Guaifenesin how does it work

Elasticity and viscosity are two of the critical properties of sputum rheology. Elasticity is the ability of a material to return to its original shape after deformation; for example, a rubber ball is highly elastic, whereas clay is plastic.

Viscosity is a material's resistance to flow. Honey has a high viscosity and is difficult to pour out of a glass, whereas water has a low viscosity and flows more easily. Mucus is an example of a non-Newtonian fluid, meaning that it has both viscous and elastic properties. Mucus is generally cleared by ciliary motion and is dependent on factors such as the volume and composition of the mucus, adequate periciliary liquid volume, and ciliary beat frequency. This balance can be upset during RTIs, resulting in the overproduction of particular mucins notably MUC5AC and MUC5B and other large polymers within the secretions, including deoxyribonucleic acid, filamentous actin, proteoglycans, and biofilms.

Coughing represents a high-stress high-velocity reflex and so has a direct relationship with viscosity but an inverse relationship with elasticity, meaning that it is easier to expectorate large amounts of viscous mucus than small amounts of elastic mucus. On the other hand, mucus clearance is a low-stress high-frequency force applied by cilia to the airway secretions.

This force has a direct relationship with the elasticity of the substance being moved and has an indirect relationship with the viscosity of the fluid.

Therefore, there are factors favoring mucus clearance from the lung such as a thin mucus layer, high mucus elasticity, and low mucus viscosity, 4 whereas a thick mucus layer, low mucus elasticity, and high mucus viscosity favor clearance through coughing. If the mucus obstruction is in the more distal airways, a drug that enhances mucus clearance is preferable. There are over 50 commercialized compounds purported to have beneficial effects on mucus or its secretion. In this report, Hoffer-Schaefer et al 1 report the effects of guaifenesin at a standardized OTC dose on subjective symptomatology and sputum rheology in adolescents and adults with a productive cough from an upper RTI URTI.

The trial is registered ClinicalTrials. The authors found no difference in any of these 3 sputum properties with guaifenesin compared to a placebo in adolescents and adults with a productive cough secondary to a URTI.

In conclusion, guaifenesin has not been shown in this study to work as an expectorant, as it did not increase the volume of sputum cleared, or as a mucolytic, as it did not alter sputum rheology or the interfacial tension of the sputum, in this cohort of patients compared to a placebo.

The FDA's progressive requirements in demonstrating proof of efficacy for new OTC medications is to be commended and suggests that, in time, increased effort should be required to demonstrate efficacy of already available OTC medications that entered the market prior to the current proof-of-efficacy requirements. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail.

We do not capture any email address. Skip to main content. Editorial Editorials. Clinical pharmacology and patient studies support the clinical utility of guaifenesin in respiratory conditions where mucus hypersecretion is prevalent: acute upper respiratory tract infections URTIs , stable chronic bronchitis, and possibly rhinosinusitis. Guaifenesin has a well-established and favorable safety and tolerability profile in adult and pediatric populations.

Multiple daily doses are needed to maintain h therapeutic effect with immediate-release formulations. Extended-release guaifenesin tablet formulations are available, providing convenience with hourly dosing and portability compared to liquids. Guaifenesin is considered as a safe and effective expectorant for the treatment of mucus-related symptoms in acute URTIs and stable chronic bronchitis. Its clinical efficacy has been demonstrated most widely in chronic respiratory conditions, where excess mucus production and cough are more stable symptoms.

Progress is being made to establish clinical models and measures that are more appropriate for studying symptomatic relief with guaifenesin in acute respiratory infections.

Respiratory conditions have been known throughout most of recorded medical history, and today mortality and morbidity associated with respiratory conditions represent a substantial global health burden. Statistics show over a hundred million people living with chronic respiratory conditions worldwide [ 1 ], while acute respiratory infections are among the most common reasons for physician office visits [ 2 ]. Pathological hypersecretion of mucus is a common feature in many acute and chronic respiratory conditions.

Expectorants are used empirically to treat cough with an underlying cause of pathological mucus, by targeting various mechanisms that promote increased mucus hydration and clearance from the respiratory tract. Guaifenesin, or glyceryl guaiacolate ether GGE , is an oral expectorant and a common ingredient in prescription and over-the-counter OTC medicines for respiratory conditions.

