pain and opioids Flashcards
Neuropeptides
Some neuropeptides also act as hormones eg. (oxytocin or vasopression)
Linear polymer made up of amino acids joined by peptide bonds
Found in CNS and peripheral nervous system
pain
Nociceptive or inflammatory pain results from activation of this circuit.
Neuropathic pain results from injuries of this circuit.
Brain interprets and modulates this noxious information to give us our experience of pain.
Descending Analgesic Pathway
Stimulation increases release of endogenous opioids that activate μ-opioid receptors in the PAG to produce analgesia.
Morphine mimics the endogenous opioid actions in the PAG to produce analgesia.
opioids
Opioidsare drugs that act at the opioid receptors
Opioid alkaloids are still harvested from opium poppies Includes: morphine (can be made into heroin), codeine and thebaine
(used as base for semi-synthetic opioids such as oxycodone, buprenorphine, naloxone & naltrexone).
actions of opioids
Analgesia –still mainstay for strong pain relief.
Euphoria- the ‘rush’ or feeling of well-being (dependence liability)
Impaired cough reflex- antitussives
Constipation-for anti-diarrhealsbut also side effect
adverse effects of opioids
Respiratory depression-major cause of death
Nausea and vomiting- usually early may need anti-nauseants
Dependence- withdrawal syndrome, intense craving.
Miosis- pupillary constriction, may be indicator of opioid use
Pruritis- Itching, particularly with iv or intrathecal admin
Opioid Receptors
drugs target GPCRs
- Agonist action-
Inhibitory – GABAergic, glutamatergic, dopaminergic neurons
Antagonist
- 3 receptors same intracellular signaling but different clinical response
Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin
μ-opioid receptor
agonist
Agonists at the μ-opioid receptor produce strong analgesia, constipation, nausea, respiratory depression, reduced cough reflex, tolerance and dependence
Important sites of opioid action
- Mesolimbic system important for euphoria reward
- Increase release of dopamine and euprhoria
- Euphoria reward
- Dopamine is ceatecholaimine
examples pf Competitive μ-Opioid Receptor Antagonists
naloxone
methylnatrexone
naltrexone
Naloxone
o Short acting
o Low oral bioavaliblity
o Used for reversal of opioid overdose
o Can be combined with opioid agonists to prevent injection
opiate antagonists
Methylnaltrexone
oBlocks peripheral receptors
oPrevents constipation
oCan reduce analgesia
opioid receptor antagonists
Naltrexone
oLong acting
oHigh oral bioavaliblity
oReduces craving in alcohol dependence
oOpioid dependency management
opioid receptor antagonists
CNS neuropharamacology
•GABA and glutamate are the fast neurotransmistters in the brain
•Neuromodulates more subtly regulate brain activity and are the targets of many clinically useful drugs
•Need to consider
oRole of target
oLocation of target
oAction of durg of the target
