modulate nociception at synapses

enkephalins, endorphins, dynorphins

endogenous painkillers

mu opioid Receptor-mediated effects include

Analgesia, euphoria, respiratory depression, bradycardia, obstipation, urinary retention, high addiction potential, miosis

delta opioid receptors

effects unknown

kappa opioid receptors - spinal levels

inhibition of Ca channels, reduction of NT release

spinal analgesia, dysphoria, psychotomimetic effects, low addiction potential

mu agonist (same effects as endorphins)

itching (histamine release)

N&V (D receptors)

hepatic metabolism to M6G

analgesic potency = 1 by definition

use during MI for pain, slow /o2 consumption

morphine sans histamine release

AP = 0.8

methylmorphine

hepatic metabolism (2D6 and 3A4) converts to morphine (10%)

AP therefore = 0.1

2D6: some people rapid metabolizers, experience sedation; slow = no pain relief

mu opioid receptor agonist but mainly NeSRI (like antidepressant) for chronic pain

mixed drug

central alpha2 agonist (?)

kappa agonist

dysphoria

unpopular drug

mu agonist and NMDA antagonist

chronic pain (?)

difficult to work with (sedation, RR depression)

long half life, used in rehab

highly selective mu agonists

-fentanil

much more potent than morphine

short duration

remifentanil = ultra short duration, since it has ester bond (plasma esterases in blood); like cocaine

most potent anticholinergic among opioids - creates large pupil instead of small

SSRI, interacts with MAOI or ecstasy, causes serotonin syndrome (hyperthermia)

too much opioid = respiratory depression

treat with naloxone

constipation, N&V

give 5HT3 blockers (-setron, expensive), D2 blockers (droperidol [clean], metoclopramid [mixed, also 5HT3 antagonist and 5HT4 agonist, emptying GI]), or muscarinic blockers in vestibular nucleus (only for motion sickness, scopolamine [transdermal])

muscarinic blocker, but do not use for motion sickness - too short duration

poem for all muscarinic blockers (central anticholinergic syndrome): dry as a bone, red as a beet, hot as a hare, blind as a bat, mad as a hatter

D = diarrhea

U = Urination
M = Miosis
B = Bronchorrhea/Bronchospasm
B = Bradykardia
E = Emesis
L = Lacrimation
L = Laxation
S = Salivation

antiemetic

H1 receptor blocker

but antiemetic because also anticholinergic (muscarinic blocker)