Koronavírus-világjárvány - a COVID-19-kaleidoszkóp ma (2022. május).

The article attempts to review the principal epidemiological data of the coronavirus pandemic (COVID-19) based on the rapidly changing and expanding international and domestic literature. The review covers the so-called "long COVID-19" as well as the latest pharmacological and immunotherapeutic developments. The manuscript deals with the future of innovative vaccinology, the so-called 'pan-vaccines' developed through artificial intelligences and nanotechnology. Orv Hetil. 2022; 163(24): 935-942.

Self-medication and drug misuse

Self-medication means to take drugs without getting permission from a doctor or without following the advice of a pharmacist. The drug could be bought without prescription in pharmacy or be available in family pharmacy. Self-medication drugs are considered to be safe for an appropriate use for the treatment of pathologies classed as "minor”. However, data about their efficacy and risk remain insufficient and non transparent. The authors describe the danger of self-medication and the misuse of these drugs by several examples, such as per os nasal decongestants used for common cold which should induce rare but serious adverse effects (cardiovascular or neurologic adverse effects). In fact, the absence of clear distinction between the different statutes of health products facilitates their status changes. The increasing shift from "medicines” to less regulated products, the trivialization of their use by the public and their increasing consumption require to raise the awareness of consumers and health professionals. Furthermore, during the COVID-19 pandemic, several products were marketed as medical device as virucidal agent (nasal spray) without any efficacy. In conclusion, taken into account the increase use of products (drugs, food supplement, medical device…) in self-medication, it should be necessary to dispose an independent public database for self-medication drugs with validated guidelines and to guarantee the marketing of these drugs with a favourable benefit/risk ratio by an active pharmacovigilance for detection of rare or serious adverse effects. © 2022 l'Académie nationale de médecine L'automédication est définie comme la prise d'un ou plusieurs médicaments, sur sa propre initiative sans avis médical et sans le conseil d'un pharmacien. Le médicament peut être acheté sans ordonnance en pharmacie ou être présent dans la pharmacie familiale. Les médicaments utilisés en automédication sont utilisés pour le traitement des pathologies dites « mineures » avec un profil d'effet indésirable « sécurisant » lorsqu'ils sont utilisés de manière appropriée. Néanmoins, pour nombreux de ces médicaments, les informations concernant leur efficacité et leur risque s'avèrent insuffisantes et non transparentes. Les auteurs décrivent les dangers de l'automédication et leur mésusage à travers divers exemples, comme l'utilisation des décongestionnants oraux dans le rhume pouvant générer des effets indésirables rares mais graves (effets indésirables cardiovasculaires ou neurologiques). En effet, la porosité des frontières entre les différents statuts des produits de santé facilite leur changement de statut. L'augmentation des passages du « médicament » aux produits plus faiblement réglementés, la banalisation de leur utilisation par le public et leur consommation croissante nécessitent la sensibilisation des consommateurs, mais aussi des professionnels de santé. Durant la pandémie de la COVID-19, plusieurs produits ont été commercialisés comme dispositif médical comme agent virucide (spray nasal) sans aucune efficacité. En conclusion, face à une utilisation croissante des produits (médicament, complément alimentaire, dispositif médical…) en automédication, il est nécessaire de disposer d'une base d'informations grand public, indépendantes, présentant une recommandation de médicaments validés par des experts et de garantir le maintien sur le marché des médicaments avec un rapport bénéfice/risque favorable, grâce à une pharmacovigilance active pour la détection des effets indésirables graves ou rares. © 2022 l'Académie nationale de médecine

