Glucosamine

Pharmacological properties

Artiflex

Pharmacodynamics Artiflex is a drug that affects metabolism in cartilage. Glucosamine sulfate is a salt of the natural low molecular weight glucosamine aminomonosaccharide, thoroughly purified from macromolecular components. The drug makes up for endogenous glucosamine deficiency, stimulates the synthesis of proteoglycans of hyaluronic acid synovial fluid. It increases the permeability of the joint capsule, restores the enzymatic processes in the cells of the synovial membrane and articular cartilage. The anti-inflammatory effect of glucosamine sulfate is due to the blocking of the formation of superoxide radicals by macrophages and the inhibition of lysosomal enzymes. The drug promotes the fixation of sulfur during the synthesis of chondroitin sulfuric acid, facilitates the absorption of calcium in bone tissue, inhibits the development of degenerative processes in the joints, restores their function, reducing the severity of pain in the joints. Sulfates are also involved in the synthesis of glucosaminoglycans and the metabolism of cartilage tissue. Side chain sulfate esters in proteoglycans are important for maintaining elasticity and the ability to retain cartilage matrix water. The severity of clinical symptoms usually decreases 2 weeks after the start of treatment with the effect remaining for 8 weeks after discontinuation of the drug.

Pharmacokinetics Glucosamine sulfate is rapidly and completely absorbed in the small intestine (90%). It easily passes through biological barriers and penetrates into tissues, mainly articular cartilage. T_½ - 68 hours

Artiflex Chondro

Pharmacodynamics The main active ingredients of the drug are the sodium salt of chondroitin sulfate A and C (average molecular weight - 11,000 Da). Chondroitin sulfate is a high molecular weight mucopolysaccharide, which is the main component of proteoglycans, which together with collagen fibers form the cartilage matrix.

The drug inhibits the degeneration process and stimulates the regeneration of cartilage, has chondroprotective, anti-inflammatory, analgesic properties; replaces chondroitin sulfate of articular cartilage catabolized by a pathological process; inhibits the activity of enzymes that cause degradation of articular cartilage: inhibits metalloproteinase, namely leukocyte elastase; reduces the activity of hyaluronidase; partially blocks the release of free oxygen radicals; helps to block chemotaxis, antigenic determinants; stimulates the synthesis of proteoglycans by chondrocytes; affects the phosphorus-calcium metabolism in cartilage; allows you to restore the mechanical and elastic integrity of the cartilage matrix. Anti-inflammatory and analgesic effects are achieved by reducing the release of inflammatory mediators and pain factors into the synovial fluid through synoviocytes and macrophages of the synovial membrane, as well as by inhibiting the secretion of leukotriene B and prostaglandin E.

The drug helps to restore the joint bag and cartilage surfaces of the joints, reduce the intensity of pain, prevents compression of the connective tissue, acts as a lubricant to the joint surfaces, normalizes the production of joint fluid, improves joint mobility and quality of life.

Artiflex chondro slows down bone resorption and reduces calcium loss, speeds up the process of bone restoration.

Pharmacokinetics After i / m administration, chondroitin sulfate penetrates into the synovial fluid. C_max in synovial fluid is achieved 4-5 hours after injection. It is excreted within 24 hours. It is eliminated mainly by the kidneys.

Indications

Artiflex

Treatment of osteoarthritis and / or its symptoms, i.e. pain and functional limitation.

Artiflex Chondro

Degenerative and degenerative diseases of the joints and spine (primary arthrosis, intervertebral osteochondrosis, osteoarthrosis), osteoporosis, periodontopathy, fractures (to accelerate the formation of bone marrow), as well as to treat the effects of surgical interventions on the joints.

Application

Artiflex

Apply inside.

Adult patients and the elderly: the contents of 1 packet is equivalent to 1.5 g of glucosamine sulfate, dissolved in a glass of water and taken 1 time per day, preferably with meals.

The course of treatment is 4-12 weeks or longer (if necessary). According to the doctor’s prescription, therapy can be repeated 2-3 times a year with an interval of 2 months, as well as with a relapse of the disease.

Artiflex Chondro

The drug is administered to adults in oil 1 ml every other day. In case of good tolerance, the dose is increased to 2 ml, starting from the 4th injection. The course of treatment is 25–35 injections. Repeated courses - after 6 months.

Contraindications

Hypersensitivity to any of the components of the drug.

Artiflex

Phenylketonuria. During pregnancy and breastfeeding.

Artiflex Chondro

Propensity to bleeding, thrombophlebitis, renal failure.

Side effects

Artiflex

From the digestive tract: pain in the stomach, flatulence, diarrhea, constipation, nausea, vomiting.

From the nervous system: headache, drowsiness, general weakness.

