COSCOF EXPECTORANT NON DROWSY

Indications

• Nasal congestion
• Sinusitis affecting the maxillary antrum

Dosage

Children: For children aged 6-11 years, the recommended dose is 30 mg 3-4 times a day. For children aged 12-17 years, the dose is 60 mg 3-4 times a day. Caution is advised in children under 6 years.

Adults: The typical adult dose is 60 mg every 4-6 hours, not exceeding 240 mg per day.

Mechanism of action

Pseudoephedrine acts primarily as a selective agonist of alpha-adrenergic receptors, which causes vasoconstriction of the nasal mucosa. This leads to a decrease in mucosal edema and congestion. It may also have some beta-adrenergic activity, contributing to bronchodilation.

Pharmacodynamics

The pharmacodynamic effects of pseudoephedrine include reduced nasal congestion and increased airflow through the nasal passages. Its action is dose-dependent, with higher doses leading to more pronounced effects. Side effects may include increased heart rate, hypertension, and CNS stimulation such as anxiety and insomnia.

Pharmacokinetics

Pseudoephedrine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-2 hours after oral administration. It is metabolized primarily in the liver and has a half-life of approximately 5-8 hours. The drug is excreted mainly in the urine, with a portion being unchanged.

Contra-indications

• Severe hypertension
• Severe renal impairment
• Severe hepatic impairment
• Hyperthyroidism
• Angle closure glaucoma
• Use in children under 6 years of age is not recommended due to safety concerns

Adverse effects

• Anxiety
• Headache
• Insomnia
• Nausea
• Dizziness
• Dry mouth
• Increased heart rate (tachycardia)
• Hypertension
• Palpitations
• Rebound congestion
• Irritability
• Tremors
• Hallucinations
• Dermatitis
• Muscle weakness
• Vomiting
• Piloerection

Interactions

• Monoamine oxidase inhibitors (MAOIs) may enhance the hypertensive effects
• Other sympathomimetics may increase the risk of cardiovascular effects
• Caution with antihypertensive medications as pseudoephedrine may counteract their effectiveness

Precautions

• Use with caution in individuals with cardiovascular disease
• Caution in patients with diabetes due to potential hyperglycemia
• Monitor patients with a history of psychiatric disorders as it may exacerbate symptoms
• Use with caution in patients with a history of seizures

Pregnancy

Manufacturer advises avoidance due to potential risks such as defective closure of the abdominal wall in newborns after first trimester exposure.

Breast-feeding

Present in breast milk; manufacturer advises avoidance due to the potential for irritability and disturbed sleep in infants.

Storage

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

Formulations

• Oral solution (e.g., Sudafed Decongestant 30mg/5ml liquid)
• Nasal drops (e.g., Galpseud 0.5% drops)

Indications

• Nitrogen supplementation in clinical nutrition
• Management of metabolic alkalosis
• Treatment of certain types of kidney disorders

Dosage

Children: Specific pediatric dosing information is not detailed in the BNF. Refer to the BNF for Children for appropriate dosing based on age and condition.

Adults: Dosage varies based on clinical indication and should be guided by specific treatment protocols. Refer to clinical guidelines for detailed dosing information.

Mechanism of action

Ammonium ions participate in various metabolic pathways, including the biosynthesis of amino acids and nucleotides. It serves as a nitrogen source for organisms, facilitating the synthesis of essential biomolecules. The presence of ammonium can influence pH levels and osmotic balance within cells, thereby affecting cellular functions and enzyme activities.

Pharmacodynamics

Ammonium affects cellular metabolism by acting as a nitrogen donor in the synthesis of organic compounds. Its role in the nitrogen cycle and as a substrate in biochemical pathways allows for the maintenance of cellular functions, including energy production and cellular growth. Alterations in ammonium levels can influence various physiological processes, including neurotransmitter synthesis and energy metabolism.

Pharmacokinetics

Ammonium is readily absorbed and distributed in biological systems. It can be produced endogenously through amino acid metabolism or obtained from dietary sources. The excretion of ammonium primarily occurs through the kidneys, where it is converted to urea for elimination. Ammonium levels are regulated by various mechanisms, including the action of renal tubular cells that either secrete or reabsorb ammonium based on the body's needs.

