Opioids Flashcards
High efficacy agonist
Rx
Morphine
Meperidine
Methadone
Fentanyl
Low/Medium efficacy ags
Codeine
Oxycodone
Hydrocodone
Mixed Ags/Antags
Pentazocine
Buprenorphine
Antags
Naloxone
Non-analgesic opioid
Dextromethorphan
Opiate
Term
Includes non-analgesics
Opioids
Name
Include synth drugs, endogenous (enkephlins)
Analgesic
Name
Pain-relieving
Endogenous Opioid
Mu receptor
Binds
- B-endorphin
- Enkephalins
MOST OPIOID EFFECTS
*analgesia, Respiratory, euphoria, dependence
Endogenous Opioids
Delta receptor
Binds
- B-endorphins
- enkephalins
Analgesia
Endogenous Opioids
Kappa receptors
Binds
*dynorphins
Analgesia, sedation, endocrine
Opioid Txs
- Analgesia (NO neuropathy)
- Antitussive (BUT NO COPD/ASTHMA (mucus)
- Antidiarrheal (CONSTIPATION)
Opioid
Analgesia effects
*threshold (discriminative)
ONLY IN OPIOIDS = *Tolerance (affective /emotion) = care less about pain
*ONLY PAIN = not temp, touch, proprioception (like LOCAL ANALGESICS)
Opioid Analgesia
Sites
Peripheral = C fiber
Spinal = stop ASCENDING PAIN pathway
Supraspinal = activate DESCENDING PAIN INHIBITORY PATHWAY
Major receptor for analgesic opioid fact
Mu
Opioids
Uses
Premedication for general anesthesia
- OR*
- general anesthetic adjunct
- primary general anesthetic (no CV risk) - fentanyl
- Spine anesthesia*
- fentanyl+anesthetic (epidural)
Antitussive effects
Mediated by (receptor)
DM receptor
NOT OPIATE RECEPTOR
L stereoisomer activates
Mu (opioid)
+
DM (Anti-tussive)
- Natural opioids
- Opiates
D stereoisomer activates
UNNATURAL STEREOISOMER
DM (antitussive ) ONLY
NO MU S.E.
*dextromethorphan
Opioid Anti-diarrheal effects
*Mu receptor
Opioid antidiarrheal
S.E
Delayed gastric emptying - other oral Rx slowed
If no cross BBB, no CNS effects
No tolerance
Opioid
General S.E.
Mostly MU RECEPTOR
- Constipation (no tolerance)
- N/V (Mu in CTZ + vestibular apparatus). = tx ondansetron
- Sedation = additive w/ other Rx
- miosis = (no tolerance, atropine)
- Pruritis = (NOT MU, from mast cell histamine)
- Respiratory depression - additive w/ other Rxs, delayed up to 12 hrs)
- urinary retention
- pinpoint pupils
- respiratory Depression
- decreased consciousness
Opioid OD
Opioid less common SE
Cardio
Meperidine - TAC (anti-musc)
Most - bradycardia
Opioid tolerance
SE change?
SE move with tolerance (except constipation + miosis) = T.I. DOESN’T change
Opioid dosing
- Cut back when pt shows…
- Switch when…
Lower dose = Higher respiratory effect
Switch = SE untenable, equi-analgesia across Rxs
Pt needs analgesia, but is Opioid abuser
Give larger dose than Naive patient
Opioid drug interactions
SSRI + Meperidine = serotonin syndrome
+ Benzos/Barbituates/alcohol = Respiratory depression
Tx
Acute severe pain
IV - morphine/fentanyl
Tx
Chronic pain (cancer)
- Underlying pain = extended-release morphine
- breakthrough pain = fast/short-acting (fentanyl lolipop, hydromorphone oral, Percocet (oxycodone), vicoden (hydrocodone)
Tx
Nociceptive/inflammatory
Opioids
Tx
Neuropathic pain
Opioids
ADD
Anticonvulsants
Change dose if patient :
- opioid dependent
- Impaired GI motility
- Hepatic/renal impairment
- Oral rx ability
High first pass effect
Morphine
only 25% bioavailable
Low first pass effect
Methadone
Almost 100% available
Opioid Analgesia
Use against this pain
GOOD **2nd (C fiber - slow) pain = dull/achy
LESS**1st (Abeta - fast) pain = sharp, intense
WORST **Neuropathic pain (ex. post-herpetic neuralgia)
Non-opioid receptors w/ opioid effects
DM receptor
*antitussive effects
Descending pain inhibitory pathway
MOR activated in PAG –> Raphe nucleus –> enkephalin-containing neuron in spinal cord releases enkephalins –>inhibit substance P releasing C-fiber + Hyperpolarize ascending spinothalamic tracts
Morphine
- absorption
- duration
- addiction-resistance
- Metab?
