Statins, bile acid sequestrants, fibrates

Question 1

Why should bile acids (e.g. colestyramine) be used in caution, especially in long term treatment?

Answer 1

They interfere with the absorption of fat soluble vitamins (A,D,E,K) and folic acid.
↳ A,D,K and folic acid supplementation might be required with long term use

Question 2

Outline the MoA of ezetimibe

Answer 2

its a cholesterol absorption inhibitor. Ezetimibe inhibits the intestinal absorption of cholesterol.
↳when used alone it had modest effect on LDL with little effect on other lipoproteins

Question 3

1) Outline the MoA of fibrates e.g. Benzafibrate

2) when should these drugs mainly used?

Answer 3

1) act by decreasing serum triglycerides, they have variable effect on LDL-cholesterol
2) mainly used when serum triglyceride concentration is > 10mmol/L or in those who cannot tolerate statin

Question 4

why should fibrates be used with caution in renal impairment?

Answer 4

Myotoxicity (rhabdomyolysis). discontinue is myotoxicity is suspected or if creatine kinase concentration increase significantly

Question 5

outline the MoA of nicotinic acid

Answer 5

Lowers both cholesterol and triglyceride concentration by inhibiting synthesis. It also increases HDL-cholesterol

Question 6

outline the MoA of statins

Answer 6

Statins competitively inhibit HMG CoA reductase, an enzyme involved in cholesterol synthesis, especially in the liver

Question 7

in which patients should statins be used with caution?

Answer 7

1) Existing hepatic impairment
2) Reduce dose in renal impairment (excreted by kidneys)
3) Avoid in pregnant and BF
4) Hypothyroidism
5) Patients at inc risk of muscle toxicity, inc myopathy
6) High alcohol intake

Question 8

how should statins be managed in patients at increased risk of muscle toxicity e.g. those with family history of muscular disorders, renal impairment and hypothyroidism?

Answer 8

1) They should not be started if the baseline creatine kinase concentration is more than 5x the upper limit of normal.
2) Hypothyroidism should be managed before treatment

Question 9

How likely is the risk of myopathy, myositis and rhabdomyolysis associated with statin use?

Answer 9

Myopathy rare- although myalgia (pain in a muscle) has been reported commonly in patients receiving statins

Question 10

How should a patient who is experiencing myopathy suspected to be caused by a statin be managed?

Answer 10

1) if creatine kinase is markedly elevated or if muscular symptoms are severe- discontinue statin
2) if symptoms resolve and creatine kinase concentrations return to normal, reintroduce statin at lower dose and monitor closely

Question 11

should statins be discontinued if there is an increase in blood glucose?

Answer 11

do not discontinue as the benefits continue to outweigh the risks

Question 12

Interstitial lung disease is a side effect of statins, what symptoms would indicate that a person may have developed this condition and what should be done?

Answer 12

If patient develops symptoms such as dyspnoea (difficult/laboured breathing), cough, and weight loss
↳ seek medical attention

Question 13

outline advice surrounding conception and contraception with regards to statins

Answer 13

Contraception is required during treatment and for 1 month afterwards.
↳ discontinue 3 months before attempting to conceive

Question 14

what should statins be avoided in pregnancy?

Answer 14

congenital anomalies have been reported and decreased synthesis of cholesterol affects fetal development

Question 15

outline what should be measured/monitored before initiating statin therapy

Answer 15

1) At least one full lipid profile should be measured inc: total cholesterol , HDL, and non-HDL cholesterol ( total cholesterol- HDL) and triglyceride concentrations
2) liver function , TSH and renal function should also be assessed
3) creatine kinase in those who have had muscle pain

Question 16

1) According to NICE, how often should liver function be monitored when taking statins?
2) How should patients with raised serum transaminases be managed?

Answer 16

1) liver enzymes measured before treatment, and repeated within 3 months and at 12 months of starting
2) If serum transaminases are raised but less than 3x the upper limit of the reference range do NOT exclude patient from statin therapy.
↳ if >3x the upper limit exclude statin therapy

Question 17

what should be done if creatine kinase is more than 5x the upper limit before initiating statin treatment?

Answer 17

1) if more than 5x upper limit of normal, repeat test in 7 days
2) if repeat remains above 5x, statin should not be started
↳ if still raised but but less than 5x upper limit of normal, start statin at a lower dose

Question 18

What should be tested in patients at risk of diabetes before statin therapy is initiated?

Answer 18

Fasting blood glucose concentration or HbA1c should be checked before starting and then repeated after 3 months

Question 19

what advice should be given to patients taking statins? (2)

Answer 19

1) promptly report any unexplained muscle pain, tenderness or weakness
2) Avoid with grapefruit juice (only in Simvastatin and Atorvastatin)

Question 20

what are the common and important side effects of taking statins?

Answer 20

1) most common adverse effects are: headache and GI disturbance
2) more serious: myopathy and rarely rhabdomyolysis and drug induced hepatitis
↳ can also cause a rise in liver enzymes (ALT)

Question 21

outline the important interactions to be aware of with the use of statins

Answer 21

1) metabolism of statins reduced by CYT P450 inhibitors such as: amiodarone, diltiazem, itraconazole, macrolides and protease inhibitors.
↳This can lead to accumulation of statin and inc in S/E
2) Amlodapine has similar effect so max dose of simvastatin to be given is 20mg, or switch to different statin if higher doses needed e.g. Atorvastatin
3) if treatment is for short duration e.g. clarithromycin, statin can be withed for a short period

Question 22

1) why is simvastatin taken in the evening?

2) why is this not an issue with the other statins?

Answer 22

1) cholesterol synthesis is greatest in the early morning hours
2) Simvastatin has short half life, the other statins have long half life