RESTIN-COUGH-LINCTUS 10MG , 4MG , 3MG SYRUP

Indications

• Allergic rhinitis (hay fever)
• Urticaria (hives)
• Allergic conjunctivitis
• Common cold symptoms

Dosage

Children: For children aged 6-12 years, the dose is typically 2 mg every 4 to 6 hours, not exceeding 12 mg per day. For children under

Adults: The usual adult dose for chlorpheniramine is 4 mg every 4 to 6 hours, not to exceed 24 mg per day.

Mechanism of action

Chlorpheniramine binds to the histamine H1 receptor, preventing endogenous histamine from exerting its effects. This leads to temporary relief from symptoms such as sneezing, pruritus, and increased vascular permeability associated with allergic reactions. The drug competes with histamine for H1-receptor sites on effector cells, thus antagonizing most of the pharmacological effects of histamine, including its actions on smooth muscle and vascular permeability.

Pharmacodynamics

In allergic reactions, allergens trigger the degranulation of mast cells and basophils, leading to the release of histamine. Chlorpheniramine, as an H1 antagonist, competes for receptor binding, effectively blocking histamine-induced effects, such as itching, vasodilation, and bronchoconstriction. This results in relief from symptoms like sneezing, watery eyes, and nasal discharge.

Pharmacokinetics

Chlorpheniramine is well absorbed from the gastrointestinal tract. It undergoes hepatic metabolism and its effects can last for several hours. The onset of action is typically observed within 1 to 2 hours following oral administration, with peak effects occurring around 2 to 6 hours. The drug is eliminated primarily through urine, with a half-life ranging from 12 to 15 hours, though this can vary based on individual factors.

Contra-indications

• Hypersensitivity to chlorpheniramine or any component of the formulation
• Acute asthma attacks
• Severe hypertension
• Narrow-angle glaucoma
• Prostatic hypertrophy

Adverse effects

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

Interactions

• Alcohol
• CNS depressants
• MAO inhibitors
• Anticholinergic agents
• Beta-blockers

Precautions

• Use with caution in patients with cardiovascular disease
• Caution in patients with liver or kidney impairment
• Avoid in elderly patients due to increased risk of sedation and anticholinergic effects
• May impair the ability to drive or operate machinery

Pregnancy

Chlorpheniramine should be used in pregnancy only if clearly needed. Consult medical professionals for guidance.

Breast-feeding

Chlorpheniramine is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Syrup
• Oral suspension

Indications

• Cough due to common cold
• Cough due to bronchitis
• Cough due to upper respiratory tract infections

Dosage

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

Adults: Refer to the relevant guidelines for specific dosing recommendations, as doses may vary based on formulation and indication.

Mechanism of action

Dextromethorphan acts primarily as a sigma-1 receptor agonist and NMDA receptor antagonist. It inhibits the reuptake of serotonin and modulates glutamate activity, leading to a decrease in cough reflex. This multifaceted action in the central nervous system contributes to its effectiveness as a cough suppressant.

Pharmacodynamics

Dextromethorphan produces its effects by suppressing the cough reflex in the medullary cough center of the brain. Its action is dose-dependent, with higher doses potentially leading to additional effects such as dissociation and euphoria, which are not typical at therapeutic dosages. The onset of action typically occurs within 15 to 30 minutes, with effects lasting for about 3 to 6 hours.

Pharmacokinetics

Dextromethorphan is rapidly absorbed following oral administration, achieving peak plasma concentrations within 2 to 3 hours. It undergoes extensive first-pass metabolism in the liver, primarily via the cytochrome P450 system (CYP2D6), resulting in various metabolites, some of which may have pharmacological activity. The elimination half-life ranges from 1.5 to 4 hours, and the drug is primarily excreted through urine, mainly as metabolites.

Adverse effects

• Dizziness
• Drowsiness
• Nausea
• Vomiting
• Constipation
• Confusion
• Hallucinations
• Respiratory depression

Interactions

• Monoamine oxidase inhibitors (MAOIs)
• Other central nervous system depressants
• Serotonergic drugs

Precautions

• Caution in patients with a history of substance abuse
• Caution in patients with respiratory conditions
• Not recommended for use in children under 2 years of age
• Use with caution in elderly patients

Pregnancy

Dextromethorphan should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus, as safety has not been established.

