[Review of taste masking techniques in Chinese patent medicine].

Single herbs and Chinese patent medicine preparations often have bad taste, such as bitterness and astringency, which is one of the key factors affecting patients' medication compliance, and would affect the therapeutic effect and restrict the extensive application in clinical practice. Therefore, how to make use of taste masking techniques to improve the bad taste of traditional Chinese medicines has become an important project. Through the collection and summarization of Chinese and foreign journals and papers in recent years, this paper discussed the generation mechanism of bitter taste, the new methods of masking bitter taste and the evaluation me-thods of bitter taste, in order to provide references for the taste masking of Chinese patent medicines preparations.

Understanding the risk of emerging bacterial resistance to over the counter antibiotics in topical sore throat medicines.

AIMS: The aims of this study were to explore the development of bacterial resistance and cross-resistance in four common human pathogens following realistic exposure to antibiotics found in over-the-counter (OTC) sore throat medicines: gramicidin, neomycin, bacitracin and tyrothricin. METHODS AND RESULTS: Bacterial exposure to in-use (concentration in the product before use) and diluted concentration (i.e. during use) of antibiotic where conducted in broth for 24 h or until growth was visible. The changes in bacterial susceptibility profile before and after exposure was determined using standardized ISO microdilution broth. Antibiotic testing was performed according to EUCAST guidelines. We demonstrated that test bacteria were able to survive exposure to the in-use concentrations of some antibiotics used in OTC medicines. Exposure to during use concentrations of bacitracin resulted in stable increase in minimal inhibitory concentration (MIC) (>8-fold) in Staphylococcus aureus and Acinetobacter baumannii. Exposure to tyrothricin resulted in a stable increase in MIC (2·4-fold) in Klebsiella pneumoniae, and exposure to neomycin resulted in a stable increase MIC (5000-fold higher than the baseline) in Streptococcus pyogenes. Clinical cross-resistance to other antibiotics (ciprofloxacin, fusidic acid, gentamicin, cefpodoxime, amoxicillin/clavulanic acid and cefotaxime) was also demonstrated following exposure to bacitracin or tyrothricin. Bacitracin exposure lead to a stable bacterial resistance after 10 passages. CONCLUSIONS: Our results indicate that OTC antibiotic medicines have the potential to drive resistance and cross-resistance in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: Tackling antibiotic resistance is a high worldwide priority. It is widely accepted that the overuse and misuse of antibiotics increase the risk of the development and spread of antibiotic resistance within communities. A number of OTC sore throat products, widely available across the world for topical use in respiratory indications, contain locally delivered antibiotics. Our findings showed that these antibiotics in OTC medicines present a risk for emerging cross-resistance in a number of bacterial respiratory pathogens.

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.

ARTICLE: Colloidal Oatmeal Part I: History, Basic Science, Mechanism of Action, and Clinical Efficacy in the Treatment of Atopic Dermatitis.

Colloidal oatmeal has a long-standing history in the treatment of dermatologic disease. It is composed of various phytochemicals, which contribute to its wide-ranging function and clinical use. It has various mechanisms of action including direct anti-inflammatory, anti-pruritic, anti-oxidant, anti-fungal, pre-biotic, barrier repair properties, and beneficial effects on skin pH. These have been shown to be of particular benefit in the treatment of atopic dermatitis. In Part 1 of this two-part series, we will explore the history of colloidal oatmeal, basic science, mechanism of action, and clinical efficacy in the treatment of atopic dermatitis. J Drugs Dermatol. 2020;19:10(Suppl):s4-7.

Factors influencing pharmacists' over-the-counter drug recommendations.

