What is the Role of Over 100 Excipients in Over the Counter (OTC) Cough Medicines?

Most medicines are white bitter powders that are formulated as tablets and capsules but cough medicines are an exception where the taste and appearance of the medicine are more important to the patient than the pharmacology of the active ingredient. Excipients are generally defined as any ingredient in a medicine other than the active ingredient. In most medicines excipients play a supportive role in delivering the medicine, but in the case of cough medicines, excipients have more important and complex roles and they can also be the main active ingredient of the cough medicine as menthol, glycerol, and sugars, which are declared as active ingredients. This review searched the United Kingdom electronic medicines compendium (emc) and found over 100 excipients in 60 different liquid formulations of over the counter cough medicines. The excipients were divided into functional groups: sweeteners, thickeners, flavors, colors, antimicrobials, and buffers, and the incidence and function of the different excipients is discussed. When considering the efficacy of a cough medicine, clinicians and pharmacists tend to think of the pharmacology of antitussives such as dextromethorphan or expectorants such as guaifenesin, and they rarely consider the role of excipients in the efficacy of the medicine. This review discusses the functions and importance of excipients in cough medicines and provides some new information for clinicians, pharmacists, and all interested in the treatment of cough when considering the composition and efficacy of a cough medicine.

Antitussive drugs--past, present, and future.

Cough remains a serious unmet clinical problem, both as a symptom of a range of other conditions such as asthma, chronic obstructive pulmonary disease, gastroesophageal reflux, and as a problem in its own right in patients with chronic cough of unknown origin. This article reviews our current understanding of the pathogenesis of cough and the hypertussive state characterizing a number of diseases as well as reviewing the evidence for the different classes of antitussive drug currently in clinical use. For completeness, the review also discusses a number of major drug classes often clinically used to treat cough but that are not generally classified as antitussive drugs. We also reviewed a number of drug classes in various stages of development as antitussive drugs. Perhaps surprising for drugs used to treat such a common symptom, there is a paucity of well-controlled clinical studies documenting evidence for the use of many of the drug classes in use today, particularly those available over the counter. Nonetheless, there has been a considerable increase in our understanding of the cough reflex over the last decade that has led to a number of promising new targets for antitussive drugs being identified and thus giving some hope of new drugs being available in the not too distant future for the treatment of this often debilitating symptom.

Efficacy and tolerability of treatments for chronic cough: a systematic review and meta-analysis.

BACKGROUND: Understanding the comparative effectiveness of treatments for patients with unexplained or refractory cough is important to increase awareness of proven therapies and their potential adverse effects in this unique population. METHODS: We performed a literature search for English-language studies published up to June 2012 that compared symptomatic therapies for chronic cough. Two investigators screened each abstract and full-text article for inclusion, abstracted data, and rated quality. Meta-analysis with random-effects models was used to summarize effects of treatments. RESULTS: We identified 49 studies (3,067 patients) comprising 68 therapeutic comparisons. Of the studied agents, opioid and certain nonopioid and nonanesthetic antitussives had demonstrated efficacy for chronic cough in adults. Compared with placebo, effect sizes (standardized mean differences for cough severity and rate ratios for cough frequency) for opioids were 0.55 (95% CI, 0.38-0.72; P < .0001) and 0.57 (95% CI, 0.36-0.91; P = .0260), respectively. For dextromethorphan, effect sizes were 0.37 (95% CI, 0.19-0.56; P = .0008) and 0.40 (95% CI, 0.18-0.85; P = .0248), respectively. The overall strength of evidence was limited by inconsistency and imprecision of results and by small numbers of direct comparisons. Nonpharmacologic therapies and the management of cough in children were infrequently studied. CONCLUSIONS: Although evidence is limited, opioid and certain nonopioid and nonanesthetic antitussives demonstrated efficacy for treating chronic cough in adults. There is a need for further studies in patients with unexplained or refractory cough as well as for more systematic study designs, assessment of patient-centered outcomes, and reporting.

Structural relationships, distribution and biological activities of stemona alkaloids.

