VICKS ACTA PLUS COUGH SYRUP

Indications

• Oral hygiene
• Prevention of dental plaque
• Management of minor infections in the oral cavity

Dosage

Children: Refer to BNF for Children for appropriate formulations and guidance on paediatric use.

Adults: Refer to BNF for specific formulations and usage instructions. Typical concentrations in mouthwashes are around 0.05% to 0.1%.

Mechanism of action

Cetylpyridinium chloride functions as a cationic surfactant that interacts with microbial cell surfaces due to its positively charged hydrophilic region. This interaction disrupts bacterial membrane integrity, leading to leakage of cytoplasmic components, interference with cellular metabolism, and ultimately, cell death. Additionally, it inhibits the synthesis of insoluble glucan by streptococcal glucosyltransferase, adsorbs to enamel surfaces, and prevents bacterial co-adhesion, enhancing its effectiveness in oral hygiene.

Pharmacodynamics

Cetylpyridinium chloride exhibits rapid bactericidal effects against gram-positive pathogens and fungicidal activity against yeasts. It is classified as a cationic disinfectant with local effects, making it suitable for managing minor infections. Its surfactant properties contribute to its efficacy in reducing microbial load in oral care applications.

Pharmacokinetics

Cetylpyridinium chloride is characterized by poor systemic absorption when used topically; therefore, its effects are primarily local rather than systemic. This property allows it to exert its antimicrobial action in the mouth without significant absorption into the bloodstream, making it safe for use in oral care products.

Adverse effects

• Mouth irritation
• Taste alteration
• Dryness of the mouth
• Nausea
• Diarrhea

Precautions

• Use with caution in individuals with a history of hypersensitivity to cetylpyridinium chloride or other quaternary ammonium compounds.
• Avoid swallowing the product.
• Not recommended for use in children under a certain age without medical advice.

Pregnancy

Cetylpyridinium chloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consultation with a healthcare provider is advised.

Breast-feeding

It is not known whether cetylpyridinium chloride is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Mouthwash
• Toothpaste
• Lozenges
• Mouth sprays

Indications

• Cough associated with respiratory tract infections
• Cough due to bronchial asthma
• Acute bronchitis
• Chronic obstructive pulmonary disease (COPD)
• Sinusitis

Dosage

Children: For children aged 6 to 12 years, the typical dosage is 100-200 mg every 4 hours as needed, not exceeding 1.2 g in 24 hours. For children aged 2 to 6 years, the dosage is generally 50-100 mg every 4 hours as needed, not exceeding 600 mg in 24 hours. Refer to the BNF for Children for specific dosing recommendations.

Adults: The usual adult dosage for guaifenesin is 200-400 mg every 4 hours as needed, not exceeding 2.4 g in 24 hours.

Mechanism of action

Guaifenesin is believed to work by increasing mucus secretion and acting as an irritant to gastric vagal receptors, which stimulates efferent parasympathetic reflexes. This leads to glandular exocytosis of less viscous mucus. Additionally, it may enhance respiratory tract fluid, thereby reducing the viscosity of secretions and improving ciliary action for more efficient mucus clearance.

Pharmacodynamics

As an expectorant, guaifenesin enhances the output of bronchial secretions and phlegm by decreasing their adhesiveness and surface tension. This results in an increased flow of less viscous gastric secretions, promoting ciliary action and converting unproductive coughs into more productive ones. Although it may also exhibit mild anticonvulsant and muscle relaxant properties, these effects are less well established.

Pharmacokinetics

Guaifenesin is rapidly absorbed from the gastrointestinal tract and reaches peak plasma concentrations within one hour of administration. It is metabolized in the liver, and its elimination half-life is approximately one hour. The drug is primarily excreted in the urine, mostly as metabolites.

Adverse effects

• Nausea
• Vomiting
• Dizziness
• Headache
• Rash

Precautions

• Use with caution in patients with chronic cough due to asthma, smoking, or emphysema
• Ensure adequate hydration while using

Pregnancy

Guaifenesin is categorized as pregnancy category C. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Guaifenesin is excreted in breast milk. Caution should be exercised when administered to breastfeeding women.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Oral syrup
• Tablets
• Extended-release capsules

Indications

• Cough suppression
• Antitussive therapy
• Potential use in managing sensory pain

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations as they may vary based on age and weight.

