Pharmacology of Opiod Analgesics Flashcards
Analgesia meaning
> to block pain neurotransmission
> antinociception
Anesthesia meaning
> to block sensory neurotransmission
Nociception
> pain sensation
Allodynia meaning
> the difference in pain sensation of a hyperalgesia and a normal pain response
Functions of pain
> pain required for survival
pain dominates other systems; demands action/attention
requires proper threshold; threshold is adaptive
Functions of pain in terms of tissue damage
> cytokines and chemical mediators
increase vascularization
sensitize somatosensory nervous system
promote recovery
Functions of pain in terms of spontaneous and exaggerated pain
> no protective or reparative role
pain becomes the pathology
maladaptive
Descriptive terms of pain
> type, temporal features, intensity, location, quality, exacerbating/alleviating factors
Comorbidity of chronic pain
> anxiety > depression > insomnia/disrupted sleep > activation of glia > hyperalgesia/allodynia
Pain transmission
> Periphery to spinal cord DRG/Posterior columns to central
Pain processing centers in the brain
> Go to the slide in the packet…NOW
Supraspinal opioid circuit
> PAG and RVM modifying factors to suppress the sensation of pain
Two types of alkaloids in opium
> Phenanthrenes: Morphine, Codeine, Thebaine
> Benzylisoquinolines: Noscapine, Papaverine
Mu opioid receptor Phenanthrenes
> Morphine, Hydrocodone, Buprenorphine, Naloxone
Mu opioid receptor non-phenanthrenes
> Tramadol, Meperidine, Fentanyl, Methadone
Metabolism of Phenanthrenes
> Glucuronidation at 3’ and 6’ position
> Morphine-6-glucuronide still active
Liver metabolism of Phenanthrenes
> CYP2D6
alcohol co-ingestion can increase serum levels
elimination T1/2 increased with liver disease
Excretion of Phenanthrenes
> glomerular filtration
> 90% excreted in 24hr
Opioid receptors type
> G protein coupled receptor - inhibition of cAMP
Mu
Kappa
Delta
Orphanin FQ receptor
Sigma receptor - not an opioid receptor
Mu opioid receptor agonists
> Beta endorphins endogenous morphine: POMC
Therapeutic target: Analgesia due to cancer, peripheral, PCA
sedation
antitussive
Side effects of mu opioid receptor agonists
> respiratory depression > constipation > pruritis > tolerance/dependance > urinary retention via ADH > nausea/vomiting > muscle rigidity > miosis > contraction of biliary tract SMC
Kappa opioid receptor agonists
> Dynorphins endogenous
potential use for treatment of addiction
counterbalance mu opioid receptor effects
salvia contains KOR agonist, salivinorin A
Delta opioid receptor agonists
> enkephalins endogenous
dynamic expressions
role in hypoxia/ischemia/stroke/hibernation
anxiety/depression/alcoholism/hyperalgesia
Action of opioid receptor signal transduction
> G-protein inhibiting Adenylyl cyclase: cAMP(D), intracellular Ca2+(D), release of NT(D)
Adenylyl cyclase activates K+ channel: hyperpolarization due to K efflux
Synaptic action of opioid receptors
> presynaptic: inhibit calcium channel(Gi) decreasing in NT release
postsynaptic: activate GIRK channel increasing K efflux resulting in hyperpolarization
Opioid agonists
> sufentanil > remifentanyl > fentanyl > hydromorphone(Dilaudid) > morphine > hydrocodone > oxycodone
clinical use of meperidine/demerol
> treat rigors
> neurotoxic: nervousness, tremors, fasciculations, seizure
clinical use of tramadol/ultram
> painkiller used when stronger not preferred
> schedule IV
clinical use of loperamide/imodium
> used as antidiarrheal
PgP substrate so low BBB penetration
schedule V
clinical use of propoxyphene/darvon
> withdrawn due to heart rhythm abnormalities
tramadol/ultram & tapentadol/nucynta
> non phenanthrene
mild opiate analgesic
SNRI properties - stimulate serotonin release
mild neuropathic pain
meperidine/demerol
> normeperidine - active metabolite - accumulate and cause CNS irritability and myoclonic seizures
renally excreted; dangerous in D renal function
methadone
> non phenanthrene > opioid dependence > t1/2 15-60hrs and fat soluble > NMDA antagonist > chronic pain
levorphanol/phenanthrene
> t1/2 16hr > analgesic half life is shorter than serum half life > accumulate > NMDA antagonist > neuropathic pain
two drugs with NMDA action
methadone and levorphanol
partial mu agonists
> buprenorphine
partial mu ag, weak k ag, delta antag
long acting, low tolerance/dependence/addiction
partial mu antagonist
naloxone and naltrexone
Opioid for surgery
> fentanyl, sufentanil, remifentanil
> fast onset and short duration
Opioid for postop, epidural
> hydromorphone, morphine
> potent, longer half life than fentanyl
opioid for management
> oxycodone, hydrocodone, oxycontin, zohydro
> oral bioavailability, longer half life than fentanyl
opioid for terminal cancer pain
> morphine
> cost, history
opioid for intolerance
> meperidine
> constipation less, risk of seizure and delirium
pharmacokinetic profile of opioids
> IV, SC/IM, oral increasing Plasma concentration but decreasing half life
Time course of opioids via IV
> hydromorphone, methadone, meperidine, morphine, sufentanil, fentanyl, alfentanil, remifentanil
