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1.
Ann Saudi Med ; 40(5): 365-372, 2020.
Article in English | MEDLINE | ID: covidwho-782327

ABSTRACT

Evidence of cardiovascular complications associated with the COVID-19 global pandemic continues to evolve. These include direct and indirect myocardial injury with subsequent acute myocardial ischemia, and cardiac arrhythmia. Some results from a limited number of trials of antiviral medications, along with chloroquine/hydroxychloroquine and azithromycin, have been beneficial. However, these pharmacotherapies may cause drug-induced QT prolongation leading to ventricular arrhythmias and sudden cardiac death. Mitigation of the potential risk in these susceptible patients may prove exceptionally challenging. The Saudi Heart Rhythm Society established a task force to perform a review of this subject based on has recently published reports, and studies and recommendations from major medical organizations. The objective of this review is to identify high-risk patients, and to set clear guidelines for management of patients receiving these pharmacotherapies.


Subject(s)
Arrhythmias, Cardiac/chemically induced , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adrenergic beta-Antagonists/therapeutic use , Advisory Committees , Antiviral Agents/adverse effects , Arrhythmias, Cardiac/diagnosis , Azithromycin/adverse effects , Betacoronavirus , Chloroquine/adverse effects , Cytochrome P-450 CYP2D6 Inhibitors/adverse effects , Drug Combinations , Drug Interactions , Drug Monitoring , Electrocardiography , Humans , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Lopinavir/adverse effects , Pandemics , Risk Assessment , Ritonavir/adverse effects , Saudi Arabia , Torsades de Pointes/chemically induced , Torsades de Pointes/diagnosis
3.
Pharmacol Res Perspect ; 8(5): e00653, 2020 10.
Article in English | MEDLINE | ID: covidwho-757850

ABSTRACT

More than ten million patients worldwide have been diagnosed with coronavirus disease 19 (COVID-19) to date (WHO situation report, 1st July 2020). There is no vaccine to prevent infection with the causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), nor a cure. In the struggle to devise potentially useful therapeutics in record time, the repurposing of existing compounds is a key route of action. In this hypothesis paper, we argue that the bisbenzylisoquinoline and calcium channel blocker tetrandrine, originally extracted from the plant Stephania tetrandra and utilized in traditional Chinese medicine, may have potential in the treatment of COVID-19 and should be further investigated. We collate and review evidence for tetrandrine's putative mechanism of action in viral infection, specifically its recently discovered antagonism of the two-pore channel 2 (TPC2). While tetrandrine's particular history of use provides a very limited pharmacological dataset, there is a suggestion from the available evidence that it could be effective at doses used in clinical practice. We suggest that further research to investigate this possibility should be conducted.


Subject(s)
Antiviral Agents/administration & dosage , Benzylisoquinolines/administration & dosage , Betacoronavirus/drug effects , Calcium Channel Blockers/administration & dosage , Calcium Channels/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Animals , Antiviral Agents/adverse effects , Benzylisoquinolines/adverse effects , Betacoronavirus/pathogenicity , Calcium Channel Blockers/adverse effects , Calcium Channels/metabolism , Coronavirus Infections/diagnosis , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Drug Interactions , Host-Pathogen Interactions , Humans , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , Signal Transduction
4.
Circ J ; 84(10): 1679-1685, 2020 09 25.
Article in English | MEDLINE | ID: covidwho-751078

ABSTRACT

The health crisis due to coronavirus disease 2019 (COVID-19) has shocked the world, with more than 1 million infections and casualties. COVID-19 can present from mild illness to multi-organ involvement, but especially acute respiratory distress syndrome. Cardiac injury and arrhythmias, including atrial fibrillation (AF), are not uncommon in COVID-19. COVID-19 is highly contagious, and therapy against the virus remains premature and largely unknown, which makes the management of AF patients during the pandemic particularly challenging. We describe a possible pathophysiological link between COVID-19 and AF, and therapeutic considerations for AF patients during this pandemic.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Anti-Arrhythmia Agents/therapeutic use , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , Atrial Fibrillation/drug therapy , Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Atrial Fibrillation/physiopathology , Catheter Ablation/methods , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Cytokines/blood , Drug Interactions , Humans , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Risk
5.
J Bras Nefrol ; 42(2 suppl 1): 36-40, 2020 Aug 26.
Article in English, Portuguese | MEDLINE | ID: covidwho-740464

