Statins

Question 1

What is the target concentration of LDL cholesterol?

Answer 1

<5mmol/L

Question 2

What dietary advice could you give to lower cholesterol?

Answer 2

Increase: fish oils, fibre, VitC/E

Reduce: dietary fat and cholesterol, alcohol

Question 3

Tell me about Statins

Answer 3

Inhibit HMG-CoA reductase, so inhibit cholesterol synthesis in hepatocytes. This stimulates increased synthesis of LDL receptors, leading to increased uptake.
May also have secondary anti-atheromatous actions (anti-inflammatory, plaque reduction, improved endothelial function)

Question 4

When to give statins

Answer 4

CVS disease risk prevention (primary or secondary)

Familial hypercholesterolaemia

Question 5

PKs, ADRs and DDIs of statins

Answer 5

PKs:
Large variation within the the group
Can be short acting (simvastatin - give at night) or long acting (atorvastatin, rosuvastatin - give any time)
Large first pass uptake, exhibit non linear kinetics
Some metabolised by phase 1, some phase 2

ADRs - rare
Increased transaminase levels
Myopathy and rhabdomyolysis
GI upset

DDIs:
Some affected by CYP inducers/inhibitors
OATP2 inhibitors can reduce the efficacy of statins that are carried by this transporter eg. Gemfribrizil

Question 6

Tell me about fibrates

Answer 6

Act as peroxisome proliferator-activated receptor agonists (PPARa) to increase the production of lipoprotein lipase. This increases uptake and oxidation of fatty acids, lowers Triglycerides.

Indications:
in combo with statins/if patient not responding to statins
First choice in hypertriglyceridaemia

ADRs: (less well tolerated)
GI upset, Cholethiasis, myositis

Question 7

Tell me about Nicotinic acid/Niacin

Answer 7

Inhibit lipoprotein a synthesis, so reduce VLDL, increase HDL.

ADRs: (poorly tolerated)
Flushing, itching, headache, hepatotoxic, GI upset, activation of peptic ulcer, hyperglycaemia

Question 8

Tell me about Ezetimibe

Answer 8

Inhibits intestinal cholesterol absorption by blocking cholesterol transport protein NPC1L1 on brush border. Reduces cholesterol delivery to the liver and increases hepatic LDL receptors.

Indications: in combo with statins or in statin intolerant patients

ADRs:
Headache, abdo pain, diarrhoea

Question 9

Describe the pro-atherogenic effects of cholesterol

Answer 9

Inhibits macrophage motility
Induces T-cell activation and vascular smooth muscle division
Is toxic to endothelial cells -> infiltration and entrapment of LDL in arterial walls
Enhances platelet aggregation