Benzydamine: Medical Use, Pharmacology, Toxicity, Use Mode, Side Effects and Overdose

Also known as Difflam or Green Tantum, it is a topical anesthetic of the chemical class of the indazole alkaloid.

It is sometimes found in small doses in over-the-counter products that are used to treat a sore throat.

In Germany and Poland, it is sold as a vaginal douche agent with the Tantum Rosa brand. This product is also easily accessible around the world through the use of online stores like eBay.

Alternatively, Benzydamine can be used as a powerful psychoactive hallucinogen for recreational purposes. In high doses, it acts as a unique and stimulating delirium of the central nervous system. Such use, particularly among adolescents, has been reported in Poland, Brazil and Romania.

This medication relieves pain and inflammation associated with sore throat or mouth sores caused by radiation therapy.

Benzamine is well tolerated. Occasionally there may be sensations of numbness or stinging in the oral tissue, as well as itching, rash, swelling or redness of the skin, difficulty breathing and wheezing.

Medical use

Odontostomatology : gingivitis, stomatitis, glossitis, aphthous ulcers, dental surgery and oral ulceration due to radiotherapy.

Otolaryngology : glandular fever, pharyngitis , tonsillitis, post- tonsillectomy , radiation or intubation mucositis.

It can be used alone or as a complement to another therapy, which offers the possibility of a greater therapeutic effect with little risk of interaction.

In some markets, the drug is supplied as an over-the-counter cream used for the topical treatment of musculoskeletal system disorders: sprains, strains, bursitis , tendinitis, synovitis, myalgia and periarthritis.

Chemistry of Benzydamine

Benzydamine, or 3- (1-benzylindazol-3-yl) oxy-N, N-dimethylpropan-1-amine, is a synthetic molecule of benzyl-indazole. It contains a ring of benzene and pyrazole fused to form a bicyclic indazole group. A benzyl substituent C6H5CH2- is attached to R1 of the indazole ring.

This indazole ring is also substituted in R3 with an ether chain consisting of the oxygen group attached to a propylamine chain. The RN terminal amine of this structure is substituted with two methyl groups (dimethyl). Benzydamine is produced as a hydrochloride salt.

Pharmacology

Benzydamine is a non-steroidal anti-inflammatory drug with local action with local anesthetic and analgesic properties. Unlike other non-steroidal anti-inflammatory drugs, it does not inhibit cyclo-oxygenase or lipoxygenase and is not ulcerogenic.

It binds selectively to inflamed tissues (prostaglandin synthetase inhibitor) and usually does not have adverse systemic effects.

Benzydamine can be synthesized with the reaction of the N-benzyl derivative of methyl anthranilate with nitrous acid to give the N-nitroso derivative. Then, it is reduced with sodium thiosulfate to give transient hydrazine.

This hydrazine may undergo spontaneous internal hydrazide formation. The treatment of this resulting enolate with 3-chloro-1-dimethylamino-propane finally produces benzydamine.

In terms of the pharmacology behind its hallucinogenic effects, this aspect of Benzydamine remains unstudied and is subject to much speculation.

Although the analgesic indazole Benzidamine is a non-steroidal anti-inflammatory drug, it has several physicochemical properties and pharmacological activities different from those of traditional non-steroidal anti-inflammatory drugs similar to aspirin.

But it facilitates the mechanism of action of Benzydamine as an effective non-steroidal anti-inflammatory with local action.

With local anesthetic and analgesic properties. In addition, unlike aspirin-like nonsteroidal anti-inflammatory drugs that are acidic or metabolized to acids, Benzamine is in fact a weak base.

Available predominantly as a liquid mouthwash, oromucosal spray or topical cream, Benzydamine is most often used as a locally-acting analgesic and anti-inflammatory treatment for the relief of painful inflammatory conditions.

When formulated as a mouthwash or spray, Benzydamine can be used to treat traumatic conditions such as pharyngitis after a tonsillectomy or the use of a nasogastric tube, inflammatory conditions such as pharyngitis, aphthous ulcers and oral ulceration due to radiation therapy, operations and procedures. dentistry

Or more general conditions such as sore throat, tongue pain, gums, ulcers in the mouth or discomfort caused by dentures.

When used as a topical cream, Benzydamine can be used to relieve symptoms associated with painful inflammatory conditions of the musculoskeletal system that include acute inflammatory disorders such as myalgia and bursitis or traumatic conditions such as sprains, strains, bruises.