ABSTRACT

During the Covid-19 pandemic, the issue is how to maintain adequate care for people with other diseases. In this document, the SBN Rare Diseases Committee (COMDORA) gives some guidelines on the care of patients with rare kidney diseases. These patients should follow the recommendations for the general population, bearing in mind that, as they have chronic kidney disease, they are included in the risk group for more serious outcomes if they develop Covid-19. Non-essential decision-making procedures should be postponed. In stable cases under appropriate treatment, we must choose to contact our patients remotely, using teleconsultations and home exam collections (if possible). In the presence of a symptom or sign of decompensation of the underlying disease, or infection with Sars-cov-2, advise the patient to seek medical assistance. The patient should not be waiting to get worse. Changes to the prescription should only be made on a scientific basis. Dosage suspension or change is not recommended, even in cases in which the patient needs to go to a center to receive his medication; in this case, the infusion center must follow the recommendations of the Ministry of Health. If the patient develops Covid-19 and uses any drugs, check the need for dose adjustment of the routine medications. Avoid the use of antimetabolics and anti-CD20 in patients with Covid-19, as they reduce viral clearance and predispose to bacterial infections. Contact between the patient and the medical team is essential; changes are recommended only with specialized medical guidance.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Kidney Diseases/therapy , Pneumonia, Viral/epidemiology , Rare Diseases/therapy , Brazil , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Drug Interactions , Humans , Pandemics , Patient Acceptance of Health Care , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Symptom Assessment
7.
J Gastrointestin Liver Dis ; 29(3): 470, 2020 09 09.
Article in English | MEDLINE | ID: covidwho-729795
8.
Cardiol Rev ; 28(5): 266-271, 2020.
Article in English | MEDLINE | ID: covidwho-707022

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a threat to the health of many humans across the world as they confront coronavirus disease 2019 (COVID-19). Previous promising in vitro data that emerged after the SARS-CoV outbreak in 2003, along with the emergent need for pharmacologic management strategies in the fight against COVID-19, prompted interest in the use of chloroquine and hydroxychloroquine across the globe. Unfortunately, the in vitro activity of these drugs did not necessarily correlate with most in vivo studies, which showed no consistent efficacy. Safety is also a major concern, with these agents having a known risk of QT prolongation and proarrhythmic effects. In addition, clinical practice guidelines provide no clear consensus on the role of chloroquine or hydroxychloroquine for the management of COVID-19. The United States Food and Drug Administration has declared that the potential benefits of these agents no longer outweigh the possible risks, and unless new emerging information suggests a more favorable risk:benefit ratio, neither chloroquine nor hydroxychloroquine should be recommended for COVID-19 treatment or prevention at this time.


Subject(s)
Arrhythmias, Cardiac/chemically induced , Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Enzyme Inhibitors/therapeutic use , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Betacoronavirus , Cytochrome P-450 CYP2D6/metabolism , Drug Interactions , Humans , In Vitro Techniques , Long QT Syndrome/chemically induced , Pandemics , Practice Guidelines as Topic , Torsades de Pointes/chemically induced , Treatment Outcome
9.
Orv Hetil ; 161(32): 1310-1321, 2020 08.
Article in Hungarian | MEDLINE | ID: covidwho-706828