Breast-feeding

Dextromethorphan is excreted in breast milk, and 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

• Respiratory conditions (e.g., asthma, chronic obstructive pulmonary disease)
• Cough (e.g., as an antitussive)
• Anxiety and sleep disorders (when associated with specific formulations)

Dosage

Children: Refer to the BNF for Children for appropriate dosing information, as it is determined based on weight and age for the specific formulation.

Adults: Refer to the specific product monograph for dosing information, as it varies based on the drug formulation and indication.

Mechanism of action

Hydrobromides often act as competitive antagonists or agonists at specific receptor sites, depending on the drug involved. The exact mechanism can vary widely, but many hydrobromide-containing drugs modulate neurotransmitter activity, impacting various pathways in the body such as those involved in the central nervous system or respiratory function. The metabolic pathways include Phase I reactions primarily mediated by cytochrome P450 enzymes, which facilitate the functionalization and clearance of these compounds.

Pharmacodynamics

The pharmacodynamics of hydrobromide salts are largely determined by the specific drug they are associated with. Generally, hydrobromides may exhibit effects such as sedation, bronchodilation, or antitussive actions. The efficacy and adverse effects are influenced by the drug's receptor selectivity, affinity, and the pharmacological properties inherent to the parent compound.

Pharmacokinetics

Hydrobromides typically exhibit variable pharmacokinetic profiles depending on the specific drug formulation. They are generally absorbed rapidly following oral administration, with peak plasma concentrations occurring within a few hours. Metabolism primarily occurs in the liver through cytochrome P450 enzymes, particularly CYP2E1, among others. The elimination half-life varies but is often in the range of several hours, allowing for once or twice-daily dosing in many formulations. Excretion is usually via the kidneys, with metabolites being eliminated in urine.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if clearly needed and the potential benefits justify the potential risks to the fetus.

Breast-feeding

Caution is advised; consider the importance of the drug to the mother against potential risks to the breastfeeding infant.

Storage

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

Indications

• Topical analgesic for muscle and joint pain
• Cough suppressant in cough drops and lozenges
• Relief of minor throat irritation
• Cooling agent in various cosmetic and personal care products

Dosage

Children: Refer to BNF for Children for specific dosing guidelines, as doses may vary based on age and formulation.

Adults: For topical use, apply a thin layer to the affected area not more than 3 to 4 times daily. For cough drops, follow the product-specific instructions as per the formulation.

Mechanism of action

Menthol acts as an agonist for the transient receptor potential subtype M8 (TRPM8), a non-selective cation channel that is activated by cold temperatures. This activation leads to calcium influx in mast cells, inducing the release of histamine, which can trigger allergic responses such as urticaria, asthma, and rhinitis. Menthol's ability to induce histamine release via TRPM8 suggests potential therapeutic applications for TRPM8 antagonists in managing cold- and menthol-induced allergies.

Pharmacodynamics

Menthol produces a cooling effect by stimulating sensory neurons that convey cold sensations. It interacts with TRPM8 channels, leading to the activation of intracellular signaling pathways that can result in vasodilation and increased blood flow to the area of application. This cooling sensation can provide symptomatic relief in conditions characterized by pain or irritation.

Pharmacokinetics

Menthol is absorbed through the skin and mucous membranes, with systemic effects depending on the route of administration. Its bioavailability can vary, and it is metabolized primarily in the liver. The elimination half-life and excretion pathways have not been extensively characterized, but menthol is generally considered to have a rapid onset of action with effects lasting for a few hours.

Adverse effects

• Allergic reactions
• Urticaria
• Asthma
• Rhinitis
• Skin irritation

Precautions

• Use with caution in patients with known allergies to menthol or related compounds
• May exacerbate asthma in sensitive individuals

Pregnancy

There are no well-controlled studies of menthol in pregnant women. Menthol should be used during pregnancy only if clearly needed.

