COVID-19 Treatment: Drug Safety Prior to Conception and During Pregnancy and Breastfeeding

In December 2019, a new viral respiratory infection known as coronavirus disease 2019 (COVID-19) was first diagnosed in the city of Wuhan, China. COVID-19 quickly spread across the world, leading the World Health Organization to declare it a pandemic on March 11, 2020. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a similar virus to those involved in other epidemics such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Epidemiological studies have shown that COVID-19 frequently affects young adults of reproductive age and that the elderly and patients with chronic disease have high mortality rates. Little is known about the impact of COVID-19 on pregnancy and breastfeeding. Most COVID-19 cases present with mild flu-like symptoms and only require treatment with symptomatic relief medications, whereas other cases with COVID-19 require treatment in an intensive care unit. There is currently no specific effective treatment for COVID-19. A large number of drugs are being used to fight infection by SARS-CoV-2. Experience with this therapeutic arsenal has been gained over the years in the treatment of other viral, autoimmune, parasitic, and bacterial diseases. Importantly, the search for an effective treatment for COVID-19 cannot expose pregnant women infected with SARS-CoV-2 to the potential teratogenic risks of these drugs. Therefore, it is necessary to determine and understand the safety of anti-COVID-19 therapies prior to conception and during pregnancy and breastfeeding.Key words: COVID-19, SARS-CoV-2, antiviral, pregnancy, breastfeeding     

Dynamics of experimental vasogenic brain oedema in the rat: changes induced by adrenergic drugs

The effects of adrenergic drugs on the formation and resolution of cerebral oedema in a rat model of cold-induced vasogenic brain oedema were studied. Evans blue dye extravasation, water content and ultrastructural alterations (pinocytotic vesicle formation in capillary endothelial cells and apparent water accumulation in the brain parenchyma) were evaluated in parietal cortex. Previous administration of the alpha-adrenoceptor antagonist phenoxybenzamine produced a reduction of Evans blue extravasation and water content, diminished vesicle formation and reduced water accumulation. Previous administration of the beta2-adrenoceptor agonist clenbuterol reduced Evans blue extravasation and water content, but did not change vesicle frequency. The effects of clenbuterol on Evans blue passage to the brain were blocked by timolol (beta-adrenoceptor antagonist) but not by metoprolol (selective beta1-adrenoceptor antagonist). When given after the application of cold, clenbuterol was also able to reduce Evans blue and water content in the brain. Isoprenaline (beta-adrenoceptor agonist that does not cross the blood-brain barrier) showed a reduction in Evans blue extravasation only when given intracerebroventricularly. Vinblastine (a drug that prevents vesicle formation) produced a reduction of the amount of pinocytotic vesicles. We conclude that there is an influence of the central adrenergic nervous system on the formation and/or resolution of vasogenic brain oedema and that the alterations on water movement and Evans blue transport mediated by adrenergic drugs seem to be due, at least in part, to alterations of pinocytotic activity in capillary endothelial cells.     

Adrenergic influences on the control of blood-brain barrier permeabilit

Summary The central adrenergic innervation of the cerebral microvessels may play a role in the control of blood-brain barrier permeability. To pursue the study of this hypothesis we investigated the effect of noradrenaline on both the permeability of the blood-brain barrier to sodium fluorescein and on the pinocytotic activity of cerebral endothelial cells in the rat. Noradrenaline, stereotactically injected in the right lateral cerebral ventricle, significantly increased the cerebral extraction ratio of sodium fluorescein in a dose-dependent way. The same effect was induced by phenylephrine. Prostaglandin F₂ had no significant effect on the passage of sodium fluorescein through the blood-brain barrier.The effect of noradrenaline (150 µg) on the cerebral extraction ratio of sodium fluorescein was totally blocked by phenoxybenzamine (25 mg/kg i.p., 24 h before noradrenaline). Noradrenaline (150 µg) significantly increased the pinocytotic activity of cerebral endothelial cells. Phenoxybenzamine (as above) reduced the effect of noradrenaline on pinocytosis.It is concluded that noradrenaline increases the blood-brain barrier's permeability to sodium fluorescein, most probably through an effect on alpha adrenoceptors. The increase induced in the blood-brain barrier's permeability by noradrenaline seems to be due, at least in part, to an increase in the pinocytotic activity of endothelial cells. Send offprint requests to A. Sarmento at the above address     

