Opioids Flashcards
What is an opiate?
morphine-like (chemical)
What is an opioid?
morphine-like (pharmacological actions), also includes antagonist drugs
What is an endorphin?
endogenous opioid peptides: enkephalins, dynorphins, B-endorphins, endomorphins
What is a narcotic?
narcosis, stupor, sleep inducing (legal term)
What are the three main therapeutic uses of opioids?
analgesia, cough suppression, constipation
What about analgesia (4)?
- occurs without LOC
- pain is selectively decreased (no effect on other senses)
- continuous dull pain is better relieved than sharp intermittent pain
- morphinized pts still feel the pain but it is not as discomforting
What are the regions that express opioid receptors involved in analgesic actions of drugs (4)?
thalamus, dorsal horn, PG periaqueductal gray, RVM rostral ventral medulla
Ascending =
transmission of pain
descending =
modulation of pain
What’s involved in the ascending pathway?
C and Ad fibers, dorsal horn, thalamus
What’s involved in the descending pathway?
PG, RVM
What are additional CNS effects of opioids (3)?
euphoria, sedation, respiratory depression (OD)
When are opioids contraindicated? Who else should they be used cautiously in?
in head trauma-respiratory depression and CO2 retention->cerebral artery vasodilation->increase in intracranial pressure. COPD, asthma
Do opioid receptor antagonists block the effect of cough suppression?
no
Two more effects of opioids? think eyes and blergh
miosis (constriction of pupil)- no tolerance to this effect. emesis: nausea and vomiting, primarily a first dose effect
How do opioids cause constipation? is there tolerance to this effect?
acts on nerves, not on smooth muscle or secretory cells. increased muscle tone in duodenum and antrum of stomach, decreased peristaltic movement in jejunum and colon. yes-intermediate tolerance
What do opioids do to the biliary tract?
constriction of sphincter of Oddi-rise in pressure in common bile duct
What do they do to the CV system?
no effect on HR and BP. opioid agonists can stimulate release of histamine and thereby cause hypotension
what are three minor effects?
urinary retention, slight decrease in body temp, convulsions at high doses
What are the three subtypes of opioid receptors?
Mu, kappa, delta. they are G-protein coupled
What’s up with mu receptors?
morphine-preferring. many clinically used drugs are selective for this receptor. mediates spinal and supraspinal analgesia. respiratory depression, niosis, GI effects.
Which drugs are selective for mu receptors?
Endomorphins (highly), B-endorphin also have high affinity
What’s up with kappa receptors?
spinal cord mediated analgesia
which drugs are selective for kappa receptors?
dynorphin peptides
what’s up with delta receptors?
spinal and supraspinal analgesia
which drugs are selective for delta receptors?
enkephalins (also B endorphin)
What are the four genes or pre-cursor proteins that yield endogenous opioid peptides?
POMC, Proenkephalin, Prodynorphin, Pro-endomorphin
What does POMC yield?
B-endorphin (metenkephalin)
What does proenkephalin yield?
metenkephalins and leuenkephalins
What does prodynorphin yield?
dynorphin A and B, and a and B-neoendorphins (leu-enkephalin)
What does pro-endomorphin yield?
endomorphin-1 and 2
how do agonists work on K channels?
open channels causing K to rush out making cell more negative (hyperpolarization)
How do agonists work on calcium channels?
reduce channel opening which inhibits calcium-dependent NT release
Is tolerance to opioids a pharmacodynamic or pharmacokinetic process?
pharmcoDYNAMIC (cellular response vs. change in metabolism)
What is dependence characterized by?
abstinence syndrome initiated with withdrawal or after administration of an antagonist
What are some main symptoms of withdrawal (4)?
dilated pupils, insomnia, abdominal cramps, exaggerated respiratory response
is withdrawal life-threatening?
no
what’s the difference between short-acting and longer-acting drugs?
short-acting are more intense, shorter in duration. longer-acting drugs are less intense but longer lasting
What are the opiate-like drugs (3)?
morphine, codeine, heroin
which of the opiate-like drugs are pro-drugs?
codeine and heroin
what about morphine?
low bioavailability due to first-pass met., given i.m. or i.v.
what about codeine?
good bioavailability, low potency (metabolized to morphine), good anti-tussive
what about heroin?
rapid entry into brain, eventually metabolized to morphine
What are the semi-synthetics (2)?
oxycodone, Dextromethorphan
what about oxycodone?
orally active, as potent as morphine. often used in combo with NSAID
what about dextromethorphan?
no analgesia, good anti-tussive (not blocked by naloxone)
What is Naloxone?
pure antagonist. IV only! zero bioavailability. used for reversal of opioid toxicity. has relatively short half-life
What are the Meperidine-like drugs (2)?
Meperidine, Diphenoxylate
What about meperidine?
variable bioavailability. less GI effects than morphine. no miosis. SEVERE INTERACTION with MAOIs!! (respiratory depression, delirium, convulsions)
What about diphenoxylate?
low solubility, antidiarrheal
What are the methadone-like drugs (2)?
Methadone, Pentazocine
What about methadone?
similar analgesic efficacy as morphine. longer half-life compared to other agonists. used to treat opioid addicts (withdrawal symptoms are minimized, easier to break habit). BLUNTS i.v. heroin-induced euphoria!
What about pentazocine?
structurally similar to opiates. Kappa receptor selective agonist (mu receptor partial agonist). used for chronic severe pain. lower abuse potential. can be used in combo with Naloxone
What are the drug interactions of opioids?
avoid other CNS depressants (barbs, benzos, alcohol, phenothiazines, tricyclics)
How are opioids compared to non-opioid analgesics?
NSAID: opioids are more efficacious, often used in combo with NSAIDS to acheive greater analgesic effect
What are the drugs to know (10)?
morphine, codeine, heroin, oxycodone, naloxone, meperidine, diphenoxylate, methadone, pentazocine, dextromethorphan
