China
Africa
Explore chapters and articles related to this topic
Inhalational Durg Abuse
Published in Jacob Loke, Pathophysiology and Treatment of Inhalation Injuries, 2020
Jacob Loke, Richard Rowley, Herbert D. Kleber, Peter Jatlow
When PCP is smoked, the onset of action may be within a few minutes; peak activity is normally reached in 15-30 min and the effects may last from 4 to 6 hr or even longer, dependent on the dose (Burns and Lerner, 1976;Petersen and Stillman, 1978). With oral administration of PCP, the onset of effects is within 45 min, peak effect is achieved by 1.5 hr and lasts for 1 to 3 hr. Immediate effects are obtained with intravenous PCP, which has a duration of prominent symptoms of 1 to 2 hr (Cook et a]., 1982a). The half-life of PCP is estimated from 11 to 89 hr (Giannini and Price, 1985). The drug is metabolized by hydroxylation in the liver into weakly active components and significant quantities of PCP are excreted unchanged in the urine (Cook et al., 1982a,b). The neurophysiologic mechanism of action of PCP is not well defined. PCP acts primarily on the central nervous system with stimulatory, depressant, hallucinogenic, and analgesic effects. It inhibits the metabolism of multiple neurotransmitters including dopamine, acetylcholine, gamma-aminobutyric acid (Giannini and Price, 1985), serotonin (Smith et al., 1977), and norepinephrine. The effects on the dopaminergic system may be the most important neurochemical activity, though nonadrenergic, serotonenergic, and cholinergic disturbances also play a role. The opiate receptors and endorphins are also affected. The drug is nonaddicting and has no withdrawal potential, though some degree of tolerance may develop.
Neurotransmitters and Receptors, Ion Channels, G Proteins and Second Messengers
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
There are at least three types of opiate receptors with different binding characteristics: μ, morphine; δ, enkephalins; and κ, dynorphin. Opioid receptors are Gi-protein-coupled receptors. When opioids bind to their receptors, inhibition of adenyl cyclase results in a decrease in cAMP. This leads to activation of K+ channels, which results in increased K+ efflux. Opioids produce hyperpolarization and depression of CNS cells by opening potassium channels. Opioids inhibit gut motility by increasing potassium or reducing calcium permeability and reducing smooth muscle excitability. In addition, a decrease in cAMP also inactivates voltage-gated Ca++ channels which inhibits neurotransmitter release (e.g. substance P) (Figure 3.9.)
Pharmacological interventions
Published in Ilana B. Crome, Richard Williams, Roger Bloor, Xenofon Sgouros, Substance Misuse and Young People, 2019
During acute opiate intoxication, opiate receptors in a number of brain regions are stimulated. In acute intoxication, the resulting opiate receptor stimulation of the respiratory centre receptors risks causing overdose and death through respiratory suppression. Chronic abuse of opiates up-regulates certain intra-cellular components and this chronic up-regulation and change in the receptor balance cause a withdrawal syndrome when there is a break in opiate consumption.
Morphine attenuates neurotoxic effects of MPTP in zebrafish embryos by regulating oxidant/antioxidant balance and acetylcholinesterase activity
Published in Drug and Chemical Toxicology, 2022
Derya Cansız, Unsal Veli Ustundag, Ismail Unal, A. Ata Alturfan, Ebru Emekli-Alturfan
Morphine is an opium alkaloid that binds to and activates specific opiate receptors to control diverse brain functions (Ghelardini et al. 2015). Although morphine is mainly used for the management of pain, it has also been shown to improve dopamine levels (Sprouse-Blum et al. 2010). The possible mechanism includes the high affinity of the µ opioid receptor for morphine as µ opioid receptor stimulation leads to the hyperpolarization of γ-amino-butyric acid (GABA) interneurons in the ventral tegmental area, to inhibit GABA release (Johnson and North 1992). Consequently, dopaminergic neurons are activated and dopamine release is enhanced. Thus, the interplay between opioid receptors and dopamine display morphine’s potential therapeutic effect in the treatment of PD (Yan et al. 2014). Moreover, neuroprotective effects of morphine have been shown in Alzheimer’s disease against Aβ oligomers induced neurotoxicity (Wang et al. 2015). This study was performed to evaluate the possible neuroprotective effects of morphine in MPTP-exposed zebrafish embryos focusing on the expressions of genes involved in the molecular mechanism of PD, oxidant-antioxidant status, acetylcholinesterase, and locomotor activity.
Naltrexone at low doses (LDN) and its relevance to cancer therapy
Published in Expert Review of Anticancer Therapy, 2022
Naltrexone is an opiate receptor antagonist preventing opiate stimulation; it has been used for decades as a treatment for addiction to opiates as it prevented the euphoria induced by recreational use of morphine and heroin [1,2]. Mechanistically, naltrexone interfered physically with the interaction between opiate and receptor, and by doing so neutralized their action [2]. In reality, however, opiate receptor expression in cells is both complex and malleable, and repeated and chronic stimulation/blockade by naltrexone could lead to changes in the expression and distribution of the receptors. Indeed, in some instances, blocking these receptors to negate opiate action could actually result in a compensatory increase in other receptors [3]. This introduces the interesting possibility that a key ‘MOA’ for naltrexone could actually be to increase the expression of related receptors. However, this could also pose a concern; not only would complicate the treatment of addiction for which naltrexone was initially used but these receptors could provide new targets for other ligands. The implication would be using naltrexone to counteract opiate addiction could unintentionally increase the action of endogenous ligands. It is thus conceivable that naltrexone could influence more than just disorders of addiction. Of particular note, and relevance to the current review, endogenous opioids were reported to be able to influence the immune system to enough of an extent to be considered as immune modulators and a role as immunotherapy was initially considered in the early 1980s [4].
Treating osteoarthritis pain: mechanisms of action of acetaminophen, nonsteroidal anti-inflammatory drugs, opioids, and nerve growth factor antibodies
Published in Postgraduate Medicine, 2021
Yvonne D’Arcy, Patrick Mantyh, Tony Yaksh, Sean Donevan, Jerry Hall, Mojgan Sadrarhami, Lars Viktrup
Though several structures within the CNS express µ-opioid receptors, and their activation can affect sensory discriminative or affective aspects of pain, components of the descending inhibitory pathway and the dorsal horn are thought to be important sites of opioid action in the context of analgesia [86]. In the PAG, opioids act on presynaptic µ-opioid receptors to block GABA release from inhibitory interneurons, resulting in increased descending inhibitory signals from the RVM and LC to the dorsal horn [86,87]. Opioids also act directly in the RVM to activate descending inhibition [86]. In the dorsal horn, activation of presynaptic opioid receptors at terminals of C polymodal nociceptors inhibits release of excitatory neurotransmitters, while activation of post-synaptic receptors on second-order projection neurons induces hyperpolarization and suppresses their excitability [87,88]. The overall effect of opioids is decreased nociceptive signaling from the dorsal horn to higher centers. Actions on opiate receptors on higher-order systems, including areas in the limbic system, may account for effects of opiates on affective components of the pain phenotype [89].