Simvastatin

Simvastatin

Do you know what simvastatin is? How does it work within your body and what changes does it generate?
Find out about this and more in the following article from Cardiosmile Chile.

Simvastatin, like other statins, is an oral antilipidemic drug that inhibits HMG-CoA reductase. It is a methylated derivative of lovastatin, so both are pro-drugs that need hydrolysis for activation.

This medication is used to treat primary hypercholesterolemia, highlighting its effectiveness, since it reduces the levels of LDL cholesterol, triglycerides and also apolipoprotein B. It should also be noted that simvastatin is the second most potent inhibitor of HMG-CoA reductase, after atorvastatin.

Simvastatin is a synthetic drug, created from the fermentation of Aspergillus terreus, which has marked a milestone in modern pharmacology since it was sought from the therapeutic target where it was desired to act. Thus, the search for substances that would block the receptor began, leading to the discovery of the first molecules that have been refined until the current statins are achieved.

Simvastatin and its passage through the body

Simvastatin is administered orally and is not affected by food. After the corresponding administration, its maximum concentration is reached after two hours.

In the case of elderly patients, the maximum concentration levels rise by 45% and multiple doses do not produce accumulation of the product in the body so it is recommended to take a single dose.

Simvastatin clings tightly to plasma proteins with an efficiency of approximately 95%. Until now it is known that it crosses the blood-brain barrier and the placental barrier, however, it has not been proven if it appears in the milk of lactating mothers under treatment with simvastatin.

Due to the intense effect of the first hepatic step that suffers when metabolized, its bioavailability only reaches 5%.

Simvastatin and its mechanism of action

Simvstatin should be hydrolyzed to mevinilinic acid, since the native drug has virtually no pharmacological effect. On the other hand, mevinolinic acid is structurally similar to HMG-CoA, so it can compete with this against the HMG-CoA reductase enzyme.

Due to the above, the activity of said enzyme is blocked, thus decreasing the amount of mevalonic acid synthesized by the hepatocyte and, since this is the precursor of cholesterol, the synthesis thereof is reduced.

In this way, a decrease in the levels of LDL cholesterol, total cholesterol, triglycerides and apolipoprotein B can be observed, reducing the risk of cardiovascular disease.

Also, simvastatin inhibits the synthesis of isoprenoids, substances that stimulate the activity of osteoclasts, reducing bone loss.

Finally, 13% of the dose of simvastatin is excreted through the urine, while 60% is excreted through the faeces.

Rosuvastatin

Rosuvastatin

What is Rosuvastatin? How does it work once you consume it?
Find out this and more in this article from Cardiosmile Chile

Rosuvastatin, like other statins, is a drug used to lower blood cholesterol levels, since it is considered a cardiovascular risk factor.

This medication is totally synthetic and its function is to inhibit the enzyme HMG-CoA reductase with the aim of decreasing the production of endogenous cholesterol in order to prevent cardiovascular diseases.

Originally, the name of this drug – also marketed as calcium salt – was Crestor, a brand belonging to the Japanese company Shionogi & Co. Ltd., however, Crestor’s worldwide rights were acquired by the pharmaceutical company AstraZeneca. This medication was first tested in 2002 in the Netherlands and later extended to 23 other countries.

Rosuvastatin, like other statins, is administered orally and is not interfered with by food intake. As observed, the maximum plasma concentration of 3-5 hours after the administration of the corresponding daily dose is reached.

Its distribution in the organism is through its binding to plasma proteins, which is close to 88%, mainly in albumins.

Rosuvastatin and its passage through the body

Rosuvastatin’s metabolism is at hepatic level and has high affinity for the active site of HMG-CoA reductase. Rosuvastatin is one of the most potent statins and the inhibition effect of cholesterol synthesis is longer than other statins. This was also observed in rats, where rosuvastatin inhibited hepatic cholesterol synthesis by 62%, well above 13% of simvastatin and 7% of atorvastatin.

There are studies where it has been observed that rosuvastatin is efficiently and selectively taken up by the liver cells, while in fibroblasts and other non-hepatic cells the uptake is lower. Likewise, it was observed that, in cultures of human myocytes, rosuvastatin is less active than simvastatin and atorvastatin as inhibitor of cholesterol synthesis. This is important because having less activity than other statins, there would also be a lower level of toxicity on muscle cells, which ultimately results in myalgia, rhabdomyolysis and increased creatine phosphokinase.

Thus, rosuvastatin decreases LDL cholesterol, total cholesterol, triglycerides and apolipoprotein B in plasma.

Rosuvastatin is excreted from the body mainly through faeces (90%) and whose elimination process lasts about 19 hours.