Saphenous vein graft bypass in the treatment of giant cavernous sinus aneurysms: report of two cases

Two cases of giant intracavernous aneurysms treated by high flow bypass with saphenous vein graft between the external carotid artery (ECA) and branches of the middle cerebral artery (MCA) are presented. Very often these aneurysms are unclippable because they are fusiform or have a large neck. Occlusion of the internal carotid artery (ICA) is the treatment of choice in many cases. This procedure has however a high risk of brain infarction. Revascularization of the brain by extra-intracranial anastomosis between the superficial temporal artery (STA) and branches of the MCA is frequently performed. This procedure provides however a low flow bypass and brain infarction may occur. We report two cases of giant cavernous sinus aneurysms treated by high flow bypass and endovascular balloon occlusion of the ICA. Immediate high flow revascularization of MCA branches was achieved and the patients showed no ischemic events. Follow-up of 8 and 14 months after operation shows patency of the venous graft and no neurological deficits. Angiographic control examination showed complete aneurysm occlusion in both cases.     

Associations of substance use, abuse, and dependence with subsequent suicidal behavior

General population survey data are used to disaggregate the associations of substance use disorders with suicide attempts in order to evaluate a number of hypotheses about the processes leading to these associations. Data are from the US National Comorbidity Survey (1990-1992). Discrete-time survival analysis is used to study the effects of retrospectively reported temporally prior substance use, abuse, and dependence in predicting first onset of suicidal behavior. Alcohol and drug use predict subsequent suicide attempts after controlling for sociodemographics and comorbid mental disorders. Previous use is not a significant predictor among current nonusers. Abuse and dependence are significant predictors among users for three of the 10 substances considered (alcohol, inhalants, and heroin). The number of substances used is more important than the types of substances used in predicting suicidal behavior. Disaggregation shows that the effects of use are largely on suicidal ideation and nonplanned attempts among ideators. In comparison, the effects of use on suicide plans and planned attempts among ideators are not significant. Clinicians need to be aware that current substance use, even in the absence of abuse or dependence, is a significant risk factor for unplanned suicide attempts among ideators.     

Suicide attempts in a sample of patients from a general hospital

BACKGROUND: Suicide in Mexico has risen steadily in recent years, increasing by 156% in the last two decades. The study of suicide precursors, such as suicide attempts, has also become an important public health topic. The aim of this study is to establish the prevalence of suicide attempts in a general hospital setting and its association with alcohol, depression, and other factors. METHODS: A cross-sectional survey of a sample of patients was carried out in all three service units (inpatient, outpatient, and the emergency room) of a general hospital in Mexico City. All patients were randomly selected to participate regardless of the reason for initial hospital admission. Each patient was administered a series of psychological and demographic scales including the Beck Depression Inventory, the Beck Hopelessness Inventory, the General Health Questionnaire, a suicide assessment scale, a scale for alcohol consumption, and several measurements of alcohol-related problems. RESULTS: The final sample was made up of 1,094 patients of both genders (68% women), aged 18-65 years. A lifetime prevalence of suicide attempts of 6.1% (95% confidence interval [CI] of 4.7-7.7%) was found. Multiple logistic regression was used to obtain estimations of the association between lifetime suicide attempt and other factors. Marital status, age, depressed mood, hopelessness, Goldberg's 30-item version of the General Health Questionnaire, and high levels of alcohol consumption were all associated with the suicide attempt. CONCLUSIONS: Prevalence of lifetime suicide attempts was mainly related to being young, divorced, or widowed, and to feeling depressed, hopeless, and under undesirable psychological distress.