Unit 3 - Narcotic Analgesics Flashcards
(43 cards)
what is the general structure of opioids?
5 ring structure with substitutions at 3, 6, and 17 that create the profile
what are endogenous opioid peptides? their function?
endorphins
- share protein sequences “Opioid motif”
- precursor has commonality with ACTH, MSH, b-LPH
- -ACTH may account for stress analgesia
- inhibit responses to painful stimuli
- modulate GI, endocrine, autonomic function
- rewarding (addicting) properties
where are opioid receptors found?
in the brain, spinal cord, and peripheral receptors
what do agonists to opioid receptors do?
- inhibit release of substance P and inhibit ascending transmission from dorsal horn
- activates pain control circuits descending from midbrain
what is the structure of opioid receptors and how they’re activated?
GPCR
- ligand recognition on extracellular domain
- transmembrane and intracellular domains
- G proteins bind to cytoplasmic aspect of receptor
- activates/binds GTP to G-protein
- activates effector protein, inhibits AC, activates receptor-operated K currents, and suppresses voltage-gated Ca currents (inhibits substance P)
what are the opioid receptor subtypes? most important?
- Mu opioid receptor (MOR) - most important for analgesia, most prescribed opioids
- Delta opioid receptor (DOR) - analgesia but not across BBB
- Kappa opioid peptide receptor (KOR)
- Nociceptin opioid receptor (N/OFQ or NOR) - orphanin FQ
what do opioid side effects depend on?
receptor subtypes
explain the mechanism of tolerance for opioids?
modification of opioid receptors
- decreased effectiveness with repeated administration
- short term desensitization: phosphorylation or receptor internalization
- long term tolerance: additional mechanisms
can also get tolerant of side effects EXCEPT constipation
what are side effects of opioids?
- analgesia
- mood alteration/reward
- neuroendocrine
- miosis
- convulsions (lowers seizure threshold)
- depressed respiration (most fatal)
- antitussive
- nausea/emesis
- GIT issues
- GU issues
- skin (vasodilation, urticaria)
what is the max serum concentration reached for the different methods of administration? the half life?
oral: 1 hour
sub-cutaneous or intra-muscular: 30 minutes
IV: 6 minutes
half life at steady state is the same for all methods = 3-4 hours
what is the duration of effect of “immediate-release” formulations (except methadone)?
3-5 hours (shorter with parenteral bolus)
what is the bolus effect?
swings in plasma concentration
- drowsiness 1/2 to 1 hour after ingestion
- pain before next dose due
- must move to ER preparation, continuous SC, or IV infusion
morphine
2 major metabolites: morphine-6-glucuronide and morphine-3-glucuronide
- M6G: active metabolite and higher potency
- M3G: little receptor affinity
- for severe pain
codeine
low recceptor affinity, but analgesia is due to conversion to morphine
- only 10% is demethylated to morphine, and for mild-moderate pain
- conversion is effected by CYP2D6
- -10% of Caucasians cannot convert, and experience side effects without analgesia
- antitussive action may involve other receptors that bind codeine itself
tramadol
synthetic codeine analog, but weak Mu agonist
- demethylated metabolite is more potent analgesic
- part of analgesia from inhibition of NE and serotonin uptake
- for mild to moderate pain, and as effective as morphine or meperidine
- less effective for severe pain
- less constipating
fentanyl
very potent, very long half life, and many forms
- much more lipid soluble than morphine
- delayed effect and toxicity are common
- transdermal patch useful for long term Rx
- -ensure adherence to skin (must shave hair)
- -may not be as effective if patient is very thin, as there is no adipose tissue
- wait a week between dose changes, or else trouble with iatrogenic overdose
- for severe pain
methadone
extended duration of action
- 90% bound to plasma proteins and gradual accumulation in tissues
- used in treatment of chronic pain, and treatment of heroin users
- affordable, but must be careful with dosage
- for severe pain
oxycodone
very effective, potent oral analgesic for severe pain
- short and long-acting
- long acting form oxycontin has seen widespread abuse and overdoses
what is Percocet?
oxycodone + acetaminophen
meperidine
no longer recommended b/c of metabolite toxicity (normeperidine)
- congeners for treatment of diarrhea:
- -diphenoxylate (Lomotil)
- -loperamide (Immodium)
- -mech: slow peristalsis via opioid receptors in intestine, and possibly decreased GI secretion
naloxone
opioid antagonist used in treatment of opioid toxicity (IV bolus and continuous infusion)
- administered parenterally (oral almost completely metabolized by liver)
- -effective immediately, but only lasts 15 minutes so require IV drip
naltrexone
opioid antagonist used in treatment of alcoholism
what is the caution of using opioids and acetaminophen?
many commonly prescribed opioids come in this combo form, which can be other the counter
-easy to inadvertantly take too much acetaminophen (max dose is 3000 mg/24 hours)
what is routine oral dosing for immediate-release preparations?
codeine, hydrocodone, morphine, hydromorphone, oxycodone
- dose q 4 h, and adjust daily
- -mild/moderate pain increase by 25-50%
- -severe/uncontrolled pain by 50-100%
