Opioids Flashcards
What do we use opioids for in anesthesia?
- dec SNS response to noxious stimuli
- adjunct w/ inhalational gas to dec anesthetic dose
- sole (fent/sufent/morph - cardiac anesthesia/critically ill)
- peri-op/post-op pain
Where do opioids work?
supraspinal - modulate pain in brain
spinal - direct pain modulation in dorsal horn
peripheral - peripheral terminals of nociceptive neurons
describe brain pain modulation
descending inhibitory pathway
periaqueductal gray, amygdala, crpus striatum, hypothal send projections to raphe magnus who send projections down SC to interneurons in substantia gelatinosa
What is TRYPV1
nociceptive receptor for thermal/chemical stimulus
Describe how TRYPV1 works
- stimulus binds to TRYP1 receptor, influx of Na+/Ca+ cause depolarization and release of bradykinin, PGs, etc
- bradykinin and PGs (inc Na+ influx) inc sensitivity to stimuli
- w/ opioids they bind to mu receptor and inc K+ eflux = hyperpolarization = dec stimulus
What makes opioids unique from other analgesics?
- they have no ceiling effect, no max dose, s/e limit
- can develop tolerance
- cross-tolerance
- analgesia w/o loss of touch, proprioception, consciounsness
What are the naturally occurring opioids?
-morphine and codeine
What are the semisynthetic opioids?
-heorin and dihydromorphone
describe agonist, partial agonist, mixed agonist/antagonist, antagonist
- agonist - mimics
- partial agonist - no matter how much you give will only give partial response
- mixed - i.e. agonist at kappa receptor and antagonist at mu receptor
- antagonist - inhibits
- pt already on partial agonist and you give full agonist then full may not be as effective bc of competition
mechanism of action: opioids
pre-synaptic - inhibit excitatory NT release (ach, DOPA, NE, sub P)
post-synaptic - inc K+ conductance (hyperpolarize), inactivate Ca+ channel (dec NT release), PLC cascade, inhibit adenyle and dec cAMP
What type of receptors are opioids?
GPCR
Describe Mu opioid receptors:
Mu
Mu1 - spinal/supra/periph
- works w/ all endo/exo opioids agonist
- causes euphoria, bradycardia (good for cardiac cases to dec myo O2 consumption and balance supply and demand), miosis, urinary retention, hypothermia
Mu2 - spinal (some supra)
- works w/ all endo/exo agonists
- hypoventilation, physical dependence, constipation
Describe Kappa/Delta receptors
Kappa - spinal/supra/periph
- works with Dynorphins (endogenous)
- opioid agonist-antagonist work at kappa receptor
- dysphoria, sedation, miosis, diuresis
Delta - spinal/supra/periph
- enkaphalins (endogenous)
- hypoventilation, constipation, urinary retention
2 reasons why people have variable responses to opioids
- genetic mutation (SNP) on mu receptor affecting opioid agonist binding and pain response
- CP450 system mutation that alters metabolism of:
[C.H.O.M.] CODEINE, HYDROCODONE, OXYCODONE, METHADONE = unpredictable PK’s
FENTANYL is least likely to be affect = predictable
**rate of metabolism may affect s/e - fast metabolizers have inc postop n/v
What are perioperative CV effects of opioids?
- minimal but inc if combined w/ other anesthetics
- dose-dependent BRADYCARDIA; opioids cause vagal stimulation that promotes SA/AV node depression
- VASODILATION (dec SVR) d/t impaired SNS response/tone causing dec CO/BP w/ venous pooling (orthostatic hypotension); inc w/ hypovolemia (=NPO pts)
What is unique about morphine and meperidine (demerol) w/ CV effects?
- both cause dose dependent and infusion dependent histamine release (itching)
- histamine causes bronchospasm and (vasodilation) dec SVR/BP
- *do not use w/ asthmatics
-meperidine - causes TACHYCARDIA w/ direct myocardial depression (diff than all)
What are perioperative CNS effects of opioids?
- analgesia, euphoria, drowsiness, miosis, nausea (d/t chemoreceptor trigger zone)
- NO amnesic effect
- can dec ICP/CBF if hypoventilation avoided
- i.e. pt. w/ head bleed or tumor given opioid begins to hypoventilates = inc co2, might push them over the edge. If you give an opioid with pts. with icp issue, make sure they don’t develop decrease respiration
What are perioperative Renal/GI/Liver effects of opioids?
- urgency with retention
- dec catecholamine and cortisol (dec stress respone = good)
- sphincter of Oddi spasm and GB contraction (can mimic angina)
- constipation d/t GI sm muscle spasm/dec motility
- n/v d/t dec gastric emptying, chemoreceptor trigger zone (4th ventricle)
Pruritis and opioids
- unknown cause
- probable d/t histamine release
- “fentanyl nose itch”
What are perioperative skeletal muscle effects of opioids?
- wooden chest syndrome = muscle rigidity chest/abd/jaw/extremities
- common w/ large/rapid doses of F.S.H. = fent/sufent/hydro
- difficult ventilation > need intubation
- high a/w pressure from inc intrathoracic pressure = dec venous return
What are perioperative ventilatory effects of opioids?
- dose dependent resp depression (#1 cause of death)
- small dose = inc TV, dec RR = dec MV
- large dose = dec TV, dec RR
- dec chest complaince
- pharyngeal/laryngeal constriction
- cough suppression
- dec response to hypercarbia and hypoxia
- bronchospasm from morphine/meperedine histamine release
What happens to the ventilatory response curve to morphine??
its reduced and shifted to the right (#1 cause of death)
Morphine
- severe acute pain
- PO used mainly for chronic/cancer pain
- large first pass effect; converted to active metabolite (same effect as morphine)
- e 1/2 life = 3-4 hours
Codeine
- e1/2t = 3 hrs
- combo with APA, guaifenesin, promethazine
- is a PRODRUG; 10% is metabolized to its active form (MORPHINE), rest is inactive metabolite
- lack of 2D6 = no analgeis ceffect (caucasians/asians)
- antitussive effect thruout conversion (better for cough than pain)
