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54 Cards in this Set
- Front
- Back
Opiod analgesic action
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act on opiod receptors
SELECTIVE pain block - no change in consciousness or other sensations |
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Opium vs. opiates vs. opiods
Narcotics |
Opium - dried resin from seed
Opiates - alkaloids found in some opium and synthetic derivatives opiods - any agent with morphine-like activity Narcotics - any drug making you sleep (rarely used this way anymore) - opiod analgesics -legal term for abused substances |
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Endogenous opiods
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made in body --> NTs/neuromodulators
mostly peptides, but also morpheine and codeine |
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families of endogenous opiods
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enkephalins - preproenkephalin
endorphins - prepro-opiomelanocortin endomorphins - don't know precursor dynorphins - preprodynorphin |
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Opiod receptors
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mu - most important
delta kappa most are full agonists, but there are also partial agonist, mixed agonist/antagonist (by receptor type), and antagonists |
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Preferred ligands for:
mu Delta Kappa |
not totally specific
Mu: beta-endorphin, endomorphins Delta: enkephalins Kappa: dynorphins |
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Cellular effects of opiods
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g-pro linked
opens K channel --> hyperpolarization close some Ca channels --> down NT release May alter adenylyl cyclase |
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receptors involved in some opiod fx
analgesia down resp down GI motility psychotomimetic (LSD-like) sedation euphoria miosis increased sphincter tones |
analgesia - mu (and some k)
down resp - mu down GI motility - mu, k psychotomimetic (LSD-like) - kappa sedation - mu, k euphoria - mu miosis - mu, kappa increased sphincter tones - mu |
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pharmacological effects of opiods
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analgesia
euphoria/psychological dependence sedation resp depression N&V antitussive miosis pruitis GI effects blilary/ureter and bladder CV effects neuro endocrine |
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pharmacological effects of Opiod - anlgesia
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affects both the psychological and emotional components
- raise pain threshold, decrease interpretation of remainign pain selective block of pain given enough opiods, you can block almost any pain (no ceiling effect) -- except neuropathic pain |
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Mech of analgesia for opiods
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action in both brain and spinal cord
augment the effects of endogenous antinociceptive systems |
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Memorize that one diagram
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yeah, that's right. Memorize it
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pharmacological effects of Opiod - euphoria/psych depend
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high abuse - only in people with abuse, not with medical use
mechanism - at least partly due to opiod activation of VTA/NA pleasure pathway |
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pharmacological effects of Opiod - sedation
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drowsiness/impaired thinking
additive with EtOH mainly at high doses still don't cause loss of consciousness no ataxia usually can get analgesia w/o sedation |
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pharmacological effects of Opiod - respiratory depression
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can be lethal, but can be useful
decreased rate and depth of breath usual cause of death in OD direct depression of brainstem resp centers (reduced responsiveness to CO2 |
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Should I give passive O2 to someone with opiod OD?
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NO!!! need to be pos pressure
if passive, the O2 will decrease the intrinsic drive to breathe even more |
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pharmacological effects of Opiod - N&V
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partly due to chemorecepor trigger zone (CTZ)
better if person lays down (vestibular contribution) |
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pharmacological effects of Opiod - antitussive
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depress cough reflex by action in 'cough center' of medulla
happens at low dose receptors aren't well known |
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pharmacological effects of Opiod - miosis
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pupil constriction - poor night vision
abuser don't like it b/c it points them out don't get tolerance to it stimulates Edinger-Westphal nuclues (increases parasympathetic tone) |
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pharmacological effects of Opiod - pruritis
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ITCHING
more common with IJ than PO histidine release from mast cells can come with flushing/sweating spinal mechanism? |
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pharmacological effects of Opiod - GI effects
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down acid production
increased constipation from decreased intestinal, pancreatic secretions partially due to local fx, partially CNS Useful for diarrhea, often bad for SEs Doesn't tolerate out |
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pharmacological effects of Opiod - biliary sphincter, ureter, bladder
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increased tone in all
bilary stone/spasm = pain enough opiod = mask pain, low dose = feel pain |
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pharmacological effects of Opiod - CV effects
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not much CV effects
postural hypotension |
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pharmacological effects of Opiod - neuroendocrine effects
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decreased gonadotropin-releasing hormone (GnRH)and corticotropin-releasing (CRH)hormone
--> erratic menstruation, decreased libio/impotence in men |
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Tolerance to opioids
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inevitable with prolonged/frequent use
10x-100x is common rate/magnitude varies by drug/dose/freq/duration rate/magnitude also vary by effect (miosis/constipation don't tolerate out) lots of cross-tolerance among MU agonists -> drug changing is common |
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Basis of tolerance to opioids
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don't know exact mech
internalization of receptors desensitization -- PO4 the receptor uncouple receptor from g pro |
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Physical dependence to opiods
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inevitable with prolonged/frequent use of MOST
morphine generally takes 10-14 days at tid/qid -- differs per person per drug |
