Pain & Opioids Flashcards
Semi-synthetic opioids
- chemical modification of the morphine molecule
- heroin (diacetylmorphine), thebaine, oxycodone, hydrocodone, hydromorphone
Synthetic opioids
-manufactured by synthesis rather than chemical modification of the morphine molecule
- morphine derivative: levorphanol, nalbuphine
- benzomorphan methadone derivatives
- benzomorphan derivatives: pentazocine
- phenylpiperidine derivatives: meperidine, fentanyl, alfentanil, sufentanil, remifentanil
Opioid receptors
-all 4 are G protein receptor and inhibit adenylate cyclase and cyclic adenosine monophosphate (cAMP) production
Mu-1, Mu-2
Delta
Kappa
Mu receptors
Mu 1 - analgesia
Mu 2 - hypoventilation, physical dependence
Generalized effects of exogenous opioids at the Mu-1 receptors include which two of the following? (supraspinal, spinal analgesia, physical dependence, constipation)
supraspinal, spinal analgesia
The respiratory depressant effects of the opioid agonists are produced by action at which receptor?
Mu2
Which opioid does NOT have an active metabolite? (Fentanyl, Meperidine, Morphine, Oxycodone)
Fentanyl
Which opioid receptor is responsible for shivering postoperatively?
Kappa
Which opioid receptor is involved in the physical dependence of opioid addiction?
Primiarly Mu 2 (also detla)
Of the opioid medications which one has constant clearance and is unaffected by liver or renal disease?
Remifentanil
Match opioid receptors with endogenous opioids:
[mu, delta, kappa] to [endomorphins, endorphins, enkephalins, dynorphins]
Mu: endomorphins, endorphins, enkephalins
Delta: endorphins and enkephalins
kappa: dynorphins
2 chemical classes of opioid alkaloids?
- phenanthrenes
2. benzylisoquinolines
Opioid MOA
- Done largely by presynaptic inhibition via Ca++ ch inactivation & reduced Ca++ influx which reduces NT release (Ach, D, NE, SubP).
- increased K+ conductance (hyperpolarizes and prevents neuronal excitation/propagation)
metabolism & excretion of opioids is via
hepatic metabolism for ALL (except remifentanil which is metabolized by non-specific esterases)
renal excretion for ALL (with some biliary, morphine)
CYP enzymes inovlved
CYP 2D6, 3A4, 2B6
active metabolite of morphine
morphine 6 gucuronide M6G
accounts for about 10% of morphine’s metabolism
Opioid effects: CNS
analgesia, sedation, euphoria/dysphoria
Opioid effects: CV
decreased tone & vasodilation
bradycardia
Opioid effects: Pulm
- depresses RR and rhythm (slow/deep) primarily through Mu2 in the brainstem
- decreased responsiveness to hypercarbia
- decrease cough
Opioid effects: ridgiidty
- cause skeletal muscle rigidity, especially thoracic and abdominal muscles (may involve actions with central mu receptors interacting with dopaminergic and GABA pathways)
- decrease in chest-wall compliance and constriction of pharyngeal and laryngeal muscles can become difficult to ventilate
opioid effects: GI
PONV
GI constipation or ileus
increase biliary pressure, spasm of sphincter of oddi
Naturally occurring opioids
morphine
codeine
opioid partial agonists or agonist/antagonists
buprenorphine
butorphanol
nalbuphine
opioid antagonists
naloxone
nalmefene
naltrexone
synthetic codeine analog
tramadol
non-narcotic analgesics
NSAIDS (ketorolac, ibuprofen)
acetaminophen
receptor activation causes presynaptic inhibition of NTs release (what NTs are involved)
Ach
Dopamine
norepi
substance P
all opioid receptors are what type?
G-protein receptors and inhibit adenylate cyclase and cyclic adenosine monophosphate (cAMP) production
True/False: naloxone and other opioid antagonists work at all 4 opioid receptors?
True
Which opioid receptor is responsible for dysphoria and sedation?
kappa
Which opioid receptors are responsible for miosis?
Mu1
Kappa
Which opioid receptor is responsible for bradycardia and hypothermia?
Mu1
Which opioid receptor is responsible for euphoria?
Mu1
Which opioid receptor is responsible for urinary retention?
Mu1
Delta
Opioid effects: cutaenous changes
flushed, warm, urticaria, puritis
Order the context-sensitive half-time for a 4 hr infusion from shortest to longest (alfentanil, fentanyl, remifentanil, sufentanil)
Shortest 1. Remifentanil 2. sufentanil 3. alfentanil 4. fentanyl Longest
Anesthesia’s uses for opioids
- analgesia
- blunting SNS response to intubation or surgical stimulation
- sedation
- reduces the amount of VA needed for MAC
Meperidine - post-op` shivering
Fentanyl IV push dose for analgesia
dose: 25-150 mcg
onset: 3-5 min
Fentanyl infusion rate
1-2 mcg/kg/hr
Alfentanil loading dose & maintenance rate
loading dose: 35-70 mcg/kg (1500-5000 mcg in 70kg pt)
onset: 1-2 min
maintenance: 0.25-0.5 mcg/kg/min
Remifentanil loading dose & maintenance rate
loading dose: 1-2 mcg/kg (70-140 mcg in 70kg pt)
onset: 1 min
maintenance: 0.05-0.25 mcg/kg/min
Order of onset/peak for bolus injection, fastest to longest(alfentanil, fentanyl, remifentanil, sufentanil)
Fastest 1. Remifentanil 2. alfentanil 3. Fentanyl 4. sufentanil 5. morphine Longest
most common pharmacokinetic interaction in opioid pharmacology?
combined IV opioids and propofol
-due to hemodynamic changes induced by propofol and their impact on pharmacokinetic processes, opioid concentrations may be larger when given with continuous propofol
most common pharmacodynamic interaction in opioid pharmacology?
synergistic interaction that occurs when opioids are given combined with sedatives
- ex: when given with volatile anesthetics, they reduce the MAC of the VA. (MAC reduction can be substantial, but not complete)
- can also be given with propofol or other hypnotics
effects of increased age on opioids
-in general older patients have lower central clearance and higher potency (lower EC50)
