Dyslipidaemias

Question 1

What is the drug class of choice for treating hypercholesterolaemia and moderate hypertriglyceridaemia?

Answer 1

Statins

Question 2

What lipid-regulating drug is given in addition to statins for severe hypercholesterolemia or hypertriglyceridemia?

Answer 2

Ezetimibe

- oral: 10 mg daily

Question 3

What drug class is more effective than statins at reducing triglyceride concentration?

Answer 3

Fibrates (e.g. fenofibrate)

Question 4

What drug would you add to statin therapy if triglycerides remain high even after the LDL-cholesterol concentration has been reduced adequately?

Answer 4

Fenofibrate

• Oral capsules: maximum 200 mg daily with concomitant statin
• Oral tablets: 160 mg daily

Fibrates are more effective than statins in reducing triglyceride concentration

Question 5

Patients with familial hypercholesterolaemia are at high risk of premature (?)

Answer 5

coronary heart disease

Question 6

What is the definition of ‘high-intensity statin’?

Answer 6

The dose at which a reduction in LDL-cholesterol of greater than 40% is achieved

Question 7

What is first-line therapy in all patients with familial hypercholesterolemia?

Answer 7

High-intensity statin

+ lifestyle changes

Question 8

What is the target reduction of LDL-cholesterol concentration in a patient with familial hypercholesterolemia?

Answer 8

Greater than 50% from baseline

Question 9

For patients with primary heterozygous familial hypercholesterolaemia who have contra-indications to, or are intolerant of statins, what drug is the used as monotherapy?

Answer 9

Ezetimibe

- Oral: 10 mg daily

Question 10

For patients with familial hypercholesterolaemia and in whom statins or ezetimibe are inappropriate, what two other drug classes can be considered?

Answer 10

Fibrates (fenofibrate)

Bile acid sequestrant (e.g. colestyramine or colestipol hydrochloride)

Question 11

Which side effect is a patient taking a combination of statin with a fibrate at increase risk of?

Answer 11

Muscle-related side-effects (including rhabdomyolysis)

Should be used under specialist supervision

Question 12

Which drug should NOT be combined with a statin because of the very high risk of rhabdomyolysis?

Answer 12

Gemfibrozil

Question 13

Which two drugs can be considered for patients with primary heterozygous familial hypercholesterolemia whose LDL-cholesterol has NOT been adequately controlled on maximum tolerated lipid-lowering therapy?

Answer 13

Alirocumab

Evolocumab

Question 14

What reduction of LDL cholesterol would you expect in the patient is taking 20 mg daily dose of atorvastatin?

Answer 14

43%

Question 15

What reduction of LDL cholesterol would you expect in the patient is taking 80 mg daily dose of atorvastatin?

Answer 15

55%

Question 16

Why is high-dose simastatin (80mg) NOT considered in the majority of patients?

Answer 16

Increased risk of myopathy

The 80 mg dose should be considered only in patients with severe hypercholesterolaemia and high risk of cardiovascular complications who have not achieved their treatment goals on lower doses, when the benefits are expected to outweigh the potential risks.

Question 17

(drug?) and (drug?) bind to a pro-protein involved in the regulation of LDL receptors on liver cells; receptor numbers are increased, which results in increased uptake of LDL-cholesterol from the blood.

Answer 17

Alirocumab

Evolocumab

Question 18

Alirocumab and evolocumab bind to a pro-protein involved in the regulation of (?) receptors on liver cells; receptor numbers are increased, which results in increased uptake of LDL-cholesterol from the blood.

Answer 18

LDL

Question 19

Alirocumab and evolocumab binds to a pro-protein involved in the regulation of LDL receptors on liver cells; receptor numbers are increased, which results in increased uptake of (?) from the blood.

Answer 19

LDL-cholesterol

Question 20

What are the two indications for the use of alirocumab?

Answer 20

1. Primary hypercholesterolaemia or mixed dyslipidaemia in patients who have not responded adequately to other appropriate measures
2. Established atherosclerotic cardiovascular disease

• Subcutaenous injection: Initially 75 mg every 2 weeks; increased if necessary to 150 mg every 2 weeks, alternatively 300 mg every 4 weeks, patients requiring an LDL-C reduction of greater than 60% may be initiated on 150 mg every 2 weeks or 300 mg every 4 weeks, dose adjustments should be made at 4 to 8 weekly intervals.