ABSTRACT

Due to the COVID-19 pandemic caused by infection with the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), transplant medicine also had to face a new, hitherto unknown challenge. To be prepared for any possibility, we consider it important to summarize the current knowledge regarding COVID-19 of liver and kidney transplant patients. Very early reports from Spanish and French registry recorded fatality rates of 18.6% and 13%, respectively, in renal patients which suggests a moderately worse outcome compared to the general population. In patients with positive PCR test but not showing clinical signs, the reduction of immunosuppression is not advised. In the case of gastrointestinal or respiratory signs with fever, the discontinuation of mycophenolate or mTOR inhibitors is recommended with decrease of the trough levels of calcineurin inhibitors to the lowest effective limit. Stop (kidney transplanted patients) or decrease (liver transplanted patients) immunosuppression and maintain corticosteroids when pulmonal injury develops and consider anti-IL1 and anti-IL6 monoclonal antibody use when hyperinflammatory syndrome is evolving. No proven effective treatment for SARS-CoV-2 exists currently. The use of lopinavir/ritonavir should be avoided because of the severe drug interaction with calcineurin inhibitors. The efficacy and tolerability of hidroxychloroquin remains to be also questionable; enroll patients into clinical trial with remdesivir or favipiravir if available. COVID-19 is characterized by virus-induced endothelial dysfunction, procoagulant state and renin-angiotensin-aldosteron system imbalance. Early thromboprofilaxis combination with low-molecular-weight heparin and low-dose aspirin is strongly recommended with the maintenance of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II-receptor blocker (ARB) therapy when they were prescribed earlier. Orv Hetil. 2020; 161(32): 1310-1321.


Subject(s)
Coronavirus Infections/complications , Kidney Transplantation , Liver Transplantation , Pneumonia, Viral/complications , Transplant Recipients , Adrenal Cortex Hormones/therapeutic use , Betacoronavirus , Calcineurin Inhibitors/adverse effects , Contraindications, Drug , Drug Combinations , Drug Interactions , Humans , Immunosuppression , Lopinavir/adverse effects , Pandemics , Ritonavir/adverse effects
10.
Med Clin (Barc) ; 155(7): 281-287, 2020 10 09.
Article in English, Spanish | MEDLINE | ID: covidwho-688732

ABSTRACT

OBJECTIVES: To determine the prevalence of potential interactions in COVID-19 patients receiving lopinavir/ritonavir (LPV/r). The secondary objective was to develop recommendations and identify the risk factors associated with presenting potential interactions with LPV/r. SUBJECTS AND METHODS: Cross-sectional and multicenter study with the participation of 2 hospitals. COVID-19 patients over 18 years of age, admitted to hospital and under treatment with LPV/r were included. A screening of potential interactions related to LPV/r and home and hospital medication was carried out. Lexicomp® (Uptodate), HIV-drug interactions and COVID-drug interactions were used as the query database. RESULTS: 361 patients with a mean age of 62.77 ± 14.64 years were included, where 59.6% (n = 215) were men. 62.3% (n = 225) had 1 or more potential interactions and 26, 87% (n = 97) 2 or more. The independent variables associated with presenting ≥1 potential interactions were age (> 65) (OR 1.95; 95% CI 1.06-3.59, P =.033), ICU admission (OR 9.22; CI 95% 1.98-42.93; P =.005), previous respiratory pathology (OR 2.90; 95% CI 1.15-7.36; P =.024), psychiatric (OR 4.14; 95 CI % 1.36-12.61; P =.013), dyslipidemia (OR 3.21; 95% CI 1.63-6.35; P =.001) and the number of drugs prescribed (OR 4.33; 95% CI 2.40-7.81; P =.000). CONCLUSION: The prevalence of potential interactions in COVD-19 patient undergoing treatment with LPV/r is high, with age (> 65), ICU admission, previous respiratory and psychiatric pathology, dyslipidemia and the number of prescribed drugs acting as risk factors.


