ASCORIL NATURA SYRUP

Indications

• Symptomatic relief of allergic rhinoconjunctivitis (hay fever)
• Chronic idiopathic urticaria (hives)

Dosage

Children: For children aged 6 to 12 years, the typical dose is 5 mg once daily for children weighing less than 30 kg, and 10 mg once daily for those weighing 30 kg or more. For children aged 2 to 5 years, 2.5 mg once daily is recommended

Adults: The usual adult dose is 10 mg once daily. In some cases, this can be adjusted based on individual response and tolerability.

Mechanism of action

Cetirizine selectively inhibits the H1 receptor, preventing the action of histamine, which is released during allergic reactions. By blocking these receptors, cetirizine reduces symptoms associated with allergic responses, including itching, sneezing, and runny nose. It also exhibits mild anticholinergic properties, which contribute to its effectiveness in alleviating symptoms.

Pharmacodynamics

Cetirizine has a faster onset of action compared to older antihistamines, providing relief from allergy symptoms within 1 hour of administration. Its effects can last for up to 24 hours, allowing for once-daily dosing. The drug is generally well-tolerated, with sedation being less common than with first-generation antihistamines due to its reduced penetration across the blood-brain barrier.

Pharmacokinetics

Cetirizine is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1-2 hours. It is approximately 93% bound to plasma proteins. The elimination half-life is about 8 hours in healthy adults, but may be prolonged in individuals with renal impairment. Cetirizine is primarily excreted unchanged in the urine, and dose adjustments may be necessary for patients with significant renal dysfunction.

Contra-indications

• Acute porphyrias
• Severe renal impairment

Adverse effects

• Drowsiness
• Headache
• Anxiety
• Increased appetite
• Asthenia
• Diarrhoea
• Dry mouth
• Dyspnoea
• Fever
• Gastritis
• Gastrointestinal discomfort
• Insomnia
• Nasal complaints
• Nausea
• Oral herpes

Interactions

• Other antihistamines (non-sedating)

Precautions

• Drowsiness may occur and affect performance of skilled tasks, such as cycling or driving
• Alcohol should be avoided

Pregnancy

Most manufacturers of antihistamines advise avoiding their use during pregnancy; however, there is no evidence of teratogenicity.

Breast-feeding

Most antihistamines are present in breast milk in varying amounts; although not known to be harmful, most manufacturers advise avoiding their use in mothers who are breast-feeding.

Storage

Store in a cool, dry place away from light.

Formulations

• Cetirizine hydrochloride 10 mg tablets
• Cetirizine hydrochloride 10 mg oral solution

Indications

• Chronic obstructive pulmonary disease (COPD)
• Asthma
• Bronchitis
• Respiratory infections with excessive mucus production

Dosage

Children: For children aged 2 to 5 years, the recommended dose is 15 mg to 30 mg daily, divided into two or three doses. For children aged 6 to 12 years, the recommended dose is 30 mg to 60 mg daily, divided into two or three doses.

Adults: The usual adult dose is 30 mg to 120 mg daily, divided into two or three doses.

Mechanism of action

Ambroxol acts by stimulating the secretion of serous mucus in the respiratory tract, which helps to reduce the viscosity of sputum. This mucolytic action enhances the clearance of mucus, facilitating expectoration. It may also influence the production of surfactant in the lungs, contributing to improved lung function.

Pharmacodynamics

Ambroxol exhibits a dose-dependent effect on mucus viscosity and secretion. By enhancing mucociliary clearance, it aids in reducing airway obstruction and improving respiratory function. The onset of action typically occurs within a few hours after administration, with peak effects observed within 1 to 2 days of treatment.

Pharmacokinetics

Ambroxol is well absorbed after oral administration, with a bioavailability of approximately 70%. It is metabolized primarily in the liver through conjugation and oxidation, resulting in active metabolites. The elimination half-life is about 10 hours, and the drug is excreted predominantly via urine, both as unchanged drug and metabolites.

Contra-indications

• Hypersensitivity to ambroxol or any of the excipients
• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Skin reactions (rash, urticaria)
• Headache
• Dizziness
• Dry mouth
• Anaphylactic reactions (rare)

Interactions

• Ambroxol may enhance the absorption of other drugs due to its mucolytic properties
• Caution should be exercised when used with other cough suppressants

Precautions

• Use with caution in patients with a history of peptic ulcer disease
• Avoid use in patients with asthma unless prescribed by a healthcare professional
• Monitor renal and hepatic function in patients with pre-existing conditions

Pregnancy

Ambroxol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data on human pregnancy are limited.

