Hyperlipidaemia Drugs Flashcards
List the drugs used for treatment of hyperlipidaemia (including the 1st line choice)
Statins
Fibrates
Cholesterol absorption inhibitors
PCSK9 inhibitors (PCSK9 inhibitors and PCSK9 translation inhibitors)
List the following for: Statins
- Use
- Example drugs
- Drug class
- Mechanism of action
- Adverse effects
- Warnings / contraindications
- Important drug reactions
Hyperlipidaemia
Atorvastatin
Simvastatin
Statins
Lower levels of LDL cholesterol in the blood
Competitive inhibition of HMG-CoA reductase enzyme, particularly in the liver
Low intracellular LDL leads to upregulation of hepatic LDL receptors, so increased clearance of circulating LDL
Many other additional benefits
- Improved vascular endothelial function
- Stabilises atherosclerotic plaques
- Improved haemostasis
- Anti-inflammatory effects
- Antioxidant
- GI disruption
- Myalgia
- Rhabdomyolysis – rare
- Upregulation of liver enzymes
- Renal impairment
- Hepatic impairment
- Pregnancy / breastfeeding
CYP 3A4 important
- Amiodarone (CCB)
- Diltiazem
- Macrolides
- Grapefruit juice!
List the following for: Fibrates
- Use
- Example drugs
- Drug class
- Mechanism of action
- Adverse effects
- Warnings / contraindications
- Important drug reactions
Hyperlipidaemia
Fenofibrate
Fibric acid derivatives
Activation of nuclear transcription factor: PPAR-alpha
Increases production of lipoprotein lipase (PPAR-alpha is responsible for regulating expression of genes controlling lipoprotein metabolism)
- More triglycerides removed from lipoprotein in plasma
- Increased fatty uptake by liver
- Increased HDL
- Increased LDL affinity for receptor
- Gall stones
- GI upset
- Myositis
- Photosensitivity
- Gall bladder disease
- Warfarin (double anti-coagulation risk)
List the following for: Cholesterol absorption inhibitors
- Use
- Example drugs
- Drug class
- Mechanism of action
- Adverse effects
- Warnings / contraindications
- Important drug reactions
Hyperlipidaemia
Ezetimibe
Cholesterol absorption inhibitors
Pro drug – requires hepatic metabolism
- Inhibits NPC1L1 transporter at brush border
- Reduces absorption of cholesterol by the gut
- Increase HDL receptors in liver
- Abdominal pain
- GI upset
- Angioedema
- Hepatic failure
- Caution with statin – theoretical increased risk of rhabdomyolysis
- Ciclosporin
List the following for: PCSK9 inhibitors
- Use
- Example drugs
- Drug class
- Mechanism of action
Hyperlipidaemia
Alirocumab
Evolocumab
PCSK9 inhibitor
Mechanism of action:
PCSK9 normally binds internalised LDL receptors, signalling for them to be degraded
PCSK9 inhibitors prevent this binding and degradation, so LDL receptors remain around for longer – reducing plasma LDL levels
List the following for: PCSK9 translation inhibitors
- Use
- Example drugs
- Drug class
- Mechanism of action
Hyperlipidaemia
Inclisiran
PCSK9 inhibitor
PCSK9 normally binds internalised LDL receptors, signalling for them to be degraded
siRNA prevents the liver from translating and forming PCSK9, prevent this binding and degradation, so LDL receptors remain around for longer – reducing plasma LDL levels
