OPIOIDS Flashcards
what is the source of nociceptive somatic pain?
tissues (skin, muscle, joints, bones, ligaments)
often known as musculoskeletal pain
what is the source of nociceptive visceral pain?
internal organs of the main body cavities (thorax, abdomen, pelvis)
characterize somatic nociceptive pain vs. visceral pain
- somatic pain – sharp and well localized, can be reproduced by touching or moving the area/tissue involved
- visceral pain –poorly localized, dull pain (ache, cramping). frequently produces referred pain to the back
differentiate useful medications for somatic vs. visceral pain
- somatic pain – may respond to combinations of weak or strong opioids AND NSAIDS
- visceral pain – very responsive to weak and strong opioids
name a natural opioid
morphine
name a synthetic opioid
fentanyl
name a semisynthetic opioid
heroin
name an opioid agonist
morphine
name an opioid agonist/antagonist
nalbuphine
name an opioid antagonist
naloxone
what is the mechanism of action of opioids?
bind specific G protein-coupled receptors (in brain and spinal cord regions) involved in transmission and modulation of pain
where do opioid agonists work?
- opioid receptors in the pre/post-synaptic CNS
* peripheral afferent nerves
what endogenous ligands do opioids mimic the effects of?
- enkaphalins
- endorphins
- dynorphins
what neurotransmitters are released in response to pain (release is decreased with opioids)
acetylcholine, dopamin, norepi, substance p
which opioid receptor’s 1º action is analgesia, produces N/V, pruritits, and bradycardia, and has low abuse potential?
Mu1
which opioid receptor is found only in the spinal cord (as opposed to spinal AND supraspinal)?
Mu2
Mu1 and Mu2 both produce euphoria. which one also produces sedation?
Mu2
which opioid receptors are responsible for physical dependence?
Mu2 and delta
which opioid receptor does not produce respiratory depression?
Mu1
which opioid receptor is responsible for dysphoria and diuresis?
kappa
which opioid receptor is the principle site for agonist-antagonists, and is highly resistant to high intensity pain?
kappa
where does nalbuphine work?
nalbuphine is an agonist-antagonist opioid – agonist at kappa receptors, and an antagonist at mu receptors
three opioid receptors modulate the body’s ability to retain or excrete urine. describe the two
- kappa receptors produced diuresis (increase excretion)
* delta and Mu1 receptors produce urinary retention
which receptors are responsive to endorphins, morphine, and synthetic opioids?
Mu1 and Mu2
which receptors are responsive to dynorphins?
kappa
which receptors are responsive to enkaphalins?
delta
where are the targets of neuraxial opioids?
mu receptors in substantia gelatinosa of spinal cord
what kind of pain are neuraxial opioids designed to suppress?
visceral pain
what are the 4 classic side effects of neuraxial opioids?
pruritis, N/V, urinary retention, ventilatory depression
what are the dosing recommendations for morphine (IV, epidural, intrathecal)
10mg IV, 1mg epidural, 0.1mg intrathecal (1/10 ratio; very hydrophilic)
what are the dosing recommendations for hydromorphone (IV, epidural, intrathecal)
1mg IV, 0.2mg epidural, 0.04mg intrathecal (1/5 ratio; intermediate hydro-/lipo-philicity
what are the dosing recommendations for fentanyl (IV, epidural, intrathecal)
100mcg IV, 33mcg epidural, 6-10mcg intrathecal (1/3 – 1/5 ratio; very lipophilic)
how well are opioids absorbed?
- well absorbed by many routes
* some have high first pass metabolism (PO)
how well are opioid distributed?
- rapidly leave blood compartment for highly perfused areas
* muscle and fat act as a reservoir
describe the metabolism of opioids
- converted to polar metabolites then excreted by kidneys
- morphine-6-glucoronide (4-6x analgesic potency than morphine – morphine is a prodrug)
- tissue esterases (heroin, remifentanil)
- normeperidine (demerol)
what are the cardiovascular side effects of opioids?