Automédication et mésusage

Résumé L'automédication est définie comme la prise d'un ou plusieurs médicaments, sur sa propre initiative sans avis médical et sans le conseil d'un pharmacien. Le médicament peut être acheté sans ordonnance en pharmacie ou être présent dans la pharmacie familiale. Les médicaments utilisés en automédication sont utilisés pour le traitement des pathologies dites « mineures » avec un profil d'effet indésirable « sécurisant » lorsqu'ils sont utilisés de manière appropriée. Néanmoins, pour nombreux de ces médicaments, les informations concernant leur efficacité et leur risque s'avèrent insuffisantes et non transparentes. Les auteurs décrivent les dangers de l'automédication et leur mésusage à travers divers exemples, comme l'utilisation des décongestionnants oraux dans le rhume pouvant générer des effets indésirables rares mais graves (effets indésirables cardiovasculaires ou neurologiques). En effet, la porosité des frontières entre les différents statuts des produits de santé facilite leur changement de statut. L'augmentation des passages du « médicament » aux produits plus faiblement réglementés, la banalisation de leur utilisation par le public et leur consommation croissante nécessitent la sensibilisation des consommateurs, mais aussi des professionnels de santé. Durant la pandémie de la COVID-19, plusieurs produits ont été commercialisés comme dispositif médical comme agent virucide (spray nasal) sans aucune efficacité. En conclusion, face à une utilisation croissante des produits (médicament, complément alimentaire, dispositif médical…) en automédication, il est nécessaire de disposer d'une base d'informations grand public, indépendantes, présentant une recommandation de médicaments validés par des experts et de garantir le maintien sur le marché des médicaments avec un rapport bénéfice/risque favorable, grâce à une pharmacovigilance active pour la détection des effets indésirables graves ou rares. Summary Self-medication means to take drugs without getting permission from a doctor or without following the advice of a pharmacist. The drug could be bought without prescription in pharmacy or be available in family pharmacy. Self-medication drugs are considered to be safe for an appropriate use for the treatment of pathologies classed as "minor”. However, data about their efficacy and risk remain insufficient and non transparent. The authors describe the danger of self-medication and the misuse of these drugs by several examples, such as per os nasal decongestants used for common cold which should induce rare but serious adverse effects (cardiovascular or neurologic adverse effects). In fact, the absence of clear distinction between the different statutes of health products facilitates their status changes. The increasing shift from "medicines” to less regulated products, the trivialization of their use by the public and their increasing consumption require to raise the awareness of consumers and health professionals. Furthermore, during the COVID-19 pandemic, several products were marketed as medical device as virucidal agent (nasal spray) without any efficacy. In conclusion, taken into account the increase use of products (drugs, food supplement, medical device…) in self-medication, it should be necessary to dispose an independent public database for self-medication drugs with validated guidelines and to guarantee the marketing of these drugs with a favourable benefit/risk ratio by an active pharmacovigilance for detection of rare or serious adverse effects.

Data on the stability of darunavir/cobicistat suspension after tablet manipulation.

The COVID-19 outbreak is now one of the most critical crises to manage for most of the national healthcare systems in the world. In the absence of authorised pharmacological treatments, many antiretrovirals, including darunavir/cobicistat fixed combination, are used off-label in the hospital wards as life-treating medicines for COVID-19 patients. Unfortunately, for most of them, the drug products available on the market are not designed to be administered by a nasogastric tube to inpatients of intensive care units. Therefore, their manipulation, even if it can strongly affect the product quality, is necessary for the preparation of suspension to meet patients' need. In this situation, it is urgent to provide data and guidance to support hospital pharmacists and clinicians in their activity. The data in this article indicate that darunavir/cobicistat suspensions compounded by pharmacists using as active ingredient a commercially available tablet can be stable at least for one week.

[COVID-19, drugs and hospital pharmacy]. / Évolution des traitements médicamenteux en cas de Covid-19.

Observation, interpretation, actions for improvement, questioning are all terms that echo the situation of caregivers since the outbreak of the COVID-19 epidemic in France at the beginning of 2020. All those involved in the healthcare chain have had to cope with the influx of patients and to show that they are capable of seeing their practices evolve on a daily basis. What was recommended a few weeks earlier could quickly become obsolete. It was necessary to be reactive and the question of drug treatments was at the heart of the concerns, requiring prescribers to keep themselves informed and pharmacists to be as mobilized as possible to respond to requests from the field as quickly as possible.

Ribavirin shows antiviral activity against SARS-CoV-2 and downregulates the activity of TMPRSS2 and the expression of ACE2 in vitro.

