ANDOLEX-C ORAL RINSE

Indications

• Painful inflammatory conditions of the oropharynx
• Oral ulceration and inflammation
• Anaesthesia of mucous membranes

Dosage

Children: For children aged 1 month to 5 years: 1-3 sprays every 1.5-3 hours, dependent on body weight and condition; refer to the BNF for Children for precise dosing.

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Benzydamine hydrochloride exerts its effects by inhibiting the synthesis of prostaglandins, which are mediators of inflammation and pain. It also possesses local anesthetic properties, providing relief from pain upon application to mucous membranes.

Pharmacodynamics

Benzydamine demonstrates anti-inflammatory, analgesic, and local anesthetic effects. It reduces pain and inflammation in the oropharynx, making it beneficial for various inflammatory conditions.

Pharmacokinetics

Benzydamine is rapidly absorbed when administered topically. It is distributed throughout the body, crosses the placenta, and is present in breast milk in small amounts. The drug undergoes hepatic metabolism and is excreted primarily in urine. Caution is advised in patients with hepatic and renal impairment due to potential accumulation.

Contra-indications

• Hypersensitivity to benzydamine or any component of the formulation

Adverse effects

• Oral disorders
• Photosensitivity reaction
• Skin reactions
• Angioedema

Interactions

• Caution with antiarrhythmics
• Caution with NSAIDs

Precautions

• Can damage plastic cuffs of endotracheal tubes
• Caution in hepatic impairment
• Caution in renal impairment

Pregnancy

Crosses the placenta but not known to be harmful in animal studies-use if benefit outweighs risk.

Breast-feeding

Present in milk but amount too small to be harmful.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Oromucosal Spray 0.15% (sugar-free)
• Mouthwash 0.15% (sugar-free)

Indications

• Oral hygiene
• Skin antisepsis
• Bladder irrigation
• Urological surgery
• Management of infections associated with indwelling urinary catheters

Mechanism of action

Chlorhexidine's antimicrobial effects arise from its ability to disrupt microbial cell membranes. The positively charged chlorhexidine molecule interacts with negatively charged phosphate groups on microbial surfaces, compromising cell integrity and causing leakage of intracellular materials. This interaction allows chlorhexidine to enter the cell, precipitate cytoplasmic components, and ultimately induce cell death. At lower concentrations, chlorhexidine acts as a bacteriostatic agent, causing leakage of substances like potassium and phosphorus, while at higher concentrations, it exerts bactericidal effects.

Pharmacodynamics

Chlorhexidine exhibits broad-spectrum antimicrobial activity, effective against a variety of bacteria, yeasts, and viruses. Its action is dose-dependent, with lower concentrations (0.02%-0.06%) providing bacteriostatic effects, while higher concentrations (>0.12%) are bactericidal. Pharmacokinetic studies indicate that about 30% of chlorhexidine remains in the mouth after rinsing, allowing for slow release into oral fluids. This property, known as 'substantivity', helps prevent microbial colonization on surfaces like dentine, although prolonged use can lead to staining of oral surfaces.

Pharmacokinetics

Chlorhexidine is retained in the oral cavity at approximately 30% following rinsing, with a slow release into saliva. The pharmacokinetics of chlorhexidine indicate a high affinity for binding to tissues, which prolongs its antimicrobial action. The systemic absorption of chlorhexidine is minimal when used topically or as a rinse, making it safe for localized use. The elimination half-life and metabolism details are not well documented due to its primarily topical application.

Adverse effects

• Mucosal irritation
• Burning sensation
• Staining of teeth and oral surfaces
• Allergic reactions

Precautions

• Use with caution in patients with a history of hypersensitivity to chlorhexidine
• May cause irritation; discontinue if severe irritation occurs
• Staining may occur with prolonged use, particularly with oral formulations

Pregnancy

Chlorhexidine is generally considered safe for use during pregnancy; however, caution is advised and pregnant individuals should consult healthcare providers.

Breast-feeding

Chlorhexidine is considered safe during breastfeeding, but it is advisable to consult a healthcare provider.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Irrigation solution (0.02% and 0.05%)
• Capsules (various strengths)
• Catheter maintenance solution (1:5000)
• Topical solutions for oral hygiene

Indications

• Sore throat
• Mouth ulcers
• Inflammatory conditions of the oral cavity
• Pain relief in conditions causing inflammation in the throat and mouth

Dosage

Children: Refer to the BNF for Children for appropriate dosing information based on the child's age

Adults: The dosage depends on the formulation and the condition being treated. Refer to the specific product information or the BNF for detailed dosing guidelines.

Mechanism of action

Benzydamine acts by inhibiting the synthesis of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β), while exerting minimal effects on other pro-inflammatory and anti-inflammatory cytokines. It is a weak inhibitor of prostaglandin synthesis, primarily affecting cyclooxygenase (COX) and lipoxygenase enzyme activity at high concentrations. Additionally, benzydamine is believed to inhibit the oxidative burst of neutrophils and stabilize lysosomes, contributing to its anti-inflammatory and analgesic effects. Its local anesthetic action is attributed to its ability to stabilize neuronal membranes.

Pharmacodynamics

Benzydamine provides local anesthetic and analgesic effects, focusing on the local mechanisms of inflammation such as pain and edema. It is absorbed through the oral mucosa and intact skin, binding selectively to inflamed tissues to exert its effects. The drug typically reaches peak plasma concentration within 2 to 4 hours, enhancing its localized therapeutic efficacy while minimizing systemic adverse effects.

