TUSSKAN SYRUP

Indications

• Reversal of hypotension from spinal or epidural anesthesia
• Reversible airways obstruction (e.g., asthma, bronchospasm)
• Nasal congestion

Dosage

Children: For children aged 1 month to 11 years, the dose is 1 mg/kg/hour by intravenous infusion, adjusted according to plasma-theophylline concentration. For children aged 12 to 17 years, administer 500–700 micrograms/kg/hour by intravenous infusion, also adjusted according to plasma-theophylline concentration.

Adults: For reversal of hypotension, administer 3–7.5 mg by slow intravenous injection every 3–4 minutes, adjusting according to response, with a maximum of 9 mg per dose. For airways obstruction, 30–60 mg may be given orally three times a day.

Mechanism of action

Ephedrine acts by stimulating adrenergic receptors, leading to bronchodilation and vasoconstriction. It increases the release of norepinephrine from sympathetic nerve endings, enhancing its action on alpha and beta-adrenergic receptors, which results in increased peripheral resistance and cardiac output.

Pharmacodynamics

Ephedrine exhibits both alpha- and beta-adrenergic activity. Its alpha-adrenergic effects lead to vasoconstriction, while beta-adrenergic stimulation results in bronchodilation. The drug also has a mild central nervous system stimulant effect, which can contribute to side effects such as anxiety and insomnia.

Pharmacokinetics

Ephedrine is well-absorbed from the gastrointestinal tract and is distributed widely throughout the body. It has a relatively long half-life due to its resistance to metabolism. The drug is primarily excreted unchanged in the urine. Its pharmacokinetic profile can be influenced by factors such as renal function and the presence of other medications that may affect its clearance.

Contra-indications

• Hypersensitivity to ephedrine or any of its components
• Severe hypertension
• Tachyarrhythmias
• Severe coronary artery disease
• Hyperthyroidism
• Prostatic hypertrophy

Adverse effects

• Anxiety
• Headache
• Insomnia
• Nausea
• Tremor
• Dry mouth
• Dizziness
• Cardiac arrhythmias
• Hypertension
• Urinary retention
• Myocardial infarction
• Psychotic disorders
• Pulmonary edema

Interactions

• Other sympathomimetics
• Xanthines (e.g., theophylline)
• Monoamine oxidase inhibitors
• Antihypertensive agents
• Antidepressants
• Corticosteroids

Precautions

• Use with caution in patients with diabetes mellitus
• Caution in elderly patients
• Hypertension
• Ischaemic heart disease
• Glaucoma (risk of angle-closure)
• Chronic obstructive pulmonary disease

Pregnancy

Manufacturer advises avoidance due to potential risks, including increased fetal heart rate.

Breast-feeding

Present in breast milk; manufacturer advises avoidance due to reported 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 suspension
• Oral solution
• Tablets (15 mg, 30 mg)
• Solution for injection (30 mg per 10 ml)

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

• Allergic rhinitis
• Allergic conjunctivitis
• Urticaria

Mechanism of action

Diphenhydramine primarily functions by antagonizing H1 (Histamine 1) receptors located in various tissues, including the respiratory system, gastrointestinal tract, and central nervous system. By acting as an inverse agonist at H1 receptors, it mitigates the effects of histamine, thereby reducing allergic symptoms. As a first-generation antihistamine, it also crosses the blood-brain barrier, leading to sedative effects. Furthermore, diphenhydramine exhibits antimuscarinic activity by competitively antagonizing muscarinic acetylcholine receptors, contributing to its use in treating parkinsonian symptoms.

Pharmacodynamics

Diphenhydramine possesses anti-histaminic, anti-emetic, anti-vertigo, and sedative properties. Its antihistaminic action blocks the effects of histamine by competing for H1 receptor sites, preventing symptoms associated with histamine release. Its anti-emetic effects are due to inhibition at the medullary chemoreceptor trigger zone, while its anti-vertigo action arises from a central antimuscarinic effect on the vestibular apparatus and the vomiting center in the midbrain.