Ribavirin is a guanosine analog with broad-spectrum antiviral activity against RNA viruses. Based on this, we aimed to show the anti-SARS-CoV-2 activity of this drug molecule via in vitro, in silico, and molecular techniques. Ribavirin showed antiviral activity in Vero E6 cells following SARS-CoV-2 infection, whereas the drug itself did not show any toxic effect over the concentration range tested. In silico analysis suggested that ribavirin has a broad-spectrum impact on SARS-CoV-2, acting at different viral proteins. According to the detailed molecular techniques, ribavirin was shown to decrease the expression of TMPRSS2 at both mRNA and protein levels 48 h after treatment. The suppressive effect of ribavirin in ACE2 protein expression was shown to be dependent on cell types. Finally, proteolytic activity assays showed that ribavirin also showed an inhibitory effect on the TMPRSS2 enzyme. Based on these results, we hypothesized that ribavirin may inhibit the expression of TMPRSS2 by modulating the formation of inhibitory G-quadruplex structures at the TMPRSS2 promoter. As a conclusion, ribavirin is a potential antiviral drug for the treatment against SARS-CoV-2, and it interferes with the effects of TMPRSS2 and ACE2 expression.

[Contribution of a hospital pharmacy team to critical care of patients infected with SARS-CoV-2]. / Contribution d'une équipe de pharmacie hospitalière à la prise en charge en réanimation des patients infectés par le SARS-CoV-2.

With regard to the hospital drug supply chain, the safest system is the individual automated drug dispensing one provided by the pharmacy. For several years we have been trying to convince hospital decision-makers to set it up. In the meantime, to mitigate the risks of medication errors incurred by patients and caregivers, we have set up several work teams within the care units. These teams, made up of one pharmacist and one or two hospital pharmacy technicians, who notably manage the medicine cabinets in care units. The close collaboration with doctors and nurses developed over the years was a determining factor when it became necessary to provide the newly created additional intensive care units with drugs and medical devices (MDs) in order to cope with the crisis triggered by the SARS-CoV-2 epidemic. Daily monitoring of the drugs consumed by each patient, particularly neuromuscular blocking agents and MDs was a key element in managing stocks and anticipating changes of drugs, packaging and/or devices references. These facts give weight to the Claris report published in France which recognizes that the interactions of pharmacy technicians and pharmacists in the care units have positive effects in terms of quality and safety of patient care. They highlight the dangers to which patients and caregivers are exposed on Saturdays, Sundays and holidays when the pharmacy is closed. They legitimize the question of extending the opening of the pharmacy with a full team 365 days a year.

Data on compounding lopinavir and ritonavir suspension for non-cooperative COVID-19 patients.

The COVID-19 outbreak is now one of the most critical crises to manage for most of national healthcare systems in the world. The situation is complicated by the absence of vaccines and authorized pharmacological treatments, except for remdesivir. In this context, many medicaments, including different Ebola and HIV antivirals, are used off-label in the hospital wards as life-treating medicines for COVID-19 patients. Authorized medicaments manipulation is sometimes necessary because they are not always formulated to be administered to non-cooperative patients or they are in shortage. It is this the case of the fixed combination of lopinavir/ritonavir, which was extensively used in the first phase of the outbreak inducing a shortage of the oral solution available in the EU market. This work provides data on size distribution, osmolarity other than drug chemical stability of a lopinavir/ritonavir extemporaneous preparation made by using the solid dosage form (i.e., tablet) available on the market as drug source. The reported data indicate that such preparation is suitable to be delivered through a nasogastric tube, and enough stable for two weeks from the preparation at room temperature.

Data on chloroquine/hydroxychloroquine content in compounded oral suspension after filtration and centrifugation.

The COVID-19 outbreak is spreading worldwide pushing the national healthcare systems to find effective protocols to prevent contagion and to reduce the patients' mortality and the severity of long-term effects. In the absence of authorised pharmacological treatments, chloroquine, and hydroxychloroquine, which are known as anti-malaria drugs, had been widely used off-label until concerns about their efficacy/safety limited their use to hospitalized patients affected by severe COVID-19. Regardless of their clinical use, their manipulation is necessary since the pure drug substance is not always promptly available and most of the drug products available on the market are tablets designed to be ingested; no liquid dosage forms are available. These are needed for children and the enteral nutrition of inpatients of intensive care units. Considering that both chloroquine and hydroxychloroquine are BCS class I, proper procedures for purifying the preparation from the insoluble excipients may be adopted to avoid clogging of a nasogastric tube and to reduce the drug content variability in the administered doses. The data in this article indicate that compounded oral suspensions containing chloroquine and hydroxychloroquine can be filtered and/or centrifuged without altering the drug assay of the preparation.