Question 21

What are the common side effects of alirocumab?

Answer 21

1. Nasal complaints
2. Oropharyngeal pain
3. Pulmonary reaction
4. Skin reactions

Question 22

Can alirocumab be used during pregnancy?

Answer 22

No unless clinical condition requires treatment

Maternal toxicity in animal studies

Question 23

What is the route of administration of alirocumab?

Answer 23

Subcutaneous injection

Question 24

What are the 4 indications for use of evolocumab?

Answer 24

1. Primary hypercholesterolaemia or mixed dyslipidaemia in patients who have not responded adequately to other appropriate measures
2. Established atherosclerotic cardiovascular disease
3. Homozygous familial hypercholesterolemia
4. Homozygous familial hypercholesterolemia in patients on apheresis

Question 25

What is the route of administration of evolocumab?

Answer 25

Subcutaneous injection

Question 26

What are the common side effects of evolocumab? (6)

Answer 26

1. Arthralgia 2. Back pain 3. Hypersensitivity 4. Increased risk of infection 5. Nausea 6. Skin reactions

Question 27

Can pregnant women take evolocumab?

Answer 27

No unless essential

Question 28

Should patients with moderate to severe hepatic impairment use evolocumab?

Answer 28

Use with caution Risk of reduced efficacy

Question 29

Name two bile acid sequestrants

Answer 29

Colestipol hydrochloride | Colestyramine

Question 30

(drug class?) act by binding bile acids, preventing their reabsorption; this promotes hepatic conversion of cholesterol into bile acids; the resultant increased LDL-receptor activity of liver cells increases the clearance of LDL-cholesterol from the plasma.

Answer 30

Bile acid sequestrants

Question 31

Bile acid sequestrants act by binding bile acids, preventing their (?); this promotes hepatic conversion of cholesterol into bile acids; the resultant increased LDL-receptor activity of liver cells increases the clearance of LDL-cholesterol from the plasma.

Answer 31

reabsorption

Question 32

Bile acid sequestrants act by binding bile acids, preventing their reabsorption; this promotes hepatic conversion of (?) into (?); the resultant increased LDL-receptor activity of liver cells increases the clearance of LDL-cholesterol from the plasma.

Answer 32

Cholesterol into bile acids

Question 33

Bile acid sequestrants act by binding bile acids, preventing their reabsorption; this promotes hepatic conversion of cholesterol into bile acids; the resultant increased (?) activity of liver cells increases the clearance of LDL-cholesterol from the plasma.

Answer 33

LDL-receptor

Question 34

What is the only indication for the use of colestipol hydrochloride?

Answer 34

Hyperlipidaemias, particularly type IIa, in patients who have not responded adequately to diet and other appropriate measures - Oral: Initially 5 g 1–2 times a day, increased in steps of 5 g every month if required, total daily dose may be given in 1–2 divided doses; maximum 30 g per day.

Question 35

Which type of hyperlipidaemia are colestipol hydrochloride and colestyramine particularly useful for treamtent?

Answer 35

Type IIa Familial hypercholesterolaemia - Elevated LDL-cholesterol

Question 36

What supplements are required if a patient is taking long-term bile acid sequestrants?

Answer 36

Vitamins A, D, K and folic acid Bile acid sequestrants interfere with the absorption of fat-soluble vitamins

Question 37

Bile acid sequestrants interfere with the absorption of (?)

Answer 37

Fat-soluble vitamins Supplements of vitamins A, D, K, and folic acid may be required when treatment is prolonged

Question 38

What are the common side effects of bile acid sequestrants?

