4. Atorvastatin

Question 1

drug class

Answer 1

HMG-CoA reductase inhibitor

Question 2

What is it used for?

Answer 2

hyperlipidaemias - lower cholesterol

It’s also taken to prevent heart disease, including heart attacks and strokes.

Question 3

Mechanism of action

Answer 3

• Competitive inhibition of HMG-CoA reductase – rate controlling enzyme in HMGCoA to mevalonate pathway
• lead to decreased concentration of cholesterol within cell
• Contributes to upregulation of hepatic LDL receptors - low intracellular cholesterol stimulates synthesis of LDL receptors
• increased number of LDL receptors promotes uptake of LDL from blood into liver - Increased clearance of circulating LDL
• low intracellular cholesterol deceases secretion of VLDL

Question 4

Important adverse drug reactions

Answer 4

• GI disruption, nausea and headache
• myalgia – diffuse muscle pain (↑CPK >5 X normal limit) - dose related (see nocebo slide)
• Rarely – rhabdomyolysis – OAT differences and skeletal muscle ATP production
• Increased liver enzymes

Question 5

Important drug-drug interactions

Answer 5

• CYP 3A4 important – amiodarone, diltiazem, macrolides - inhibit CYP 3A4 and increases [plasma] statin
• Remember amlodipine (CCB) also increases [plasma] statin

Question 6

warnings, contraindications

Answer 6

renal or hepatic impairment

pregnancy! and breastfeeding