Subject(s)
Antiviral Agents/adverse effects , Betacoronavirus , Coronavirus Infections/drug therapy , Lopinavir/adverse effects , Pneumonia, Viral/drug therapy , Ritonavir/adverse effects , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Cross-Sectional Studies , Drug Combinations , Drug Interactions , Female , Humans , Lopinavir/therapeutic use , Male , Middle Aged , Pandemics , Risk Factors , Ritonavir/therapeutic use , Treatment Outcome
11.
J Nanosci Nanotechnol ; 20(12): 7311-7323, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-680345

ABSTRACT

We started a study on the molecular docking of six potential pharmacologically active inhibitors compounds that can be used clinically against the COVID-19 virus, in this case, remdesivir, ribavirin, favipiravir, galidesivir, hydroxychloroquine and chloroquine interacting with the main COVID-19 protease in complex with a COVID-19 N3 protease inhibitor. The highest values of affinity energy found in order from highest to lowest were chloroquine (CHL), hydroxychloroquine (HYC), favipiravir (FAV), galidesivir (GAL), remdesivir (REM) and ribavirin (RIB). The possible formation of hydrogen bonds, associations through London forces and permanent electric dipole were analyzed. The values of affinity energy obtained for the hydroxychloroquine ligands was -9.9 kcal/mol and for the chloroquine of -10.8 kcal/mol which indicate that the coupling contributes to an effective improvement of the affinity energies with the protease. Indicating that, the position chosen to make the substitutions may be a pharmacophoric group, and cause changes in the protease.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Betacoronavirus/enzymology , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Cysteine Endopeptidases/chemistry , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/chemistry , Adenine/administration & dosage , Adenine/analogs & derivatives , Adenine/chemistry , Adenine/pharmacology , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/pharmacology , Alanine/administration & dosage , Alanine/analogs & derivatives , Alanine/chemistry , Alanine/pharmacology , Amides/administration & dosage , Amides/chemistry , Amides/pharmacology , Antiviral Agents/administration & dosage , Binding Sites , Chloroquine/administration & dosage , Chloroquine/chemistry , Chloroquine/pharmacology , Drug Interactions , Humans , Hydrogen Bonding , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/chemistry , Hydroxychloroquine/pharmacology , Ligands , Molecular Docking Simulation , Nanotechnology , Pandemics , Protease Inhibitors/administration & dosage , Pyrazines/administration & dosage , Pyrazines/chemistry , Pyrazines/pharmacology , Pyrrolidines/administration & dosage , Pyrrolidines/chemistry , Pyrrolidines/pharmacology , Ribavirin/administration & dosage , Ribavirin/chemistry , Ribavirin/pharmacology , Static Electricity
12.
Gastroenterol Hepatol ; 43(6): 332-347, 2020.
Article in English, Spanish | MEDLINE | ID: covidwho-658769

ABSTRACT

The set of measures proposed by SEPD, AEEH, GETECCU and AEG are aimed to help departments in their resumption of usual activity. We have prepared a number of practical recommendations regarding patient management and the stepwise resumption of healthcare activity. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. The general objectives of these recommendations include: (a)To protect our patients against the risks of infection with SARS-CoV-2 and to provide them with high-quality care. (b)To protect all healthcare professionals against the risks of infection with SARS-CoV-2. (c)To resume normal functioning of our departments in a setting of ongoing risk for infection with SARS-CoV-2.


Subject(s)
Coronavirus Infections/prevention & control , Gastroenterology/organization & administration , Hospital Departments/organization & administration , Infection Control/organization & administration , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Appointments and Schedules , Clinical Laboratory Techniques , Clinical Trials as Topic , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/transmission , Cross Infection/prevention & control , Diagnostic Techniques, Digestive System/instrumentation , Digestive System Diseases/complications , Digestive System Diseases/diagnosis , Digestive System Diseases/therapy , Disinfection , Drug Interactions , Equipment Contamination/prevention & control , Home Care Services/organization & administration , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Infectious Disease Transmission, Professional-to-Patient/prevention & control , Liver Transplantation , Mass Screening/organization & administration , Occupational Diseases/prevention & control , Pneumonia, Viral/drug therapy , Pneumonia, Viral/transmission , Protective Devices , Symptom Assessment , Telemedicine/organization & administration , Universal Precautions
15.
BMC Med ; 18(1): 215, 2020 07 15.
Article in English | MEDLINE | ID: covidwho-645688