Breast-feeding

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

Storage

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

Formulations

• Oral solution
• Syrup
• Tablets
• Effervescent tablets

Indications

• Allergic rhinitis (seasonal and perennial)
• Chronic idiopathic urticaria
• Allergic asthma
• Physical urticaria
• Atopic dermatitis

Dosage

Children: For children aged 6 to 12 years, the usual dose is 5 mg twice daily or 10 mg once daily. For children aged 2 to 5 years, the usual dose is 2.5 mg twice daily or 5 mg once daily

Adults: The usual adult dose is 10 mg once daily, which can be taken with or without food.

Mechanism of action

Cetirizine selectively inhibits peripheral H1 receptors, leading to a reduction in the effects of histamine, a chemical responsible for allergic symptoms. The drug demonstrates negligible anticholinergic and antiserotonergic activity. It has shown to have minimal penetration into the central nervous system, thereby reducing the likelihood of sedation, a common side effect associated with antihistamines.

Pharmacodynamics

Cetirizine exhibits antihistaminic and anti-inflammatory effects that are beneficial in managing allergic conditions. It effectively alleviates symptoms of chronic idiopathic urticaria and both perennial and seasonal allergic rhinitis. Clinical trials have established its efficacy in improving symptoms of allergic respiratory diseases, and it significantly inhibits wheal and flare responses within 20 minutes of administration, with effects lasting for up to 24 hours.

Pharmacokinetics

Cetirizine is well absorbed after oral administration, with peak plasma concentrations typically occurring within 1 hour. It has a long half-life, allowing for once-daily dosing. The drug is primarily eliminated via the kidneys, with a portion being excreted unchanged. Its pharmacokinetic profile demonstrates low potential for significant central nervous system penetration, contributing to its reduced sedation compared to first-generation antihistamines.

Adverse effects

• dry mouth
• drowsiness
• fatigue
• headache
• nausea
• dizziness

Precautions

• Caution in patients with renal impairment
• Caution when driving or operating machinery due to potential drowsiness

Pregnancy

Cetirizine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult relevant guidelines.

Breast-feeding

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

Storage

Store below 25°C. Protect from light and moisture. Keep out of reach of children.

Formulations

• tablets
• oral solution
• chewable tablets

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

• 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

Cetirizine, a metabolite of _hydroxyzine_, is an antihistamine drug. Its main effects are achieved through selective inhibition of peripheral H1 receptors. The antihistamine activity of cetirizine has been shown in a variety of animal and human models. _In vivo_ and _ex vivo_ animal models have shown insignificant anticholinergic and antiserotonergic effects. In clinical studies, however, dry mouth was found to be more frequent with cetirizine than with a placebo. In vitro receptor binding studies have demonstrated no detectable affinity of cetirizine for histamine receptors other than the H1 receptors. Studies with radiolabeled cetirizine administration in the rat have demonstrated insignificant penetration into the brain. _Ex vivo_ studies in the mouse have shown that systemically administered cetirizine does not occupy cerebral H1 receptors significantly. Cetirizine, a human metabolite of hydroxyzine, is an antihistamine; its principal effects are mediated via selective inhibition of peripheral H1 receptors. The antihistaminic activity of cetirizine has been clearly documented in a variety of animal and human models. In vivo and ex vivo animal models have shown negligible anticholinergic and antiserotonergic activity. In clinical studies, however, dry mouth was more common with cetirizine than with placebo. In vitro receptor binding studies have shown no measurable affinity for other than H1 receptors. Autoradiographic studies with radiolabeled cetirizine in the rat have shown negligible penetration into the brain. Ex vivo experiments in the mouse have shown that systemically administered cetirizine does not significantly occupy cerebral H1 receptors.

Pharmacodynamics

**General effects and respiratory effects** Cetirizine, the active metabolite of the piperazine H₁-receptor antagonist hydroxyzine, minimizes or eliminates the symptoms of chronic idiopathic urticaria, perennial allergic rhinitis, seasonal allergic rhinitis, allergic asthma, physical urticaria, and atopic dermatitis. The clinical efficacy of cetirizine for allergic respiratory diseases has been well established in numerous trials. **Effects on urticaria/anti-inflammatory effects** It has anti-inflammatory properties that may play a role in asthma management. There is evidence that cetirizine improves symptoms of urticaria. Marked clinical inhibition of a wheal and flare response occurs in infants, children as well as adults within 20 minutes of one oral dose and lasts for 24 h. Concomitant use of cetirizine reduces the duration and dose of topical anti-inflammatory formulas used for the treatment of atopic dermatitis.

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

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/