China
Africa
Explore chapters and articles related to this topic
Medical Management of Chemical Warfare Agents
Published in Brian J. Lukey, James A. Romano, Salem Harry, Chemical Warfare Agents, 2019
While the normal functions of BuChE and CaE in the human body are unknown, BuChE is responsible for hydrolyzing drugs that contain ester linkages. These include ester local anesthetics such as cocaine, procaine, chloroprocaine, and tetracaine; the depolarizing muscle relaxant succinylcholine; and the non-depolarizing neuromuscular blocking drug mivacurium (Jensen et al., 1995). Other drugs hydrolyzed (broken down by combining with water) by plasma cholinesterase include the short acting beta blocker esmolol, remifentanil (an opioid), the intravenous anesthetic induction drug etomidate (often used in situations of cardiovascular instability), propanidid (not available within the United States), monoamine oxidase inhibitors (anti-depression medications), and the anti-cancer medication methotrexate (Iohom et al., 2004). Human carboxylesterase 1 hydrolyzes heroin and cocaine (Redinbo et al., 2003).
Physiology of the immune system
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2015
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
The reported incidences of adverse reactions to induction agents, muscle relaxants and plasma volume expanders vary widely. Allergic reactions to propanidid (1 in 540 to 1 in 1,700) and althesin (1 in 900–1 in 1,100) were more common than reactions to thiopental (1 in 14,000). Non-depolarizing muscle relaxants are the most common cause of life-threatening reactions during anaesthesia, the reported incidence being as high as 1 in 1,200 exposures. Most are IgE-mediated, and suxamethonium is the most common causative agent. Alcuronium and atracurium have a high incidence of reactions compared with pancuronium and vecuronium. True allergy to local anaesthetic drugs is rare, and is by IgE-mediated reactions. IgE-mediated allergies to methylparaben, a preservative in local anaesthetic solutions, have been reported.
GABA(A) receptor-targeted drug development -New perspectives in perioperative anesthesia
Published in Expert Opinion on Drug Discovery, 2019
Bernd Antkowiak, Gerhard Rammes
AZD-3043 (previously named THRX-918661) is a structural analog of propanidid, an agent, introduced by Bayer in 1963. In a study including 123 human subjects, AZD-3043 caused sedation and hypnosis with no pain on injection [43]. The pharmacokinetic properties were determined from bolus injections and 30-min infusions [44]. A rapid onset and fast recovery of sedation or hypnosis was observed. These findings were consistent with a high clearance and a low apparent volume of drug distribution. Clinically relevant changes in respiratory rate or arterial blood pressure were not observed and ventilation was maintained. However, these studies also reported some undesirable effects. Most important, AZD-3043 induced allergic-type reactions (erythema, chest discomfort and dyspnea) in three subjects. Another disadvantage is that the drug is formulated in a lipid, so the respective problems known from propofol emulsion possibly come into play. On the molecular level, AZD-3043 acts as a positive allosteric modulator at GABAA receptors [45]. The potency and efficacy of AZD-3043 to enhance currents through GABAA receptors expressed in Xenopus oocytes was dramatically reduced by point mutations in the β2- (β2(N289M)) and β3- (β3(N290M)) subunits of the GABAA receptor. Since similar mutations (β2(N265S and β3(N265M)) strongly attenuated the hypnotic effect of propofol in mice, it seems likely that propofol and AZD-3043 act via similar binding sites on GABAA receptors.