Pharmacokinetics

Diphenhydramine is well-absorbed following oral administration and reaches peak plasma concentrations within 1 to 2 hours. It is metabolized in the liver and has a half-life of approximately 4 to 8 hours, although this can vary based on individual factors. The drug is excreted primarily in the urine, with a significant portion eliminated as metabolites rather than unchanged drug. Due to its lipophilic nature, diphenhydramine readily crosses the blood-brain barrier, contributing to its sedative effects.

Contra-indications

• Severe asthma exacerbation
• Hypersensitivity to diphenhydramine or any of its components
• Newborns or premature infants

Adverse effects

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

Interactions

• CNS depressants (e.g., alcohol, sedatives, tranquilizers) may enhance sedative effects
• MAO inhibitors can prolong and intensify anticholinergic effects

Precautions

• Use with caution in patients with glaucoma
• Prostatic hypertrophy
• Cardiovascular disease
• Elderly patients may be more sensitive to side effects

Pregnancy

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

Breast-feeding

Diphenhydramine is excreted in breast milk. Use caution when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Capsules
• Liquid formulations
• Topical preparations

Indications

• Bronchial asthma
• Hypotension
• Nasal congestion
• Cardiac arrest

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing information.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated.

Mechanism of action

Ephedrine acts by activating alpha-adrenergic and beta-adrenergic receptors. Directly, it stimulates these receptors, leading to vasoconstriction (alpha-1), increased cardiac chronotropy and inotropy (beta-1), and bronchodilation (beta-2). Indirectly, it inhibits norepinephrine reuptake and promotes the release of norepinephrine from nerve cells, resulting in prolonged sympathetic stimulation.

Pharmacodynamics

Ephedrine elevates blood pressure through increased heart rate and cardiac output, while also variably raising peripheral resistance. It induces bronchodilation through beta-adrenergic receptor activation in the lungs. Additionally, it enhances urine outflow resistance by stimulating alpha-adrenergic receptors in bladder smooth muscle. The therapeutic dose range is broad, with potential dosages from 5mg to 50mg, and caution is advised regarding the risk of hypertension and tachyphylaxis.

Pharmacokinetics

Ephedrine is rapidly absorbed and reaches peak plasma concentrations within 1 to 2 hours following oral administration. It is metabolized in the liver and excreted primarily via the kidneys. The duration of action is variable, but it generally lasts for 2 to 4 hours. Its pharmacokinetic profile can be influenced by individual patient characteristics, including renal function.

Adverse effects

• Tachycardia
• Hypertension
• Palpitations
• Nervousness
• Dizziness
• Nausea
• Vomiting

Interactions

• mianserin+ephedrine: Unknown (decreases effects)
• volatile halogenated anaesthetics+ephedrine: Unknown (additive effect)

Precautions

• Use with caution in patients with cardiovascular disorders
• Monitor blood pressure and heart rate during treatment
• Consider potential for tachyphylaxis with prolonged use

Pregnancy

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

Breast-feeding

Caution is advised; ephedrine may pass into breast milk.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Oral tablets
• Injectable solution

Indications

• Cough associated with colds
• Bronchitis
• Respiratory tract infections
• Other conditions with excessive mucus production

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines based on age and

Adults: The typical adult dose is 200-400 mg orally every 4 hours as needed, not exceeding 2.4 g per day.

Mechanism of action

Guaifenesin is believed to function by increasing mucus secretion and acting as an irritant to gastric vagal receptors. This action recruits efferent parasympathetic reflexes that stimulate glandular exocytosis, resulting in a less viscous mucus mixture. Consequently, this may provoke coughing, facilitating the clearance of congealed mucopurulent material from obstructed airways, thereby improving respiratory function. Additionally, it is thought to enhance the output of phlegm and bronchial secretions by reducing their viscosity and adhesiveness, thus promoting ciliary action and improving the efficiency of the cough reflex.

Pharmacodynamics

Guaifenesin acts as an expectorant that enhances the output of phlegm and bronchial secretions by decreasing their adhesiveness and surface tension. By increasing the flow of less viscous gastric secretions, it promotes ciliary action, leading to more productive coughs. This mechanism ultimately aids in the removal of accumulated secretions from the upper and lower airways, making coughs less frequent and more effective.

