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      Autoinjector device for rapid administration of drugs and antidotes in emergency situations and in mass casualty management

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          Abstract

          There are several situations such as medical emergencies and incidents involving mass casualties where drugs and antidotes have to be administered immediately along with other first aid at the site of the event. Self-administration by the affected person or by a companion is required as a life-saving measure. Autoinjector devices (AIDs) are useful for the rapid administration of drugs and antidotes and they can also be used by those who have not been medically trained. This makes them very convenient for emergency and mass casualty management. An AID has a drug cartridge with an embedded needle for subcutaneous or intramuscular injection, which is usually painless. The drugs are delivered slowly by the AID across a large area in the muscle, which increases the absorption and the drug effects are equal to that of intravenous administration. A variety of AIDs are available, such as atropine and pralidoxime for nerve agent poisoning, epinephrine for anaphylactic shock and allergy, diazepam for seizures, sumatriptan for migraine, amikacin for antibacterial treatment, buprenorphine for pain relief and monoclonal antibodies for a variety of diseases. This review describes the published peer-reviewed literature identified by online searches of journal databases.

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          Most cited references62

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          Twelve reasons for considering buprenorphine as a frontline analgesic in the management of pain.

          Buprenorphine is an opioid that has a complex and unique pharmacology which provides some advantages over other potent mu agonists. We review 12 reasons for considering buprenorphine as a frontline analgesic for moderate to severe pain: (1) Buprenorphine is effective in cancer pain; (2) buprenorphine is effective in treating neuropathic pain; (3) buprenorphine treats a broader array of pain phenotypes than do certain potent mu agonists, is associated with less analgesic tolerance, and can be combined with other mu agonists; (4) buprenorphine produces less constipation than do certain other potent mu agonists, and does not adversely affect the sphincter of Oddi; (5) buprenorphine has a ceiling effect on respiratory depression but not analgesia; (6) buprenorphine causes less cognitive impairment than do certain other opioids; (7) buprenorphine is not immunosuppressive like morphine and fentanyl; (8) buprenorphine does not adversely affect the hypothalamic-pituitary-adrenal axis or cause hypogonadism; (9) buprenorphine does not significantly prolong the QTc interval, and is associated with less sudden death than is methadone; (10) buprenorphine is a safe and effective analgesic for the elderly; (11) buprenorphine is one of the safest opioids to use in patients in renal failure and those on dialysis; and (12) withdrawal symptoms are milder and drug dependence is less with buprenorphine. In light of evidence for efficacy, safety, versatility, and cost, buprenorphine should be considered as a first-line analgesic.
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            Epinephrine absorption in children with a history of anaphylaxis.

            Prompt injection of epinephrine is the cornerstone of systemic anaphylaxis treatment. The rate of epinephrine absorption has not been reported previously in allergic children. Our objective was to study the clinical pharmacology of epinephrine in this population. We performed a prospective, randomized, blinded, parallel-group study in 17 children with a history of anaphylaxis to food, Hymenoptera venom, or other substances. We injected 0.01 ml/kg epinephrine solution (maximum 0.3 ml [0.3 mg]) subcutaneously, or 0.3 mg epinephrine intramuscularly from an autoinjector. Plasma epinephrine concentrations, heart rate, blood pressure, and adverse effects were monitored. In nine children who received epinephrine subcutaneously, the mean maximum plasma epinephrine concentration (+/- SEM) was 1802 +/- 214 pg/ml, achieved at a mean time of 34 +/- 14 minutes (range, 5 to 120 minutes). Only two of the nine children achieved maximum plasma concentrations by 5 minutes. In eight children who received epinephrine intramuscularly, the mean maximum plasma concentration was 2136 +/- 351 pg/ml, achieved at a mean time of 8 +/- 2 minutes, which was significantly faster than the mean time at which maximum plasma concentrations were achieved after subcutaneous epinephrine injection (p < 0.05). Six of the eight children achieved maximum plasma concentrations by 5 minutes. The terminal elimination half-life was 43 +/- 15 minutes. No serious adverse effects were noted in any child. In children, recommendations for subcutaneous epinephrine injection are based on anecdotal experience, and should be reevaluated in view of our finding of delayed epinephrine absorption when this route is used. This delay might have important clinical implications during an episode of systemic anaphylaxis. The intramuscular route of injection is preferable.
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              Serotonin receptor agonists in the acute treatment of migraine: a review on their therapeutic potential

              Migraine is an important socioeconomic burden and is ranked the sixth cause of years of life lost because of disability in the general population and the third cause of years of life lost in people younger than 50 years. The cornerstone of pharmacological treatment is represented by the acute therapy. The serotonin (5-hydroxytryptamine [5-HT]) receptor subtype 1B/1D agonists, called triptans, are nowadays the first-line acute therapy for patients who experience moderate-to-severe migraine attacks. Unfortunately, a high percentage of patients are not satisfied with this acute treatment, either for lack of response or side effects. Moreover, their mechanism of action based on vasoconstriction makes them unsuitable for patients with previous cardio- and cerebrovascular diseases and for those with uncontrolled hypertension. Since the introduction of triptans, no other acute drug class has passed all developmental stages. The research for a new drug lacking vasoconstrictive effects led to the development of lasmiditan, a highly selective 5-HT1F receptor agonist with minimized interactions with other 5-HT receptor subtypes. Lasmiditan is considered to be the first member of a new drug category, the neurally acting anti-migraine agent (NAAMA). Phase II and III trials had shown superiority compared to placebo and absence of typical triptan-associated adverse events (AEs). Most of the AEs were related to the central nervous system, depending on the high permeability through the blood–brain barrier and mild to moderate severity. The results of ongoing long-term Phase III trials will determine whether lasmiditan will become available in the market, and then active triptan comparator studies will assess patients’ preference. Future studies could then explore the safety during pregnancy and breastfeeding or the risk that overuse of lasmiditan leads to medication overuse headache.
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                Author and article information

                Journal
                J Int Med Res
                J. Int. Med. Res
                IMR
                spimr
                The Journal of International Medical Research
                SAGE Publications (Sage UK: London, England )
                0300-0605
                1473-2300
                21 May 2020
                May 2020
                : 48
                : 5
                : 0300060520926019
                Affiliations
                [1-0300060520926019]Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
                Author notes
                [*]Rajagopalan Vijayaraghavan, Director of Research, Department of Research and Development, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Thandalam, Chennai, 602105, India. Email: jai_vijay@ 123456hotmail.com
                Author information
                https://orcid.org/0000-0002-2805-5404
                Article
                10.1177_0300060520926019
                10.1177/0300060520926019
                7243406
                32436421
                e1521841-1910-4df4-af16-5cb9f8f1c304
                © The Author(s) 2020

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 4 January 2020
                : 21 April 2020
                Categories
                Review
                Custom metadata
                corrected-proof
                ts2

                autoinjector device,nerve agent,anaphylaxis,seizures,migraine,antimicrobial,analgesic,drugs,antidotes,monoclonal antibodies

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