Opioid Anagelsics Flashcards
Opioid vs narcotic
Opioid is anything that binds to the Mu receptor and inhibits pain
Narcotics are anything that produce sedation/drowsiness
Classification 1: weak vs strong
Codeine is weak
Everything else is considered strong
Antitussives and antidiarrheals are excluded
Mu receptor agonists
Antagonists
Morphine, merperidine, hydromorphone, etc.
Mu antagonists, bind to this receptor and elicit no response (also but less at kappa and delta)- naloxone and naltrexone
Agonist/antagonists
Partial agonist
Kappa agonist/Mu antagonist: nalbuphine
Partial Mu agonist but HIGH affinity: buprenorphine (used for opioid maintenance in addiction)
High vs low lipophilicity
High- fast onset (1min IV), short duration (20 min): fentanyl, merperidine
Low- slow onset (10 min IV), long duration (hour): morphine, hydromorphone
Opioid receptors
Mu, kappa, delta: one gene codes for each one. Subtypes come from splice variants. All involved in spinal and supraspinal sites
Mu receptor produces:
Site:
Analgesia, euphoria, dependence, respiratory depression, miosis
Mu1 is more supraspinal, Mu2 is more spinal
Kappa receptors produce:
Mild analgesia, less respiratory depression, psychomimetic effects (unlike euphoria)
Locations of opioid receptors and what they elicit
Thalamus/amygdala:suffering of pain, emotional perception of it
Brainstem ventilation nuclei: can knock out and stop breathing
PAG: gateway in MB when switched on to send endorphins down spinal cord to blunt pain transmission and reduce suffering
Area postrema: nausea
Spinal trigeminal nucleus: itchy AEs
Substantial gelatinosa: pain relief
*GI tract (enteric NS layer): constipation
Opioid mechanism
Work via G receptor proteins which then inhibit cellular adenylyl cyclase. Increase K+ and decrease Ca++ currents, causes hyperpolarization, and decreased nociceptive transmission.
Doesn’t affect touch and motor fibers like with alcohol and local anesthetics dampening touch receptors
In SG, the opioid receptors are primary pre-synaptic on C fibers.
Opioids also activate the PAG- trigger descending inhibitory paths to release endorphins by inhibiting GABA releasing inhibitory neurons in the PAG (freeing them of inhibition)
What drug is notable for having a half life of 24 hours?
Methadone. Can range from 12-104 hours. Which is why you never start treatment with methadone*
What is special about the miosis effect of opioids?
There is no tolerance built to this effect
Same with constipation, if this SE is present.
What is a good opioid to use/switch to deal with opioid side effects?
Antagonist
Agonist/antagonist
Amphetamines
Abstinence syndrome
Withdrawal occurs after cessation of use
Unique to someone who has been exposed to the opioid before
Symptoms of opioid withdrawal
Sweating, HTN/tachycardia, hyperventilation, mydriasis- essentially opposing sympathetics of each opioid parasympathetic effect, except diarrhea/abdominal cramping occurs via direct withdrawal from gut receptors.
NON LETHAL WITHDRAWAL
Opioid agonists
Morphine, codeine, oxycodone, hydrocodone (Vicodin), heroin, meperidine, hydromorphone (Dilaudid), fentanyl, methadone, tramadol
Antagonists
Naloxone- near an. IV form
Naltrexone- oral form
Agonist/antagonist
Nalbuphine
Buprenorphine (technically a partial agonist)
Diarrhea opioids
Loperamide
Dephenoxylate
Antitussive
Dextromethorphan
Morphine metabolites
Morphine 3-Glucoronide and 6-Glucoronide in liver. If there is kidney dysfunction, build up of 6-G in blood will harm, get into spinal fluid and be 50-100x more potent than morphine, cannot cross BBB unless you have a lot of it by mass effect
Oxycontin
Extended release oxycodone. Matrix releases during GI transit. Abuse by crushing- but no ER should be crushed. Started new formulations that prevented this.
What is special about methadone?
Takes 3-5 half lives to see full effect: takes this long to see the steady state, so need to watch for accumulation, keep on same dose for a full week to watch for sedation.
NMDA receptor blocker- blunts central sensitization, but analgesic mechanisms are unknown
Meperidine caution
Metabolite: normeperidine- half life is 10 hours, cleared by kidneys, can cause seizures, DO NOT use in kidney failure patients
Fentanyl uses
Transdermal- chronic or cancer pain. NOT FOR ACUTE PAIN or for the opioid naive, do not apply heat, sub-Q depot before absorbed in blood so watch for overdose, depot continues in blood even after patch is removed
Lollipop is for cancer pain breakthrough- not for sustained effect
Tramadol- works by two mechanisms
Mu receptor agonism and blocks reuptake of 5-HT and NE
Technically a pro-drug and the M1 metabolite is Mu agonist
Agonist/antagonist: Nalbuphine
Analgesia is kappa mediated, weak Mu antagonism (avoids Mu side effects), ceiling effects, less GI side effects and less respiratory suppression
DO NOT USE IN OPIOID TOLERANT PERSON- will cause withdrawal
Problem- kappa agonism causes psychomimetic effects
Low doses used to reverse opioid side effects while maintaining analgesia
Partial agonist- buprenorphine
Only partial Mu agonist
HIGH affinity, makes naloxone reversal difficult in OD
Has ceiling on agonism*
Currently use for opioid maintenance: less intense than heroin withdrawal and briefer than methadone withdrawal
suboxone= buprenorphine +naltrexone
What is special about naloxone?
It can reverse the effects of a placebo and acupuncture
Reversal is SHORT LIVED
Opioids for diarrhea
Poorly absorbed orally, do not enter CNS very well, constipation side effect (naloxone type formulations exist designed to stay in gut and block this side effect)
Loperamide (Imodium)
Dephenoxylate- with atropine: Lomotil
Dextromethorphan antitussive
No analgesic or habituation get properties
Acts centrally, but not via opioid receptors
NMDA antagonist
Similar potency to codeine