Stemona alkaloids represent a unique class of natural products exclusively isolated from the monocotyledonous family Stemonaceae comprising three genera mainly distributed in southeast Asia. Structurally the alkaloids are characterised by a pyrrolo[1,2- a]azepine nucleus usually linked with two carbon chains mostly forming terminal lactone rings. Based on biosynthetic considerations and their various distribution the present review describes 82 Stemona alkaloids grouped into three skeletal types. Due to different carbon chains attached to C-9 of the pyrroloazepine nucleus they were classified into stichoneurine-, protostemonine- and croomine-type alkaloids. The genera Croomia and Stichoneuron only accumulate croomine or stichoneurine derivatives, respectively, whereas the genus Stemona produces all three types of alkaloids. However, species-specific accumulation trends towards certain structural types represent valuable chemosystematic criteria. Bioassays with larvae of Spodoptera littoralis exhibited very high insect toxicity for the roots of Stemona species containing certain protostemonine derivatives, especially didehydrostemofoline, whereas those with dominating stichoneurine or croomine derivatives showed low toxicity but sometimes remarkable repellence due to an accumulation of tuberostemonine. Tuberostemonine also showed effects on the motility of helminth worms and reduced the excitatory transmission at the crayfish neuromuscular junction. Significant antitussive activity was shown for the stereoisomeric neotuberostemonine in guinea-pig after cough induction by citric acid aerosol stimulation. Studies on structure-activity relationship with seven related compounds revealed that the saturated tricyclic pyrrolobenzazepine nucleus of tuberostemonines is the prerequisite for antitussive activity.

Levocloperastine in the treatment of chronic nonproductive cough: comparative efficacy versus standard antitussive agents.

The medical and social impact of cough is substantial. Current antitussive agents at effective doses have adverse events such as drowsiness, nausea and constipation that limit their use. There is also recent evidence that standard antitussive agents, such as codeine, may not reduce cough during upper respiratory infections. Therefore, there is a need for more effective and better-tolerated agents. The efficacy of levocloperastine, a novel antitussive, which acts both centrally on the cough center and on peripheral receptors in the tracheobronchial tree in treating chronic cough, was compared with that of other standard antitussive agents (codeine, levodropropizine and DL-cloperastine) in six open clinical trials. The studies enrolled patients of all ages with cough associated with various respiratory disorders including bronchitis, asthma, pneumonia and chronic obstructive pulmonary disease. Levocloperastine significantly improved cough symptoms (intensity and frequency of cough) in all trials, and improvements were observed after the first day of treatment. In children, levocloperastine reduced nighttime awakenings and irritability, and in adults it was effective in treating cough induced by angiotensin-converting enzyme inhibitors. When compared with other antitussive agents, levocloperastine had improved or comparable efficacy, with a more rapid onset of action. Importantly, no evidence of central adverse events was recorded with levocloperastine, whereas drowsiness was reported by a significant number of patients receiving codeine. Levocloperastine is an effective antitussive agent for the treatment of cough in patients of all ages. It has a more rapid onset of action than standard agents with an improved tolerability profile.

Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-counter human use; final monograph for combination drug products. Final rule.

The Food and Drug Administration (FDA) is issuing a final rule in the form of a final monograph that establishes conditions under which over-the-counter (OTC) cold, cough, allergy, bronchodilator, and antiasthmatic (cough-cold) combination drug products are generally recognized as safe and effective and not misbranded as part of its ongoing review of OTC drug products. FDA is issuing this final rule after considering public comments on the agency's proposed regulation (tentative final monograph) and new data and information on OTC cough- cold combination drug products that have come to the agency's attention.

The pharmacological treatment of voice disorders.

The increasing diversity of purpose-built, synthetic and biogenetically engineered pharmaceuticals has led to a revival of interest in the pharmacological possibilities for the treatment of voice disorders. Where dysphonias arise as a part of a pathophysiological process, the pharmacological treatment of either the pathology or its associated symptoms may improve dysphonic voicing patterns. The treatment of symptoms such as cough and vocal fatigue are discussed together with treatment of allergic and other causes of inflammation or stiffening of the vocal tract. The pharmacological logical treatment of dysphonia due to defective neuromuscular control in dyskinetic and dystonic conditions is also discussed. Dysphonic voicing patterns are commonly multifactorial, and the author wishes to highlight problems encountered when attempting to adjust the performance of the vocal tract: imprecise targeting of the pathophysiological problems either by the physician or by the drug employed, and the systemic and attendant side-effects of drugs which may be thought to be appropriate.