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2.3 – “Utopia resort”: Opiates, naloxone, naltrexone

Physiology
 An opioid is any compound that that acts on at an opioid receptor (utopia resort). 3 endogenous receptors, all expressed
throughout the central & enteric nervous systems (colon shaped table):
o μ (mu-ssage parlor): major analgesic receptor (pain relieving massage); also responsible most adverse effects including
sedation, constipation, respiratory depression, miosis, physical dependence??. Exist in high density in the GI tract &
modulate enteric NS. Stomach, SI, LI decrease motility & increase tone → delayed passage of stool & increased H2O
absorption
oκ
oΔ
 At the molecular level, activated opiate receptors interact with G i proteins and open ion channel. In nn, open K+ channels →
hyperpolarization of the membrane (open banana barrels). Also close VG Ca channels on presynaptic nn terminals (calci-YUM
ice cream; unplugging presynaptic wire) →↓transmitter release (glutamate, ACh, Ne, serotonin, substance P). These effects
combines to stop transmission of pain signals to brain
Opioid withdrawal
 Tolerance is accompanied by physical dependence. Stopping abruptly can cause withdrawal (“withdraw to the spa” sign).
Referred to as abstinence syndrome when occurs abruptly d/t stoppage of analgesics or illegal substances; also in neonates
with opioid withdrawal.
 Presentation: “anxious, hot, & moist” – anxiety, hyperventilation, hyperthermia, muscle aches, rhinorrhea, lacrimation,
yawning, nausea/vomiting, diarrhea, mydriasis.
 With Morphine or heroin: withdrawal SSx start within 6-10 h of last dose, peak 36-48 h, slowly decrease over a few days.
 Detox involves curbing withdrawal SSx and minimizing symptoms using a long-acting opioid agonist (white tapering flag)
o Methadone is a long-acting opioid full agonist used to attenuate withdrawal symptoms (done timer). Once tapered off,
effects slowly subside with much less intense withdrawal. Patient can be slowly weaned off all opiates.
o Buprenorphine is another long acting mu-opioid partial agonist (blueprint). Safer than methadone. Effects slowly subside as
tapered.
 Neonatal abstinence syndrome (irritable, moist, tachypneic baby in pool). Occurs when a newborn undergoes withdrawal from
transplacental transmitted opiates.
o Treatment: full mu-agonist, usually morphine or methadone.
Pure μ agonists
 Morphine & derivatives (hydromorphone) (“More fun, less pain”)
o Prototypic drugs
o μ receptor agonist
o Used in management of chronic pain
 Fentanyl (“make your pain a fantasy”)
o μ receptor agonist
o Used for post-operative & chronic pain
 Tramadol (tram)
o Weak μ receptor agonist (in the background). Used for management of chronic pain.
o Centrally acts on blockade of 5-HT & norepinephrine reuptake (N/S compass), making effective for neuropathic pain
specifically.
 Loperamide (lop-eared rabbits), diphenoxylate (dolphins)
o Don’t cross BBB; work on enteric system.
o Increase colonic phasic segmental activity (i.e. tract squeezes down on stool rather than moving it along) (dolphins back &
forth between haustra)
o Antidiarrheals (muddy footprints)
 Codeine (barcode), dextromethorphan (coughing orphan on package)
o Opioid antitussives (coughing patron). MOA is poorly understood as the physiology of coughing is complicated.
o dextromethorphan also antagonizes NMDA receptors (Nomadic camel on package)
 Shared adverse effects
o Direct extensions of pharmacologic action and may be utilized clinically in certain situations:
 Because principal effects are in CNS, can cause significant sedation & respiratory depression (lady with towel on head).
Drowsiness & clouding of mentation are common adverse effects especially in the elderly, or in combo with other
sedatives
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 ↓brainstem respiratory mechanisms. Dose dependent. May initially be seen as ↑PCO2. Can be fatal with underlying
respiratory disease (deflating lung vest).
 Constipation. Major problem with chronic use or ↑↑dosing, as in the case of managing cancer pain (plunger for clogged
bathroom).
 Miosis (constricted hoodie)
 Biliary colic d/t contraction of biliary smooth muscle (biliary tree with seagull)
o Side effects that are always undesirable
 Tolerance (“All are welcome” sign). Repeated doses have decreasing analgesic effect. After only a few days of exposure,
high tolerance for euphoric, sedating, and respiratory effects.
 No tolerance develops to miosis and constipation (“Out of order” bathroom). Anyone on prolonged opiates should be
on prophylactic bowel regimen.
 LT use (chronic) activation of opioid receptor on nociceptive nn can cause ↑ pain sensitivity; this is referred to as opiate
induced hyperalgesia (masseuse hurting client). Not known how this phenomenon occurs. May be due in part to
downregulation of opiate receptors and/or upregulation of glutamatergic pathways.
Partial agonists (partial foot massage)
 Include buprenorphine, nalbuphine, butorphanol (-buphin = bluefin)
 Used as analgesic.
o Exception is in patients who have developed tolerance to full agonists and still have full agonists onboard. Giving such
patients a partial agonist has the same effect as giving a direct antagonist & may precipitate withdrawal (waiter tripping into
withdrawal spa)
Pure antagonists
 Naloxone (“No Lax Zone” trainer)
o Used to reverse acute opioid toxicity. Completely & dramatically reverses OD effects within 3-5 minutes. Will virtually
instantaneously precipitate withdrawal.
o IF you suspect someone of OD’ing on opiates, IMMEDIATELY administer Naloxone!!!
 No ill effects of administering naloxone when someone has OD’d on something else.
 Naltrexone (“No Tricks” trainer)
o helps maintain abstinence in addicts. Blocks virtually all the effects of heroin, so useful in rehab.
o May also reduce craving for alcohol & nicotine (trainer with XXX beer).
o When combined with bupropion, can provide synergistic approach for weight loss (guy working out).