Hyperlipidaemia

Question 1

Name some drugs used to treat hyperlipidaemia

Answer 1

Statins

Fibrates - fibric acid derivatives

Nicotinic acid

Cholesterol absorption inhibitors

Monoclonal antibody

Question 2

How do statins work and how do they lower cholesterol levels

Answer 2

Statins competitively inhibit HMG-CoA reductase in hepatocytes

This increases clearance as there is a decreased cholesterol concentration within the cell

This stimulates LDL receptor synthesis which increases number of LDL receptors on the cell membrane

This increases uptake of LDL from the blood

The low intracellular cholesterol decreases VLDL secretion

Question 3

Name some statins

Answer 3

Atorvastatin - t1/2 of 30hrs

Simvastatin - t1/2 of 2hrs

Fluvastatin

Pravastatin

Rosuvastatin

Lovastatin

Question 4

Name some additional benefits of statin therapy

Answer 4

Improved vascular endothelial function as there is increased NO, VEGF and decreased endothelin

There is stabilisation of atherosclerotic plaques so they are less likely to rupture

There is imporved haemostasis

There are anti-inflammatory effects

There are anti-oxidant effects as statins decrease superoxide formation

Question 5

Name some ADRs caused by statins

Answer 5

Transient serum transaminase elevation

Myalgia - diffuse muslce pain typically related to dose

Rhabdomyolysis - rare

GI disruption

Headache

Nausea

Question 6

What metabolises statins

Answer 6

CYP 3A4

Question 7

What are the NICE guidlines for statin use

Answer 7

Primary prevention is atorvastatin once daily (20mg)

Secondary prevention is atorvastatin once daily (80mg)

Stay away from grapefruit juice/grapefruits

Recommend taking low t1/2 statins before bed, e.g. simvastatin, as LDL receptor synthesis is highest during night

Question 8

Describe how fibrates work in helping to lower cholesterol levels

Answer 8

Fibrates activate nuclear transcription factor (PPAR alpha) which regulates the expression of genes that control lipoprotein metabolism

FIbrates increase lipoprotein lipase production

This causes: increase clearance of TAG from lipoprotein, increase fatty acid uptake by liver, increase LDL affinity for receptor, increase levels of HDL

Question 9

Name some fibrates

Answer 9

Fenofibrate

(Ciprofibrate)

(Gemfibrozil)

Question 10

What are the indications for the use of fibrates in treatment of hyperlipidaemia

Answer 10

Adjunctive therapy to diet with hypertriglyceridaemia

Combined hyperlipidaemia with low HDL

Fenofibrates widely distributed and albumin bound

Question 11

Name some side effects and contraindications of fibrate therapy

Answer 11

Side effects: GI upset, cholelithiasis, myositis, abnormal LFTs, warfarin potentiation

Contraindications - hepatic or renal dysfucntion, pre-existing gallbladder disease

Question 12

Describe nicotinic acid and its effect on lipid levels

Answer 12

Nicotinic acid is a B3 Vitamin that has effects on lipids at pharmacological levels

It decreases fatty acid supply and TAG synthesis

It decreases VDL and LDL while increasing HDL greatly

Often poorly tolerated but can be overcome by slowly increasing the dose

Question 13

Name a nicotinic acid drug used in therapy

Answer 13

Niacin

Question 14

Name some ADRs of nicotinic acid use

Answer 14

Flushing

Headache

Pruritus

Hepatotoxicity

GI disturbance

Question 15

Describe how cholesterol absorption inhibitors work

Answer 15

Cholesterol absorption inhibitors act at the brush border of the small intestine mucosa to inhibit NCPC1L1 transporter to decrease cholesterol absoprtion in the gut

Increases hepatic LDL receptor

Is a pro-drug (liver) with metabolite having greater efficacy. Metabolite enters enterohepatic circulation where it stays, limiting systemic exposure

Question 16

Name some ADRs of cholesterol absorption inhibitors

Answer 16

Headache

Abdominal pain

Diarrhoea

Question 17

Name a cholesterol absorption inhibitor

Answer 17

Ezetimibe

Question 18

What are the lipid target levels for hyperlipidaemie therapy

Answer 18

LDL-C of 2.0 mmol/L

Total cholesterol of 4.0 mmol/L

Question 19

Describe how monoclonal antibody therapy for hyperlipidaemia works

Answer 19

Monoclonal antibodies that inhibit PCSK9 to cause a reduction in LDL-C

These antibodies prevent LDL-R from being degraded in the cell so there are more on the surface so there is increased LDL recycling

Question 20

Name some PCSK9 inhibitors

Answer 20

Alirocumab

Evolocumab

Question 21

Name some non-prescription only medication (POM) options in the treatment of hyperlipidaemia

Answer 21

Plant sterols - lower LDL-C. Competivitely inhibit cholesterol receptors as they have a similar structure. Work with statins but not ezetimibe

Fish oils - contain Omega 3 FA which increases LDL-C and HDL-C but lowers TAG

Fibre

Vitamins C/E

Alcohol - raises HDL-C and raises TAG