Pharmacokinetics

Benzydamine is primarily administered topically, resulting in limited systemic absorption. Once applied, it accumulates in inflamed tissues, allowing for effective local action. The pharmacokinetic profile indicates that peak concentrations are achieved within 2 to 4 hours post-application, although specific systemic absorption metrics are not extensively characterized due to its localized use.

Adverse effects

• local irritation
• burning sensation
• dryness of the mouth
• nausea
• dizziness

Precautions

• Caution in patients with hypersensitivity to benzydamine or other NSAIDs
• Use with caution in patients with asthma or history of allergic reactions

Pregnancy

Benzydamine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult healthcare provider before use.

Breast-feeding

It is unknown whether benzydamine is excreted in human milk. Caution is advised when administering to breastfeeding women.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• oral rinse
• topical gel
• spray

Mechanism of action

Despite being categorized as a non-steroidal anti-inflammatory drug (NSAID), benzydamine demonstrates various mechanisms of action that differ from those of traditional aspirin-like NSAIDs. In particular, benzydamine predominantly acts by inhibiting the synthesis of pro inflammatory cytokines like tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) without largely affecting other pro inflammatory cytokines (ie. such as IL-6 and IL-8) or anti-inflammatory cytokines (ie. like IL-10 or IL-1 receptor antagonist). Moreover, benzydamine is largely a weak inhibitor of prostaglandin synthesis as it has been shown to effectively inhibit cyclooxygenase (COX) and lipoxygenase enzyme activity only at concentrations of 1mM or greater. Considering most contemporary usages of benzydamine are topical applications that are generally not well absorbed through the skin and/or non-specialized mucosae, benzydamine does not often achieve the kind of absorption or blood concentrations necessary to cause any extraneous distant systemic effects or COX inhibition, allowing it to localize its action. Additionally, it is also hypothesized that benzydamine is capable of inhibiting the oxidative burst of neutrophils and membrane stabilization. These actions are exhibited by the substance’s ability to inhibit the release of granules from neutrophils and to stabilize lysosomes. Furthermore, benzydamine is capable of a local anaesthetic effect that may be related to its capability for inhibiting the release of inflammatory mediators like substance P and calcitonin gene related peptide from sensory nerve endings. Since substance P is capable of causing the release of histamine from mast cells, benzydamine’s prevention of substance P release further contributes to an anti-inflammatory effect. Benzydamine also demonstrates a non-specific antibacterial activity against various bacterial strains that are resistant to broad-spectrum antibiotics such as ampicillin, chloramphenicol, and tetracycline at concentrations of about 3 mmol/L. Combinatorial use of benzydamine and other antibiotics like tetracycline and chloramphenicol are also synergistic against antibiotic resistant strains of *Staphylococcus aureus* and *Pseudomonas aeruginosa*.

Pharmacodynamics

Benzydamine is a non-steroidal anti-inflammatory drug (NSAID) designed to elicit local anesthetic and analgesic effects mainly for the mouth and throat. It specifically acts on the local mechanisms of inflammation such as pain, oedema, or granuloma. Typically applied topically, the drug demonstrates anti-inflammatory activity reducing oedema as well as exudate and granuloma formation. Moreover, benzydamine exhibits analgesic properties and local anaesthetic activity if pain is caused by an inflammatory condition. Benzydamine can be absorbed into 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 peak plasma concentration. Benzydamine can be synthesized with the reaction of the N-benzyl derivative from methyl anthranilate with nitrous acid to give N-nitoso derivative. This is next reduced by sodium thiosulfate to give transient hydrazine. This hydrazine can then undergo spontaneous internal hydrazide formation. Treating this resultant enolate with 3-chloro-1-dimethylamkino propane ultimately yields benzydamine.

Mechanism of action

Chlorhexidine’s broad-spectrum antimicrobial effects are due to its ability to disrupt microbial cell membranes. The positively charged chlorhexidine molecule reacts with negatively charged phosphate groups on microbial cell surfaces - this reaction both destroys the integrity of the cell, allowing leakage of intracellular material, and allows chlorhexidine to enter the cell, causing precipitation of cytoplasmic components and ultimately cell death. The specific means of cell death is dependent on the concentration of chlorhexidine - lower concentrations are bacteriostatic and result in leakage of intracellular substances such as potassium and phosphorous, whereas higher concentrations are bactericidal and cause cytoplasmic precipitation.

Pharmacodynamics

Chlorhexidine is a broad-spectrum antimicrobial with demonstrated activity against both gram-positive and gram-negative bacteria, yeasts, and viruses. Antimicrobial activity is dose-dependent - chlorhexidine is bacteriostatic at lower concentrations (0.02%-0.06%) and bactericidal at higher concentrations (>0.12%). Pharmacokinetic studies of oral chlorhexidine rinses indicate that approximately 30% of the active ingredient is retained in the mouth following rinsing, which is subsequently slowly released into oral fluids. This ability to adsorb to dentine, shared with tetracycline antibiotics such as [doxycycline], is known as "substantivity" and is the result of chlorhexidine's positive charge - it is likely that this substantivity plays at least some role in chlorhexidine's antimicrobial activity, as its persistence on surfaces such as dentine prevent microbial colonization. Dental chlorhexidine rinses may result in staining of oral surfaces, such as teeth. This effect is not ubiquitous and appears to be more significant with extended therapy (i.e. up to 6 months) - nevertheless, patients for whom oral staining is unacceptable should use chlorhexidine rinse with caution and for the shortest effective interval. Allergic reactions to chlorhexidine have been associated with the development of anaphylaxis.