CV: Lipid-regulating drugs Flashcards

1
Q

Individuals at high risk of developing cardiovascular disease include who? (4)

A
  1. Those who have diabetes mellitus.
  2. Chronic kidney disease (eGFR <60mL/minute/1.73m2 and/or albuminuria.
  3. Those with familial hypercholesterolaemia.
  4. Those aged over 85 who smoke or have hypertension.
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2
Q

Both QRISK2 and JBS3 assess cardiovascular risk (coronary heart disease [angina and myocardial infarction], stroke and TIA based on what factors? (12)

A
  1. Lipid profile
  2. Systolic blood pressure
  3. Gender
  4. Ethnicity
  5. Smoking status
  6. BMI
  7. Chronic kidney disease
  8. Diabetes mellitus
  9. Atrial fibrillation
  10. Treated hypertension
  11. RA
  12. Family history of premature cardiovascular disease.
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3
Q

Risk assessment tools such as QRISK2 and JBS3 underestimate risk in patients with additional risk due to existing conditions or medication, such as what?

A
  1. Serious mental disorder
  2. Autoimmune disorders such as systemic lupus erythematous and other systemic inflammatory disorders.
  3. Antiretroviral treatment
  4. Medication causing dyslipidaemia as a side-effect e.g. antipsychotics, corticosteroids, or immunosuppressants.
  5. Triglycerides >4.5 mmol/litre
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4
Q

A statin reduces the risk of cardiovascular disease events, and is the drug of first choice for primary and secondary prevention of cardiovascular disease. Before starting treatment with statins, secondary causes of dyslipidaemia such as what should be addressed? (5)

A
  1. Uncontrolled diabetes
  2. Hepatic disease
  3. Nephrotic syndrome
  4. Excessive alcohol consumption
  5. Uncorrected hypothryoidism as correcting hypothyroidism may resolve the lipid abnormality.
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5
Q

For primary prevention, NICE CG 181 recommends what high-intensity statin be prescribed at an unlicensed dose of at least 20mg/day to all those with a 10-year risk of CVD of equal to or greater than what?

A

Atorvastatin 20mg od to all with 10% or more

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6
Q

For secondary prevention what high intensity statin is recommened?

A

also atorvastatin also unlicensed indication

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7
Q

A statin should be considered for all adults with type 1 diabetes mellitus, particularly those aged 40 years and over, or who have what other risk factors? (3)

A
1. Diabetes more than 10 years 
OR
2. established nephropathy 
OR 
3. any of the other CVD risk factors
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8
Q

Total cholesterol, HDL-cholesterol, and non-HDL cholesterol concetration should be checked how long after starting treatment with a high intensity statin?

A

3 months.

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9
Q

NICE CG 181 recommends aiming for a reduction in non-HDL cholesterol of greater than what value if a patient is receiving a high intensity statin?

A

reduction in non-HDL cholesterol greater than 40%.

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10
Q

JBS3 recommends a target non-HDL cholesterol concentration below what value?

A

2.5mmol/litre

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11
Q

If a reduction in non-HDL cholesterol greater than 40% or a target non-HDL cholesterol concentration of below 2.5mmol/litre is not achieved, what should be done?

A

Ensure lifestyle modifications are optimised and consider increasing the dose of the statin if started on less than atorvastatin 80mg.

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12
Q

What drugs should not routinely be used for primary or secondary prevention of CVD?

A

Fibrates.

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13
Q

The use of what drugs is now no longer recommended for either the primary or secondary prevention of CVD?

A

Nicotinic acid
Bile acid sequestrants
Omega-3 fatty compounds

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14
Q

A statin is also the drug of choice for treating hypercholesterolaemia and moderate hypertriglyceridaemia. Severe hyperlipidaemia not adequately controlled with a maximal dose of a statin may require the use of what?

A

Severe hyperlipidaemia not adequately controlled with a maximal dose of a statin may require the use of an additional lipid-regulating drug such as ezetimibe; such treatment should generally be supervised by a specialist.

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15
Q

What can be added to statin therapy if triglycerides remain high even after the LDL-cholesterol concentration has been reduced adequately?

A

Fenofibrate.

Nicotinic acid may also be used to further lower triglyceride or LDL-cholesterol concentration.

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16
Q

Combination of a statin with a fibrate or with nicotinic acid carries an increased risk of side-effects such as what?

A

Rhabdomylsis: monitoring of liver function and creatine kinase should also be considered.

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17
Q

The concomitant administration of gemfibrozil with a statin greatly increases what?

A

Gemfibrozil + statin = rhabdomyolysis and should not be used.

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18
Q

A statin is recommended for all patients with familial hypercholesterolaemia. A high-intensity statin such as what should be considered in order to achieve the recommended reduction in LDL-cholesterol of greater than 50% from baseline?

A

rosuvastatin or atorvastatin.

19
Q

What is a high-intensity statin defined as?

A

A high-intensity statin is one that produces a greater LDL-cholesterol reduction than simvastatin 40mg.

20
Q

Patients with heterozygous familial hypercholesterolaemia who have contra-indications to, or are intolerant or, statins should receive what?

A

Ezetimibe (can also be used in combination)

21
Q

Patients for whom statins and ezetimibe are inappropriate, should be referred to a specialist for consideration of treatment with what?

A

Either a bile acid sequestrant, nicotinic acid, or a fibrate.

22
Q

The MHRA have advised that there is an increased risk of myopathy associated with what dose simvastatin?

A

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.