ABSTRACT

BACKGROUND: The novel coronavirus pandemic calls for a rapid adaptation of conventional medical practices to meet the evolving needs of such vulnerable patients. People with coronavirus disease (COVID-19) may frequently require treatment with psychotropic medications, but are at the same time at higher risk for safety issues because of the complex underlying medical condition and the potential interaction with medical treatments. METHODS: In order to produce evidence-based practical recommendations on the optimal management of psychotropic medications in people with COVID-19, an international, multi-disciplinary working group was established. The methodology of the WHO Rapid Advice Guidelines in the context of a public health emergency and the principles of the AGREE statement were followed. Available evidence informing on the risk of respiratory, cardiovascular, infective, hemostatic, and consciousness alterations related to the use of psychotropic medications, and drug-drug interactions between psychotropic and medical treatments used in people with COVID-19, was reviewed and discussed by the working group. RESULTS: All classes of psychotropic medications showed potentially relevant safety risks for people with COVID-19. A set of practical recommendations was drawn in order to inform frontline clinicians on the assessment of the anticipated risk of psychotropic-related unfavorable events, and the possible actions to take in order to effectively manage this risk, such as when it is appropriate to avoid, withdraw, switch, or adjust the dose of the medication. CONCLUSIONS: The present evidence-based recommendations will improve the quality of psychiatric care in people with COVID-19, allowing an appropriate management of the medical condition without worsening the psychiatric condition and vice versa.


Subject(s)
Coronavirus Infections/complications , Drug Interactions , Mental Disorders/drug therapy , Pneumonia, Viral/complications , Psychotropic Drugs/adverse effects , Betacoronavirus , Evidence-Based Medicine , Humans , Mental Disorders/epidemiology , Pandemics , Psychotropic Drugs/therapeutic use , Public Health , Randomized Controlled Trials as Topic , Risk , Systematic Reviews as Topic
16.
Subst Use Misuse ; 55(11): 1900-1901, 2020.
Article in English | MEDLINE | ID: covidwho-643514

ABSTRACT

BACKGROUND: Alarms have been raised that COVID-19 may disproportionately affect certain populations with substance use disorders, particularly Opioid Use Disorder (OUD), however warnings have largely focused on social risks such as reduced availability of services. Objectives: This commentary highlights three plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19. Results: Opioid-related respiratory depression may amplify risks of hypoxemia from COVID-19 viral pneumonia. Complex opioid immune modulation may impact host response to COVID-19, though the effect direction and clinical significance are unclear. Drug-drug interactions may affect individuals with OUD who are co-administered medications for OUD and medications for COVID-19, particularly due to cardiac adverse effects. Conclusions/Importance: There are plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19; these mechanisms require further study, and should be considered in individuals with OUD.


Subject(s)
Analgesics, Opioid/adverse effects , Arrhythmias, Cardiac/chemically induced , Coronavirus Infections/complications , Immunocompromised Host/immunology , Opioid-Related Disorders/complications , Pneumonia, Viral/complications , Respiratory Insufficiency/chemically induced , Adaptive Immunity/immunology , Analgesics, Opioid/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Drug Interactions , Humans , Immunity, Innate/immunology , Methadone/adverse effects , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/immunology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Pneumonia, Viral/physiopathology , Prognosis , Respiratory Insufficiency/physiopathology
17.
Med Clin (Barc) ; 155(7): 281-287, 2020 10 09.
Article in English, Spanish | MEDLINE | ID: covidwho-643123