BACKGROUND: Self-care is a growing trend all over the world, and pharmacists have a major role in it since they are the most easily accessible medical experts. OBJECTIVES: Our aim was to investigate factors influencing pharmacists' over-the-counter (OTC) drugs recommendations in Croatia. SETTING: A random sample of 565 (50%) of all pharmacies in Croatia. METHODS: A cross-sectional study with a five-point Likert scale online questionnaire covering medical and non-medical factors influencing OTC drug recommendation was distributed in October 2017 to a random sample of pharmacies. RESULTS: 206/565 (response rate 36.5%) responses were collected. The most important factors influencing pharmacists' recommendation were: composition of the OTC product and its active component (4.76±0.47), scientific evidence of effectiveness (4.54±0.60), feedback from the patients (4.32±0.61) and information from professional journals (4.22±0.67). On average, medical factors had greater importance (4.5±0.58) for pharmacists' OTC recommendation than marketing (3.18±0.84) and social factors (3.15±0.79). Female pharmacists appeared less inclined to recommend an OTC product based on advice of other pharmacists (OR=0.61, CI=0.43 to 0.86, p=0.005) and pharmacists working directly in a pharmacy attached more importance to active components of OTC products during their OTC product counselling (OR=2.28, CI=0.92 to 5.65, p=0.03). CONCLUSION: It is vital to know that pharmacists' OTC recommendations are mainly influenced by medical factors and to a lesser degree by marketing and social factors.

Pharmacological Aspects of Over-the-Counter Opioid Drugs Misuse.

Several over-the-counter (OTC) drugs are known to be misused. Among them are opioids such as codeine, dihydrocodeine, and loperamide. This work elucidates their pharmacology, interactions, safety profiles, and how pharmacology is being manipulated to misuse these common medications, with the aim to expand on the subject outlined by the authors focusing on abuse prevention and prevalence rates. The reviewed literature was identified in several online databases through searches conducted with phrases created by combining the international non-proprietary names of the drugs with terms related to drug misuse. The results show that OTC opioids are misused as an alternative for illicit narcotics, or prescription-only opioids. The potency of codeine and loperamide is strongly dependent on the individual enzymatic activity of CYP2D6 and CYP3A4, as well as P-glycoprotein function. Codeine can also be utilized as a substrate for clandestine syntheses of more potent drugs of abuse, namely desomorphine ("Krokodil"), and morphine. The dangerous methods used to prepare these substances can result in poisoning from toxic chemicals and impurities originating from the synthesis procedure. OTC opioids are generally safe when consumed in accordance with medical guidelines. However, the intake of supratherapeutic amounts of these substances may reveal surprising traits of common medications.

Effect of Over-the-counter Whitening Products associated or Not with 10% Carbamide Peroxide on Color Change and Microhardness: in vitro Study.

Aim: The purpose of this in vitro study was to evaluate the color and microhardness of teeth subjected to different over-the-counter (OTC) whitening products in association or not with 10% carbamide peroxide (10% CP). Materials and methods: Enamel-dentin specimens (n = 210) were obtained from bovine incisors and stained. Half of the specimens were then subjected to daily cycles of staining (5 minutes), 10% CP bleaching (8 hours) in association with OTC products, and artificial saliva storage until complete 24 hours, for 2 weeks; the other half was subjected to daily cycles of staining, OTC treatment, and storage in artificial saliva for 12 weeks. The specimens were divided into 14 groups according to the OTC: CP-Water and Water (deionized water); CP-Listerine and Listerine (whitening mouth rinse); CP-Brushing and Brushing (mechanical brushing); CP-Colgate and Colgate (conventional toothpaste), CP-ColgateW and ColgateW, CP-OralBW and OralBW, and CP-CloseUpW and CloseUpW (whitening toothpaste). After staining and whitening, color and microhardness were measured. Data were submitted to analysis of variance (ANOVA) and the Tukey's test for multiple comparisons for color analysis and the paired t-test for microhardness analysis. Results: The CP and CloseUpW groups had the largest color change (AE00). The teeth treated with Colgate increased significantly in microhardness after whitening. Conclusion: The association of 10% CP with OTC whitening agents did not increase the whitening effect or microhardness. The OTC agents containing hydrogen peroxide and abrasives had a similar effect to one another but were not as effective as the CP groups and the subgroup brushed only with blue covarine toothpaste. Clinical significance: The current study provides information about the mechanism of OTC whitening products. None of the whitening agents evaluated damaged the enamel when used according to the manufacturers' instructions. The use of toothpaste containing hydrogen peroxide or abrasives cannot provide a whitening effect similar to at-home bleaching, and this does not improve with the association with 10% CP. However, toothpaste containing blue covarine has a satisfactory whitening effect immediately after brushing. Keywords: Laboratory research, Mouthwashes, Tooth bleaching, Toothpaste.

