In addition, no serious adverse events, including hepatotoxicity, were reported [71,72,73,74,75,76,77,78,79,80,81]. Maximum plasma concentration of rimegepant after oral administration is achieved after 1.5 h, and its bioavailability is 64%. antibodies, the issue of pharmacodynamic interactions related to the modulation of the immune system functions was addressed. It also focuses on the effect of monoclonal antibodies on expression of class Fc gamma receptors (FcR). Keywords: migraine, lasmiditan, gepants, monoclonal antibodies, drugCdrug interactions 1. Introduction Migraine is a chronic neurological disorder characterized by a repetitive, usually unilateral, pulsating headache with attacks typically lasting from 4 to 72 h. The pain is characterized by a varying degree of intensity and frequency of occurrence and is accompanied, among others, by photophobia, phonophobia, osmophobia, and nausea and vomiting [1,2]. An average of 11C12% of the population in Europe and North America suffer from migraines, of which 75% are women. Chronic migraine occurs through the chronification of episodic migraine, MDM2 Inhibitor thus increasing the frequency of attacks and the accompanying change of nature of some of them into pain more reminiscent of a tension-type headache than migraine. Patients with chronic migraine also very often Mouse monoclonal to CCND1 develop MDM2 Inhibitor drug-overuse headache, which is usually very difficult to differentiate from primary headache . As shown in observational studies in the current epidemiological situation, headache can also be a quite vital symptom in patients with COVID-19, appearing both in presymptomatic and symptomatic phases [2,3,4,5,6]. It was observed that from 11% to 34% of hospitalized patients (mainly young women under 50 years of age) infected with SARS-CoV-2 reported headaches similar to typical migraines or tension headaches. Mean incidence of headaches in all symptomatic COVID-19 patients is approximately 8% [3,4,5,6]. The probable pathophysiology of headache development in COVID-19 patients is associated with neurogenic inflammation in the olfactory and trigeminal nerves due to MDM2 Inhibitor release of pro-inflammatory mediators, e.g., cytokines and chemokines, as well as activation of prostaglandins in response to penetration of SARS-CoV-2 into the body through the nasal passages [7,8]. Current guidelines for treatment of mild to moderate migraine attacks [9,10,11,12] recommend non-opioid analgesics. In moderate to severe attacks, usually triptans alone or in combination therapy with non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol and antiemetics are recommended. However, due to their vasoconstriction effect, triptans are contraindicated in patients with ischemic heart disease or peripheral vascular disease. Neither do they yield satisfactory results in approximately 30% of patients with severe and moderate migraine [3,13]. Currently, promising novelties in moderate and severe migraine therapy include: lasmiditan (selective 5-HT1F receptor agonist) [13,14], gepants (calcitonin gene-related peptide (CGRP) receptor antagonists) , and, in prevention of migraine attacks, anti-CGRP monoclonal antibodies (mAbs) [16,17]. As has been shown so far, all of the above anti-migraine medications can be used in patients with migraine and COVID-19 [3,5,6,8,18]. DrugCdrug interactions (DDIs) in the pharmacokinetic phase can significantly affect blood concentration and bioavailability of a drug and, thus, its safety and efficacy [19,20]. Pharmacodynamic drugCdrug interactions, such as acting as an agonist or antagonist at the receptor, may also increase or decrease the effects of a drug. The risk of interaction increases with each new drug being taken. If two drugs are used simultaneously, there is already a clinically significant risk of interaction; if there are more than seven drugs, interaction is relatively certain . MDM2 Inhibitor This is of particular importance in the context of the ever-increasing number of chronically ill patients and aging population. After oral administration, the factor determining the occurrence of DDI is mainly drug metabolism mediated by the cytochrome P450 (CYP) system  and efflux transporters such as P-glycoprotein (P-gp), the multidrug resistance protein 2 (MRP2), and the breast cancer resistance protein (BCRP) . Significant pharmacokinetic interactions of orally administered drugs may also occur during the absorption phase. In this case, the effect is a decrease rather than an increase in the drug absorption, and a distinction must be made between interactions resulting in a reduced absorption rate and those affecting the total amount of the drug absorbed [19,20]. Treatment of migraine, especially of moderate and severe intensity, is often based on polypharmacotherapy and the need to use not only typical analgesics but MDM2 Inhibitor also such.
In addition, no serious adverse events, including hepatotoxicity, were reported [71,72,73,74,75,76,77,78,79,80,81]
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