9) Hyperlipidaemias

Question 1

Outline the pathophysiology of the formation of an Atheroma

Answer 1

1) Endothelial Damage e.g. High Bp, Hyperlipidaemia
2) LDLs build up within the Tunica Intima
3) LDLs become oxidised and engulfed by macrophages => Foam Cells
4) Accumulation of Foam Cells lead to formation of fatty streak as smooth muscle cells # increase
5) Formation of Fibrous Cap over the top and centre undergoes necrosis => Cholesterol Clefts seen

Question 2

Give example some examples of Statins

Answer 2

> ArtovaSTATIN
SimvaSTATIN
Pro drug activated by 1st Pass Metabolism,t 1/2 2h
FluvaSTATIN

Question 3

What is the main mechanism of action ?

Answer 3

Inhibits HMG CoA Reductase preventing the formation of Cholesterol in Hepatocytes

Question 4

What are some additional benefits of Statin Therapy ?

Answer 4

1) Up regulation of LDL receptor s
2) Improved Vascular Endothelial Function
- > Increase NO and VEGF
- > Endothelin
3) Stabilisation of Atherosclerotic Plaque
- > Decreased SMC proliferation
4) Improved Haemostasis
- > Decreased Plasma Fibrinogen, platelet aggregation,
- > Increased Fibrinolysis
5) Anti - Inflammatory
- > Decreased Proliferation of Inflammatory cells into Plaque , plasma CRP, Adhesion Molecules and Cytokines
6) Antioxidant

Question 5

What Considerations should be taken into account when prescribing Statins ?

Answer 5

Contraindications/Warnings :
> GI disruption, Nausea and Headache
>Myalgia - Dose Related
> Rhabdomyolysis - RARE

Important Interactions / Considerations:
> Renal Impairment
> Pregnancy - Need Cholesterol for development
> Breast Feeding
> CYP3A4 importance
> Interactions with other drugs such as Amiodarone, Diltiazem, Macrolides (ABx) or Amlodipine
==> Withhold statin short term

Question 6

What is the NICE guideline for starting Statin Treatment ?

Answer 6

> Start statins for those with a 10% (QRisk) 10 year risk of developing CVD or have familial hypercholesteraemia
Up dosage for patients with CVD
Aim is to lower non HDL cholesterol by 40% (Under 5 mmol/L)

Question 7

Give an example of Fibric Acid Derivatives Drug (Fibrates)

Answer 7

FenoFIBRATE

Question 8

What is the mechanism of action in Fibrates ?

Answer 8

> Activation of Nuclear Transcription Factor - PPar alpha
=> regulate expression of genes that control lipoprotein metabolism, increase lipoprotein lipase

1) Increase TAGs from lipoprotein in plasma
2) Increase FAs uptake by the liver
3) [HDLs]
4) LDL affinity for receptor

Question 9

What considerations must be taken into account when prescribing Fibrates ?

Answer 9

Contraindications/Warnings:
> Cholelithiasis (Gall Stones), Myositis

Important Interactions/Considerations:
> Warfarin

Question 10

Give an example of a Cholesterol Absorption Inhibitor

Answer 10

Ezetimibe

Question 11

What is the mechanism of action of a Cholesterol Absorption Inhibitor ?

Answer 11

Inhibits Intestinal Cholesterol Absorption (NPC1L1 Transporter) and Increase expression of hepatic LDL receptors

There is limited exposure as it stays in the enterohepatic circulation

Question 12

What considerations must be taken into account when prescribing Cholesterol Absorption Inhibitors ?

Answer 12

Contraindications/Warnings:
> GI Upset
> Abdominal Pain

Considerations/ Interactions:
>Hepatic Failure

Question 13

What are some other treatments of Hyperlipidaemia (Non Drug)

Answer 13

> Plant Sterols - Provide LDL lowering effects
> Fish Oils
> Fibre
> Vitamins C/E
> Resins - Sequestrate bile acids