[Establishment and verification of risk assessment scale for clinical safety medication of aconitine].

Chinese patent medicine containing aconitine is the key in clinical rational drug use. These drugs contain Chuanwu, Caowu or Fuzi, and Aconitum brachypodum with functions of expelling wind-dampness or tonifying Yang, all of which shall be used by strictly following the indications and dosage. However, there are many kinds of such drugs. Not only the unfamiliar knowledge of some Chinese and Western physicians about the characteristics of them, but also the combination of multiple drugs from different clinical departments, would increase the risk of aconitine poisoning. Based on the previous research, this paper proposed three core elements "syndrome differentiation-dosage differentiation-toxicity differentiation" from the prescription review and pharmacy consulting work, and objective and standardized evaluation was used to build a risk assessment scale containing 3 categories, 9 items and 36 indicators with Hulisan Jiaonang and Qufeng Zhitong Jiaonang as the example. This scale was used to evaluate the risk of a therapeutic regimen before and after the implementation. According to the verification of the existing adverse reaction cases, the risk assessment scale can be used to indicate the risk of drug treatment program and identify the risk level of drug treatment status. This paper tried to provide a methodological paradigm for scientific and objective evaluation on the safety of Chinese patent medicines, and help to identify the key links and risk prevention in the rational use by Chinese medicine physicians and pharmacists.

Inhibitory Effects of Gastrointestinal Drugs on CYP Activities in Human Liver Microsomes.

OTC drugs have an important role in self-medication. However, the pharmacokinetic properties of some OTC drugs have not been fully investigated and reports concerning their drug interactions are insufficient. Several gastrointestinal drugs are available as OTC drugs. Because of their pharmacological properties, these drugs are often used concomitantly with other drugs. Therefore, it is important to predict the possible drug interactions among these drugs. In the current study, we investigated the inhibitory effects of five gastrointestinal drugs, namely loperamide, oxethazaine, papaverine, pirenzepine, and trimebutine, on CYP activities in human liver microsomes. Furthermore, we calculated the ratio of the intrinsic clearance of each CYP substrate in the presence or absence of the gastrointestinal drugs. The possibility of drug interactions in vivo was predicted by cut-off criteria. CYP3A4 activity was markedly inhibited by trimebutine, papaverine, and oxethazaine. Their inhibitory properties were competitive and the Ki values were 6.56, 12.8, and 3.08 µM, respectively. Alternative R values of CYP3A4 exceeded the cut-off level. These results suggested that drug interactions mediated by CYP3A4 may occur during treatment with these gastrointestinal drugs, necessitating the confirmation of the clinical significance of these drug interactions to prevent unexpected adverse effects.

Recreational use of dextromethorphan, "Robotripping"-A brief review.

BACKGROUND: Dextromethorphan (DXM) in combination with antihistamines and/or pseudoephedrine is widely available as an over-the counter remedy commonly used for relief of colds and cough. In supra-therapeutic amounts, DXM has psychoactive effects. These cough preparations have been adopted by many young users of recreational drugs for these effects. OBJECTIVES: This paper aims to highlight the increasingly prevalent practice of Robotripping, review pharmacokinetic and dynamic data and discuss potential tolerance and withdrawal from the substance as well as treatment modalities. METHODS: A Medline search (1985-2015) for literature concerning the DXM was conducted. This was supplemented by references gleaned from recent epidemiological surveys and credible online sources to ensure most up to date information is gathered. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Use in amounts exceeding those recommended, a practice known as "Robotripping", may result in a toxidrome of psychomotor agitation, hallucinations and paranoia best characterized as Intoxication Delirium. Increasing misuse places greater numbers at risk. Providers should be alert to such presentations and be aware of methods for managing the symptoms. With chronic use, tolerance and withdrawal has been noted along with prolonging psychiatric sequelae. (Am J Addict 2016;25:374-377).