Indications

• Cough associated with respiratory tract infections
• Acid-base disorders
• Edema management

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing guidelines based on age and condition.

Adults: Refer to the BNF for specific adult dosing guidelines as they depend on the indication and clinical context.

Mechanism of action

Ammonium chloride increases acidity by raising hydrogen ion concentrations. It dissociates into ammonium and chloride ions; the ammonium is converted to urea in the liver, releasing hydrogen ions that lower pH. The chloride ions displace bicarbonate in extracellular fluid, leading to acidosis and increased renal excretion of electrolytes and water, resulting in fluid mobilization.

Pharmacodynamics

Ammonium chloride acts as a systemic acidifier, facilitating the excretion of chloride and sodium, while also increasing the acidity of body fluids. The conversion of ammonium to urea in the liver with the release of hydrogen ions contributes to a decrease in blood pH, affecting acid-base balance in the body.

Pharmacokinetics

Ammonium chloride is absorbed from the gastrointestinal tract and metabolized in the liver, where it is converted to urea. The dissociated ions impact renal function, leading to increased excretion of sodium, potassium, and water. The elimination half-life and specific metabolism details are not explicitly defined.

Adverse effects

• Nausea
• Vomiting
• Abdominal pain
• Diarrhea
• Dizziness
• Headache

Interactions

• Antacids may reduce the effectiveness of ammonium chloride
• Potassium-sparing diuretics may increase the risk of hyperkalemia

Precautions

• Use with caution in patients with renal impairment
• Monitor electrolyte levels during prolonged therapy
• Consider potential for acidosis in patients with liver disease

Pregnancy

Ammonium chloride should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Consult a healthcare provider for individualized advice.

Breast-feeding

Ammonium chloride is excreted in breast milk. Use caution and consult a healthcare provider if breastfeeding.

Storage

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

Formulations

• Oral solution
• Powder for oral solution

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

• Nasal congestion due to cold
• Allergic rhinitis
• Sinusitis
• Eustachian tube dysfunction

Dosage

Children: For children aged 6 to 12 years, the recommended dose is 30 mg every 6 hours, not exceeding 120 mg per day. For children aged 2 to 6 years

Adults: The typical adult dose is 60 mg every 4 to 6 hours, not exceeding 240 mg per day.

Mechanism of action

Pseudoephedrine acts mainly as an agonist of alpha adrenergic receptors and less strongly as an agonist of beta adrenergic receptors. The agonism produces vasoconstriction in the mucosa of the respiratory tract, leading to decreased nasal congestion. It also inhibits norepinephrine, dopamine, and serotonin transporters, which may contribute to its sympathomimetic effects such as increased arterial pressure and heart rate. Additionally, pseudoephedrine has anti-inflammatory actions through the inhibition of NF-kappa-B and other transcription factors.

Pharmacodynamics

Pseudoephedrine causes vasoconstriction resulting in a decongestant effect. Its sympathomimetic properties can lead to increased heart rate and blood pressure. The duration of action is typically short unless formulated as an extended-release product. Patients may experience central nervous system stimulation, which should be considered when prescribing.

Pharmacokinetics

Pseudoephedrine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 1 to 2 hours after oral administration. The drug is metabolized in the liver, primarily by the cytochrome P450 system, and has a half-life of about 6 hours. It is excreted mainly through the kidneys, with about 55-70% of the dose eliminated unchanged in the urine.

Adverse effects

• Increased blood pressure
• Centrally mediated side effects such as insomnia
• Nervousness
• Dizziness
• Headache
• Dry mouth

Interactions

• pseudoephedrine + linezolid: Severe (increases risk of elevated blood pressure)
• volatile halogenated anesthetics + pseudoephedrine: Unknown (additive effect)

Precautions

• Use with caution in patients with hypertension
• Use with caution in patients with cardiovascular disease
• May exacerbate conditions like hyperthyroidism or diabetes

Pregnancy

Use only if clearly needed, as safety in pregnancy has not been established.

