CEPACOL COUGH LINCTUS

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
• Pseudobulbar affect

Dosage

Children: Refer to the BNF for Children for specific dosing information tailored to paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines based on the formulation and clinical context.

Mechanism of action

Dextromethorphan acts as a low-affinity uncompetitive antagonist of NMDA receptors and as an agonist at sigma-1 receptors. It also antagonizes α3/β4 nicotinic receptors. The clinical effects are thought to arise from NMDA receptor blockade and serotonin (5-HT) uptake inhibition, which may lead to increased serotonin receptor stimulation. However, the precise mechanisms by which these actions translate into therapeutic effects remain incompletely understood.

Pharmacodynamics

Dextromethorphan is considered an opioid-like molecule with a moderate therapeutic window, indicating that while it is effective at standard doses, higher doses can lead to intoxication. It has a moderate duration of action, making it suitable for use in cough management. Due to its potential for abuse and risk of intoxication, patients are advised to use it cautiously.

Pharmacokinetics

Dextromethorphan is metabolized primarily in the liver through the cytochrome P450 enzyme system, leading to the formation of its active metabolite, dextrorphan. The pharmacokinetics may be influenced by individual variations in metabolic pathways, which can affect the drug's efficacy and safety profile.

Contra-indications

• Hypersensitivity to dextromethorphan or any of its components
• Concurrent use with monoamine oxidase inhibitors (MAOIs)
• Severe respiratory insufficiency or asthma
• Persistent cough due to smoking, emphysema, or chronic bronchitis

Adverse effects

• Dizziness
• Nausea
• Vomiting
• Drowsiness
• Confusion
• Constipation
• Abdominal discomfort
• Euphoria or dysphoria
• Serotonin syndrome (when used with serotonergic drugs)

Interactions

• May interact with MAOIs, leading to serious side effects
• Potential interactions with other CNS depressants, leading to increased sedation
• May enhance the effects of alcohol
• Can interact with medications that affect serotonin levels, increasing the risk of serotonin syndrome

Precautions

• Use with caution in patients with a history of substance abuse
• Monitor use in patients with hepatic impairment
• Caution advised in patients with a history of seizures
• Should not be used in children under 2 years unless directed by a physician

Pregnancy

Dextromethorphan should be used during pregnancy only if clearly needed. Consult a healthcare provider for advice.

Breast-feeding

Dextromethorphan is excreted in breast milk. Caution is advised when administered to nursing mothers.

Storage

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

Formulations

• Oral syrup
• Tablets
• Capsules
• Lozenges

Indications

• Insomnia
• Allergic rhinitis
• Urticaria
• Other allergic reactions

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing guidance.

Adults: Refer to the BNF for specific adult dosing guidelines as it varies based on indication.

Mechanism of action

Doxylamine acts by competitively inhibiting histamine at H1 receptors, which reduces the effects of histamine in the body, leading to decreased allergy symptoms and sedation. Its substantial sedative and anticholinergic effects enhance its utility in treating sleep disturbances.

Pharmacodynamics

Doxylamine is widely recognized for its anti-allergic properties, surpassing many antihistamines in effectiveness, particularly in managing allergy symptoms and inducing sleep. It is more sedating than many prescription hypnotics and has been shown to be superior to phenobarbital in its sedative effects. Its potent anticholinergic properties further contribute to its overall therapeutic profile.

Pharmacokinetics

Doxylamine is well absorbed following oral administration. It undergoes hepatic metabolism and has a relatively long elimination half-life, which contributes to its prolonged sedative effects. The drug's pharmacokinetics may vary based on individual patient factors, including age and liver function.

Contra-indications

• Hypersensitivity to doxylamine or any component of the formulation
• Glaucoma
• Prostatic hypertrophy
• Bladder neck obstruction

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Constipation
• Blurred vision
• Urinary retention

Interactions

• Alcohol may enhance the sedative effects of doxylamine
• CNS depressants can increase sedation and respiratory depression
• MAO inhibitors can prolong and intensify the anticholinergic effects

Precautions

• Use with caution in patients with asthma or other respiratory conditions
• Caution in elderly patients due to increased sensitivity to anticholinergic effects
• Should not be used in patients with severe liver impairment

Pregnancy

Doxylamine is classified as category A in pregnancy; it is generally considered safe when used as directed for short-term management of nausea and vomiting in pregnancy.

Breast-feeding

Doxylamine is excreted in breast milk; caution is advised when administering to nursing mothers as it may cause sedation in the infant.