Over-the-counter anti-oxidant therapies for use in multiple sclerosis: A systematic review.

BACKGROUND: Anti-oxidant compounds that are found in over-the-counter (OTC) supplements and foods are gaining interest as treatments for multiple sclerosis (MS). They are widely used by patients, sometimes without a clear evidence base. OBJECTIVE: We conducted a systematic review of animal and clinical research to determine the evidence for the benefits of OTC anti-oxidants in MS. METHODS: Using predefined criteria, we searched key databases. Two authors scrutinized all studies against inclusion/exclusion criteria, assessed study risk-of-bias and extracted results. RESULTS: Of the 3507 titles, 145 met criteria and included compounds, α(alpha)-lipoic acid (ALA), anti-oxidant vitamins, Ginkgo biloba, quercetin, resveratrol and epigallocatechin-3-gallate (ECGC). The strongest evidence to support OTC anti-oxidants was for compounds EGCG and ALA in animal models; both consistently showed anti-inflammatory/anti-oxidant effects and reduced neurological impairment. Only vitamin E, Ginkgo biloba and ALA were examined for efficacy in pilot clinical trials with either conflicting evidence or evidence of no benefit. CONCLUSION: OTC anti-oxidants EGCG and ALA show the most consistent benefit, however only in preclinical studies. There is no evidence that they alter MS relapses or progression. Future work should focus on testing more of these therapies for clinical efficacy before recommending them to MS patients.

The Case of Pharmacological Neuroenhancement: Medical, Judicial and Ethical Aspects from a German Perspective.

Pharmacological neuroenhancement (PN) describes the use of psychoactive drugs for the purpose of enhancing cognition (e. g., fatigue, concentration, memory etc.) by healthy subjects without medical need. Drugs used for this purpose can be divided into freely available, over-the-counter drugs (e. g., methylxanthines such as caffeine), prescription drugs (e. g., antidementia drugs, methylphenidate) and illicit drugs (e. g., illicit amphetamines). Clinical studies have shown that the aforementioned substances only have limited pro-cognitive effects and have considerable safety risks and side effects.The German judicial perspective shows legal differences between substances (drugs, food, food supplements, fortified food) that can be bought in a supermarket, drugs that can be bought in a pharmacy as over-the-counter- (OTC-) drugs, drugs with or without the need for a prescription and illicit drugs. Supermarket drugs and fortified food can be sold freely and follow the general rules of civil and penal law; regarding acquisition, parents are responsible for their children. OTC drugs require special information about therapy. Regarding prescription drugs, there are legal problems caused by an off-label use and the non-medical purposes of PN drugs. Furthermore, prescription stimulants for PN are governed by the specialized law for narcotics, and their use might be punished. Beyond the general lack of rules for regulation for PN drug use there are specific needs for prevention (e. g., control of the black market, etc.).Possible future policy will depend, among others, on the probability with which effective PN drugs with an acceptable risk-benefit ratio will be available, on individual and societal implications, and on public opinion towards PN. While 4 different general policy scenarios can be identified, it is important to advance a broad societal debate on PN to collect relevant empirical data and to address enhancement-related conceptual issues.

Acute over-the-counter pharmacological intervention does not adversely affect behavioral outcome following diffuse traumatic brain injury in the mouse.

