Statins and Cholesterol Modulators
Many drugs aim to reduce plasma cholesterol levels, as this is the main component which causes atherosclerosis, being found in LDLs.
Statins – Simvastatin, Atorvastatin
These drugs inhibit cholesterol synthesis by inhibiting HMG-CoA reductase.
They can reduce total cholesterol by 30–50%.
Reduced cholesterol synthesis in the liver leads to increased uptake from the blood, thus lowering blood cholesterol levels.
To maximise their effectiveness, it is recommended that statins are taken in the evening, as most cholesterol synthesis occurs at night.
When prescribing statins, LFTs are checked at 3 months and 12 months as they can cause hepatic toxicity.
It is advised to stop if ALT is > 3x the upper limit of the normal range.
Statins also have pleiotropic effects – this means the reduction in ischaemic events is proportionally much higher than would be expected from the lipid-lowering alone:
– Reduction of oxidative stress
– Decrease stroke and cancer risk
– Decrease inflammation
– Aid immune system
Side Effects
– Headaches
– GI disturbance – constipation, diarrhoea, flatulence, nausea, dyspepsia
– Myalgia and muscle toxicity – elevated CK with rhabdomyolysis
– Hepatic toxicity – deranged LFTs, hepatitis, jaundice, hepatic failure
– Hyperglycaemia and development of diabetes mellitus in at-risk individuals
Monitoring
According to NICE:
– Baseline blood tests before starting statins should include:
– Full lipid profile, LFTs, renal function, HbA1c, TSH
(+ Creatinine Kinase only if the patient has persistent, generalised unexplained muscle pain)
Follow-up blood tests after starting statins should include:
– Full lipid profile after 3 months to determine effectiveness of treatment
– LFTs after 3 months and 12 months – stop if > 3x the upper limit of the normal range
Interactions
Metabolism of statins involves the cytochrome enzyme CYP3A4
Do not co-prescribe with CYP3A4 inhibitors, e.g., macrolides (clarithromycin and erythromycin), azole antifungals and HIV protease inhibitors
Contraindications
Pregnancy, due to reports of congenital anomalies
Breastfeeding
Active liver disease
Fibrates – Fenofibrate, Gemfibrozil
VLDLs and chylomicrons can be catabolised by the liver.
This process is regulated by peroxisome proliferator-activating receptors, which upregulate the enzyme lipoprotein lipase.
Fibrates therefore activate PPARs, increasing HDLs whilst decreasing LDLs.
HDLs are protective against atherosclerosis as they reduce blood cholesterol levels.
Side effects
Can displace other albumin bound drugs like warfarin
Cholecystitis, nausea
Nicotinic acid
This inhibits triglyceride and VLDL secretion in high doses
In low levels, it is used to treat pellagra, a disease caused by low niacin (Vitamin B3 levels)
Ezetimibe
This inhibits intestinal absorption of cholesterol by targeting Niemann-Pick transporter.
It circulates enterohepatically, redelivered to intestine so works again
It is mainly used in hypercholesterolaemia patients who cannot tolerate statin therapy
Cholestyramine
This is an anion exchange resin which binds bile salts and prevents them from being reabsorbed by the intestine.
Therefore, it leads to an increase in cholesterol breakdown in the liver to synthesise more bile salts.
It is also used in diseases like primary biliary cirrhosis to reduce pruritus, which is caused by excessive levels of bile salts irritating the skin.
Side effects
GI disturbance (constipation, diarrhoea, nausea, vomiting)
Reduced absorption of fat-soluble vitamins (A, D, E and K)
Disclaimer
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