The use of guaifenesin as a natural remedy dates back to the s, when guaiac tree extracts were used by Native Americans to treat various illnesses Table 1. Inclusion in the Monograph established guaifenesin as a safe and effective expectorant for the symptomatic treatment of acute URTIs and also allowed use of the drug in stable chronic bronchitis.

The purpose of this article is to review scientific evidence for the use of guaifenesin in different respiratory conditions and to summarize the key clinical studies. As a single-ingredient product, guaifenesin has an acceptable safety profile in both adult and pediatric populations.

The respiratory tract is covered with a layer of mucus, which maintains airway humidification and acts as a protective barrier to inhaled particles and microorganisms. Mucus entraps inhaled particles and is then transported out of the lungs by the sweeping movements of epithelial cilia—a process termed mucociliary clearance MCC [ 4 ]—before being swallowed or expectorated.

A dynamic balance of production, secretion, and clearance of mucus is needed to maintain airway function and health. Respiratory conditions can dramatically alter airway mucus composition and properties.

Upregulation of mucins, high molecular-weight extracellular mucopolysaccharides that are critical components of mucus, increases mucus viscosity; this can worsen congestion [ 5 ].

Pathological overproduction and hypersecretion of mucus feature prominently in chronic respiratory conditions such as chronic bronchitis, chronic obstructive pulmonary disease COPD and asthma [ 4 , 6 ]. Since excessive respiratory mucus dramatically hinders MCC and serves as a trigger for cough [ 4 ], normalization of pathological mucus is a central goal of many therapeutic interventions in respiratory disease.

Therapy with mucoactive drugs is an important factor in the treatment of respiratory conditions in which mucus hypersecretion is prevalent. A large number of drugs acting directly or indirectly on mucus have been well studied and reviewed [ 5 , 8 — 12 ].

There are four main classes of mucoactive drugs with different mechanisms of action Table 2. Out of these, only mucolytic and expectorant drugs act directly on mucus properties or its secretion. Earlier studies showed that guaifenesin has multiple effects on mucus, such as increasing the volume of bronchial secretions and decreasing mucus viscosity.

This modulation of airway secretions enhances their clearance by promoting more effective expectoration. Guaifenesin may also have direct effects on respiratory tract epithelial cells, including suppressed mucin production, reduced mucus viscoelasticity, and improved MCC [ 13 ].

One study indicated that guaifenesin does not act directly on mucus viscosity [ 14 ]. The effects of guaifenesin are not limited to affecting mucus consistency e. Guaifenesin [3- 2- methoxyphenoxy -1,2-propanediol] has been well characterized chemically [ 17 ].

Animal studies showed that guaifenesin is generally well absorbed and has an established pharmacokinetic profile. The time to reach C max T max in rats was faster when given as an oral bolus 27 min than with gastric, jejunal or cecal infusions min [ 18 ].

Guaifenesin is well absorbed from the human GI tract. Following a single oral dose of guaifenesin in pediatric subjects, C max was reached in approximately 0. In adult subjects, C max was achieved in 1. Once absorbed, guaifenesin is efficiently metabolized and subsequently excreted in the urine. Guaifenesin is not known to interfere with the cytochrome P CYP system, nor is it an inhibitor or inducer of this system.

Guaifenesin appears to undergo both oxidation and demethylation. O-demethylase seems to be the main enzyme for the metabolism of GGE [ 22 , 23 ]. The major metabolites of guaifenesin both inactive are betamethoxyphenoxy-lactic acid [ 21 , 25 ] and hydroxy-guaifenesin [ 22 ]. To date, several mechanisms of action have been described for guaifenesin. It has been postulated that guaifenesin exerts its expectorant activity via a neurogenic mechanism: a stimulation of vagal afferent nerves in the gastric mucosa activates the gastro-pulmonary reflex, and increases the hydration of airway mucus [ 26 , 27 ].

In support of this hypothesis, a study in rats demonstrated that oral but not intravenous guaifenesin administration increased respiratory secretions [ 18 ]. The viscoelastic behavior of bronchial mucus has important consequences for mucociliary clearance. This mucus is an adhesive, viscoelastic gel, the biophysical properties of which are largely determined by entanglements of long polymeric gel-forming mucins: MUC5AC expressed in goblet cells and MUC5B originating from submucosal glands [ 11 ].

Inflammatory airway diseases and infections cause mucus including mucin glycoproteins overproduction and hypersecretion from metaplastic and hyperplastic goblet cells which contributes to mucus obstruction of airways [ 6 ]. Medications that decrease viscoelasticity, such as certain mucolytics, may benefit ciliary clearance.