Following mild traumatic brain injury (TBI), patients may self-treat symptoms of concussion, including post-traumatic headache, taking over-the-counter (OTC) analgesics. Administering one dose of OTC analgesics immediately following experimental brain injury mimics the at-home treated population of concussed patients and may accelerate the understanding of the relationship between brain injury and OTC pharmacological intervention. In the current study, we investigate the effect of acute administration of OTC analgesics on neurological function and cortical cytokine levels after experimental diffuse TBI in the mouse. Adult, male C57BL/6 mice were injured using a midline fluid percussion (mFPI) injury model of concussion (6-10 min righting reflex time for brain-injured mice). Experimental groups included mFPI paired with either ibuprofen (60 mg/kg, i.p.; n = 16), acetaminophen (40 mg/kg, i.p.; n = 9), or vehicle (15% ethanol (v/v) in 0.9% saline; n = 13) and sham injury paired OTC medicine or vehicle (n = 7-10 per group). At 24 h after injury, functional outcome was assessed using the rotarod task and a modified neurological severity score. Following behavior assessment, cortical cytokine levels were measured by multiplex ELISA at 24 h post-injury. To evaluate efficacy on acute inflammation, cortical cytokine levels were measured also at 6 h post-injury. In the diffuse brain-injured mouse, immediate pharmacological intervention did not attenuate or exacerbate TBI-induced functional deficits. Cortical cytokine levels were affected by injury, time, or their interaction. However, levels were not affected by treatment at 6 or 24 h post-injury. These data indicate that acute administration of OTC analgesics did not exacerbate or attenuate brain-injury deficits which may inform clinical recommendations for the at-home treated mildly concussed patient.

Substances used and prevalence rates of pharmacological cognitive enhancement among healthy subjects.

Pharmacological "cognitive enhancement" (CE) is defined as the use of any psychoactive drug with the purpose of enhancing cognition, e.g. regarding attention, concentration or memory by healthy subjects. Substances commonly used as CE drugs can be categorized into three groups of drugs: (1) over-the-counter (OTC) drugs such as coffee, caffeinated drinks/energy drinks, caffeine tablets or Ginkgo biloba; (2) drugs being approved for the treatment of certain disorders and being misused for CE: drugs to treat attention-deficit/hyperactivity disorder (ADHD) such as the stimulants methylphenidate (MPH, e.g. Ritalin(®)) or amphetamines (AMPH, e.g. Attentin(®) or Adderall(®)), to treat sleep disorders such as modafinil or to treat Alzheimer's disease such as acetylcholinesterase inhibitors; (3) illicit drugs such as illicit AMPH, e.g. "speed", ecstasy, methamphetamine (crystal meth) or others. Evidence from randomized placebo-controlled trials shows that the abovementioned substances have limited pro-cognitive effects as demonstrated, e.g. regarding increased attention, increased cognitive speed or shortening of reaction times, but on the same time poses considerable safety risks on the consumers. Prevalence rates for the use of CE drugs among healthy subjects show a broad range from less than 1 % up to more than 20 %. The range in prevalence rates estimates results from several factors which are chosen differently in the available survey studies: type of subjects (students, pupils, special professions, etc.), degree of anonymity in the survey (online, face-to-face, etc.), definition of CE and substances used/misused for CE, which are assessed (OTC drugs, prescription, illicit drugs) as well as time periods of use (e.g. ever, during the past year/month/week, etc.). A clear and comprehensive picture of the drugs used for CE by healthy subjects and their adverse events and safety risks as well as comprehensive and comparable international data on the prevalence rates of CE among healthy subjects are of paramount importance for informing policy makers and healthcare professionals about CE.

The effect of three whitening oral rinses on enamel micro-hardness.

The purpose of this study was to determine the effect on human enamel micro-hardness of three over-the-counter whitening oral rinses available in South Africa. Enamel fragments were gathered into three groups of 15 each. One group was exposed to Colgate Plax Whitening Blancheur, the second group to White Glo 2 in 1 and the third to Plus White, in each case for periods recommended by the respective manufacturers. Surface micro-hardness of all groups was measured before and after a 14 day treatment period. pH levels of the oral rinses were also determined with a combination pH electrode. Pre- and post- treatment data were analysed by the Wilcoxon Signed Rank Sum Test. According to the micro-hardness values no significant (p > 0.05) enamel damage was found as a result of treatment. However, it was observed that Colgate Pax and White Glo decreased the enamel hardness, an early sign of enamel damage, while Plus White showed a small increase in hardness. The three whitening oral rinses on the South African market do not damage the tooth enamel significantly when used as recommended by the manufacturers. However, extending the contact period and increasing the frequency of application might lead to damage of enamel.

