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

e.g. 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 often recommended that statins are taken in the evening, as most cholesterol synthesis occurs at night

 

Statins also have pleiotropic effects:

– Improvement of endothelial function                   

– Decrease inflammation

– Decrease stroke and cancer risk                               

– Aid immune system

Side Effects
  • Headaches

  • Gastrointestinal disturbance -> constipation, diarrhoea, flatulence, nausea, dyspepsia

  • Myalgia

  • Hepatic toxicity –> deranged LFTs, hepatitis, jaundice, hepatic failure

  • Muscle toxicity –> elevated CK with rhabdomyolysis

  • Hyperglycaemia and development of diabetes mellitus in at-risk individuals

Monitoring
  • According to NICE CKS1:

    – 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 –> macrolides (clarithromycin, erythromycin), azole antifungals, HIV protease inhibitors

Contraindications
  • Pregnancy -> due to reports of congenital anomalies

  • Breastfeeding

  • Active liver disease

Fibrates

e.g. Fenofibrate + Gemfibrozil

VLDLs and chylomicrons can be catabolised by the liver.

– This process is regulated by peroxisome proliferating 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, leads to an increase in cholesterol breakdown in liver to synthesise more bile salts.

– It is also used in diseases like primary biliary cirrhosis to stop 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

The intended purpose of this website is to be used as a resource for revision for exams. It should not be used as a guideline or reference for clinical practice/decision making or by patients looking for medical information or advice. In2Med takes no responsibility for any loss or damaged resulting from the use of information from this website.

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