B7.005 Prework 3: Opioids Flashcards
what is an opioid
any drug, natural or synthetic that acts at opioid receptors
mu receptors
produce analgesic, sedative, and euphoric effects of opiates as well as side effects
delta receptors
contribute to analgesia at spinal levels
kappa receptors
may contribute to analgesia, but primarily result in dysphoria
action of opioid drugs at the different receptors
various opioid compounds have different affinities for these sites and may be full or partial agonists, antagonists, or have mixed activity
clinical uses of opioids
analgesics
cough suppressants
antidiarrheal
where are opioid receptors located
brain
spinal cord
various peripheral tissues
CNS pharmacological effects of prototype drug: morphine
analgesia euphoria/dysphoria sedation resp depression cough suppression miosis (parasympathetic activation) truncal rigidity (impairs ventilation) nausea and vomiting
peripheral pharmacological effects of prototype drug: morphine
arterial and venous dilation decreased gut motility (constipation) biliary colic (cholinergic) decreased renal blood flow decreased uterine tone endocrine alterations -increased ADH, PRL, somatotropin -decreased LH histamine release
toxicity of opioids
resp depression (primary cause of death) dysphoria nausea and vomiting constipation seizures tolerance / withdrawal / addiction
important differences between opioid drugs
potency
efficacy
duration of action
oral bioavailability
equianalgesic dose
equal to 10 mg morphine
low efficacy opioids
low efficacy for analgesia and produce only “side effects”
don’t cross the BBB
used as anti-diarrheals
high efficacy analgesic opioids
used for severe pain (trauma, post surgical, MI) morphine methadone meperidine fentanyl
morphine
prototype drug
poor oral bioavailability due to 1st pass effect
duration: 4-5 hours
hepatic metabolism, renal excretion
morphine metabolite
glucuronidated metabolite M-6G is even more potent, but has poor BBB penetration
methadone
longer acting than morphine: 6 hrs, plasma t1/2 24 hr
good oral bioavailability
used as maintenance in addicts, but also for pain
meperidine
duration: 2-4 hr
antimuscarinic > may cause tachycardia
metabolized to an active metabolite that is psychoactive and can cause seizures
fentanyl
short acting duration: 1-1.5 hr 100x more potent than morphine primarily acts at mu receptors poor oral bioavailability transdermal available
low to medium efficacy analgesic opioids
administered orally
used for moderate pain (broken bones, dental procedures)
often formulated with aspirin, APAP, or ibuprofen
codeine
hydrocodone
oxycodone
tramadol
codeine
low efficacy
metabolized to morphine by CYP2D6
ineffective in people with decreased enzyme levels
hydrocodone
moderate efficacy
oxycodone
moderate-high efficacy
available in ER formation
high levels of addiction (esp with ER)
tramadol
low efficacy
also inhibits NE and 5HT reuptake
may have efficacy for neuropathic pain
partial agonist or mixed agonist-antagonist analgesic opioids
believed to have less addictive potential and risk of resp depression
used for moderate to severe pain
used for opioid addiction
buprenorphine
mu partial agonists
pentazocine
kappa agonist
mu partial agonist or antagonist
antidiarrheal opioids
poor permeation of the BBB
diphenoxylate
loperamide (OTC)
eluxadoline
eluxadoline
mu and kappa agonist
delta antagonist
used for IBD with diarrhea
antitussive opioids
poor permeation of the BBB
codeine
dextromethorphan (OTC)
opioid drug of abuse
heroin
no medical uses
opioid antagonists
naloxone
naltrexone
reverse the effects of opioids after overdose
prevent opioids from having an effect
can induce withdrawal when administered IV or in high dose
naloxone
IV
intranasal
naltrexone
oral
depot injection
opioid antagonists for constipation
poor BBB penetration
increase risk of bowel perf
-methylnaltrexone (subQ)
-naloxegol (oral)
contraindications / interactions associated with opioids
head injuries
-vasodilation can increase intracranial pressure
pregnancy
-fetal addiction, sedation
impaired pulmonary function (except acute pulmonary edema)
hepato- or renal compromised patients
increased sedation and resp depression with sedatives or antipsychotics
