Exam 4 - Opioids Flashcards
Endogenous Opioids
3 families and Receptors
BED
1) Beta
2) enkephalins
3) dynorphins
Endogenous Opioids
Beta Receptor, Gene
- mu and delta receptor
- POMC gene
- pituitary
- gene related to ACTH, MSH
Endogenous Opioids
Enkephalin Receptor, Gene
- delta and mu receptor
- pro-enkephalin gene
- brain, spine
Endogenous Opioids
Dynorphine Rceptor, Gene
- kappa receptor
- pro-dynorphin gene
- brain, spinal cord
Endogenous Opioids
Mu receptor effects
-analgesia, resp depression,
euphoria, dependence
Endogenous Opioids
Delta receptor effects
-analgesia, otherwise unclear
Endogenous Opioids
Kappa receptor effects
-spinal analgesia, sedation, endocrine,
dysphoria, psychotomimetic
Endogenous Opioids
Non-opioid receptor
-DM: antitussive effects
Opioids
Therapeutic effects
- analgeisa (not neuropathic)
- antitussive (not SOPD, emphysema)
- antidiarrheal (but constipation :( )
- acute Pulm Edema relief (but resp depress)
- good mood! (but don’t abuse it)
Opioids
Analgesia
- not neuropathic (shingles)
- best for slow pain (C fiber)
- increase threshold/tolerance
- selective for pain
- inhibit ascending pathway (C fiber)
- activate supra-spinal descending inhibitory pathway (PAG
- pre-med anasthesia
- spinal anasthesis (local + fentanyl)
Opioids
Antitussive
- not opioid receptor mediated
- DM receptors /(not stereoselective)
- dextro isomers only have antituss effects
Opioids
Ant-diarrheal
- mu enteric receptors
- decrease peristalsis, secretions
- no long-term tolerance
- delays other drug absorption
Opioids
Adverse effects
-constipation (use stool softeners)
-nausea/vomit (tx w/ ondansetron)
-sedation (dimishes w/ time)
-miosis (tx w/ atropine)
-pruritus from mast cell stim
LESS COMMON
-urinary retention
-resp depression
-CV effects, truncal rigidity, dysphoria, addiction
Opioids
OD triad
1) pinpoint pupils
2) resp depression
3) coma
Opioids
Tolerance
- after 2 weeks of use
- w/ high/fx dosing
- cross-tolerance between opioids
- therapeutic index unchanged
- constipation and miosis unchanged
Opioids
equi-analgesia
-same potency across class
Opioids
Contraindications
- head injury, preg,
- pulm/renal/hepatic dysfx’n
- Addison’s/hypothyroidism
- abuse hx
- drug interactions
Opioids
Drg Interactions
-MAOIs w/ meperidine, propoxyphene
(causinbg serotonin syndrome)
-sedative hypnotics and antipsychotics
(causing resp depression)
Opioids
Routes
oral, buccal, sublingual, transdermal,
nasal, suppository, parenteral
Opioids
ADME
- liver 1st pass (morphine high, methadone low)
- higher oral dose than IV
Opioids
High efficacy
1) morphine, methadone, fentanyl
2) meperidine, (heroin)
Opioids
Morphine
- high 1st pass (25% avail)
- IV more potent
- don’t crush ‘em!
- glucuronidation to M6G (full) and M3G (partial)
- crosses BBB
- M3G no analgesia, causes seizures
Opioids
Fentanyl
-1st line high efficacy class
-compared to morphine: more potent, lipophilic,
short-acting
-chronic pain patch, breakthrough pain lozenge
-epidural for preggos
-primary anesthesia for CV surg
Opioids
Methadone
-1st line high efficacy class
-lower first pass, high bioavailability,
long half-life
-tx heroin addiction
-analgesia
-no histamine release
-blocks K channel -> long QT syn
Opioids
Meperidine
- 2nd line high efficacy class
- less potent, faster acting than morph
- demethylation to normeperdine
- normeperidine can have fatal CNS effects, seizure
- tachycardia, mydriasis; no miosis
Opioids
Heroin
- 2nd line high efficacy class
- pro-drug w/ rapid conversion
Opioids
low/med efficacy
-usuall combo’d w/ aspirin/ibu
Codeine
Oxycodone
Opioids
Codeine
- demethylation by CYP2D6
- poor and ultra metabolizers
- higher antitussive effects
- high histamine effects
Opioids
Oxycodone
- highest low/med efficacy
- CYP2D6
- slow release preparations available
- hilbilly heroin (crush to abuse)
Opioids
mixed/other
-agonism at kappa (analgesia); anatagonism at mu
-side effects: dysphora, hallucinations
pentazocine, tramadol, buprenorphine
Opioids
Pentazocine
- high kappa agonism, low mu antagonism
- parenteral site necrosis; use orally
- combo w/ acetominophen
Opioids
Tramadol
- Weak mu agonist
- inhibits NE and 5HT reuptake, blocks NMDA receptors
- mod pain tx
- risk seizures
- avoid MAOIs
Opioids
Buprenorphine
- partial mu agonism, kappa antagonism
- sublingual to avoid 1st pass
- opioid dependence tx
- combo with naxolone to prevent IV abuse
Opioids
Anatagonist
- naxolone
- competes w/ all opioid receptors (not DM)
- tx for opioid overdose
Opioids
non-analgesics
dextromethorphan, loperamide
Opioids
dextromethorphan
- antitussive
- only active at DM receptors
Opioids
loperamide
- no BBB pen
- Imodium AD antidiarrheal
Pain Mgmt
3 steps
MILD: ASA/APAP/NSAIDs
MOD: combo ASA/APAP/NSAID w/ low/med efficacy
SEVERE: high eff opioid w/ or w/o adjuncts