23
Q

Statins are more effective than other lipid-regulating drugs at lowering LDL-cholesterol concentration but are less effective than the fibrates at reducing what?

A

Trigylcerides

However, statins reduce cardiovascular disease events and total mortality irrespective of the initial cholesterol concetration.

24
Q

Alirocumab and evolucumab are both licensed for what?

A

Alirocumab and evolocumab are licensed for the treatment of primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia as an adjunct to dietary measures. They can be used in combination with a statin, or with a statin and other lipid-regulating therapies, in patients unable to achieve their LDL-cholesterol treatment goals with the maximum tolerated dose of a statin. They can be used alone or in combination with other lipid-regulating therapies if a statin is contra-indicated or not tolerated. Evolocumab is also licensed for the treatment of homozygous familial hypercholesterolaemia in combination with other lipid-lowering therapies.

25
Q

As well as for the treatment of primary hypercholesterolaemia or mixed dyslipidaemia as an adjunct to dietary measures, Evolocumab is also licensed for what?

A

Alirocumab and evolocumab are licensed for the treatment of primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia as an adjunct to dietary measures. They can be used in combination with a statin, or with a statin and other lipid-regulating therapies, in patients unable to achieve their LDL-cholesterol treatment goals with the maximum tolerated dose of a statin. They can be used alone or in combination with other lipid-regulating therapies if a statin is contra-indicated or not tolerated. Evolocumab is also licensed for the treatment of homozygous familial hypercholesterolaemia in combination with other lipid-lowering therapies.

26
Q

Bile acid sequestrants effectively reduce LDL- cholesterol but can aggravate what?

A

Bile acid sequestrants effectively reduce LDL-cholesterol but can aggravate hypertriglyceridaemia. Treatment with bile acid sequestrants may be appropriate under specialist supervision if statins and ezetimibe are inappropriate, and when LDL-cholesterol is severely raised, for example in familial hypercholesterolaemia.

27
Q

Fibrates are mainly used in those whose serum-triglyceride concentration is above what?

A

10 mmol/litre or in those who cannot tolerate a statin.

28
Q

What is lomitapide?

A

Lomitapide is an inhibitor of the microsomal triglyceride transfer protein (MTP or MTTP) which is necessary for very low-density lipoprotein (VLDL) assembly and secretion in the liver.

It is licensed as an adjunct to dietary measures and other lipid-regulating drugs for the treatment of familial hypercholesterolaemia.

29
Q

The value of nicotinic acid is limited by what?

A

Its side effects, especially vasodilation.

30
Q

Acipimox differs from nicotinic acid how?

A

Acipimox seems to have fewer side-effects than nicotinic acid but may be less effective in its lipid-regulating capabilities.

31
Q

How does acipimox work?

A

Like niacin (nicotinic acid), acipimox acts on the niacin receptor 1, inhibiting the enzyme triglyceride lipase. This reduces the concentration of fatty acids in the blood plasma and their inflow into the liver.

Consequently, VLDL cholesterol production in the liver is reduced, which leads indirectly to a reduction in LDL and increase in HDL cholesterol.

32
Q

Statins interact with potent inhibitors of what CYP?

A

CYP3A4:

Itra + ketoconazole, erythromycin, clarithromycin, telithromycin, and HIV protease inhibitors.

33
Q

Can simvastatin be used with ketoconazole?

A

No.

All CYP3A4 inhibitors are contrainidicated with simvastatin.

34
Q

Can atorvastatin be used with erythromycin?

A

Avoid if possible: consider temporary suspension of atorvastatin if interacting drug is taken for a short period.

35
Q

Can atorvastatin be used with itraconazole?

A

Avoid if possible.

If needed, do not exceed 40mg atorvastatin daily if itraconazole is being used.

36
Q

Can atorvastatin be used with clarithromycin?

A

Do not exceed 20mg clarithromycin daily.

37
Q

Can simvastatin or atorvastatin be used with HIV protease inhibitors?

A

Sim: no
Atorvastatin: the advice is to monitor lipid levels to ensure lowest necessary dose of atorvastatin is used.

38
Q

What are the dose restrictions on statin use in patients receiving ciclosporin treatment?

A

Do not exceed 10mg daily of either simvastatin or atorvastatin.

Ciclosporin interacts with all statins and is contraindicated with rosuvastatin.

39
Q

Can Danazol be used with statins? What is Danazol used for?

A

Danazol is a mediacation which is used in the treatmet of endometriosis, fibrocystic breast disease, hereditary andiodema etc.

Fine with Atorvastatin but simvastatin should not exceed 10mg daily.

40
Q

Verapamil and amiodarone interact with statins. What are the restrictions on the use of simvastatin and atorvastatin in patients taking verapamil or amiodarone?

A

Do not exceed 20mg sim daily,

Monitor lipid levels to ensure lowest dose of atorvastatin is used.

41
Q

What does of simvastatin should not be exceeded in a patient taking diltiazem?

A

40mg daily (atorvastatin: monitor lipid levels to esure lowest dose needed is used(

42
Q

Can you drink grapefruit juice when taking simvastatin or atorvastatin?

A

Avoid if on sim, small amounts or avoid if on atorv

43
Q

What is the recommendations for patients on warfarin who need a statin?

A

The INR should be monitored before initiating a statin, during treatment and at any dose change.

Statins may affect coumarin anticoagulation and increase the risk of haemorrhagic events.

44
Q

Inducers of CYP3A4, such as what may reduce plasma concentrations of simvastatin and atorvastatin?

A

Efavirenz
Rifampicin
St John’s Wort
Colestipol