Drug Regulation of Serum Lipids

Question 1

What is dyslipidaemia?

Answer 1

An abnormal lipid profile

Question 2

What are the three types of dyslipidaemia?

Answer 2

hypercholesterolaemia, hypertriglyceridaemia, mixed hyperlipidaemia

Question 3

What is the target level for total cholesterol?

Answer 3

< 4.0 mmol/L

Question 4

What is the target level for triglycerides?

Answer 4

< 2.0 mmol/L

Question 5

What is the target level for HDL cholesterol?

Answer 5

> 1.0 mmol/L

Question 6

What is the target level for LDL cholesterol?

Answer 6

< 2.5 mmol/L

Question 7

What are the non-pharmalogical interventions for dyslipidaemia?

Answer 7

treat secondary causes and manage modifiable risk factors

Question 8

How does smoking increase risk?

Answer 8

Damages the lining of the blood vessels - this both increases the likelihood of atherosclerosis and increases clotting so a greater risk of thrombosis

Question 9

How does alcohol increase risk?

Answer 9

Increases triglyceride levels

Question 10

How does a Mediterranean diet decrease risk?

Answer 10

By reducing cardiovascular risk

Question 11

How do plant sterol esters decrease risk?

Answer 11

By reducing LDL cholesterol

Question 12

How does fish oil decrease risk?

Answer 12

reduces triglycerides and increases HDL

Question 13

Which lipoproteins can deposit lipids into artery walls?

Answer 13

Lipoproteins containing apoB-100 - LDL, VLDL, IDL

Question 14

What are statins?

Answer 14

HMG CoA reductase inhibitors

Question 15

How were statins discovered?

Answer 15

By screening microbes for their ability to inhibit cholesterol - initially found penicillium citrinum and then later aspergillus terreus

Question 16

How do statins decrease cholesterol levels?

Answer 16

Initially by inhibiting HMG CoA reductase which decreases synthesis, but this results in a compensatory increase in hepatic LDL receptors which increases clearance of LDL from the blood and also leads to increased synthesis of HDL (so that more cholesterol can be taken back to the liver and recycled)

Question 17

What is the ceiling effect in statins?

Answer 17

Once the initial dose is given, doubling or tripling dose will have little benefit but may still increase adverse effects

Question 18

Why do statins have poor compliance?

Answer 18

Because patients don’t feel any different when taking them and it can take 1-2 years to improve lipid profile

Question 19

What should patients taking statins avoid?

Answer 19

Excessive amounts of grapefruit juice or other drugs which will create competition for cytochrome P450 metabolism and can lead to toxicity

Question 20

What is the interaction of antibiotics, antifungals and fibrates with statins?

Answer 20

Will increase statin level

Question 21

What is the interaction of phenytoin, barbiturates and glitazones with statins?

Answer 21

Will decrease statin level

Question 22

What is the result of increased serum aminotransferase in some patients taking statins?

Answer 22

Liver toxicity

Question 23

What is the result of creatine kinase in patients taking statins?

Answer 23

can lead to muscle pain and tenderness

Question 24

What are the common mild adverse effects of statins?

Answer 24

mild GI symptoms, headache, insomnia, dizziness

Question 25

What are the serious adverse effects of statins?

Answer 25

myopathy, rhabdomyolysis, renal failure, liver failure

Question 26

Why are statins contraindicated in pregnancy?

Answer 26

Causes impaired fetal myelination

Question 27

Why are statins withheld in infection, pre surgery and post trauma?

Answer 27

Because of drug drug interactions

Question 28

What are bile acid resins?

Answer 28

A granular preparation that is taken orally to treat hypercholesterolaemia

Question 29

What is the mechanism of bile acid resins?

Answer 29

Binds to bile acids to prevent their gut absorption which causes increased demand in cholesterol for bile acid synthesis so the body will up regulate hepatic LDL receptors and remove LDL from the plasma

Question 30

What are the common mild adverse effects of bile acid resins?

Answer 30

abdominal discomfort, constipation, bloating, flatulence

Question 31

What are the rare adverse effects of bile acid resins?

Answer 31

increased triglycerides, faecal impaction, decrease absorbance of fat soluble vitamins, fatty stools

Question 32

Why must other drugs be taken at a a different time to bile acid resins?

Answer 32

Because it will decrease absorption of other drugs

Question 33

What is ezetimibe?

Answer 33

A drug which inhibits the absorption of cholesterol by acting at sterol transporters in the intestines - lowers LDL while still allowing the absorption of bile acids and fat soluble vitamins

Question 34

What are the side effects of eztetimibe?

Answer 34

diarrhea, headache, tiredness, allergic reaction, joint pain

Question 35

When are ezetimibes used?

Answer 35

In patients who are intolerant to statins or in combination with statins to lower statin dose required

Question 36

What is niacin?

Answer 36

Vitamin B3 - used to decrease secretion of VLDL from the liver, reduce plasma LDL, increase plasma HDL and also potentially lowers atherogenic lipoprotein a (a protein which stops thrombolysis)

Question 37

What is the mechanism of niacin?

Answer 37

unknown

Question 38

What are the common adverse effects of niacin?

Answer 38

flushing, nausea, hypotension, vomiting

Question 39

What are the rare adverse effects of niacin?

Answer 39

itching, glucose intolerance, uric acid retention, hepatic impairment

Question 40

What are fibrates?

Answer 40

Drugs used to treat hypertriglyceridaemia

Question 41

What is the mechanism of fibrates?

Answer 41

regulates gene expression to result in an increased synthesis of LPL to breakdown triglycerides

Question 42

What is the effect of fibrates on HDL and LDL?

Answer 42

causes a moderate increase of HDL and has a variable effect on LDL - possibility for increase

Question 43

What are the common adverse effects of fibrates?

Answer 43

nausea, dry mouth, headache, rash

Question 44

What are the rare adverse effects of fibrates?

Answer 44

arrhythmias, gall stones, photosensitivity, impotence, depression and potential for liver toxicity