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The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
At their site of action, drugs interact with molecules termed drug ‘receptors’ or ‘targets’. These are often actual biological receptors, such as hormone receptors, but they may also be any other type of molecule, such as an enzyme or membrane channel. The affinity of a drug-receptor interaction is a measure of how tightly the two molecules bind. An agonist is a substance that has an effect on a specific drug receptor, causing activation of the function of the receptor molecule. A partial agonist has the same type of effect on the function of the receptor molecule, but even at the maximal effect of the drug, the function of the receptor molecule is not activated to its maximal level. An antagonist is a drug that binds, to but opposes, the natural activity of the receptor molecule. Competitive antagonists compete with agonists for the same receptor, but they do not exert an agonist effect themselves and so reduce the effect of any agonist present. In these circumstances, the overall effect will depend on the relative concentrations of agonist and antagonist. A non-competitive antagonist does not compete for the same site but opposes the effect of the agonist by another mechanism. Finally, an irreversible antagonist is an antagonist that inactivates the receptor molecule permanently once it has bound. This effect cannot be reversed, even at high concentration of agonist. Many drug receptors are bound by naturally occurring agonists and antagonists, including hormones and neurotransmitters.
Dopamine Receptors, Signaling Pathways, and Drugs
Published in Nira Ben-Jonathan, Dopamine, 2020
To encompass the full range of drug actions at the DARs, an updated drug definition was proposed [63]. According to this terminology, an agonist is defined as a substance that binds to a specific receptor and stimulates the signaling pathway known to be associated with it. A partial agonist causes a less than maximal response but can also act as a partial antagonist. An antagonist has no effects on its own but, rather, blocks an agonist-induced signaling. A somewhat confusing term is inverse agonist, defined as a ligand that binds to a receptor and inhibits agonist-independent (constitutive) signaling. These concepts are schematically presented in Figure 2.11.
Acute management of substance use disorders in youth
Published in Ilana B. Crome, Richard Williams, Roger Bloor, Xenofon Sgouros, Substance Misuse and Young People, 2019
As described above, patients with alcohol use disorder should be considered for withdrawal management using benzodiazepines, as well as thiamine. Patients with moderate to severe opiate use disorders may benefit from partial agonist therapy (i.e., buprenorphine). Through a randomised controlled trial, Marsch et al. (2005) found that treatment retention and opiate-negative urine screens were significantly higher for people who received buprenorphine, relative to clonidine.
Open-label, rapid initiation pilot study for extended-release buprenorphine subcutaneous injection
Published in The American Journal of Drug and Alcohol Abuse, 2023
Howard Hassman, Stephanie Strafford, Sunita N. Shinde, Amy Heath, Brent Boyett, Robert L. Dobbins
An ongoing concern with induction of buprenorphine is that precipitated withdrawal symptoms will emerge when a full opioid agonist is replaced by the partial agonist. For this reason, various low-dose approaches have been proposed for gradually transitioning patients from methadone to buprenorphine (26) or starting buprenorphine treatment over a period of several days (27). Given the challenges of retaining patients during buprenorphine induction and the risk of overdose with patients who do not receive medications for opioid use disorder, we have explored single-day induction with BUP-XR to quickly achieve sustained concentrations of buprenorphine that address symptoms of withdrawal, reduce opioid craving, and block the reinforcing effects of illicit opioids (14). This protocol is more consistent with the procedures proposed by Mariani et al. for clinic induction7 and Herring et al. for emergency department induction28. The potential risks of this approach are POW and sedation following the 300-mg dose of BUP-XR. In this sample of 26 subjects, the single-day induction protocol did not result in marked sedation or a protracted period of POW, as illustrated by adverse events reporting and frequent measures of sedation VAS and COWS scores up to 48 hours after BUP-XR injection.
Aripiprazole for the treatment of Tourette syndrome
Published in Expert Review of Neurotherapeutics, 2021
Joanna H. Cox, Andrea E. Cavanna
Aripiprazole is a quinolinone derivative antipsychotic characterized by a distinct pharmacological profile when compared to other antidopaminergic medications. Specifically, it acts as a partial dopamine receptor agonist (at the D2 receptor), as well as having functionally selective properties [51]. This differs from other antidopaminergic medications, which work as dopamine receptor antagonists. Partial agonism occurs when a drug binds to a particular receptor, but causes a fraction of the response that a full agonist would. Despite binding the D2 dopamine receptor with the same affinity as a full agonist, aripiprazole triggers a response that is lower compared to a full agonist, but higher compared to an antagonist. Aripiprazole is commonly used in the treatment of schizophrenia, as it has been shown to treat both positive and negative symptoms, according to its flexible mechanism of action. It has been shown to have similar efficacy to older antidopaminergic drugs, and an overall lesser propensity for extrapyramidal and metabolic adverse effects [52]. This makes aripiprazole an attractive option, where problems with tolerability affect medication compliance and ultimately quality of life.
Variants of opioid genes and response to treatment of opioid use disorder with buprenorphine-naloxone versus extended-release naltrexone in Caucasians
Published in The American Journal of Drug and Alcohol Abuse, 2020
Matthew Randesi, John Rotrosen, Edward V Nunes, Joshua D Lee, Patricia Novo, Orna Levran, Jurg Ott, Martina Pavlicova, Jennifer Scodes, Mary Jeanne Kreek
Gene variants, particularly those affecting pharmacodynamics and/or pharmacokinetics, can influence pharmacotherapy outcomes (8–12). Both buprenorphine and naltrexone are partial kappa agonists and both act at the mu opioid receptor, buprenorphine as a partial agonist and naltrexone as an antagonist. Thus, one might expect gene variants in the mu opioid receptor to be associated with better response to one than the other – i.e., gene variant by treatment interaction. Both medications also act as kappa opioid receptor antagonists, and thus one might expect variants in the kappa system to predict outcome similarly for both medications, or perhaps to predict differently (i.e., gene variant by treatment interaction) if, for example, kappa antagonism has different effects in the setting of mu partial agonism versus antagonism.