From the immune system: allergic reactions in the form of a variety of skin rashes and itching.

On the part of the organ of vision: visual impairment.

On the part of the skin: hair loss.

Artiflex Chondro

When using the drug in people with hypersensitivity to the drug, the following violations are possible:

from the immune system: allergic reactions, anaphylactic shock, angioedema;

on the part of the skin and subcutaneous tissue: rash, itching, erythema, urticaria, dermatitis, alopecia; redness and itching are possible at the injection site;

from the gastrointestinal tract: nausea, vomiting, abdominal pain, flatulence, dyspeptic symptoms;

others: visual impairment, keratopathy, dizziness, peripheral edema.

special instructions

Use during pregnancy or lactation. do not apply.

Children. The drug is not used.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Does not affect.

Artiflex

Due to the fact that glucosamine is obtained from the shell of mollusks, patients with allergies to mollusks should take Artiflex with caution.

Powder for oral use contains sorbitol. Patients with a rare hereditary form of fructose intolerance, the drug in this dosage form is not recommended.

Patients on a diet with a controlled sodium content should take into account the presence of sodium in the dosage form for oral administration (151 mg in 1 daily dose per 1500 mg).

At the beginning of treatment for patients with diabetes, it is advisable to monitor the level of glucose in the blood.

In patients with severe hepatic or renal failure, the drug is used only under medical supervision.

Artiflex is contraindicated in patients with phenylketonuria, since it contains aspartame.

Artiflex Chondro

To achieve a stable clinical effect, at least 25 injections of the drug are necessary. The effect persists for many months after the end of treatment. To prevent exacerbations, repeated courses of treatment are used. It is recommended that the dose be increased under the supervision of a doctor for patients with excess body weight, a stomach ulcer or duodenal ulcer, while taking diuretics, and also at the beginning of treatment, if necessary, a quick clinical response.

In case of allergic reactions or hemorrhages, treatment must be discontinued.

Interactions

Artiflex

With combined use, an increase in the effect of coumarin anticoagulants is noted. In this regard, it is advisable for patients to monitor coagulation indicators.

Possible increased gastrointestinal absorption of tetracycline. The drug is compatible with NSAIDs and GCS.

Artiflex Chondro

With the simultaneous use of corticosteroids and NSAIDs, chondroitin sulfate can reduce the need for their use, as well as painkillers. It has a synergistic effect when used simultaneously with glucosamine and other chondroprotectors. The effectiveness of treatment increases with the enrichment of the diet with vitamins A, C and salts of manganese, magnesium, copper, zinc and selenium.

With simultaneous administration with acetylsalicylic acid or other anticoagulants or antiplatelet agents, it is recommended that blood coagulation be monitored.

Overdose

No cases of overdose were noted.

Artiflex

In case of accidental overdose, gastric lavage and symptomatic treatment are performed.

Artiflex Chondro

It is assumed that if the daily dose is exceeded, a possible increase in the severity of the side effects of the drug. The treatment is symptomatic.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 ° C.

Actual information

Artiflex is a complex drug for the treatment of pathology of the musculoskeletal system. for the purpose of the most effective use, it is available in two forms - a cream for topical use and a soluble powder for oral administration.

The mechanism of action and therapeutic effects of glucosamine

The main active substance ArtiflexThe powder for oral solution is glucosamine hydrochloride.

Glucosamine is an aminosaccharide, that is, by chemical composition it is a low molecular weight derivative of carbohydrates with the inclusion of an amino group. It is synthesized from glucose and utilized in the synthesis of glycosaminoglycans and proteoglycans (Dahmer S., 2008). Glucosamine is involved in many biochemical processes in the body, including the synthesis of chondroitin. In modern pharmacology, glucosamine is presented in the form of two compounds: glucosamine hydrochloride and glucosamine sulfate. Glucosamine sulfate requires additional stabilizing components, so its purity is 74%. Glucosamine hydrochloride does not have a sulfate group, which helps to achieve 99% purity. That is why, in terms of the pure active ingredient, glucosamine hydrochloride at a dose of 1500 mg is equivalent to 2608 mg of glucosamine sulfate (Owens S., 2004), although the difference in bioavailability between the two forms is so insignificant that it is not taken into account in clinical practice (Aghazadeh-Habashi A. , 2011). Glucosamine is easily absorbed by the gastrointestinal mucosa and is rapidly metabolized in the liver (first-pass effect), excreted in the feces or urine. Peak concentrations of the drug in the blood are observed within 8 hours after ingestion. The half-life of the drug is quite long - 68 hours. This is primarily due to the high degree of glucosamine binding to proteins - about 90% (Fox B.A., 2007). Glucosamine bioavailability is 26% (Barclay T.S., 1998).