Answer 38

``` Constipation GI discomfort Headache Nausea Vomiting ```

Question 39

Why should bile acid sequestrants be used with caution in pregnancy and breastfeeding?

Answer 39

May cause fat-soluble vitamin deficiency on prolonged use

Question 40

What is the mode of administration of bile acid sequestrants?

Answer 40

Oral - sachet should be mixed with water, fruit juice, skimmed milk or thin soup Colestipol hydrochloride - mixed with 100 mL of liquid Colestyramine - mixed with 150 mL of liquid

Question 41

What are the indications for use of colestyramine? (5)

Answer 41

1. Hyperlipidaemias, particularly type IIa, in patients who have not responded adequately to diet and other appropriate measures 2. Primary prevention of coronary heart disease in men aged 35-59 years with primary hypercholesterolemia who have not responded to diet and other appropriate measures 3. Pruritis associated with partial biliary obstruction and primary biliary cirrhosis 4. Diarrhoea associated with Crohn's disease, ileal resection, vagotomy, diabetic vagal neuropathy, and radiation 5. Accelerated elimination of teriflunomide

Question 42

What is the contra-indications for the use of colestyramine?

Answer 42

Complete biliary obstruction Not likely to be effective

Question 43

Should bile acid sequestrants be taken at the same time as other drugs?

Answer 43

NO Take other drugs at least 1 hour before or 4 hours after

Question 44

What is the mode of action of ezetimibe?

Answer 44

Inhibits the intestinal absorption of cholesterol If used alone, it has a modest effect on lowering LDL-cholesterol, with little effect on other lipoproteins.

Question 45

What are the indications for the use of ezetimibe?

Answer 45

1. Adjunct to dietary measures and statin treatment in primary hypercholesterolaemia 2. Adjunct to dietary measures and statin in homozygous familial hypercholesterolaemia 3. Primary hypercholesterolaemia (if statin inappropraite) 4. Adjunct to dietary measure in homozygous sitosterolaemia (body stores plant sterols)

Question 46

What are the common side effects of ezetimibe? (4)

Answer 46

1. Asthenia 2. Diarrhoea 3. GI discomfort 4. GI disorders

Question 47

Fibrates act by decreasing serum (?); they have variable effect on LDL-cholesterol.

Answer 47

triglycerides

Question 48

(drug class?) act by decreasing serum triglycerides; they have variable effect on LDL-cholesterol.

Answer 48

Fibrates (e.g. fenofibrate)

Question 49

What are the indications for the use of the drug fenofibrate? (3)

Answer 49

1. Adjunct to diet and other appropriate measures in mixed hyperlipidaemia if statin contraindicated or not tolerated 2. Adjunct to diet and other appropriate measures in severe hypertriglyceridaemia 3. Adjunct to statin in mixed hyperlipidaemia if triglycerides and HDL-cholesterol inadequately controlled in patients at high cardiovascular risk

Question 50

What is the route of administration of fenofibrate?

Answer 50

Oral using capsules or tablets

Question 51

What are the contra-indications for the use of fenofibrate? (4)

Answer 51

1. Gall-bladder disease 2. Pancreatitis (unless due to severe hypertriglyceridaemia) 3. Photosensitivity to fibrates 4. Photosensitivity to ketoprofen

Question 52

What condition needs to be corrected before initiating treatment with fenofibrate?

Answer 52

Hypothyroidism

Question 53

What are the common side effects of the drug fenofibrate? (5)

Answer 53

``` Abdominal pain Diarrhoea Flatulence Nausea Vomiting ```

Question 54

Why must caution be taken when prescribing fenofibrate to patients with renal disease?

Answer 54

Increased risk of myotoxicity (rhabdomyolysis) Discontinue if myotoxicity suspected or creatine kinase concentration increases significantly

Question 55

In which condition do you need to make dose adjustments for the drug fenofibrate?

Answer 55

Renal impairment Max. 67 mg daily if eGFR 30-59 mL/minute/1.73m^2 Avoid if eGFR < 30

Question 56

What needs to be monitored when using the drug fenofibrate?

Answer 56

1. Hepatic transaminases (every 3 months during the first 12 months) 2. Serum creatinine levels (during the first 3 months and then periodically)

Question 57

(drug class?) are mainly used in those whose serum-triglyceride concentration is greater than 10 mmol/litre or in those who cannot tolerate a statin (specialist use).

Answer 57

Fibrates

Question 58

Fibrates are mainly used in those whose serum-(?) concentration is greater than 10 mmol/litre or in those who cannot tolerate a statin (specialist use).

Answer 58

triglyceride

Question 59

Fibrates are mainly used in those whose serum-triglyceride concentration is greater than (?) mmol/litre or in those who cannot tolerate a statin (specialist use).

Answer 59

10

Question 60

Fibrates are mainly used in those whose serum-triglyceride concentration is greater than 10 mmol/litre or in those who cannot tolerate a (?) (specialist use).