Also pain of muscles, rigid joints, or even the consequences of fractures.

Antimicrobial activity of Benzydamine

Studies indicate that Benzydamine has a remarkable antibacterial activity in vitro and also shows synergy in combination with other antibiotics, especially tetracyclines, against strains of Staphylococcus aureus and Pseudomonas aeruginosa resistant to antibiotics.

Toxicity and potential for damage

Douching agents such as Tantum Rosa and other products consistently contain large amounts of salt that, if consumed, can cause severe kidney damage.

It is believed that the relatively high lipid solubility of weakly based benzylamine is associated with considerable passive resorption within the renal tubule, suggesting that only about 5% of Benzidine is excreted unchanged in the urine.

At the same time, however, other studies have suggested that considerably greater amounts (50-65%) of the drug are excreted unchanged in the urine.

While several inactive oxidized metabolites of Benzidine are excreted in the urine, the metabolite of Benzamine N-oxide can remain in the plasma and demonstrate a half-life that is longer than the original compound of Benzydamine.

Tell your doctor if you have kidney problems or any allergies. This medicine should be used only if clearly needed during pregnancy. Discuss the risks and benefits with your doctor. Because this medication may appear in breast milk, consult your doctor before breast-feeding.

The toxicity and long-term health effects of the recreational use of Benzydamine do not appear to have been studied in any scientific context and the exact toxic dose is unknown. This is because Benzidine is a research chemist with very little human use history.

Anecdotal evidence from people within the community of psychonauts who have tried Benzydamine suggests that there are no negative health effects attributed to simply testing the drug on its own in low to moderate doses and using it sparingly (but nothing can be fully guaranteed). ).

An independent investigation should always be conducted to ensure that a combination of two or more substances is safe before consumption.

Tell your doctor any over-the-counter or prescription medications you can take. Do not start or stop any medication without the approval of a doctor or pharmacist.

Extraction of Benzydamine

Benzydamine is usually extracted from the vaginal washes of Tantum Rosa, which are available online. To consume the substance safely, you must first eliminate the dangerous levels of salt contained in the envelope.

This can be done by dissolving the substance in a small amount of water (25 ml / sachet).

After the substance has mostly dissolved after stirring (lukewarm or boiled water works better since the salt will dissolve more easily), wait 10 minutes.

After 10 minutes, Benzydamine must have formed a layer on top and the salt has settled on the bottom.

Benzidine should be filtered using filter paper, but do not pour the salt that can be deposited on the bottom, as it will simply add back most of the salt that you have tried to eliminate. It is best to consume the remaining pasta by stirring it in a very strong pumpkin and drinking it.

How to use

This medicine is a mouthwash and / or gargle. It should not be swallowed. Use this as indicated. This can be diluted with the same amount of water before rinsing or gargling if it causes irritation or burning.

For sores in the mouth, place the prescribed amount in the mouth and try to keep the liquid in contact with the sores for at least 30 seconds before spitting. For sore throat, gargle with the prescribed amount for at least 30 seconds before spitting.

Oral doses of Benzydamine are well absorbed and plasma drug concentrations peak fairly rapidly and then decrease with a half-life of about 13 hours.

When applied topically, although local drug concentrations are relatively large, the systemic absorption of topically applied Benzidine is relatively low compared to oral doses.

This low topical absorption contributes to a decreased potential for any systemic side effect of the drug when Benzydamine is administered in this manner.

Side effects

This can cause burning, stinging or numbness in the mouth or throat. It has also been reported throat irritation, cough, dry mouth with thirst and headache. If any of these effects continue or become bothersome, inform your doctor.

A possible adverse reaction associated with the use of mouthwash or benzodiamine formulations in the form of oromucosal is a possible numbness and / or stinging in the mouth and / or throat.

Some possible adverse reactions that tend to be associated more with Bencidamine topical cream formulations include increased sensitivity to sunlight and localized itching, rash, redness or swelling.

However, the prescription information for all Benzydamine formulations warns against the possibility of a severe allergic reaction ( anaphylaxis ) associated with swelling of the throat and mouth, difficulty swallowing, speaking and breathing, or wheezing.

As Benzidine is a non-steroidal anti-inflammatory drug (NSAID), it is necessary to determine if a patient is allergic to non-steroidal anti-inflammatory drugs before considering their use.

Poisoning is expected as a consequence of the accidental ingestion of large amounts of Benzydamine (more than 300 mg of ingestion).