Adults: Refer to the BNF for specific dosing recommendations as they may vary based on clinical context.

Mechanism of action

Pentoxyverine is thought to act as an agonist at sigma-1 receptors in the central nervous system. These receptors are believed to play a role in modulating the cough reflex by influencing the nucleus tractus solitarius, which is closely associated with the cough center in the brainstem. Additionally, it may inhibit voltage-gated sodium currents, contributing to its local anesthetic effects.

Pharmacodynamics

Pentoxyverine induces an antitussive effect, as demonstrated in animal studies where it inhibited cough responses induced by citric acid. It has shown potential anticonvulsant effects in certain studies, with varying degrees of efficacy in protecting against induced seizures. Furthermore, it can produce a sensory-selective spinal blockade, differentiating its action from that of other local anesthetics like lidocaine.

Pharmacokinetics

Pentoxyverine is lipophilic, which may facilitate its penetration into the central nervous system when administered systemically. The pharmacokinetic profile, including absorption, distribution, metabolism, and elimination specifics, are not extensively detailed in the available literature.

Adverse effects

• Dizziness
• Drowsiness
• Nausea
• Vomiting
• Dry mouth

Precautions

• Use with caution in patients with a history of respiratory problems
• Caution in the elderly due to potential for increased sedation
• Not recommended for use in children without medical supervision

Pregnancy

There is limited data on the safety of pentoxyverine during pregnancy. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether pentoxyverine is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

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

Formulations

• Oral solution
• Tablets

Mechanism of action

When incorporated into mouthwashes, toothpastes, lozenges, or mouth sprays, cetylpyridinium chloride is expected to elicit a mechanism of action that decreases new dental plaque growth, decreases or removes existing dental plaque, diminishes the growth of pathogenic bacteria, and inhibits the production of virulence factors. Cetylpyridinium chloride is a quaternary ammonium compound that demonstrates a broad spectrum anti-bacterial activity. It possesses a cationic surface active agent surfactant which can absorb readily to oral surfaces. The molecules of this agent have both hydrophilic and hydrophobic groups. In action, the positively charged hydrophilic region of cetylpyridinium chloride molecules enables the compound to interact with microbial cell surfaces and even integrate into the bacterial cytoplasmic membrane. Consequently, there is a resultant disruption of bacterial membrane integrity causing a leakage of bacterial cytoplasmic components, interference with cellular metabolism, inhibition of cell growth, and ultimately - cell death. Moreover, cetylpyridinium chloride can also inhibit the synthesis of insoluble glucan by streptococcal glucosyltransferase, adsorb to pellicle-covered enamel, and inhibit co-adhesion of bacteria, and bind streptococcus mutans biofilms. This ability of cetylpyridinium chloride to be able to adsorb to pellicle covered enamel imparts substantivity to the compound molecules - that is retention in the mouth and continued antimicrobial activity for a period of time after rinsing. Taking these mechanisms into consideration, cetylpyridinium chloride may be considered an active ingredient that is effective in the treatment and prevention of bacterial or fungal disorders of the oropharyngeal cavity.

Pharmacodynamics

Cetylpyridinium chloride is considered a cationic disinfectant with properties and uses similar to other such cationic surfactants. In particular, cetylpyridinium chloride has demonstrated a rapid bactericidal and fungicide effect on gram-positive pathogens and yeasts, respectively. Cetylpyridinium chloride is subsequently utilized in a variety of preparations for the local treatment of minor infections. Despite the variety of formulations in which cetylpyridinium chloride may appear as an active ingredient, it is generally accepted that it only elicits a local effect owing to the compound's relatively poor absorption by route of exposure.