- SE
*High 1st pass
*4-5 hours
*slow-release = chronic pain
*MS-Contin = crush resistant
*metab = glucuronidation
*SE= seizure (M3G metabolyte)
=renal fail pt (M3G)= lower dose
=histamine release = bronchoconstriction, HypoTN,
Hydromorphone
*SE
- dilauded
- no Histamine = NO bronchoconstriction/hypoTN/pruritis
- M3G, NO M6G
- So NO dose change w/ renal fail
Fentanyls
- onset
- forms
- SE
- more lipophilic
- Fast acting
- Can’t tolerate oral opioids? –> many forms
- Poor cardio function but need surgery antalgesic? - IV fentanyl
- No Histamine releases = NO pruritis, bronchoconstriction, hypoTN
Methadone
- Uses
- absorb
- SE
- treat heroin addicts, analgesic
- well absorbed in GI
- long t 1/2
- non opoid receptor effects –> analgesia
- no histamine
- PROLONGED QT
Low-medium efficacy opiods
- combos
- contraindications
All oral
NO WITH LIVER DZ
Combine with aspirin (=dan)
Combine w/ acetaminophen (=cet)
*liver toxicity
Ultrametabolizer (CYP2D6) of codeine?
Use alternative:
- buprenporphine
- hydromorphine
Codeine
- uses
- SE
- converted by CYP 2D6 to moprhine
- antitussive (bind direct to DM - no CYP conversion needed)
- histamine release
Oxycodone
- efficacy
- Metab
- slow release
- highest efficacy
- CYP2D6 = metab to oxymorphone (NOT AFFECTED BY RECESSIVE CYP FORMS)
- slow-release = Oxycontin
Hydrocodone
- efficacy
- metab
- SE
- moderate efficacy
- CYP2D6 to hydromorphone = NOT AFFECTED by RECESSIVE CYP FORMS
- antitussive, pruritis
- most prescribed
Kappa agonists
Effects
- kappa agonist = analgesia
* partial/full mu agonist = anagonizes other mus
Misc Opioid Analgesics
Buprenorphine
- receptors
- use
- combo
*partial mu ag
Kappa antag
*sublingual
- 1st line - opioid dependence (opioid receptor full-ag blockers)
- combo = +naxolone (Suboxone)
Opioid antags
Naloxone
*parenteral
- Use - Opioid OD
- short duration = give multiple doses to OD
Opioid Antags
Naltrexone
- Duration
- use
Long-acting
*use - alcohol addiction + other addiction
Neuropathic pain
Fibers
A-beta
NOT C + A-delta
Amitriptyline
Imipramine
Desipiramine
- mech
- use
NE reuptake inhibitor
*neuropathic pain
ADDs
Diabetic neuropathy
Tx
Carbamazepine
Pregabalin
Postherpetic neuralgia
Tx?
Gabapentin
Pregabalin
TX pain
1) Mild pain
Aspirin
NSAIDS
Acetaminophen
TX Pain
2) Moderate pain
+ low/medium efficacy opioids
NEW GUIDELINES CDC = start w/ atypical opioids + lifestyle change
TX pain
3). Severe pain
High efficiacy opioids
Dextromethrophan
- receptor
- SE
- DM receptor
- less addiction = no MU effects
Antitussives