Answer 60

statin

Question 61

(drug class?) competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, an enzyme involved in cholesterol synthesis, especially in the liver

Answer 61

Statins

Question 62

Statins competitively inhibit (?), an enzyme involved in cholesterol synthesis, especially in the liver.

Answer 62

3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase

Question 63

Statins competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, an enzyme involved in cholesterol synthesis, especially in the (?).

Answer 63

Liver

Question 64

Which patients are at an increased risk of muscle toxicity if they use a statin? (5)

Answer 64

1. Personal or family history of muscular disorders 2. Previous history of muscular toxicity 3. High alcohol intake 4. Renal impairment 5. Hypothyroidism

Question 65

In patients at increased risk of muscle effects, a statin should not usually be started if the baseline (?) concentration is more than 5 times the upper limit of normal

Answer 65

creatine kinase Some patients may present with an extremely elevated baseline creatine kinase concentration, for example because of a physical occupation or rigorous exercise—specialist advice should be sought regarding consideration of statin therapy in these patients

Question 66

In patients at increased risk of muscle effects, a statin should not usually be started if the baseline creatine kinase concentration is more than (?) times the upper limit of normal

Answer 66

5 Some patients may present with an extremely elevated baseline creatine kinase concentration, for example because of a physical occupation or rigorous exercise—specialist advice should be sought regarding consideration of statin therapy in these patients

Question 67

Which medical condition needs to be managed adequately before starting treatment with a statin?

Answer 67

Hypothyroidism

Question 68

What are the common side effects for all statins?

Answer 68

1. Asthenia 2. Constipation 3. Diarrhoea 4. Dizziness 5. Flatulence 6. GI discomfort 7. Headache 8. Myalgia 9. Nausea 10. Sleep disorders 11. Thrombocytopenia

Question 69

What side effects of statins are rare but have serious effects?

Answer 69

Myopathy, myositis and rhabdomyolysis

Question 70

In addition to all side effects for statins, what are common side effects for atorvastatin?

Answer 70

1. Epistaxis 2. Hyperglycaemia 3. Hypersensitivty 4. Joint disorders 5. Laryngeal pain 6. Muscle complaints 7. Nasopharyngitis 8. Pain

Question 71

In women of child bearing potential, what must be prescribed during treatment with a statin and 1 month afterwards?

Answer 71

Adequate contraception Congenital anomalies have been reported and the decreased synthesis of cholesterol possibly affects fetal development.

Question 72

How long prior to attempting to conceiving should a woman discontinue taking a statin?

Answer 72

3 months Congenital anomalies have been reported and the decreased synthesis of cholesterol possibly affects fetal development.

Question 73

What needs to be measured at least once before treatment with statins is started? (6)

Answer 73

1. Full lipid panel (non-fasting) - total cholesterol, HDL-cholesterol, non-HDL cholesterol, triglyceride concentrations 2. Thyroid-stimulating hormone 3. Renal function 4. Liver function (recommended by NICE but no rationale) 5. Creatine kinase (in patients who have had persistent, generalised, unexplained muscle pain) 6. Fasting blood-glucose (if at high-risk of diabetes)

Question 74

According to NICE guidelines, how often should liver function tests be performed on a patient taking a statin?

Answer 74

1. Before starting treatment 2. Within 3 months 3. At 12 months of starting treatment Any other times signs or symptoms suggest hepatotoxicity

Question 75

Which patients need to have creatine kinase measured before starting treatment with a statin?

Answer 75

Those with persistent, generalised, unexplained muscle pain If the concentration is more than 5 times the upper limit of normal, a repeat measurement should be taken after 7 days. If the repeat concentration remains above 5 times the upper limit, statin treatment should not be started; if concentrations are still raised but less than 5 times the upper limit, the statin should be started at a lower dose.

Question 76

What advice needs to be given to all patients who are started on a statin?

Answer 76

Report promptly unexplained muscle pain, tenderness or weakness

Question 77

What drink should patients taking atorvastatin or simvastatin avoid?

Answer 77

Grapefruit juice

Question 78

Why should patients taking atorvastatin or simvastatin avoid grapefruit juice?

Answer 78

Reduces the body's ability to breakdown the statin, increases the risk of side effects