Pharmacokinetics

Guaifenesin is rapidly absorbed from the gastrointestinal tract and is metabolized in the liver. It has a relatively short half-life, with peak plasma concentrations typically occurring within one hour of administration. The drug is eliminated primarily through renal excretion, with both unchanged drug and metabolites being excreted in the urine.

Adverse effects

• Nausea
• Vomiting
• Dizziness
• Headache
• Rash
• Gastrointestinal discomfort

Precautions

• Caution in patients with chronic cough associated with smoking, asthma, or emphysema
• Use with caution in patients with a history of gastrointestinal disorders

Pregnancy

Guaifenesin is categorized under FDA pregnancy category C. Risk cannot be ruled out; consult a healthcare provider.

Breast-feeding

Limited data available; exercise caution and consult a healthcare provider before use.

Storage

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

Formulations

• Oral solution
• Tablet
• Extended-release tablet
• Syrup

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

Diphenhydramine predominantly works via the antagonism of H1 (Histamine 1) receptors. Such H1 receptors are located on respiratory smooth muscles, vascular endothelial cells, the gastrointestinal tract (GIT), cardiac tissue, immune cells, the uterus, and the central nervous system (CNS) neurons. When the H1 receptor is stimulated in these tissues it produces a variety of actions including increased vascular permeability, promotion of vasodilation causing flushing, decreased atrioventricular (AV) node conduction time, stimulation of sensory nerves of airways producing coughing, smooth muscle contraction of bronchi and the GIT, and eosinophilic chemotaxis that promotes the allergic immune response. Ultimately, diphenhydramine functions as an inverse agonist at H1 receptors, and subsequently reverses effects of histamine on capillaries, reducing allergic reaction symptoms. Moreover, since diphenhydramine is a first-generation antihistamine, it readily crosses the blood-brain barrier and inversely agonizes the H1 CNS receptors, resulting in drowsiness, and suppressing the medullary cough center. Furthermore, H1 receptors are similar to muscarinic receptors. Consequently, diphenhydramine also acts as an antimuscarinic. It does so by behaving as a competitive antagonist of muscarinic acetylcholine receptors, resulting in its use as an antiparkinson medication. Lastly, diphenhydramine has also demonstrated activity as an intracellular sodium channel blocker, resulting in possible local anesthetic properties. 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 both the vasoconstrictor effects of histamine and, to a degree, the more rapid vasodilator effects mediated by activation of H1 receptors on endothelial cells (synthesis/release of NO and other mediators). /H1 Receptor Antagonists/ H1 antagonists suppress the action of histamine on nerve endings, including the flare component of the triple response and the itching caused by intradermal injection. /H1 Receptor Antagonists/ The first-generation antihistamines are widely prescribed medications that relieve allergic reactions and urticaria by blocking the peripheral histamine H(1) receptor. Overdose of these drugs often results in serious neuronal toxic effects, including seizures, convulsions and worsening of epileptic symptoms. The KCNQ/M K(+) channel plays a crucial role in controlling neuron excitability. Here, we demonstrate that mepyramine and diphenhydramine, two structurally related first-generation antihistamines, can act as potent KCNQ/M channel blockers. Extracellular application of these drugs quickly and reversibly reduced KCNQ2/Q3 currents heterologously expressed in HEK293 cells. The current inhibition was concentration and voltage dependent. The estimated IC(50) (12.5 and 48.1 microM, respectively) is within the range of drug concentrations detected in poisoned patients (30-300 microM). Both drugs shifted the I-V curve of KCNQ2/Q3 channel to more depolarized potentials and altered channel gating properties by prolonging activation and shortening deactivation kinetics. Mepyramine also inhibited the individual homomeric KCNQ1-4 and heteromeric KCNQ3/Q5 currents. Moreover, mepyramine inhibited KCNQ2/Q3 current in an outside-out patch excised from HEK293 cells and the inhibitory effect was neither observed when it was applied intracellularly nor affected by blocking phospholipase C (PLC) activity, indicating an extracellular and direct channel blocking mechanism. Finally, in cultured rat superior cervical ganglion (SCG) neurons, mepyramine reduced the

