5.2 pharmacological managment

key drugs classes used in hyperlipodaemia

1. statins, HMG-CoA reductase inhibitor

2. ezetimibe, cholesterol absorption inhibitor

3. fibrates

4. PCSK9 inhibitors

1. statin mechanism of action

competitive inhibitors of the enzyme 3-hydroxy-3-methyl-glutaryl-coenzymeA = HMG-CoA reductase which plays a key role in the mevalonate pathway

mevalonate pathway

responsible for cholesterol biosynthesis in the liver

by inhibiting the enzyme statins decrease the synthesis of cholesterol within hepatocytes

resulting in reduced intracellular cholesterol levels

the decrease in intracellular cholesterol promotes hepatocytes to upregulate LDL receptors on their surface

thus increasing the clearance of LDL cholesterol from the bloodstream significantly reducing LDL levels crucial for reducing risk of atherosclerosis

statins also exert pleiotropic effects, benefits beyond cholesterol lowering like

improving endothelial function

reducing oxidative stress

stabilising atherosclerotic plaques

1. statin: HMG-CoA reductase inhibitor rationale for use

first like therapy for hyperlipidaemia and high effective at reducing LDL cholesterol

starins are reccomended for 

• primary rpevention: individuals at increased risk of cardiocasculat disease but without revious events

• secondary rpevention: individuals who have already experience a cardiocascular event

1. statin: HMG-CoA reductase inhibitor example

• atorvastatin

• simvastatin

• rosuvastatin

1. statin: HMG-CoA reductase inhibitor dose regimen

OD with/ without food

simvastatin taken at night because cholesterol synthesis mainly occurs during sleep

atorvastatin/rosuvastatin can be taken at any time in the day due to their longer half life

1. statin: HMG-CoA reductase inhibitor monitoring

LFT should be monitored before treatment + after 3 months to check for potential liver enzyme elvation

regular lipid profiles should be checked every 3 months

to assess the reduction in LDL cholesterol and adjust the dose if necessary

1. statin: HMG-CoA reductase inhibitor side effects

• myopathy and rhabdomyolysis

• elevated liver enzymes

• gastrointestinal disturbances

myopathy and rhabdomyolysis

statins can cause muscle pain, tenderness or weakness especially in higher doses + rarely progress to rhabdomyolysis a serious condition where muscle breakdown products can damage the kidneys

elevated liver enzymes

statins can increase liver enzymes particularlt alanine aminotransferase ALT 

regular monitoring required ro avoid liver toxicity

gastrointestinal disturbances

nausea

indigestion

diarrhoea

1. statin: HMG-CoA reductase inhibitor patient counselling

take statins consistently at the same time each day to ensure steady effect

report any unexplained muscle pain/ weakness as it may be early signs of muscle damage

avoid grapefruit juice especially with simvastatin as it inhibits CYP3A4 enzymes in the liver → higher levels of statin in the bloodstream and higher risk of side effects