Recent in vitro studies using differentiated human airway epithelial cells, grown at an air-liquid interface to mimic physiological conditions in the respiratory tract, revealed direct effects of guaifenesin on the airway epithelium [ 13 , 28 ].

At clinically relevant doses, guaifenesin was found to significantly decrease mucin MUC5AC production, mucus viscosity and elasticity, and to enhance MCC [ 13 ]. These results were replicated in another study on airway epithelial cells pre-treated with an inflammatory mediator, IL, to increase secretions prior to treatment with guaifenesin, N-acetylcysteine, or ambroxol [ 28 ].

Guaifenesin was more effective than N-acetylcysteine or ambroxol at increasing MCC rates, inhibiting mucin secretion, and improving mucus rheology. Figure 1 shows some of these putative mechanisms of action Fig. Additional in vivo pharmacology and clinical studies will be needed to further elucidate these findings and determine how these mechanisms can be most effectively recruited to produce clinically relevant effects in the target populations. Putative effects of guaifenesin on mucus in chronic or acute hypersecretory respiratory conditions.

The mucociliary complex can be subdivided into two layers — an upper mucus gel layer containing MUC5AC and MUC5B mucins, and a lower layer of periciliary fluid containing cell surface-tethered mucins.

Mucociliary clearance MCC is effected by the rhythmic sweeping motion of cilia. Prolonged exposure to irritants such as cigarette smoke or allergens can lead to overproduction and hypersecretion of mucus.

Guaifenesin has been postulated to promote mucociliary clearance via a number of mechanisms. Guaifenesin also affects secretion from goblet and Clara cells red stars , resulting in 2 decreased mucin production and secretion green circles, goblet cells; blue squares, Clara cells , and 3 reduced viscoelasticity of mucus, which increases the ability of ciliary movement to remove mucus.

Together these changes serve to enhance MCC and mucus clearance. Panels b-d adapted from Seagrave et al. Studies in patients with chronic bronchitis demonstrated that guaifenesin increases MCC [ 29 ] and reduces sputum viscosity [ 30 ]. Bennett and coworkers compared the effects of guaifenesin and placebo on in vivo MCC by measuring the rate of removal of inhaled radioactive tracer particles from the lungs of healthy, non-smoking adults.

A study in healthy volunteers with a history of sinus disease did not detect significant differences between guaifenesin and placebo treatment in terms of their effects on in vivo nasal MCC [ 33 ]. Guaifenesin has been shown to make coughs more productive [ 34 ], and additionally has been found to inhibit cough reflex sensitivity in subjects with acute URTIs [ 15 , 16 ]. Guaifenesin significantly reduced cough reflex sensitivity in patients with viral URTIs [ 15 , 16 ], but not in healthy volunteers.

The authors suggested that this effect was limited to patients with URTIs due to their transiently increased cough receptor sensitivity. Details of clinical studies mentioned in this section are in Table 3.

Despite the large number of clinical studies on different clinical aspects of guaifenesin therapy, its expectorant indication is currently the only one that the FDA considers to be supported by sufficient medical evidence. The Monograph indication for guaifenesin is limited to symptomatic treatment of acute URTIs and stable chronic bronchitis [ 3 ].

The FDA approved labels for guaifenesin include an OTC label for its use in the treatment of chest congestion associated with an URTI but also a professional label for chest congestion associated with stable chronic bronchitis for its detailing to healthcare professionals.

This professional label indication mirrors the outcome of clinical studies conducted on chronic bronchitis patients. The exact wording of the indications is listed below:. A review of the literature supporting the clinical utility of guaifenesin shows effects across three categories of respiratory conditions: chronic bronchitis and chronic respiratory conditions Table 4 , URTIs Table 5 , and rhinosinusitis Table 6.

Almost all studies discussed here were conducted in adults, with the exception of one published study in children on the use of guaifenesin for relieving cough symptoms [ 35 ]. It should be noted that stable chronic respiratory conditions, such as chronic bronchitis, have proved more reliable as clinical models for studying the effects of expectorants and other mucoactive drugs.

Mucus production and associated cough symptoms tend to be more stable in chronic respiratory conditions, allowing the effects of guaifenesin to be observed more consistently. The inclusion of guaifenesin in the Final OTC Monograph was essentially supported by four clinical studies in patients with chronic bronchitis [ 36 — 39 ].