Lovastatin

Lovastatin

What is lovastatin? How does it work?
Know this and more in this article from Cardiosmile Chile

Lovastatin is a medication used for the treatment and control of cholesterol. It is a selective and competitive inhibitor of the enzyme HMG-CoA reductase, which is responsible for the conversion of HMG-CoA to mevalonate, the precursor of cholesterol.

Lovastatin acts at the liver level, inhibiting the synthesis of cholesterol and reducing the production of LDL cholesterol. It is an effective drug in the reduction of bad cholesterol in patients with homozygous familial hypercholesterolemia who do not usually respond to lipid-lowering medications.

Lovastatin and its passage through the body

As previously indicated, lovastatin is a drug belonging to the statin family that serves to reduce cholesterol and prevent cardiovascular diseases.

Lovastatin is administered orally and consists of a substance derived from Aspergillus terreus that originated in the late 1970s, making it one of the first statins developed.

Like other statins, the absorption of lovastatin is limited, reaching a maximum of 30%. As result, it has a very low bioavailability, close to 5%, and its maximum concentration is reached approximately two hours after consuming it. Subsequently, lovastatin is excreted by 80% through faeces and 10% through urine. Lovastatin and its mechanism of action

When Lovastatin blocks the hepatic synthesis of cholesterol activates the SREBP regulatory proteins, which activate the transcription of proteins and, therefore, increase the number of receptors in the hepatocyte due to increased expression of the LDL cholesterol receptor gene.

Given the above, it is possible to observe a reduction in the levels of total cholesterol and LDL cholesterol, both indicators related to atherosclerosis and increased cardiovascular risk.

However, as with other statins, it is important to consider the interactions they produce with other medications and foods, in addition to their side effects.

For example, both niacin and fibrates increase the risk of myopathy associated with lovastatin. Likewise, there are other drugs that interact with it in relation to hepatic metabolism such as erythromycin, protease inhibitors, grapefruit juice and azole antifungals, among others.

 

Atorvastatin

Atorvastatin

Do you know atorvastatin? Do you know how it works and what is it used for?

Discover this and more in the following article from Cardiosmile Chile.

Within the statin family we can find different drugs, among them, atorvastatin, a medicine used to reduce the levels of cholesterol in the blood and thus prevent cardiovascular diseases.

Atorvastatin also stabilizes plaques and prevents embolism through anti-inflammatory mechanisms. As a result of the aforementioned, atorvastatin has become one of the most used drugs in the world since cholesterol is considered a cardiovascular risk factor.

Like the other statins, atorvastatin inhibits the enzyme HMG-CoA reductase which plays a fundamental role in the production of cholesterol in the body. Despite this similarity, atorvastatin is a completely synthetic compound, unlike simvastatin and pravastatin.

The origin of atorvastatin takes place in 1985 and was developed by Bruce Roth, who at that time worked at Parke-Davis Warner-Lambert Company, now known as Pfizer.

Atorvastatin and its passage through the body

Atorvastatin is rapidly absorbed after oral administration, reaching its maximum levels in the blood after 1-2 hours, and its degree of absorption increases in proportion to the administered dose of atorvastatin.

With respect to its bioavailability, atorvastatin tablets are between 95-99%, and their absolute bioavailability is approximately 12%. Its systemic bioavailability of the inhibitory activity of HMG-CoA reductase is approximately 30%. This low figure is attributed to a presystemic clearance in the gastrointestinal mucosa and / or to a first-pass hepatic metabolism in the upper intestine.

It has been observed that the administration of nocturnal doses favors the reduction of the speed of absorption and the extension of concentration by 30%. However, the administration time of atorvastatin does not affect its efficacy. However, in the presence of food in the stomach, the absorption of the statin can decrease up to 25%

Regarding its distribution in the organism, it is important to emphasize that atorvastatin binds strongly to plasma proteins, reaching a percentage equal to or greater than 98%.

The primary mechanism of metabolism of atorvastatin is by cytochrome P450 3A4 to its active metabolites ortho and parahydroxylated, in addition to various products of beta-oxidation. It has been observed in vitro that the inhibition of HMG-CoA reductase by said metabolites is equivalent to that of atorvastatin. Thus, these metabolites are responsible for 70% of the systemic activity of HMG-CoA reductase.

On the other hand, atorvastatin is also a substrate of the intestinal P-glycoprotein efflux transporter, which pumps the drug out of the cell, into the intestinal lumen, during the absorption of the drug.

Finally, atorvastatin is eliminated mainly through bile, after hepatic and / or extrahepatic metabolism. Its plasma elimination process is approximately 14 hours and the half-life of the inhibitory activity of HMG-CoA reductase is 20 to 30 hours due to the effect of the ortho and parahydroxylated active metabolites. At least 2% of atorvastatin can be detected in the urine.

