Narcotic Analgesics Flashcards
molecular structure of morphine and related opioids
five ring structure. modifications at positions 3, 6, and 17 account for variations in potency, efficacy, lipid solubility, metabolism, side effects, and agonism/antagonism.
endogenous opioid peptides
endorphins. natural opioids share the same protein sequences, or opioid motif. inhibit response to painful stimuli, modulate GI, endocrine, autonomic function. rewarding (addicting) properties.
where are opioid receptors found/what do they do?
brain, spinal cord, and peripheral nerves. opioid receptors are G protein-coupled receptors. receptor agonists inhibit release of substance P and ascending transmission of pain from dorsal horn neurons.
opioid receptor subtypes
mu or MOR: most important for analgesia
delta or DOR: analgesia but not across BBB
kappa or KOR
N/OFQ or NOR
effects and side effects of opioids
analgesia. mood alteration (stimulation of reward centers). miosis. convulsions. decreased respiration. cough suppression. nausa and emesis. constipation. urinary retention. mast cell degranulation leading to hives
opioid absorption
orally administered are rapidly absorbed in the GI. sublingual, transmucosal, and rectal are rapidly absorbed. significant first pass metabolism in thel iver.
opioid metabolism
liver, with glucuronidation being primary metabolic pathway. excreted by kidney.
bolus effect
occurs most commonly with IV or intramuscular administration, resulting in swings in plasma concentration with sedation occuring as a result of high blood levels and breakthrough pain when the serum levels are in a trough. continuous IV infusion or extended release oral formulations should be considered to prevent.
morphine
prototype of opioids. metabolites include morphine 6 glucuronide and morphine 3 glucuronide. M6 is the active one with high potency, M3 has little receptor affinity
codeine
low receptor affinity, and the analgesia it provides is due to demethylation to form active morphine. only 10% is converted. depends on CYP2D6 pathway. good antitussive effect
tramadol
synthetic codeine analog, weak mu agonist. demethylated metabolite is a more potent analgesic. thought to work through inhibition of norepi and 5HT uptake. good for moderate pain
fentanyl
strong opioid used IV and in a patch. highly lipid soluble. long half life. dont change dose more than once a week. new patch every 72 hours
methadone
extended duration of action. accumulates in tissues and is highly protein bound. used for chronic pain and heroin addicts. dont change dose more than once a week
oxycodone
effective, widely used, potent. commonly abused
meperidine
no longer recommended because of toxicity of metabolite normeperidine. accumulates and causes mental status changes and seizures
naloxone
treatment of acute opioid toxicity. only administered parenterally. short half life, usually continuous infusion
naltrexone
treatment of alcoholism
what is problem with acetominophen and opioids?
many opioids come in combination with acetaminophen, and people will try to take their own tylenol on the side and get problems
physical dependence
result of neuroadaptation. abrupt cessation of opioid use may precipitate in withdrawal symptoms. to prevent, reduce dose by 50% every 2-3 days
breakthrough dosing
pain may break through in the middle of the interval between doses. breakthrough doses should be taken as needed after the maximum serum concentration is reached. for IV, this would be in 10-15 minutes, for SC or IM after 30 minutes, for oral after 1 hour. oral breakthrough should be immediate release preparation
equianalgesic dosing
when changing from IV to oral routes or from one drug to another, must calculate dose equivalent. can use tables to make this easy. when switching, doses usually adjusted downward 25-50% of the calculated equianalgesic dose.
managing side effects
use drugs that counter them
