Opioid Analgesics Flashcards
Mechanism of action of opioids
Opioid receptors couple to Gi/o proteins
Close voltage-gated Ca2+ channels on presynaptic nerve terminals–> reduce transmitter release
Open K+ channels–>hyperpolarize–> inhibit postsynaptic neurons
Receptor mechanisms
1) opioids act at mu-opioid receptors (MOR)–>attenuate in periphery or in afferent axon
2) block presynaptic endings of dorsal horn
3) inhibit postsynaptic neuron
Ascending pathway(transmits pain) Afferent nociceptor, dorsal horn, ventral caudal thalamus
Descending pathway (pain control system)
Dorsal horn, rostral ventral medulla, periaqueductal gray
Inhibit inhibitory GABA system–> increase activity of descending pathway–> decrease nociceptive processing
CNS effects of opioids
Analgesia: reduces both sensory and emotional aspects of pain (unique); act at spinal and supraspinal sites; acute pain but NOT chronic pain
Behavior: sedation, relaxation, euphoria, dysphoria, anxiety
Respiratory: depressed neuronal activity in brainstem, decreased sensitivity of neurons to CO2, reflexive vasodilation in brain–> increase intracranial pressure (cautious use in head trauma); respiratory arrest–>death
Cough suppression: via brain stem chemoreceptor trigger zone (antitussive)
Nausea/vomiting: area postrema in medulla, vestibular contribution,
Miosis (pupil constriction)
Neuroendocrine: decreased release of ACTH and GnRH, enhanced release of ADH–>oliguria
Cardiovascular effects of opioids
hypotension, bradycardia, decreased cardiac O2 consumption, peripheral vasodilation (histamine release)
Respiratory effects of opioids
decreased respiratory drive by central mechanism, bronchoconstriction via histamine (concern for asthma and COPD)
GI effects of opioids
increased tone-->decreased motility-->constipation increased tone-->spasm and biliary colic antidiarrheal agent (imodium)
Renal effects of opioids
Increased muscle tone of bladder, ureters, and urethral sphincter–>urinary retention
Increased release of ADH and peripheral reduction in renal plasma flow–>oliguria
Uterus effects of opioids
diminished contractions and force–>prolonged labor
Side effects and toxicities of opioids
Side effects: sedation, respiratory depression, nausea, vomiting, euphoria/dysphoria, seizures, hypotension, constipation, increased intracranial pressure, urinary retention, uticaria (hives
Drug interactions:
Sedatives/hypnotics–>increased CNS depression
Antipsychotics–> increased respiratory depression
MAO inhibitors–>hyperpyretic reaction (increased temperature) and hypertension; NEVER use meperidine with MAOIs
morphine
hydromorphone
oxymorphone
Strong opioid agonist
Pharmacological effects: analgesia, relief of anxiety, sedation, respiratory depression, pupil miosis, slowed GI (constipation), urinary retention, cough suppression, nausea and vomiting, vasodilation (avoid use with head trauma)
Use: severe pain, adjunctive anesthesia, pulmonary edema
Metabolism: first-pass effect
Toxicity: respiratory depression, severe constipation, addiction liability, convulsions
Hydromorphone and oxymorphone like morphine in efficacy but higher potency
fentanyl (Sublimaze)
sufentanil
Strong opioid agonist
Similar to morphine but more potent
Use: severe pain, adjunct anesthesia
Route of admin: transdermal patch
methadone (Dolophine)
Strong opioid agonist
similar to morphine
Slow onset, longer duration of action
Use: maintenance of opioid addiction (dependence develops more slowly and withdrawal symptoms milder)
Adverse effects: cardiac arrhythmias
merperidine (Demerol)
Strong opioid agonist
Anticholinergic properties: no miosis, tachycardia, no spasms GI/GU/gallbladder
P450 metabolized–> active metabolite normeperidine–> serotonin reuptake inhibitor–> stimulant–>interaction with MAOI
Side effects: serotonin syndrome, seizures
codeine
hydrocodone
oxycodone
Moderate (partial) opioid agonists
Similar to morphine
Metabolism:
Hepatic CYP2D6–>active form (morphine)–>caution with children
Use: mild-moderate pain, combination with other analgesics, cough suppressant (antitussive)
buprenorphine
butorphanol
nalbuphine
pentazocine
Mixed opioid agonist-antagonist
MOA: agonists at some receptor subtypes and antagonists at other receptor subtypes
Analgesic effects, buprenorphine reduces alcohol craving
Use: moderate pain
Side effects: less respiratory depression than morphine, psychomimetic effects, abuse potential
Caution: unpredictable when used with agonist (analgesic effect blunted), resistant to naloxone reversal, precipitate withdrawal
dextromethorphan
Opioid agonist
Use: antitussive by reducing cough reflex, acute debilitating cough
Minimal toxicity
