Utopia Resort Opiates, Naloxone, Naltrexone

2.3 – “Utop “Utopia ia resort”: Opiates, naloxone, naltre naltrexone xone 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 withdr withdrawal awal • 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 ▪ ↓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 agon agonists ists (partial foo foott 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 antagoni antagonists sts • 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).