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opioid withdrawal
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provoked with sudden decrease in dose or opioid receptor antagonist
symptoms - opioid craving, psych/physical effects (opposite of opioid effects) unpleasant, but rarely lethal onset/duration varies by agent half-life |
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opioid withdrawal symptoms
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insomnia,
anxiety irritability dysphoria sesitivity to pain abdominal cramps N&V diarrhea muscle aches mydriasis sweating piloerection tachycardia hypertension fever |
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Opioid detoxification
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only prevents PHYSICAL dependence
1. switch to long acting opioid (methadone) 2. gradually change dose to wean off 3. eventually stop |
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Toxic OD of opioids
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common cause of death in abuse
Triad of symptoms - resp depression, miosis (dilate with enough hypoxia) and coma pulmonary edema = cause of death for 50% of cases - initiated by mu receptors - not reversible by antagonist therapy is vital fcn support, opiod (MU) antagonist - don't give too much - very fast action (~5min) |
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Therapeutic effects of opioids
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analgesia
cough supression antidiarrheal |
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Adverse effects of opioids
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Psych dependence
physical dependence resp depression N&V dizziness sedation constipation miosis pruritis biliary spasm urinary retention hypotension |
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Opioid kinetics (general rules)
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well-absorbed
low F due to 1st pass highly lipid soluble - lots of routes available (nasal, buccal, skin, IM, SC, IV, intrathecal, epidural) |
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Morphine
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full MU agonist
most common, inexpensive terminal cancer use! 25% oral F, but ok due to low cost morphine 6-glucuronide = active metabolite - longer t1/2 - accumulates in chronic use - lots of effects |
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Heroin
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full MU agonist
no legit use in US most widely abused opioid more lipid soluble = more crosses BBB active metabolite (monoacetyl morphine) which also crosses BBB metabolised to morphine in brain |
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codeine (3 methyl-morphine)
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low affinity MU agonist
10% metabolized by 2D6 to morphine (lots of polymorphisms = OD or no fx) alone = not potent, but good when combined w/ NSAIDS relatively high F PSYCH dependence UNLIKELY but POSSIBLE - common abuse = kids or people trying to avoid withdrawal to other opioid PHYSICAl dependence extremely unlikely regardless of dose/duration |
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meperidine
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DEMEROL, pethidine
1/10th as potent, shorter action less constipation, miosis and urineary retention toxic CNS stimulant is metabolite (normeperidine), long t1/2 Interact with MAOI - serotonin syndrome mainly abused by HC pro's |
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Fentanyl
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SUBLIMAZE
80-100x more potent high lipid solubility short duration (0.5-2h) versatile |
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Fentanyl uses
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pre-, intra-, post-op ANALGESIA
opioid ANESTHESIA - not unconsicous, but not aware of pain TRT chronic pain (patch) or breakthru pain (lollypop) animal tranquilizer (esp w/ droperidol) dart gun |
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methadone
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good F
long t1/2 (15-40h), strong tissue binding |
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methadone uses
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analgesia
facilitate detox of opioid physical dependence methadone maintenance: no high, but occupies receptors no withdrawal, craving get person out of drug scene makes person methadone-dependent, but they aren't an addict |
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diphenoxylate
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LOMOTIL
exclusively for diarrhea abuse unlikely --> added atropine = atropine poisoning b/f high |
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loperaminde
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IMMODIUM
poor F exclusively for diarrhea abuse unlikely --> F ~0 therefore, action is only in gut |
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propoxyphene HCl
propoxyphene napsylate |
DARVON/DARVON N
potency about same/less than codeine for mild/moderate pain PSYCH dependence, but not physical |
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Partial MU agonists and Mixed KAPPA agonist/ MU antagonist
Shared characteristics |
big dose can cause withdrawal
minimal cross dependence LOW: -resp depression -physical dependence Low to Mod: -psych dependence |
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buprenorphine
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BUPRENEX
partial MU agonist - bind tightly, slow dissociation = long duration 25-50x potency for analgesia VERY low F --> only IJ or sublingual Used as analgesic (vet med) and detox (subs for methadone) |
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pentazocine
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TALWIN
strong KAPPA agonist, weak MU ANTagonist analgesia from kappa agonism Low F --> only slightly more potent than coediene (when PO) psychotomimetic at large doses |
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TALWIN NX
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petazocine + antihistimine = abuse as an IJ(similar to heroin)
add naloxone --> no effect when PO, but blocks effect when injected for abuse |
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butorphanol
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STADOL
mixed kappa/mu antagonist similar to pentazocine |
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Opioid antagonists shared charactersists
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pure antagonist at ALL receptors
prevent/reverse all clinically active opioids Used to treat OD and excessive Post-op effets |
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Examples of opioid antagonists
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naloxone/NARCAN
naltrexone/REVIA nalmefene/REVEX |
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tramdol
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ULTRAM
weak MU agonist - similar to codeine/propoxyphene inhibits 5HT/NE reuptake moderate to severe pain abuse potential low, but increasing |
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dextromethorphan
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stereoisomer of opioid
NOT an opioid b/c no action at any known opioid receptor No opioid or high/physical dependence Increasingly abused for hallucinogenic effects -Binds to PCP site |