Opioids Flashcards
Opioid
drug, natural or synthetic, that acts at opioid receptors
have diff affinities for diff sites and receptors- full/partial agonists, antagonists, etc.
Opiates
derived from opium poppy- contains opiate cpds including morphine, codeine
Morphine
prototype opioid
work on mu, kappa, delta G protein coupled receptors
-close Ca2+ channels, reducing evoked transmitter release (presynaptic)
-open K+ channels, hyperpolarizing membranes (postsynaptic)
mu receptors
produce analgesic, sedative, euphoric effects of opiates and untoward side effects
delta receptors
contribute to analgesia at spinal levels
kappa receptors
contribute to anagesia but primarily results in dysphoria
sigma receptor
not an opioid receptor- but contributes to dysphoric effects of opioids
Analgesic MOA
interact with body’s endogenous opioid peptide system for limiting pain
- afferent pain transmission from periphery to CNS- opioid receptors in peripheral tissues, dorsal horn of spinal cord (pre and post synaptic) and ventral caudal thalamus
- pain modulating descending pathways from CNS- periaqueductal gray matter (PAG), rostral ventral medulla, dorsal horn of SC
works both centrally and peripherally
CNS pharmacological effects
analgesia- changes perception and experience of pain (does not decrease sensation)
euphoria/dysphoria
sedation
miosis (cholinergic effect- pinpoint pupils)
nausea and vomiting through chemoreceptor trigger zone (CTZ)
truncal rigidity- impairs ventilation
peripheral pharma effects
dec gut motility- constipation arterial and venous dilation biliary colic via cholinergic dec renal blood flow--> dec renal fxn dec uterine tone histamine release endocrine alterations: inc adh, prl, somatotropin; dec LH
use of opioids
-no apparent maximal dose acute or chronic pain less effective for neuropathy decreases sensation of crisis in pulmonary edema or MI diarrhea anesthesia/preop meds cough- antitussive
toxicity of opioids
respiratory depression- #1 cause of death dysphoric constipation nausea and vomiting seizures
tolerance
starts with 1st dose and becomes clinically apparent in 2-3 weeks
-tolerance to different things develops at different times
-days- euphoria, resp dpression,
weeks- analgesia, sedation, nausea
months- cough suppression, antidiuressis
tolerance reverses in order it occurs
minimal or no tolerance to constipation, miosis, seizures
Withdrawal
abstinence syndrome- dysphoria, rhinorrhea, lacrimation, yawning, chills, anorexia, insomnia, anxiety, hostility
-not life threatening
compulsive drug seeking in dependent individuals due to avoiding withdrawal
craving can persist
relative efficacy
doses needed to produce a given effect
-fentanyl is 100 times more potent than morphine
high efficacy drugs
used for severe pain- trauma, post surgical, MI
morphine, methadone, meperdine, hydromorphone, oxymorphone
morphine
high efficacy
poor oral bioavailability
duration 4-5 hrs
glucuronidated–> M-6G which makes it more potent than morphine, but with poor BBB permeability
methadone
high efficacy long acting 6 hrs plasma 1/2 life 24 hrs good oral bioavailability maintenance in opiate addicts
meperdine
high efficacy med acting 2-4 hrs anti muscarinic, may cause tachycardia metabolized to active metabolite normeperidine pyschoactive can cause seizures
fentanyl
high efficacy short acting 1-1.5 hrs 100x more potent than morphine, primarily acts in u receptors poor oral bioavailability transdermal dosage forms available
alfentanil
high efficacy
very short acting 15-45 min
potent, parenteral only, brief painful procedures
low to medium efficacy analgesics
partial agonist or drugs not tolerated at high doses
all adminstered orally
moderate pain- broken bones, dental procedures
often formulated with aspirin, acetaminophen, ibuprofen
codeine
low efficacy, metabolized into morphine by cyp2d6
can also be used as an antitussive agent
hydrocodone
moderate efficacy analgesic
oxycodone
full agonist, moderate-high efficacy analgesic
propoxyphene
v. low efficacy but withdrawn due to cardiac toxicity
tramadol
low to med efficacy analgesic
inhibits NE and 5-HT reuptake
neupathic pain
Partial or m ixed agonist-antagonist analgesic
believed to have less addictive potential and risk of respiratory depression
used for moderate to severe pain
used for opioid addiction
buprenorphine
mu partial agonist
used for maintenance of opioid dependence as depot infxn or in combination with naloxone
butorphanol
k agonist, mu partial agonist or antagonist
nasal spray
nalbuphine
k agonist, mu antagonist
parenteral only
pentazocine
k agonist, mu partial agonist or antagonist
antidiarrheals
poor permeation of blood brain barrier
diphenoxylate
loperamide (otc)
antitussives
codeine
doextromethorphan- otc (poor permeation of bbb)
heroin
drug of abuse, no medical use
naloxone
-IV, IM, SC, intranasal
-opioid antagonist for acute overdose
1-2 hr duration (likely to be shorter than the opioid that is being antagonized- so must be on the look out for opioid effects)
-high affinity for mu receptors, also antagonises k and delta receptors
IV admin can precipitate withdrawal symptoms
naltrexone
used to prevent relapse in recovering addicts
oral
t1/2= 10 hrs
opioid induced constipation
poor bbb penetration
inc risk of bowel perforation
methylnaltrexone
naloxegol
contraindications
head injuries because they cause vasodilation increasing intracranial pressure
pregnancy- cause fetal addiction
impaired pulmonary fxn
hepato or renal compromised pts
endocrine disorders which can result in exaggerated and prolonged effects (hypothyroidism, addison’s)
drug interactions- pure agonists and mix agonist-antagonists can cause
dec analgesia
can precipitate withdrawal symptoms
opioid and antipsychotics
inc sedation and resp depression
inc risk of seizures
MAOIs and opioids
inc risk of hyperpyrexic coma
htn