Other symptoms associated with Benzydamine ingested overdose include gastrointestinal and central nervous system symptoms such as nausea, vomiting, abdominal pain, esophageal irritation, dizziness, hallucinations, agitation, anxiety and irritability.

The official prescription information for Benzydamine generally suggests that mouth rinses with Benzydamine and aerosols should not be used during pregnancy.

Similarly, official prescribing information for Benzydamine generally also suggests that mouth rinses with Benzydamine and aerosols should not be used during breastfeeding, unless a physician deems it essential.

The prescription information for Bencidamine topical cream formulations indicates that Benzidine cream should not be used during pregnancy or lactation unless the doctor deems it necessary.

In general, non-clinical data do not show special risks for humans according to conventional studies of safety pharmacology, repeated toxicity, genotoxicity, cardiogenic potential and toxicity for reproduction.

In addition, there is no evidence of teratogenic effects in animal studies. Notify your doctor if you experience: drowsiness, nausea or vomiting. If you notice other effects not mentioned above, contact your doctor or pharmacist.

Benzydamine overdose

If an overdose is suspected, contact the local poison control center or the emergency room immediately. This medicine can be harmful if swallowed.

The use of this medication is not recommended in children under 5 years of age because they may tend to swallow the medication instead of spitting it out.

If you miss a dose, use this as soon as you remember and then resume your usual dosing schedule. Do not double the dose to catch up.

Storage

Store at room temperature between 59 and 86 degrees F (15 to 30 degrees C) as directed. Keep out of the reach of children.

Mechanism of action of Benzydamine

Benzamine is a non-steroidal anti-inflammatory drug designed to cause local anesthetic and analgesic effects mainly in the mouth and throat. It specifically acts on the local mechanisms of inflammation such as pain, edema or granuloma.

Applied topically, the drug demonstrates anti-inflammatory activity reducing edema as well as the formation of exudate and granuloma.

In addition, Benzydamine exhibits analgesic properties and local anesthetic activity if the pain is caused by an inflammatory condition. Benzydamine can be absorbed in the oral mucosa and intact skin.

Once absorbed in the local area of ​​pain or inflammation, Benzydamine binds selectively to local inflamed tissues, usually, allowing it to act with few adverse systemic effects. On average, a period of 2 to 4 hours is necessary for the substance to reach the maximum plasma concentration.

Despite being categorized as a non-steroidal anti-inflammatory drug, Benzydamine demonstrates several mechanisms of action that differ from those of traditional non-steroidal anti-inflammatory drugs similar to aspirin.

In particular, Benzydamine acts predominantly by inhibiting the synthesis of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) without greatly affecting other proinflammatory cytokines (ie, as IL). -6 and IL-8) or anti-inflammatory cytokines (ie, as IL-10 or IL-1 receptor antagonist).

In addition, Benzydamine is largely a weak inhibitor of prostaglandin synthesis, since it has been shown to effectively inhibit the activity of the enzyme cyclooxygenase (COX) and the activity of the lipoxygenase enzyme only at concentrations of 1 mM or greater.

Whereas most contemporary uses of Benzydamine are topical applications that are generally not well absorbed through the skin and / or non-specialized mucosae.

Benzydamine generally does not achieve the type of absorption or blood concentrations necessary to cause distant systemic effects or inhibition of the enzyme cyclooxygenase, which allows it to localize its action.

In addition, it is also hypothesized that Benzydamine is able to inhibit the oxidative burst of neutrophils and the stabilization of the membrane. These actions are manifested by the ability of the substance to inhibit the release of neutrophil granules and to stabilize lysosomes.

In addition, Benzydamine is capable of having a local anesthetic effect that may be related to its ability to inhibit the release of inflammatory mediators such as substance P and the peptide related to the calcitonin gene of the sensory nerve endings.

Since substance P is capable of causing the release of histamine from mast cells , preventing the release of substance P by Benzidine contributes even more to an anti-inflammatory effect.

Benzydamine also demonstrates non-specific antibacterial activity against various bacterial strains that are resistant to broad spectrum antibiotics such as ampicillin, chloramphenicol and tetracycline at concentrations of approximately 3 mmol / l.

The combinatorial use of Benzydamine and other antibiotics such as tetracycline and chloramphenicol are also synergistic against strains of Staphylococcus aureus and Pseudomonas aeruginosa resistant to antibiotics.