Opioids Flashcards
- Opium
- Opioid
- Opiate
- mixture of alkaloids derived from the poppy plat soniferum
- any naturally occurring, semi- or synthetic compounds that bind to opioid receptors and share the properties of endogeneous opioids
- any naturally occurring opioid derived from opium
Good vs. Bad pain
Good - acute, nociceptive (when you touch something sharp), inflammatory (caused by inflammatory mediators), peripheral, protective
Bad - chronic, neuropathic (due to peripheral nerve damage, ex: diabetes), non-neuropathic/ non- inflammatory (no tissue/nerve damage, doctors cannot find the cause), sensitization…
The good pain pathway (4)
- Transduction (hot, cold, pressure, fire…)
- Conduction (to nerves)
- Transmission (to brain)
- Perception (withdrawal, pain avoidance, emotional reaction)
Reception and modulation of pain (10)
- something causes pain
- 1st neuron
- dorsal horn of spinal cord
- goes in opposite direction - 2nd neuron
- thalamus
- brain cortex
A fibers - myelinated - responsible for acute pain
C fibers - responsible for chronic pain
Descending neurons - a type of pain relief (NE and serotonin)
Ascending neurons - perception of pain
Mediators of:
- Facilitatory pathways
- Inhibitory pathways
- Glutamate, Aspartate, 5-HT
2. Opioids, GABA, 5-HT, NE
- Transduction mediators (nonciceptive terminals) (7)
2. Mediators are inhibited by:
- Capsaicin, Seronin, Histamine, Norepinephrine, Bradykinin, Prostaglandin, Canabinoids
- NSAIDS
Nociceptive terminals pic
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Endogenous Opioid Peptides
-3 families (names and from where they are synthesized)
- enkephalins –> met-ENK, leu-ENK
- endorphins –> alpha, beta, gamma END
- dynorphins –> DYN-A, DYN-B, alpha-neodynorphin, beta-neodynorphin
- synthesized from pro-enkephalin or pro-enkaphalin A
- synthesized from POMC (pro-opiomelacortin)
- synthesized from pro-dynorphin or pro-enkaphalin B
Opioid receptors (6)
- G-protein coupled receptors
- inhibit adenylate cyclase
- active phospholipase C
- facilitate opening of potassium channels at post-synaptic level
- inhibit opening of calcium channels at pre-synaptic level
- mu, delta, kappa
Opioid receptors
-what happens when they are activated (mu, delta, kappa table)
- mu - analgesia in all levels, respiratory depression, pupil constriction, decrease GI motility, euphoria, sedation, physical dependence
- delta - spinal analgesia, respiratory depression, decrease GI motility
- kappa - spinal and peripheral analgesia, pupil constriction, decrease GI motility, dysphoria, sedation, physical dependence
Opioids
-area where they act in the CNS
-act on descending inhibitory pathways - medulla and midbrain in the periaqueductal area, rostral ventral medulla, dorsal horn
Morphine
- actions (10)
- therapeutic indications (5)
- analgesia, sedation, respiratory depression, decreases GI motility, decrease baroreceptor reflexes, histamine release from mast cells, pupillary constriction, euphoria, depression of cough reflexes, nausea and vomiting
- analgesia, euphoria, depression of baroreceptor reflexes (acute pulmonary edema), depression of cough, effects on GI tract
- Overdose triad
- main cause of death in intoxication
- treatment for intoxication
- pupillary constriction, comatose state, respiratory depression
- respiratory depression
- antagonists (ex: naloxone)
Tolerance vs. Dependence
Tolerance - adaptive up-regulation of adenylyl cyclase –> opioids inhibit adenylyl cyclase, so if you increase it’s concentration (ac) they will counteract each other
Dependence - satisfied by mu-receptor agonists (euphoria) and withdrawal syndrome happens due to mu-receptor antagonists
- Physical dependence: withdrawal syndrome lasting for a few days
- Psychological dependence: craving lasting for months or years
Methadone
- function
- pharmacokinetics
- other drugs
- used to relief withdrawal symptoms
- weak, long acting, mu-receptor agonist, half-life is >24h, little euphoric and less sedative effects, slow onset of action and recovery
Other drugs - much less physical or psychological dependence
- Codeine - partial mu agonist
- Pentazocine - mu antagonist, kappa agonist