Since glucosamine is a structural component of the cartilage matrix of joints, traditionally the treatment of articular pathology has been associated precisely with its additional supply from the outside. Subsequently, studies were conducted on the biochemical principles of glucosamine action. The mechanism of its anti-inflammatory effect is based on the inhibition of proinflammatory mediators such as NO, cyclooxygenase (COX) -2 and matrix metalloproteinases. In addition, the same effect is associated with the reduction of nuclear factor κβ, which is induced by interleukin-1 (Gouze J.N., 2006). Studies (Nakamura H., 2004) have also demonstrated that glucosamine inhibits the production of catabolic enzymes and inflammatory markers (e.g. prostaglandin E₂) chondrocytes and synovial cells stimulated by interleukin-1.

In addition, glucosamine is a precursor to glycosaminoglycans (in particular hyaluronic acid and keratan sulfate) and proteoglycans, which are found in articular cartilage, intervertebral disc and synovial fluid (Henrotin Y., 2012). This property is also used in cosmetology - by increasing the synthesis of hyaluronic acid, glucosamine accelerates wound healing, moisturizes the skin and helps reduce wrinkles (Bissett D.L., 2006). In addition, it acts as a tyrosinase inhibitor, that is, indirectly reduces the production of melanin, therefore, it can resist the development of hyperpigmentation.

Studies (Hua J., 2005) have shown that the local use of glucosamine significantly reduces the severity of the manifestations of adjuvant arthritis (an experimental model of arthritis of any joint in the body, which is similar in pathogenesis to rheumatoid arthritis).

According to the Cochrane review (Towheed T., 2009), glucosamine is the drug of choice in the treatment of osteoarthritis, as it improves joint function, increases the volume of active and passive movements (da Camara CC, 1998), reduces the severity of pain and hyperesthesia, and also probably not causing side effects. The FDA classifies glucosamine as dietary supplements, but it is characterized by its ability to reduce the severity of pain, inhibit the development of damage, and even restore cartilage in patients with osteoarthritis or other joint diseases (Kirkham S.G., 2009). Real-time studies (Bruyère O., 2016) demonstrate that the systematic use of glucosamine in patients with osteoarthritis delays the need for additional painkillers. It contributes to the restructuring of not only cartilage and synovial tissue, but also subchondral areas of the bone (Henrotin Y., 2012).

When choosing a therapeutic dose, it should be borne in mind that in order to achieve an effect with systemic use (for example, in the form of tablets or powder for solution preparation), the daily dose of glucosamine should be at least 1500 mg. However, a tablet containing 1.5 g of active ingredient may seem very large to the patient, and several smaller tablets (and, accordingly, with a lower content of active ingredient) may produce a subjective impression of an overdose with subsequent non-compliance with the doctors prescriptions (Aghazadeh-Habashi A., 2011 ) That is why Artiflex available in powder form for solution preparation. One dose contains the equivalent of 1,500 mg of glucosamine. A portion of the powder is dissolved in a glass of clean water and consumed once a day. To achieve a sustainable therapeutic effect, the drug must be taken in long courses - 4-12 weeks each. Such courses can be repeated 2-3 times a year, while between courses you need to maintain an interval of 2 months.

Possible uses of glucosamine-based drugs:

- cervical spondylosis (Li Y., 2018);

- osteochondrosis (localized or common);

- osteoarthritis (Matheson A.J., 2003), especially of the hip and knee joints;

- other inflammatory and degenerative diseases of the musculoskeletal system;

- after surgical interventions on the joints, including meniscus repair and total arthroplasty;

- due to its healing properties, glucosamine can be used as an adjuvant for the treatment of inflammatory bowel diseases (for example, Crohns disease) (Bissett D.L., 2006);

- glucosamine is used in cosmetology to reduce skin pigmentation and reduce wrinkles (Bissett D.L., 2006).

Characteristics of cream components Artiflex

The main therapeutic effect is achieved by using glucosamine inside in the form of a powder for the preparation of a solution.For the maximum result in the treatment of osteoarthritis, a comprehensive approach is required, which includes not only pharmacotherapy, but also therapeutic gymnastics, physiotherapy, skeletal traction, as well as lifestyle changes (weight loss, dietary review). You can enhance the therapeutic effect by additionally applying topically cream Artiflex. The cream is applied to the skin surrounding the affected joint 2-3 times a day and rubbed for several minutes until completely absorbed. To achieve a sustainable effect, a topical course of cream Artiflex must be at least 2 weeks. In addition to glucosamine hydrochloride, the cream also contains ibuprofen and allantoin, which enhance its effect. In addition, a specialized carrier methylpyrrolidone is used to more effectively penetrate the drug into tissues.