Storage

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

Formulations

• Tablets
• Liquid formulations

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

Dextromethorphan is a low-affinity uncompetitive NMDA antagonist and sigma-1 receptor agonist. It is also an antagonist of α3/β4 nicotinic receptors. However, the mechanism by which dextromethorphan's receptor agonism and antagonism translate to a clinical effect is not well understood. Dextromethorphan (DXM) is the dextro isomer of levomethorphan, a semisynthetic morphine derivative. Although structurally similar to other /CNS depressants/, DXM does not act as a mu receptor opioid (eg, morphine, heroin). DXM and its metabolite, dextrorphan, act as potent blockers of the N-methyl-d-aspartate (NMDA) receptor. Amantadine and dextromethorphan suppress levodopa (L-DOPA)-induced dyskinesia (LID) in patients with Parkinson's disease (PD) and abnormal involuntary movements (AIMs) in the unilateral 6-hydroxydopamine (6-OHDA) rat model. These effects have been attributed to N-methyl-d-aspartate (NMDA) antagonism. However, amantadine and dextromethorphan are also thought to block serotonin (5-HT) uptake and cause 5-HT overflow, leading to stimulation of 5-HT(1A) receptors, which has been shown to reduce LID. We undertook a study in 6-OHDA rats to determine whether the anti-dyskinetic effects of these two compounds are mediated by NMDA antagonism and/or 5-HT(1A) agonism. In addition, we assessed the sensorimotor effects of these drugs using the Vibrissae-Stimulated Forelimb Placement and Cylinder tests. Our data show that the AIM-suppressing effect of amantadine was not affected by the 5-HT(1A) antagonist WAY-100635, but was partially reversed by the NMDA agonist d-cycloserine. Conversely, the AIM-suppressing effect of dextromethorphan was prevented by WAY-100635 but not by d-cycloserine. Neither amantadine nor dextromethorphan affected the therapeutic effects of L-DOPA in sensorimotor tests. We conclude that the anti-dyskinetic effect of amantadine is partially dependent on NMDA antagonism, while dextromethorphan suppresses AIMs via indirect 5-HT(1A) agonism. Combined with previous work from our group, our results support the investigation of 5-HT(1A) agonists as pharmacotherapies for LID in PD patients. Dextromethorphan (DM) is a dextrorotatory morphinan and an over-the-counter non-opioid cough suppressant. We have previously shown that DM protects against LPS-induced dopaminergic neurodegeneration through inhibition of microglia activation. Here, we investigated protective effects of DM against endotoxin shock induced by lipopolysaccharide/d-galactosamine (LPS/GalN) in mice and the mechanism underlying its protective effect. Mice were given multiple injections of DM (12.5 mg/kg, s.c.) 30 min before and 2, 4 hr after an injection of LPS/GalN (20 ug/700 mg/kg). DM administration decreased LPS/GalN-induced mortality and hepatotoxicity, as evidenced by increased survival rate, decreased serum alanine aminotransferase activity and improved pathology. Furthermore, DM was also effective when it was given 30 min after LPS/GalN injection. The protection was likely associated with reduced serum and liver tumor necrosis factor alpha (TNF-alpha) levels. DM also attenuated production of superoxide and intracellular reactive oxygen species in Kupffer cells and neutrophils. Real-time RT-PCR analysis revealed that DM administration suppressed the expression of a variety of inflammation-related genes such as macrophage inflammatory protein-2, CXC chemokine, thrombospondin-1, intercellular adhesion molecular-1 and interleukin-6. DM also decreased the expression of genes related to cell-death pathways, such as the DNA damage protein genes GADD45 and GADD153. In summary, DM is effective in protecting mice against LPS/GalN-induced hepatotoxicity, and the mechanism is likely through a faster TNF-alpha clearance, and decrease of superoxide production and inflammation and cell-death related components. This study not only extends neuroprotective effect of DM, but also suggests that DM may be a novel compound for the therapeutic intervention for sepsis. /The

Pharmacodynamics

Dextromethorphan is an opioid-like molecule indicated in combination with other medication in the treatment of coughs and pseudobulbar affect. It has a moderate therapeutic window, as intoxication can occur at higher doses. Dextromethorphan has a moderate duration of action. Patients should be counselled regarding the risk of intoxication.

Mechanism of action

Like other antihistamines, doxylamine acts by competitively inhibiting histamine at H1 receptors. It also has substantial sedative and anticholinergic effects.

Pharmacodynamics

Doxylamine is an antihistamine commonly used as a sleep aid. This drug is also used to relieve symptoms of hay fever (allergic rhinitis), hives (rash or itching), and other allergic reactions. Doxylamine is a member of the ethanolamine class of antihistamines and has anti-allergy power far superior to virtually every other antihistamine on the market, with the exception of diphenhydramine (Benadryl). It is also the most powerful over-the-counter sedative available in the United States, and more sedating than many prescription hypnotics. In a study, it was found to be superior to even the barbiturate, phenobarbital for use as a sedative. Doxylamine is also a potent anticholinergic.