- decreased sympathetic tone
- decreased BP
- decreased HR
- minimal contractility effects
what are the cardiovascular side effects of demerol?
anti-muscarinic effect (like atropine) – increase HR
what are the respiratory effects of opioids?
- respiratory depression due to agonist effect at Mu2
- dose dependent depression of ventilatory response to CO2
- increased PaCO2 (almost becomes an anesthetic)
- decreased RR
- increased tidal volume
- decreased minute ventilation
- cough suppression (dextramethorphan – no analgesia or ventilatory depression)
what are the CNS effects of opioids?
- sedation and analgesia vs. euphoria
- reduces MAC
- decreased CBF and CMRO2
- increases ICP with hypoventilation
- seizures with meperidine use (normeperdine buildup)
- miosis (edinger-wetphal nucleus of oculomotor nerve – no developed tolerance)
describe biliary colic side effect of opioids
- spasm of sphincter of Odi (can present similarly to angina)
- less with meperidine
- naloxone relieves pain
- glucagon 2mg IV reverses
how are opioid side effects expressed in the GI?
- N/V
- constipation
- delayed gastric emptying
- biliary colic
how are opioid side effects expressed in the GU?
- urinary retention due to increase in tone of ureter and vesicle sphincter
how do opioids affect histamine release?
increase histamine release – flushing, itching (more with morphine and meperidine)
describe side effects observed in the thoracic cavity
truncal rigidity
for which side effects do pts develop tolerance?
tolerance to depression of ventilation
what is the onset, peak effect, and duration times of morphine?
- onset: 15-30min
- peak effect: 45-90min
- duration: 3-4hr
how is morphine metabolized?
metabolized via conjugation with glucuronic acid in hepatic, extra hepatic, and kindneys
what is the active metabolite of morphine?
morphine-6-glucaronide
* accumulation of morphine and metabolite in kidney failure pts leading to prolonged narcosis and ventilatory depression
how potent is meperidine compared to morphine?
0.1 potency of morphine
meperidine peak effect, duration
- peak effect: 5-7min
* duration: 2-4hr
describe the local/atropine-like side effects of demerol
- block Na channels
* tachycardia, dry mouth, mydriasis
how is demerol most of used?
Tx for post op shivering (12.5-25mg)
fentanyl peak effect, duration
- peak effect 3-5min
* duration 30-60min
how much fentanyl undergoes 1st pass pulmonary uptake?
75% (metabolized in lungs, not liver)
what characteristic of fentanyl makes it last so long?
highly lipid soluble and protein bound
which opioid is hemodynamically stable?
fentanyl
induction dose – fentanyl
2-6mcg/kg with a sedative hypnotic
what is the infusion rate of fentanyl
0.5-5mcg/kg/hr
how potent is sufentanil compared to fentanyl?
10X as potent as fentanyl (greater affinity for opioid receptor – great for neurosurgery)
peak, duration – sufentanil
same as fentanyl — peak 3-5min, duration 30-60min
what is the dosing of sufentanil?
- 0.3-1.0mcg/kg 1-3min before DL
* 0.5mcg/kg followed by 0.5mcg/kg/hr
how potent is alfentanyl compared to fentanyl?
1/10 as potent as fentanyl
what procedures is alfentanyl good for?
anesthetic for RBB, DL
* 5-10mcg/kg provide good analgesia with rapid recovery
how potent/long acting is remifentanyl compared to fentanyl?
similar potency to fentanyl, short duration (~10min)
where is remifentanyl metabolized?
plasma and tissue esterases
compare dilaudid to morphine
- 8x more potent than morphine but shorter acting (~2hr)
- more sedation but less euphoria
- less histamine release
what are opioid antagonists useful for?
Tx overdose, respiratory depression
what is the duration of opioid antagonists?
30-45min
what is the dose of opioid antagonists?
1-4mcg/kg