Methylpyrrolidone is a drug from the group of ketopyrroles. In its chemical structure, it is close to β-lactams, and in addition it is a universal solvent. It is used in medicine as an inert universal carrier for transdermal penetration, that is, it improves the penetration into the tissues of substances that are applied to the skin (Ameen D., 2017). It has moderate immunomodulatory activity, which leads to the potentiation of the therapeutic effect in local inflammatory processes. This substance is non-toxic and non-carcinogenic to humans (Schortt J., 2014), however if Artiflex in the form of a cream for a long time and in large quantities, a peculiar staining of urine in yellow may be observed.

Ibuprofen belongs to the group of non-steroidal anti-inflammatory drugs and is a derivative of propionic acid. Its anti-inflammatory and analgesic effect is based on the inhibition of prostaglandin E and F synthesis, and the effect is carried out both at the peripheral and central levels. This mechanism is realized due to the indiscriminate blocking of the COX-1 and COX-2 enzymes. Due to the decrease in prostaglandin synthesis, the severity of such manifestations of the inflammatory process as hyperemia and pain is reduced. Moreover, the analgesic effect is ensured thanks to a complex mechanism: prostaglandins increase the irritability of sensitive nerve fibers (Ershad M., 2019). In addition, the antiplatelet activity inherent in ibuprofen improves local capillary blood flow.

Allantoin is an anti-inflammatory drug of vegetable or animal origin. Today, it is most often obtained by extraction from the roots of a plant comfrey officinalis (Symphytum), better known among the people as a lapwort. This product is also known for its astringent and analgesic, antioxidant and cytoprotective properties (da Silva D.M., 2018). The analgesic effect of allantoin is provided due to the effect on peripheral opioid receptors (Florentino I.F., 2016). In addition, allantoin is characterized by effects such as reduced irritation, keratolytic activity, and stimulation of cell mitosis (Araujo A., 2010).

Application features

Since glucosamine is a low molecular weight derivative of carbohydrates, it is likely that it can be included in the processes of carbohydrate metabolism and affect the level of glucose in the blood. In animal experiments, it was proved that glucosamine is involved in glucose metabolism by hexosamine biosynthesis (Dostrovsky N.R., 2011). In addition, the results of experimental studies in animals (Kajinuma H., 1975) demonstrate an increase in blood levels of immunoreactive glucagon (which is a contra-hormonal hormone) when exogenous glucosamine is introduced into the body.

Thus, the use of glucosamine requires caution in patients with diabetes mellitus (Stumph J.L., 2006).In such cases, it is recommended to monitor the level of glucose and glycosylated hemoglobin in the blood, as well as adjust the dose of insulin or other sugar-lowering drugs.

In addition, since glucosamine in modern pharmaceutical industry is produced by hydrolysis of crustacean exoskeletons, it should be used with caution in patients with food allergies to fish and shellfish (Dahmer S., 2008).

There are few reports of glucosamine potentiating the action of warfarin (Dahmer S., 2008), so patients who receive anticoagulants need to control the parameters of their blood coagulation system.

Since high doses of methylpyrrolidone are characterized by teratogenic effects (Shortt J., 2014), the use of cream Artiflex during pregnancy is contraindicated.

Due to the local use of ibuprofen in the cream Artiflex its systemic influence is small. However, it is necessary to remember the undesirable effects characteristic of all non-steroidal anti-inflammatory drugs: gastropathic manifestations (pain in the stomach, nausea, heartburn), decreased blood coagulation, as well as nephrotoxicity.

Since glucosamine is a non-toxic substance, cases of drug overdose Artiflex not fixed. But patients should keep in mind that a short-term excess of the recommended dose will not lead to an increase in the therapeutic effect. This is due to the fact that the regeneration of cartilage and synovial tissue occurs slowly - over several months.

Conclusion

Degenerative-dystrophic diseases of the musculoskeletal system are one of the leading medical and social problems in the modern world. Osteoarthritis in the general population affects approximately 10% of men and 18% of women over the age of 60 years (OARSI, 2016), with 80% of them having motor limitations that significantly impair the quality of life. It is worth noting that the incidence of osteoarthritis is steadily increasing due to an aging population and an increase in the prevalence of obesity (ESCEO, 2019). The search for optimal treatment strategies for osteoarthritis includes reducing the severity of symptoms and, ultimately, slowing the progression of pathology.

The use of glucosamine-based drugs is of interest in connection with their effects aimed at maintaining the normal structure of cartilage and joint function along with alleviating the symptoms of the disease. Two forms of the drug Artiflex allow you to make a convenient therapeutic combination, which provides both systemic and local effects on the pathological process in diseases of the musculoskeletal system. And the lack of risk of overdose and a minimum of side effects make Artiflex promising tool for long-term use.