Blockade of melanin synthesis, activation and distribution pathway by a nonprescription natural regimen is equally effective to a multiple prescription-based therapeutic regimen.

BACKGROUND: Disorders characterized by cutaneous hyperpigmentation (HP) are among the most common complaints in dermatologists' offices. These patients are also some of the most difficult to treat since current therapeutic regimens have high irritation rates and mediocre efficacy. Moreover, current regimens have the potential to induce post-inflammatory HP (PIH), a secondary disease that is more difficult to treat. OBJECTIVE: To measure the effectiveness of a novel blend of primarily natural ingredients that inhibits all but one of the steps in melanin synthesis, activation and distribution. Three common types of HP were treated and compared with one of the most commonly prescribed available regimens. This comprises two prescription products and two nonprescription products containing known depigmenting lightening ingredients. MATERIALS AND METHODS: The initial trial consisted of 56 females of 3 different races were treated in a 3-armed parallel, investigatorblinded prospective controlled clinical trial of 18 weeks duration. The treatment phase was 12 weeks long, followed by a 6 week, nontreatment regression phase. This trial was conducted in the winter at over 6,000 feet above sea level. The natural ingredient (NI) blend consists of two cosmeceutical products together containing 22 ingredients. A second 1-year open trial of 31 panelists of 3 races was instituted to document continual improvement using both NI products without irritation and sensitization. RESULTS: The novel herbal blend regimens had comparable efficacy in treating HP and preventing rebound of mottled HP, dyschromia and melasma as the commercial regimen containing two prescription products. The 12-month open study demonstrated continued visible improvement of the HP with NI regimens without irritation and sensitization. CONCLUSION: The novel primarily natural ingredient product regimens are equally effective in treating three types of cutaneous HP as is a regimen containing prescription hydroquinone 4%, tretinoin 0.05% and two nonprescription leave on products.

Efficacy of OTC analgesics.

For many 'over-the-counter' (OTC) analgesics, there is little information available about their relative efficacy. We have examined information available in a series of Cochrane reviews of single doses of analgesic drugs in acute pain and migraine for its relevance for analgesic products commonly available without prescription, at doses generally equivalent to two tablets. Pain following third molar extraction was used as a homogeneous acute pain model; with the outcome of at least 50% maximum pain relief over 6 h. For many OTC drugs, there was no information available. For some OTC drugs, there was at least some information available either for the marketed product itself, or from studies that used the same doses of drug or drugs. For acute pain, data from third molar extraction studies showed that several OTC products were highly efficacious, principally non-steroidal anti-inflammatory drugs (ibuprofen, naproxen, diclofenac) and combination products based on ibuprofen; aspirin and paracetamol-based products were less efficacious. Fixed-dose combinations, especially those with ibuprofen, provided high levels of analgesia. For migraine headache, the outcome used was pain initially moderate or severe becoming no worse than mild pain (no pain, mild pain) at 2 h. Single-dose ibuprofen 400 mg was better than aspirin and paracetamol.

Headache: insight, understanding, treatment and patient management.

Tension-type headache and migraine are the most frequent primary headaches. Diagnosis is based on the patient's history and a normal neurological examination. Most patients with these two headache entities treat headache episodes with over-the-counter analgesics or non-steroidal anti-inflammatory drugs (NSAIDs). There is good scientific evidence from randomised, placebo-controlled trials indicating that aspirin, ibuprofen, ketoprofen, diclofenac and naproxen are effective in tension-type and migraine headache. Paracetamol seems to be less effective. In patients with migraine who do not respond to analgesics or NSAIDs, triptans should be prescribed. Frequent primary headaches should not be treated with frequent intake of analgesics or triptans. In these cases, preventive therapy needs to be implemented.