Mechanism of action

Although the exact mechanism of action of guaifenesin may not yet be formally or totally elucidated, it is believed that expectorants like guaifenesin function by increasing mucus secretion. Moreover, it is also further proposed that such expectorants may also act as an irritant to gastric vagal receptors, and recruit efferent parasympathetic reflexes that can elicit glandular exocytosis that is comprised of a less viscous mucus mixture. Subsequently, these actions may provoke coughing that can ultimately flush difficult to access, congealed mucopurulent material from obstructed small airways to facilitate a temporary improvement for the individual. Consequently, while it is generally proposed that guaifenesin functions as an expectorant by helping to loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive, there has also been research to suggest that guaifenesin possesses and is capable of demonstrating anticonvulsant and muscle relaxant effects to some degree possibly by acting as an NMDA receptor antagonist. Guaifenesin is thought to act as an expectorant by increasing the volume and reducing the viscosity of secretions in the trachea and bronchi. Thus it may increase the efficiency of the cough reflex and facilitate removal of the secretions; however, objective evidence for this is limited and conflicting. By increasing respiratory tract fluid, guaifenesin reduces the viscosity of tenacious secretions and acts as an expectorant. Guaifenesin, a commonly used agent for the treatment of cough, is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity, thereby promoting effective cough. Despite its common usage, relatively few studies, yielding contrasting results, have been performed to investigate the action and efficacy of guaifenesin. To evaluate the effect of guaifenesin on cough reflex sensitivity. Randomized, double-blind, placebo-controlled trial. Fourteen subjects with acute viral upper respiratory tract infection (URI) and 14 healthy volunteers. On 2 separate days, subjects underwent capsaicin cough challenge 1 to 2 hr after receiving a single, 400-mg dose (capsules) of guaifenesin or matched placebo. Measurements and results: The concentration of capsaicin inducing five or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14, respectively (p = 0.028). No effect on cough sensitivity was observed in healthy volunteers. /The/ results demonstrate that guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume serving as a barrier shielding cough receptors within the respiratory epithelium from the tussive stimulus.

Pharmacodynamics

Guaifenesin is categorized as an expectorant that acts by enhancing the output of phlegm (sputum) and bronchial secretions via decreasing the adhesiveness and surface tension of such material. Furthermore, guaifenesin elicits an increased flow of less viscous gastric secretions that subsequently promote ciliary action - all actions that ultimately change dry, unproductive coughing to coughs that are more productive and less frequent. Essentially, by decreasing the viscosity and adhesiveness of such secretions, guaifenesin enhances the efficacy of mucociliary activity in removing accumulated secretions from the upper and lower airway.

Mechanism of action

While the mechanism of antitussive action of pentoxyverine is not fully understood, it is thought to be mediated via sigma-1 receptors expressed in the central nervous system. Pentoxyverine acts as an agonist at sigma receptors with the Ki of 75±28 nM, as demonstrated in a competitive binding assay. The function of sigma receptors on cough suppressant activities is unclear, however these receptors are highly expressed in the nucleus tractus solitarius (NTS) of the brainstem where the afferent fibres first synapse. NTS is located very close to the cough centre in the brainstem thus may function as a ‘gate' for the cough reflex and allow sigma-1 receptor agonists to modulate afferent activity prior to reaching the cough center. It is suggested that highly lipophilic sigma-1 agonists may penetrate the CNS following systemic administration. When administered as aerosols, sigma-1 receptor agonists may temporarily act in the periphery to modulate cough by acting activate sigma receptors expressed in the lungs. However there is limited evidence of peripheral localization of the sigma agonists following aerosol administration and the ruling out of systemic exposure. The local anesthesia action of pentoxyverine may occur through inhibition of voltage-gated Na(+) currents. NUMBER OF DRUGS ARE KNOWN TO REDUCE COUGH AS RESULT OF THEIR CENTRAL ACTIONS, ALTHOUGH EXACT MECHANISMS ARE STILL NOT ENTIRELY CLEAR. /NONOPIOID ANTITUSSIVES/

Pharmacodynamics

Pentoxyverine induces an antitussive action. In animal studies, intraperitoneal administration of pentoxyverine inhibited citric-acid-induced cough in guinea-pigs _in vivo_. Some mice and rat studies suggest that pentoxyverine may also exert anticonvulsant activities without inducing a protective effect from NMDA-induced lethality. Protective effects against maximal electroshock-induced seizures in a dose-related fashion was also observed following either intraperitoneal or oral administration. In hERG-transfected cells, pentoxyverine inhibited the outward current of the hERG ion channel with half-maximal inhibition concentrations (IC50) of 3.0 µM. In rats receiving intrathecal administration, pentoxyverine exhibited dose-dependent spinal blockade with a more sensory-selective action over motor blockade. It induced a spinal blockade with a more sensory/nociceptive-selective action over motor blockade compared to lidocaine.