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Accutane is a form of vitamin A. It reduces the amount of sebum produced by the sebaceous glands, and also accelerates the natural regeneration of the skin. Accutane is used to treat strong acne manifestations that are not amenable to treatment with other drugs, including antibiotics. Accutane can also be used for other purposes that are not listed in the instructions for use.

Pharmacological action Accutane (Isotretinoin)

Isotretinoin is a stereoisomer of all-transretinoic acid (tretinoin). The exact mechanism of action of Accutane has not yet been elucidated, but it has been established that the improvement in the clinical picture of severe acne is associated with the suppression of the activity of the sebaceous glands and a histologically confirmed decrease in their size. In addition, the anti-inflammatory effect of isotretinoin on the skin has been proven.

Hyperkeratosis of the epithelium cells of the hair follicle and the sebaceous gland leads to desquamation of the corneocytes in the duct of the gland and to the occlusion of the latter with keratin and an excess of sebaceous secretion. This is followed by the formation of comedo and, in some cases, the addition of the inflammatory process. Accutane inhibits sebocyte proliferation and acts on acne, restoring the normal process of cell differentiation. Sebum is the main substrate for the growth of Propionibacterium acnes, therefore reducing the formation of sebum suppresses bacterial colonization of the duct.

Since the kinetics of isotretinoin and its metabolites is linear, its plasma concentrations during therapy can be predicted on the basis of data obtained after a single dose. This property of the drug also suggests that it does not affect the activity of liver enzymes involved in the metabolism of drugs.

Isotretinoin absorption from the gastrointestinal tract fluctuates. The absolute bioavailability of isotretinoin was not determined, since the release form of the drug for intravenous use is not available in humans. However, extrapolating the data obtained in the experiment on dogs suggests a rather low and variable systemic bioavailability. In patients with acne, the maximum plasma concentrations (Cmax) in the equilibrium state after taking 80 mg of isotretinoin on an empty stomach were 310 ng / ml (range 188-473 ng / ml) and were reached in 2-4 hours. Plasma concentrations of isotretinoin are approximately 1.7 times higher than concentrations in blood due to poor penetration of red blood cells into isotretinoin. Taking isotretinoin with food increases the bioavailability by 2 times compared to fasting.

Isotretinoin strongly (99.9%) binds to plasma proteins, mainly albumin, so that in a wide range of therapeutic concentrations the content of the free (pharmacologically active) fraction of the drug is less than 0.1% of its total amount.

The amount of distribution of isotretinoin in humans has not been determined, since the dosage form for intravenous administration does not exist. The equilibrium blood concentrations of isotretinoin (Cmin ss) in patients with severe acne, taking 40 mg of the drug 2 times a day, ranged from 120 to 200 ng / ml. The concentrations of 4-oxo-isotretinoin in these patients were 2.5 times higher than those of isotretinoin. Data on the penetration of isotretinoin into human tissue is insufficient. The concentration of isotretinoin in the epidermis is two times lower than in serum.

After oral administration, three major metabolites are found in plasma: 4-oxo-isotretinoin, tretinoin (fully transretinoic acid) and 4-oxo-retinoin. The main metabolite is 4-oxo-isotretinoin, the plasma concentrations of which in equilibrium are 2.5 times higher than the concentrations of the original preparation. Less significant metabolites have also been found, which also include glucuronides, however, the structure of not all metabolites has been established.

Metabolites of isotretinoin have biological activity, confirmed in several laboratory tests. Thus, the clinical effects of the drug in patients may be the result of the pharmacological activity of isotretinoin and its metabolites.

Since isotretinoin and tretinoin (fully transretinoic acid) are reversibly transformed into each other in vivo, the metabolism of tretinoin is associated with the metabolism of isotretinoin. 20-30% of the dose of isotretinoin is metabolized by isomerization. In the pharmacokinetics of isotretinoin in humans, enterohepatic circulation may play a significant role.

In vitro metabolism studies have shown that several enzymes of the cytochrome P450 (CYP) system are involved in the conversion of isotretinoin to 4-oxo-isotretinoin and tretinoin. Apparently, none of the isoforms at the same time does not play a dominant role. Accutane and its metabolites have no significant effect on the activity of CYP system enzymes.

After ingestion of radioactively labeled isotretinoin, approximately the same amount is detected in urine and feces. The half-life of the terminal phase for unchanged drug in patients with acne averages 19 hours. The half-life of the terminal phase for 4-oxo-isotretinoin appears to be longer and averages 29 hours. Isotretinoin is a natural (physiological) retinoid. Endogenous concentrations of retinoids are restored approximately 2 weeks after the end of taking Accutane.

Since isotretinoin is contraindicated in violation of the liver, data on the pharmacokinetics of the drug in this group of patients is limited. Renal failure does not affect isotretinoin pharmacokinetics.

Indications. Severe acne (nodular / cystic, conglobate acne or acne with the risk of scarring). Acne, not amenable to other therapies.

Contraindications. Pregnancy, breastfeeding period (see section “Pregnancy and breastfeeding period”), liver failure, hypervitaminosis A, severe hyperlipidemia, concomitant tetracycline therapy. Hypersensitivity to the drug or its components (including soy). Children's age up to 12 years.

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History

External treatment depends on the ability of the active molecule to reach a certain part of the follicle at an effective concentration. It has been proven that systemic administration is more effective than topical administration of the most powerful retinoid comedolytics.

The first retinoid, vitamin A (retinol), was used for generations in the form of such weak and harmless external agents as an ointment with vitamin A & D, and was also part of all multivitamin complexes for oral administration. Its effect when applied topically with any type of acne is essentially zero. Oral administration in high doses (300,000–400,000 IU per day) has a significant effect, even before the appearance of obvious toxic effects.