All of these definitive studies demonstrated statistically superior efficacy of guaifenesin versus controls in improving ease of expectoration, decrease in sputum surface tension and viscosity, or reduction in the frequency and severity of cough Table 4.

Although results for cough assessments in patients with chronic bronchopulmonary disease were mixed, guaifenesin-treated patients reported increased sputum volume compared with placebo, as well as greater ease of expectoration [ 41 ]. These findings are consistent with an earlier study on objective sputum changes in patients with chronic bronchitis; guaifenesin was found to significantly decrease sputum adhesiveness and quantity dry weight , and was also reported to improve expectoration [ 30 ].

The efficacy of guaifenesin as an expectorant has also been examined in the context of acute URTIs Table 5. In adults with acute URTIs, guaifenesin significantly reduced sputum thickness and quantity compared to placebo [ 41 ].

A large placebo-controlled pilot study explored a range of objective and subjective outcome measures in patients with acute URTIs. The most promising measures included a daily diary for patient-reported outcome PRO parameters.

These described symptoms such as severity of chest congestion, mucus thickness and cough. Some of these 11 exploratory parameters showed strong trends or statistically significant differences between guaifenesin and placebo. A PRO validation process served to qualify more focused subsets of 4 and 8 questions. To explore effects on sputum as objective endpoints, laboratory analyses were performed on patient mucus samples from the pilot study. The laboratory analyses could not demonstrate differences in mucus properties with guaifenesin compared to placebo; however, it should be noted that methodological issues with mucus sample collection and shipping were present, raising some questions about the interpretation of the laboratory results [ 44 ].

Guaifenesin was reported to be effective for improving symptomatic rhinitis and sinusitis by decreasing nasal congestion and postnasal discharge in immunocompromised HIV positive patients [ 45 , 46 ]. Despite some conflicting data available, some patients with rhinitis benefit from using guaifenesin [ 12 ]. As a single agent, guaifenesin has a well-established and favorable safety and tolerability profile.

Its safety record is supported by data from published clinical studies and a history of post-marketing surveillance safety reports covering more than 50 years in the US and around the world. Common side effects reported for the drug include dizziness, headache, and gastrointestinal disturbances at high doses [ 17 ]. Guaifenesin had the lowest frequency of mentions for non-fatal AEs by system organ class SOC at estimated supra-therapeutic and even at estimated unknown dosing; and the second lowest frequency of mentions for non-fatal AEs by SOC at estimated therapeutic dosing.

The few published reports of serious adverse events related to the use of guaifenesin have mostly been in the context of overdose and use as part of multiple-drug combinations for various cough and cold indications.

Published reports include renal stone formation with chronic guaifenesin overdose [ 49 ], and acute fatal intoxication by a combination of guaifenesin, diphenhydramine, and chlorpheniramine, although the relative contribution of guaifenesin to the fatality could not be determined [ 50 ].

Pregnancy category C status for GGE was determined by the FDA based on the absence of definitive studies assessing potential risks to the fetus [ 3 , 51 ]. Results of a recently published study in female, pregnant rats, after testing very high doses of guaifenesin, suggest that the risk of fetal abnormalities cannot be ruled out [ 52 ].

The medical literature and safety databases do not show meaningful signals suggesting a significant risk of fetal development issues after pregnant women used guaifenesin. Store it at room temperature and away from excess heat and moisture not in the bathroom. Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them.

However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. It is important to keep all medication out of sight and reach of children as many containers such as weekly pill minders and those for eye drops, creams, patches, and inhalers are not child-resistant and young children can open them easily.

To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location — one that is up and away and out of their sight and reach. In case of overdose, call the poison control helpline at If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at It is important for you to keep a written list of all of the prescription and nonprescription over-the-counter medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements.

You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Guaifenesin pronounced as gwye fen' e sin. Why is this medication prescribed? How should this medicine be used? Other uses for this medicine What special precautions should I follow? What special dietary instructions should I follow? What should I do if I forget a dose? What side effects can this medication cause? What should I know about storage and disposal of this medication? Brand names Brand names of combination products.

Other uses for this medicine. What special precautions should I follow? Before taking guaifenesin, tell your doctor and pharmacist if you are allergic to guaifenesin, any other medications, or any of the ingredients in the guaifenesin product you plan to take.

Check the package label for a list of the ingredients.