Breast-feeding

Use with caution; small amounts may pass into breast milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Oral tablets
• Extended-release oral tablets
• Liquid formulations

Mechanism of action

Ammonium chloride increases acidity by increasing the amount of hydrogen ion concentrations. Ammonium chloride can be used as an expectorant due to its irritative action on the bronchial mucosa. This effect causes the production of respiratory tract fluid which in order facilitates the effective cough. The acid-forming properties of ammonium chloride result from dissociation of the salt to an ammonium cation and a chloride anion. In patients with normal hepatic function, the ammonium cation is converted to urea by the liver and a hydrogen cation is released which reacts with a bicarbonate ion to form water and carbon dioxide. The chloride anion combines with fixed bases in the extracellular fluid, thereby reducing the alkaline reserve of the body. The net result is the displacement of bicarbonate ions by chloride anions. The displacement of bicarbonate by chloride alters the bicarbonate:carbonic acid ratio if the body and acidosis results. The increased chloride concentration in the extracellular fluid produces an increased load to the renal tubules and appreciable amounts of chloride anions escape reabsorption. These anions are excreted along with cations and water. Sodium is the principal cation excreted; however, potassium excretion may also be increased to some degree. By increasing the excretion of both extracellular electrolytes and water, ammonium chloride causes a net loss of extracellular fluid and promotes the mobilization of edema fluid.

Pharmacodynamics

Systemic acidifier. In liver ammonium chloride is converted into urea with the liberation of hydrogen ions ( which lowers the pH) and chloride.

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

Pseudoephedrine acts mainly as an agonist of alpha adrenergic receptors and less strongly as an agonist of beta adrenergic receptors. This agonism of adrenergic receptors produces vasoconstriction which is used as a decongestant and as a treatment of priapism. Pseudoephedrine is also an inhibitor of norepinephrine, dopamine, and serotonin transporters. The sympathomimetic effects of pseudoephedrine include an increase in mean arterial pressure, heart rate, and chronotropic response of the right atria. Pseudoephedrine is also a partial agonist of the anococcygeal muscle. Pseudoephedrine also inhibits NF-kappa-B, NFAT, and AP-1. THESE AGENTS /BRONCHODILATORS/ ACT ON BETA-2 RECEPTORS TO RELAX BRONCHIAL SMOOTH MUSCLE & PERIPHERAL VASCULATURE, APPARENTLY BY STIMULATING PRODN OF CYCLIC ADENOSINE-3.5-MONOPHOSPHATE (CAMP)... Pseudoephedrine acts on alpha-adrenergic receptors in the mucosa of the respiratory tract, producing vasoconstriction. The medication shrinks swollen nasal mucous membranes; reduces tissue hyperemia, edema, and nasal congestion; and increases nasal airway patency. Also, drainage of sinus secretions may be increased and obstructed eustachian ostia may be opened. The pharmacological properties of the ephedrine derivative pseudoephedrine were investigated at the nuclear level. Following intraperitoneal injection of Sprague Dawley rats with pseudoephedrine, Fos induction was measured in various brain areas by Western blots and immunocytochemistry. Pseudoephedrine induced Fos-like immunoreactivity in the nucleus accumbens and striatum in a time and concentration-dependent manner with maximal effect at 60 mg/kg 2 hr after injection. Immunocytochemical studies confirmed that the majority of the signal was detectable in the nucleus accumbens and striatum. Pre-injection with the D1 dopamine receptor antagonist SCH23390 partially and completely blocked pseudoephedrine-induced Fos-like immunoreactivity in the striatum and nucleus accumbens, respectively, suggesting that the action of pseudoephedrine is mediated via dopamine release and results in the activation of D1 dopamine receptors. With the exception of the higher doses required, the actions of pseudoephedrine were similar to those previously described for the psychostimulant amphetamine.

Pharmacodynamics

Pseudoephedrine causes vasoconstriction which leads to a decongestant effect. It has a short duration of action unless formulated as an extended release product. Patients should be counselled regarding the risk of central nervous system stimulation.