Farmacia comunitaria, adherencia al tratamiento y COVID-19 / Community pharmacy, treatment adherence and COVID-19

La falta de adherencia es un problema mundial cada vez mayor y es la responsable de que los resultados esperados en salud se alejen de la realidad, aumentando el gasto sanitario. Comprender por qué un paciente no es adherente requiere identificar los factores implicados en su caso concreto y personalizar las estrategias a seguir. Para abordar la no adherencia desde la farmacia comunitaria tenemos el protocolo de la guía ADHe+ de dispensación y uso racional del medicamento, que clasifica a los pacientes no adherentes en tres perfiles (confundido, desconfiado y banalizador), facilitando la tarea de evaluación de sus creencias hacia un medicamento en concreto y en un momento determinado. Siguiendo el protocolo propuesto por la guía, el farmacéutico puede detectar la no adherencia en los medicamentos que el paciente recoge y en los que no e indagar en las causas. Pero el momento actual que estamos viviendo de pandemia por COVID-19 está cambiando el paradigma de la cronicidad. El miedo al contagio, la ralentización de los procesos asistenciales por las nuevas medidas de higiene, la telemedicina, el confinamiento y el desconocimiento de la nueva situación por parte de pacientes y sanitarios puede afectar mucho a la adherencia terapéutica

Non-adherence to treatment is becoming more and more of a global issue and is responsible for the fact that expected health results are getting further away from reality and increasing spending on healthcare. To understand why a patient is not adhering to treatment it is necessary to identify the factors involved in his or her specific case and personalize the strategies to be followed. In order to approach non-adherence to treatment from the community pharmacy perspective, we use the protocol from the ADHe+ guide on the dispensing and rational use of the drug, which classifies non-adhering patients into three profiles (confused, wary and trivializing), facilitating the task of assessing their beliefs with regards to a certain medicine and at a given time. Following the protocol suggested by the guide, pharmacists can detect non-adherence to the medicines the patient collects and does not collect and look into the causes. However, the current times of pandemic that we are experiencing-caused by COVID-19-are changing the pattern of chronicity. Fear of infection, the slowing down of care processes due to the new hygiene measures, telemedicine, quarantine, and the lack of awareness about the new situation by both the patients and healthcare professionals may have a great impact on therapeutic adherence

Opposite vascular activity of (R)-apomorphine and its oxidised derivatives. Endothelium-dependent vasoconstriction induced by the auto-oxidation metabolite.

We have synthetised a series of oxidised apomorphine derivatives (orto and para quinones 2-5), in order to analyse their vascular activity. We have performed radioligand binding assays on rat cortical membranes and functional studies on rat aortic rings. Instead the relaxant activity exhibited by (R)-apomorphine, o-quinones 2, 4, show contractile activity dependent on endothelium in rat aortic rings. Compound 2, the main metabolite of (R)-apomorphine auto-oxidation, was the product which showed enhanced contractile activity by a complex mechanism related to activation of Ca(2+) channels through release and/or inhibition of endothelial factors. Moreover, this compound disrupts the endothelial function as shows the lack of response to acetylcholine observed in vessels pretreated with it.

Interleukin 1 beta-induced inhibition of gastric acid secretion involves glutamate, NO and cGMP synthesis in the brain.

This study examines the role of a central pathway involving glutamate receptors, nitric oxide (NO) and cGMP in the acute inhibitory effects of central interleukin 1beta on pentagastrin-stimulated acid production.The acid-inhibitory effect of central interleukin 1beta was prevented by intracisternal (i.c.) microinjections of interleukin 1beta together with the NMDA receptor antagonist, dizocilpine maleate (MK-801). Intracisternal co-administration of the nitric oxide synthase inhibitor, N(G)-nitro- L-arginine methyl esther ( L-NAME) or 1H-[1,2,4]oxazodiolo[4,3-a]quinoxalin-1-one (ODQ), a soluble guanylyl cyclase (sGC) blocker, both reversed the hyposecretory effect of central interleukin 1beta. Peripheral administration of endotoxin significantly reduced pentagastrin-stimulated gastric acid secretion. I.c. pre-treatment with the interleukin 1 receptor antagonist, IL-1ra, failed to restore acid secretory responses in these rats. In addition, endotoxin did not modify the levels of endogenous mRNA for IL-1beta in the brainstem. We conclude that central glutamate receptors are involved in the acid inhibitory effect of centrally administered interleukin 1beta. This central pathway involves synthesis of NO, which acts on the enzyme sGC. However, endogenous interleukin 1beta does not seem to be involved in the inhibition of gastric acid secretion elicited by peripheral endotoxin.

Downregulation of nNOS and synthesis of PGs associated with endotoxin-induced delay in gastric emptying.

A single intraperitoneal injection of endotoxin (40 microg/kg) significantly delayed gastric emptying of a solid nutrient meal. Blockade of nitric oxide synthase (NOS) with 30 mg/kg ip N(G)-nitro-L-arginine methyl ester or 20 mg/kg ip 7-nitroindazole [neuronal NOS (nNOS) inhibitor] significantly delayed gastric emptying in control animals but failed to modify gastric emptying in endotoxin-treated rats. Administration of 2.5, 5, and 10 mg/kg ip N(6)-iminoethyl-L-lysine [inducible NOS (iNOS) inhibitor] had no effect in either experimental group. Indomethacin (5 mg/kg sc), NS-398 (cyclooxygenase-2 inhibitor; 10 mg/kg ip), and dexamethasone (10 mg/kg sc) but not quinacrine (20 mg/kg ip) significantly prevented delay in gastric emptying induced by endotoxin but failed to modify gastric emptying in vehicle-treated animals. Ca(2+)-dependent NOS activity in the antrum pylorus of the stomach was diminished by endotoxin, whereas Ca(2+)-independent NOS activity was not changed. In addition, decreased nNOS mRNA and protein were observed in the antrum pylorus of endotoxin-treated rats. Our results suggest that downregulation of nNOS in the antrum pylorus of the stomach and synthesis of prostaglandins mediate the delay in gastric emptying of a solid nutrient meal induced by endotoxin.

Inhibition of mitochondrial respiration by endogenous nitric oxide: a critical step in Fas signaling.

We have found that activation of human adult T cell leukemia (Jurkat) cells with anti-Fas Ab leads, in a concentration-dependent manner, to an early burst of production of nitric oxide (NO), which inhibits cell respiration. This results in mitochondrial hyperpolarization, dependent on the hydrolysis of glycolytic ATP by the F1F(o)-ATPase acting in reverse mode. During this early phase of activation, there is a transient release of superoxide anion. All these processes can be prevented by an inhibitor of NO synthase. Approximately 2 h after stimulation with anti-Fas Ab, a distinct second phase can be detected. This comprises a concentration-dependent collapse in mitochondrial membrane potential, a second wave of free radical production, and activation of caspase-8 leading to apoptosis. This second phase is abolished by an inhibitor of caspase activation. In contrast, inhibition of NO synthesis leads to an enhancement and acceleration of these latter processes, suggesting that the early NO-dependent phase represents a protective mechanism. The significance of the two phases in relation to cell survival and death remains to be studied.