Kligman (Kligman) et al. worked with such high doses until the appearance of isotretinoin on the scene. The use of such doses was associated with registered teratogenicity, therefore, where there is a likelihood of pregnancy, its use should be avoided.

Isotretinoin works much better when it enters the follicular unit through the bloodstream after oral administration, although in some countries it is presented as an external agent on a gel basis. The same can be said about the need to deliver it to the sebaceous gland, a trick that cannot be carried out with external use.

After the introductory article by Peck (Rivers) in 1979, isotretinoin appeared on the scene in 1982, and the whole picture of acne treatment changed. Known as Accutane in North America and as Roaccutane in other countries, it was quickly recognized as the most effective treatment available. Despite pronounced side effects, almost all of which are easy to handle with careful dosing and careful monitoring, isotretinoin retains the place of honor of the most effective acne treatment.

Isotretinoin is a powerful drug and should be treated with respect, with particular attention to the following five important issues.

The risk that isotretinoin poses to developing children has led to the creation of quite reasonable controls to minimize it. Unfortunately, many of the specialists who in the past have designated isotretinoin have been lost to the system as a result of the unsuccessful implementation of the iPLEDGE program in the United States, the triumph of constructive obstructionism. And although this program initially complicated the difficult situation even more, it helped to maintain the availability of this extremely valuable drug.

Nevertheless, hundreds of caring doctors prescribing isotretinoin were lost due to iPLEDGE, which suffered a fiasco, being counterproductive and incompatible with the provision of comprehensive and proper medical care.

A similar patient-unfriendly set of rules emerged in the European Union, the so-called European Directive (Article 29 of Directive 2001/83 / EC), with recommendations to preserve isotretinoin for those who "have severe acne ... resistant to an adequate course of standard therapy with the use of systemic antibacterial drugs and external agents. " The international group of dermatologists noted: “New recommendations suggest using isotretinoin only for severe acne (nodal and conglobate forms) when there is no response to the appropriate antibacterial and external treatment.

From this we can conclude that it should not be used at all as a first-line treatment. ” It is impossible to find out how many unnecessary cases of inflammatory bowel disease, candidiasis, Malassezia-folliculitis have arisen due to the inappropriate use of oral antibiotics, following this rule. How much delay in prescribing effective treatment prolonged physical and psychological suffering? This unfortunate Directive simply added the weight to the burden of acne patients in the EU.

To be fair, we say that it was created before the discussion of issues related to the risk of inflammatory bowel disease due to isotretinoin, therefore it is time to revise this Directive.

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General Tips for Combating Acne

Wash your face twice a day. Do this carefully and do not use a dirty towel - acne is caused by bacteria that live on dirty towels.

  • Once a week, use a facial scrub to remove dead skin cells. Scrub removes the top layer of skin called the epidermis. This procedure is useful to do once a week.
  • Moisturize your skin after every wash. The skin is also an organ of the body. Like your kidneys, it needs moisture to maintain health. Moisturize it after every wash.

    Do not touch the face. Try not to touch the face - consciously or unconsciously. Your hands are very dirty carriers of bacteria. The less you touch your face, the better your skin will feel.

    Do sports. Exercise is a great way to get rid of acne. During a workout you get rid of stress. It is believed that acne causes stress, although doctors have not yet found a clear connection.

    Get rid of stress and anxiety with the help of sports. Join a sports team, sign up for a gym or just do a daily gymnastics. All this will help you clean the skin.

    After class, take a shower immediately. When you exercise, you sweat (at least if you exercise correctly). After an intense workout on your skin is full of dirt, salt and dead skin cells.

    Do not drink alcohol. Alcohol aggravates acne. Alcohol dehydrates your body, depriving it of a vital ingredient. Alcohol has a very large amount of sugar, which contributes to the appearance of acne. If you want to protect yourself, try to drink less alcohol and follow the reaction of your body. And if there is a case when alcohol cannot be avoided, drink more water.

    Do not squeeze acne. Do not squeeze, do not pick, and do not scratch them. So redness and inflammation will only intensify. Easy to say, but hard to do. If you do not squeeze out acne, scars may not form at all, and acne will go faster.

  • Be careful when using toothpaste. Toothpaste dries the skin, so be sure to moisturize it after the procedure.
  • Wash your face twice a day.
  • Do not pay attention to the stories that sugar and chocolate cause acne. This is not true. Poor nutrition and sensitivity to certain foods cause acne. Some people can safely eat chocolate, but a piece of cheese will make them have a rash. Remember that you need to eat right. Eat healthy foods and pay attention to the foods that cause acne.
  • If you apply an ice cube to the affected skin, the redness will decrease.
  • NEVER take a shower right after work. Otherwise, you will only make things worse - your pores will become clogged, and you will also damage your skin. When you arrive home, wait 30 minutes and then take a shower.
  • Always pat on the face to dry it, never rub. Friction will only increase redness.
  • Never touch your acne with your hands. On the hands of a mass of germs, besides the hands are very fat. If you touch the acne with your hands, you run the risk of infection.
  • Drink plenty of water on a regular basis.
  • Take apple cider vinegar overnight. It does not smell very nice, but it actually helps.
  • If possible, use mint-free toothpaste. It will burn less.
  • Products such as aloe vera gel and charcoal-based soap will help cleanse the skin and make it less oily. Continued use of these products will help prevent acne and rashes.
  • Aloe vera gel is truly an amazing thing! And if you apply baking soda to acne, there will be no trace of them left.
  • Use an exfoliating scrub every two days.
  • Initially, the toothpaste will burn very much, but do not rub it, as this will aggravate the burning sensation. If you have sensitive skin, do not use toothpaste.

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