Opioid Analgesics Flashcards
Opitate
Synthetics
Endogenous
Opiate - derived from poppy plants…morphine and codeine
Synthetic - fentanyl and oxycodone
Endo - endorphin, enkephalin, dynorphin
Narcotics
Originally associated with drugs that induce sleep…now think opioids
Legally associated with any that have abuse potentil
Partial agonist
Mixed agonist
Inverse agonist
Exerts effect less than full
Agonist ojn some and antagonist on other
Binds receptor and opposite effect of agonist
POtency vs. efficacy
[] needed to acheive half maximumu effect
Amount of effect exerted
Opioid receptors
Localized to synapses
Promote release of endogenous opioids
Gi/o protein coupled (reduce neuronal activity)
decrease cAMP (alpha) Increase K current and decrease Ca influx (beta and gamma)
Types of opioid receptors
Mu and kappa - midbrain periaqueductal grau
Gamma - amygdala
Mu is the most common
All three play a role in anagesia
Endogenous expression
Pre-pro
endorphins - POMC cleaved to ACTH and B-LPH…B-LPH cleaved to hamma-LPH and B-endorphin
Enkephalins - preproenkephalin cleaved to leu and met enkephalin
Dynorphins - preprodynorphin to dynorphin A, B or Beta neoendorphin
Dynorphins different because
Dynorphin A may be involved in spinal cord dorsal horn pain sensation (hyperalgesia)
May be unqiue human
Opioid levels
Periphery Spinal level (Dorsal horn) Supraspinal (NRPG and PAG)...these both inhibit dorsal horn
Phenanthrenes
Morphine
Codeine
Hydrocodone
Oxycodone
More pheanthrenes arrive COD
Phenypiperidines
Meperidine Fentanyl Alfentanil Sufentanil Remifentanil
Me feal sure about phenylpiperadines
Phenylhepatanone
Methadone alone
If can’t tolerate side ffects
Switch to a different class of opioid
Morphine peripheral
Analgesia
Constipation
GI spasm
Morphine centrAL
Analgesia Resp depression Antitussive Misosis Tolerance and dependance
Morphine effectiveness, selectivity, how to administer, divisions, and what type of pain best for
Many are as effective, none more
Other sensory modalities are preserved
Best achived by titrating to patient (2/3 adequate with 10mg IM)
Sensory discriminative - ID and localization of pain source
Motivational-affective - subjective reactions
Beetter against continous, dull pian
Antitussive, pruritis effects of morhine
Suppresses brainstem cough centers…close to breathing centers but not same…occurs at subanalgesic/resp depressing dose
Peripheral mast cell and leukocyte stimulateh istamine reelease
Truncal rgidity and N/V with morphine
Interferes with ventiilaiton (surgically concomitant NM blocking agents…in overdose, mechanial ventilaiton may be ineffective)
INitally, Stimulate CTZ (worse in ambulatory or oral dosage)
With prolonged high dose could supress BS medullay vomiting center
Analgesic, renal, GI, biliary, CV effect of morhpine
Efficacy increased with inflammation
Reduced function
Increase smooth muscle tone and decrease propulsion…could lead to spasm that can increase pain
Decrease secretions
Decrease BP (due to histamine release)…can cause orthostatic hypotension
Can be used to treat pulmonary edema
Genetics of morhpine
People with AA report less pain than GG
Absorpition fate and excretion of morphine
Not as effective orally
55% as excitotixc mirphine-3-glucuronide
10% as analgesic morphine-6-glucuroine
Metabolites build up in blood over long term exposure
Nearly all excreted in usrine within 24 hours
3-4 half life with enterohepatic recycling
Acute toxoicty of morphine
Death from profound resp depression (worry about with sleep apnea)
Miosis, decreased respiration, coma
Tx - restore airway physicially or with opioid antagonist (be careful with half life0
Tolerance, dep ,and addiction of morhpine
Dose and freq dependent (begin at about 1 week and clinically after 2-3)
Dep - only evident when drug withdrawn…drug and drug class selective….neuronal modifications
Addiction - continud use, impaired ocntrol, craving despite harm
Morhpine contraindications
Mixing any other opioid and with MAO-I (esp meperidine)