Atorvastatin and its mechanism of action

Atorvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the enzyme responsible for conversion to mevalonate, the precursor of sterols (including cholesterol). When HMG-CoA reductase is inhibited, the amount of mevalonate decreases and, consequently, the hepatic cholesterol levels are reduced. In this way, the LDL cholesterol receptors are regulated, generating an uptake of said lipoproteins. Thus, a reduction in total cholesterol and LDL cholesterol is observed, both closely related to arteriosclerosis and increased cardiovascular risk.

With all the above, it is important to consider that the inhibition of HMG-CoA reductase by atorvastatin or any other type of statin, results in unwanted side effects. And is that HMG-CoA reductase is part of the metabolic route of mevalonic acid, a route that is also vital for the synthesis of coenzyme Q10, which in turn is essential for the production of energy in the mitochondria.

In this way, statins not only inhibit the synthesis of cholesterol, but also that of coenzyme Q10, causing a reduction in the energy needed to live. As a result of this, symptoms are manifested in tissues with higher energy requirements such as the kidneys, the brain or musculoskeletal tissue. Thus, the ailments and myopathies begin in patients treated with statins.

What are statins?

What are statins?

What are statins? What are the statins used for? What effects do they produce?

Discover this and more at Cardiosmile Chile

Statins are a group of drugs used to reduce cholesterol and triglycerides in patients who, for example, have high levels of hypercholesterolemia and who, therefore, have a higher risk of developing atherosclerosis and / or suffer episodes of cardiovascular pathology.

In pharmacology, statins are called “inhibitors of HMG-CoA reductase” and it is precisely this enzyme inhibition that generates a decrease in lipoproteins in the body, which is why statins have been positioned as a drug of great importance to the intervening cardiovascular risk factors whose pathologies are currently the main cause of death in Chile and the world. In fact, 30% of deaths in Chile correspond to ECV.

The finding of statins has marked modern pharmacology. In the beginning, the researchers defined that they should act on HMG-CoA reductase, the enzyme involved in the synthesis of cholesterol. In this way, they began to look for substances that would block the receptor, thus finding the first molecules that were refined until the current statins were achieved.

Citrinin was discovered in 1971 and was cataloged as a potent inhibitor of HMG-CoA reductase. Later, between 1972 and 1973, it was possible to isolate mevastatin (also known as compactin) which was defined as the first statin. However, due to its toxicity, its efficacy to inhibit HGM-CoA reductase was limited.

Then, between 1978 and 1979, the company Merck Research Laboratories developed the lovastatin that was authorized by the FDA for sale to the public in 1987.

Later, they appeared: fluvastatin, which was the first totally synthetic statin, and pravastatin, a fungal metabolite isolated from Nocardia autotrophica cultures. Simvastatin followed, synthesized as a result of a product of the fermentation of Aspergillus terreus, and so all the others, keeping research in this line to these days.

Here is a summary of the statins that have been studied and approved by the FDA in the United States and the AEM in the European Union, in order of appearance:

  • Lovastatin
  • Simvastatin
  • Pravastatin
  • Fluvastatin
  • Atorvastatin
  • Cerivastatin. This was withdrawn from the market by Bayer (its manufacturer) in 2001 due to its side effects.
  • Rosuvastatin
  • Pitavastatin

To date, all statins are orally ingested and are known to decrease their absorption in the presence of food in the stomach. However, the change in cholesterol levels is not affected, which is why it is advisable to take them at any time of day and in most cases with or without food.

The only general recommendation is not to drink grapefruit juice while taking a statin treatment because it causes an interference in the metabolism. This is one of the interactions of the most known statins to date and there are also other medications with which they can interact generating adverse effects (link statins: interaction with food and medication).

Remember that, if you have high cholesterol levels, as well as your triglycerides, you can also consume Cardiosmile.

Cardiosmile is a natural product, with no proven side effects, based on phytosterols, which contributes LDL cholesterol by 12% and triglycerides by 14% *.

Each Canister of Cardiosmile contains 30 sachets (quantity for one month) with 2 g of phytosterols each, the recommended daily portion to help reduce cholesterol and triglycerides effectively.
In addition, it is free gluten, sodium, fat, sugar, calories and lactose so anyone can consume it from 5 years.

The formulation process of Cardiosmile is unique and patented, which allows you to incorporate your daily Cardiosmile sachet to the food you prefer, without altering its taste or smell. You can see results after 28 days and, to keep your cholesterol and triglyceride levels within normal ranges, you must continue to consume Cardiosmile permanently.

Watch your health. Cholesterol? Cardiosmile, it works.

 

**AS SEEN IN THE CLINICAL STUDY OF AMIR SHAGHAGHI, ET AL. 2014. J FUNCT FOODS. 6: 280-289