ABSTRACT

OBJECTIVES: To determine the prevalence of potential interactions in COVID-19 patients receiving lopinavir/ritonavir (LPV/r). The secondary objective was to develop recommendations and identify the risk factors associated with presenting potential interactions with LPV/r. SUBJECTS AND METHODS: Cross-sectional and multicenter study with the participation of 2 hospitals. COVID-19 patients over 18 years of age, admitted to hospital and under treatment with LPV/r were included. A screening of potential interactions related to LPV/r and home and hospital medication was carried out. Lexicomp® (Uptodate), HIV-drug interactions and COVID-drug interactions were used as the query database. RESULTS: 361 patients with a mean age of 62.77 ± 14.64 years were included, where 59.6% (n = 215) were men. 62.3% (n = 225) had 1 or more potential interactions and 26, 87% (n = 97) 2 or more. The independent variables associated with presenting ≥1 potential interactions were age (> 65) (OR 1.95; 95% CI 1.06-3.59, P =.033), ICU admission (OR 9.22; CI 95% 1.98-42.93; P =.005), previous respiratory pathology (OR 2.90; 95% CI 1.15-7.36; P =.024), psychiatric (OR 4.14; 95 CI % 1.36-12.61; P =.013), dyslipidemia (OR 3.21; 95% CI 1.63-6.35; P =.001) and the number of drugs prescribed (OR 4.33; 95% CI 2.40-7.81; P =.000). CONCLUSION: The prevalence of potential interactions in COVD-19 patient undergoing treatment with LPV/r is high, with age (> 65), ICU admission, previous respiratory and psychiatric pathology, dyslipidemia and the number of prescribed drugs acting as risk factors.


Subject(s)
Antiviral Agents/adverse effects , Betacoronavirus , Coronavirus Infections/drug therapy , Lopinavir/adverse effects , Pneumonia, Viral/drug therapy , Ritonavir/adverse effects , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Cross-Sectional Studies , Drug Combinations , Drug Interactions , Female , Humans , Lopinavir/therapeutic use , Male , Middle Aged , Pandemics , Risk Factors , Ritonavir/therapeutic use , Treatment Outcome
18.
Antiviral Res ; 181: 104866, 2020 09.
Article in English | MEDLINE | ID: covidwho-638667

ABSTRACT

In the context of the COVID-19 pandemic, several drugs have been repurposed as potential candidates for the treatment of COVID-19 infection. While preliminary choices were essentially based on in vitro potency, clinical translation into effective therapies may be challenging due to unfavorable in vivo pharmacokinetic properties at the doses chosen for this new indication of COVID-19 infection. However, available pharmacokinetic and pharmacokinetic-pharmacodynamic studies suffer from severe limitations leading to unreliable conclusions, especially in term of dosing optimization. In this paper we propose to highlight these limitations and to identify some of the major requirements that need to be addressed in designing PK and PK-PD studies in this era of COVID. A special attention should be paid to pre-analytical and analytical requirements and to the proper collection of covariates affecting dose-exposure relationships (co-medications, use of specific organ support techniques and other clinical and para-clinical data). We also promote the development of population PK and PK-PD models specifically dedicated to COVID-19 patients since those previously developed for other diseases (SEL, malaria, HIV) and clinical situations (steady-state, non-ICU patients) are not representative of severe patients. Therefore, implementation of well-designed PK and PD studies targeted to COVID-19 patients is urgently needed. For that purpose we call for multi-institutional collaborative work and involvement of clinical pharmacologists in multidisciplinary research consortia.


Subject(s)
Antiviral Agents/pharmacology , Antiviral Agents/pharmacokinetics , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Antiviral Agents/administration & dosage , Antiviral Agents/blood , Clinical Trials as Topic , Coronavirus Infections/complications , Coronavirus Infections/virology , Data Collection , Dose-Response Relationship, Drug , Drug Interactions , Humans , Models, Biological , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology
20.
Encephale ; 46(3S): S3-S13, 2020 Jun.
Article in French | MEDLINE | ID: covidwho-634328

