarely used alone. Often in combination

Question 31

Examples of fibrates

Answer 31

Gemfibrozil, fenofibrate

Question 32

Mechanism of action of fibrates
1)
2)
3)

Answer 32

1) Agonists at nuclear receptors
2) Bind peroxisome proliferator activated receptor alpha
3) Increased synthesis of lipoprotein lipase

Question 33

Effect of increasing lipoprotin lipase levels 
1)
2)
3)
4)

Answer 33

1) Increase lipolysis of lipoprotein triglyceride
2) Moderate reduction in plasma triglycerides
3) Moderate increase in HDL
4) Variable effects on LDL

Question 34

Use of fibrates for cholesterol treatment

Answer 34

Generally used as adjunct to dietary changes for high TGs, mixed hyperipidaemia, and second line therapy for hypercholesterolaemia

Question 35

PPARa

Answer 35

Peroxisome proliferator activated receptor alpha.

A nuclear receptor, which encodes lipoprotein lipase.

Question 36

Precautions to take with fibrates

Answer 36

Mild elevation of serum aminotransferase can present.

Monitor levels at three-month intervals. Reduce dose or discontinue fibrates if necessary

Question 37

Common adverse events with fibrates 
1)
2)
3)
4)

Answer 37

1) Nausea
2) Dry mouth
3) Headache
4) Rash

Question 38

Rare adverse events with fibrates 
1)
2)
3)
4)
5)

Answer 38

1) Arrhythmias
2) Gallstones
3) Photosensitivity
4) Impotence
5) Depression

Question 39

Effect of fish oil omega-3 fatty acids on bloop lipid composition

Answer 39

Reduce TAGs and VLDL

Question 40

Possible side effects of fish oils

Answer 40

Diarrhoea, abdominal discomfort

BLood-thinning effect

Question 41

Drugs that decrease LDL
1)
2)
3)
4)
5)
6)

Answer 41

1) Statins (biggest decrease)
2) Bile acid resins
3) Ezetimibe
4) Niacin
5) Fibrates
6) Fish oil (also decreases VLDL)

Question 42

Drugs that increase LDL receptor expression in liver
1)
2)
3)

Answer 42

1) Statins
2) Bile acid resins
3) Niacin

Question 43

Drugs that increase HDL levels 
1)
2)
3)
4)

Answer 43

1) Statins
2) Niacin (biggest increase)
3) Fibrates
4) Fish oil

Question 44

Drugs that decrease TAG levels
1)
2)
3)
4)

Answer 44

1) Statins
2) Niacin
3) Fibrates (increase lipoprotein lipase)
4) Fish oil

Question 45

Effects of statins on blood lipid concentrations 
1)
2)
3)
4)

Answer 45

1) Decrease LDL
2) Increase LDL receptor
3) Increase HDL
4) Decrease TAGs

Question 46

Effects of ezetimibe on blood lipid concentrations

Answer 46

Decreases LDL

Question 47

Effects of bile acid resins on blood lipid concentrations
1)
2)

Answer 47

1) Decrease LDL

2) Increase LDL receptor

Question 48

Effects of niacin on blood lipid concentrations 
1)
2)
3)
4)

Answer 48

1) Decrease LDL
2) Increase LDL receptor
3) Increase HDL
4) Decrease TAGs

Question 49

Effects of fibrates on blood lipid concentrations 
1)
2)
3)
4)

Answer 49

1) Decrease LDL
2) Increase HDL
3) Decrease TAGs
4) Increase lipoprotein lipase

Question 50

Effects of fish oils on blood lipid concentrations
1)
2)
3)

Answer 50

1) Decrease LDL and VLDL
2) Increase HDL
3) Decrease TAGs

Question 51

Dyslipidaemia drugs that act on intestine

Answer 51

Ezetimibe, bile acid resins

Question 52

Dyslipidaemia drugs that act on capillaries

Answer 52

Fibrates

Question 53

Dyslipidaemia drugs that act on extrahepatic tissues

Answer 53

Statins