Breast-feeding

Menthol is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Topical ointment
• Cream
• Liquid

Mechanism of action

Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Antihistamines used in the treatment of allergy act by competing with histamine for H1-receptor sites on effector cells. They thereby prevent, but do not reverse, responses mediated by histamine alone. Antihistamines antagonize, in varying degrees, most of the pharmacological effects of histamine, including urticaria and pruritus. Also, the anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa. /Antihistamines/ H1 antagonists inhibit most responses of smooth muscle to histamine. Antagonism of the constrictor action of histamine on respiratory smooth muscle is easily shown in vivo and in vitro. /Histamine Antagonists: H1 Antagonists/ H1 antagonists strongly block the action of histamine that results in increased permeability and formation of edema and wheal. /Histamine Antagonists: H1 Antagonists/ Within the vascular tree, the H1 antagonists inhibit both the vasoconstrictor effects of histamine and, to a degree, the more rapid vasodilator effects that are mediated by H1 receptors on endothelial cells. Residual vasodilatation reflects the involvement of H2 receptors on smooth muscle and can be suppressed only by the concurrent administration of an H2 antagonist. Effects of the histamine antagonists on histamine induced changes in systemic blood pressure parallel these vascular effects. /Histamine Antagonists: H1 Antagonists/ Many of the H1 antagonists tend to inhibit responses to acetylcholine that are mediated by muscarinic receptors. These atropine like actions are sufficiently prominent in some of the drugs to be manifest during clinical usage ... . /Histamine Antagonists: H1 Antagonists/

Pharmacodynamics

In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H₁-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal H₁-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.

Mechanism of action

Exposure to low temperatures often causes allergic responses or urticaria. Similarly, menthol, a common food additive is also known to cause urticaria, asthma, and rhinitis. However, despite the obvious clinical implications, the molecular mechanisms responsible for inducing allergic responses to low temperatures and menthol have not been determined. Because a non-selective cation channel, transient receptor potential subtype M8 (TRPM8) is activated by cold and menthol, we hypothesized that this channel mediates cold- and menthol-induced histamine release in mast cells. Here, we report that TRPM8 is expressed in the basophilic leukemia mast cell line, RBL-2H3, and that exposure to menthol or low temperatures induced Ca(2+) influx in RBL-2H3 cells, which was reversed by a TRPM8 blocker. Furthermore, menthol, a TRPM8 agonist, induced the dose-dependent release of histamine from RBL-2H3 cells. When TRPM8 transcripts were reduced by siRNA (small interfering RNA), menthol- and cold-induced Ca(2+) influx and histamine release were significantly reduced. In addition, subcutaneous injection of menthol evoked scratching, a typical histamine-induced response which was reversed by a TRPM8 blocker. Thus, our findings indicate that TRPM8 mediates the menthol- and cold-induced allergic responses of mast cells, and suggest that TRPM8 antagonists be viewed as potential treatments for cold- and menthol-induced allergies. /DL-Menthol/ Menthol's characteristic cooling sensation is due, in part, to the activation of sensory neurons generally termed transient receptor potential (TRP) channels, in particular transient receptor potential melastatin family member 8 (TRPM8) and transient receptor potential subfamily A, member 1 (TRPA1). Menthol acts upon TRPM8 receptors by rapidly increasing intracellular calcium and mobilizing calcium flux through the channels to induce cold response signals at the application site. Aside from its cold-inducing sensation capabilities, menthol exhibits cytotoxic effects in cancer cells, induces reduction in malignant cell growth, and engages in synergistic excitation of GABA receptors and sodium ion channels resulting in analgesia. /DL-Menthol/ In recent years, the transient receptor potential melastatin member 8 (TRPM8) channel has emerged as a promising prognostic marker and putative therapeutic target in prostate cancer. We have found that forced overexpression of TRPM8 in PC-3 cells can inhibit the cell proliferation and motility probably through the TRPM8 activation. In this study, we aimed to investigate whether activating the TRPM8 channel by its selective agonist menthol can inhibit the proliferation and motility of androgen-independent prostate cancer (AIPC) with remarkable expression of TRPM8. Menthol is a naturally occurring compound, which has been widely used in cosmetics and pharmaceutical products, and also as flavoring in food. DU145 cells are androgen-independent but have a remarkable expression of TRPM8. The demonstration of the existence of TRPM8 and the absence of TRPA1 in DU145 cells provided the foundation for the following experiments, because both TRPM8 and TRPA1 are molecular targets of menthol. The outcome of MTT assay indicated that menthol inhibited the cell growth (p < 0.01). Cell cycle distribution and scratch assay analysis revealed that menthol induced cell cycle arrest at the G(0)/G(1) phase (p < 0.01). Furthermore, menthol inhibited the migration of DU145 cells by downregulating the focal-adhesion kinase. So it suggests that the activation of the existing TRPM8 channels may serve as a potential and pragmatic treatment for those AIPC with remarkable expression of TRPM8, and menthol is a useful compound for future development as an anticancer agent. /DL-Menthol/