ABSTRACT

OBJECTIVE: The lack of ressources and coordination to face the epidemic of coronavirus raises concerns for the health of patients with mental disorders in a country where we keep in memory the dramatic experience of famine in psychiatric hospitals during the Second World War. This article aims at proposing guidance to ensure mental health care during the SARS-CoV epidemy in France. METHODS: Authors performed a narrative review identifying relevant results in the scientific and medical literature and local initiatives in France. RESULTS: We identified four types of major vulnerabilities in patients suffering from mental disorders during this pandemic: (1) medical comorbidities that are more frequently found in patients suffering from mental disorders (cardiovascular and pulmonary pathologies, diabetes, obesity, etc.) which represent risk factors for severe infections with Covid-19; (2) age (the elderly constituting the population most vulnerable to coronavirus); (3) cognitive and behavioral troubles which can hamper compliance with confinement and hygiene measures and finally and (4) psychosocial vulnerability due to stigmatization and/or socio-economic difficulties. Furthermore, the mental health healthcare system is more vulnerable than other healthcare systems. Current government plans are poorly adapted to psychiatric establishments in a context of major shortage of organizational, material and human resources. In addition, a certain number of structural aspects make the psychiatric institution particularly vulnerable: many beds are closed, wards have a high density of patients, mental health community facilities are closed, medical teams are understaffed and poorly trained to face infectious diseases. We could also face major issues in referring patients with acute mental disorders to intensive care units. To maintain continuity of psychiatric care in this pandemic situation, several directions can be considered, in particular with the creation of Covid+ units. These units are under the dual supervision of a psychiatrist and of an internist/infectious disease specialist; all new entrants should be placed in quarantine for 14 days; the nurse staff should benefit from specific training, from daily medical check-ups and from close psychological support. Family visits would be prohibited and replaced by videoconference. At the end of hospitalization, in particular for the population of patients in compulsory ambulatory care situations, specific case-management should be organized with the possibility of home visits, in order to support them when they get back home and to help them to cope with the experience of confinement, which is at risk to induce recurrences of mental disorders. The total or partial closure of mental health community facilities is particularly disturbing for patients but a regular follow-up is possible with telemedicine and should include the monitoring of the suicide risk and psychoeducation strategies; developing support platforms could also be very helpful in this context. Private psychiatrists have also a crucial role of information with their patients on confinement and barrier measures, but also on measures to prevent the psychological risks inherent to confinement: maintenance of sleep regularity, physical exercise, social interactions, stress management and coping strategies, prevention of addictions, etc. They should also be trained to prevent, detect and treat early warning symptoms of post-traumatic stress disorder, because their prevalence was high in the regions of China most affected by the pandemic. DISCUSSION: French mental healthcare is now in a great and urgent need for reorganization and must also prepare in the coming days and weeks to face an epidemic of emotional disorders due to the containment of the general population.


Subject(s)
Betacoronavirus , Continuity of Patient Care/organization & administration , Coronavirus Infections/epidemiology , Mental Disorders/therapy , Mental Health Services/organization & administration , Pandemics , Pneumonia, Viral/epidemiology , Aftercare , Age Factors , Aged, 80 and over , Antiviral Agents/pharmacokinetics , Antiviral Agents/therapeutic use , Child , Cognition Disorders/epidemiology , Cognition Disorders/therapy , Comorbidity , Coronavirus Infections/psychology , Drug Interactions , France/epidemiology , Hospital Units/organization & administration , Hospitals, Psychiatric/organization & administration , Humans , Infection Control/methods , Mental Disorders/epidemiology , Mental Disorders/etiology , Mental Health Services/supply & distribution , Patient Care Team , Patient Compliance , Pneumonia, Viral/psychology , Prisoners/psychology , Stress Disorders, Post-Traumatic/etiology , Stress Disorders, Post-Traumatic/therapy , Stress, Psychological/etiology , Stress, Psychological/therapy , Substance-Related Disorders/epidemiology , Substance-Related Disorders/therapy , Suicide/prevention & control , Vulnerable Populations
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