Statins : Uses, Mechanism of action, Contraindications and Adverse effects

statins also known as hmg co-aeroductus inhibitors are a group of drugs which are widely used in the treatment of cardiovascular disease they are most effective in reducing ldl cholesterol by several mechanisms there are naturally occurring statins in synthetic statins natural ones are provastatin simvastatin and low vastatin synthetic ones are adivastatin and blue vastatin the actions of adivastatin and flu vastatin are long lasting compared to others first let's discuss about the mechanism of action of statins the pharmacological effects of statins are due to reversible inhibition of hmg coerductus enzyme by the drug to see what this is first let's recall our knowledge on the cholesterol synthesis pathway now we know that cholesterol synthesis takes place within the liver at first two acetyl coa molecules combined together to form acetoacetyl coa then this is zedo acetyl coa molecule binds with another acetyl coa molecule to form hmg coa then this hmg coa is converted to mavalenate by the enzyme hmg coeroductus this is the rate limiting step of cholesterol synthesis pathway ultimately mevalinate is converted to cholesterol after several steps what statins do is they reversibly inhibit the rate limiting enzyme hmg coeroductus by doing this they reduce the synthesis of cholesterol within the liver not only that reduction of cholesterol synthesis will activate a molecule called sterol regulatory element binding protein or srebp which diffuses into the hepatocyte nucleus and induced gene transcription to synthesize more ldl receptors increased ldl receptor expression will increase the uptake of ldl from the blood which in turn will cause reduction in blood ldl cholesterol level so statins will reduce blood ldl cholesterol by about 25 to 55 percent increase blood hdl cholesterol by about five percent and reduce triglycerides by about 10 to 35 percent they also have what are called pleiotropic effects these are some effects of drugs which can be either beneficial or harmful and are not related to its main pharmacological action the mechanism of these effects are somewhat complicated and related to the intermediate products of the mevalinate pathway luckily for statins there are many beneficial pleiotropic effects some of these effects of statins are improve endothelial function reduce vascular inflammation reduce platelet aggregability neovascularization of ischemic tissue increase circulating endothelial progenitor cells stabilization of atherosclerotic plaques antithermatic action enhanced vibranolysis and protection against sepsis but they inhibit germ cell migration during development therefore statins are contraindicated during pregnancy because it can cause impaired fetal development as we have discussed earlier statins are almost exclusively given in the treatment of cardiovascular disease they are commonly used in primary prevention of arterial disease especially indicated for patients with diabetes and renal failure with elevated serum ldl cholesterol and they are also used in the secondary or long-term management of myocardial infarction and stroke indicated in angina transient ischemic attacks and following myocardial infarction and stroke at this instance statins are given along with other anticoagulants like aspirin and capital statins are also given in the treatment of non-cardiovascular diseases like alzheimer's disease and prostate cancer statins are taken priorly and they are taken at night because the maximum activity of hmg coerductus enzyme is during night time they are well absorbed in the gi tract but has a low bioavailability this is because the main action of statins are in the liver and they undergo extensive pre-systemic metabolism therefore only a small amount of the drug reaches the systemic circulation ones in the bloodstream they are highly protein bound statins are predominantly excreted in vcs therefore they are usually indicated in renal impairment adverse effects of statins are less compared to other drugs they are usually well tolerated mild unwanted effects include muscle pain gi disturbances like abdominal pain and diarrhea insomnia and rash serious adverse effects are rare and may include hepatotoxicity and elevated serum alt and ast levels rhabdomyolysis especially when given along with fibrates which are used to reduce serum triglyceride levels and angioedema so in summary this is what we have discussed in this short video thanks for watching see you soon in the next video