Pharmacodynamics

Diphenhydramine has anti-histaminic (H1-receptor), anti-emetic, anti-vertigo and sedative and hypnotic properties. The anti-histamine action occurs by blocking the spasmogenic and congestive effects of histamine by competing with histamine for H1 receptor sites on effector cells, preventing but not reversing responses mediated by histamine alone. Such receptor sites may be found in the gut, uterus, large blood vessels, bronchial muscles, and elsewhere. Anti-emetic action is by inhibition at the medullary chemoreceptor trigger zone. Anti-vertigo action is by a central antimuscarinic effect on the vestibular apparatus and the integrative vomiting center and medullary chemoreceptor trigger zone of the midbrain.

Mechanism of action

Ephedrine is a direct and indirect sympathomimetic amine. As a direct effect, ephedrine activates alpha-adrenergic and beta-adrenergic receptors. As an indirect effect, it inhibits norepinephrine reuptake and increases the release of norepinephrine from vesicles in nerve cells. These actions combined lead to larger quantities of norepinephrine present in the synapse for more extended periods of time, increasing stimulation of the sympathetic nervous system. Ephedrine acts as an agonist of alpha-1, beta-1 and beta-2-adrenergic receptors. The stimulation of alpha-1-adrenergic receptors causes the constriction of veins and a rise in blood pressure, the stimulation of beta-1-adrenergic receptors increases cardiac chronotropy and inotropy, and the stimulation of beta-2-adrenergic receptors causes vasodilation and bronchodilation. Ephedrine alkaloids are members of a large family of sympathomimetic compounds that include dobutamine and amphetamine. Members of this family increase blood pressure and heart rate by binding to alpha- and beta-adrenergic receptors present in many parts of the body, including the heart and blood vessels. These compounds are called sympathomimetics because they mimic the effects of epinephrine and norepinephrine, which occur naturally in the human body. In addition to their direct pharmacological effects, many of these compounds also stimulate the release of norepinephrine from nerve endings. The release of norepinephrine further increases the sympathomimetic effects of these compounds, at least transiently. Ephedrine does not contain a catechol moiety, and it is effective after oral administration. The drug stimulates heart rate and cardiac output and variably increases peripheral resistance; as a result, ephedrine usually increases blood pressure. Stimulation of the alpha-adrenergic receptors of smooth muscle cells in the bladder base may increase the resistance to the outflow of urine. Activation of beta-adrenergic receptors in the lungs promotes bronchodilation. Ephedrine stimulates both alpha- and beta-adrenergic receptors. It is believed that beta-adrenergic effects result from stimulation of the production of cyclic adenosine 3',5'-monophosphate (AMP) by activation of the enzyme adenyl cyclase, whereas a-adrenergic effects result from inhibition of adenyl cyclase activity. In contrast to epinephrine, ephedrine also has an indirect effect by releasing norepinephrine from its storage sites. With prolonged use or if doses are given frequently, ephedrine may deplete norepinephrine stores in sympathetic nerve endings and tachyphylaxis may develop to the cardiac and pressor effects. Tachyphylaxis to the bronchial effects of the drug may also occur, but it is not the result of norepinephrine depletion.

Pharmacodynamics

Ephedrine increases blood pressure by stimulating heart rate and cardiac output and variably increasing peripheral resistance. It causes bronchodilation due to the activation of beta-adrenergic receptors in the lungs. By stimulating alpha-adrenergic receptors in bladder smooth muscle cells, ephedrine also increases the resistance to the outflow of urine. The therapeutic window of ephedrine is wide, as patients can be given doses of 5mg up to 50mg. Patients should be counselled regarding the pressor effects of sympathomimetic amines and the risk of tachyphylaxis. Also, the use of ephedrine for hypotension prophylaxis is associated with a higher risk of hypertension, compared to when ephedrine is used to treat hypotension.

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.