Opioids Flashcards
Which opioid is naturally occurring? Semisynthetic opioids?
Natural: Morphine
Semisynthetic: Heroin, hydromorphone, codeine
Opioid structures: phenanthrene vs. benzylisoquinolines?
Phenanthrene: contains benzene rings
Benzylisoquinoline: from alkaloid plant
What are the four types of exogenous synthetic opioids?
- Morphinan derivatives: levorphenol, butorphenol
- Diphenyl derivatives: methadone
- Benzomorphans: phenazoncine, pentazocine
- Phenylpiperidines: meperidine, fentanyl, alfentanil, sufentanil, remifentanil
Opioid partial agonist vs. mixed agonist/antagonist?
Agonist: buprenorphine, regardless of dose, it can’t produce full mu receptor effects like morphine
Mixed agonist/antagonist: nalbuphine, agonist at kappa receptor and antagonist at mu reversing respiratory depression (good for chronic pain patients)
What acts on Mu-1 receptor? What are the effects?
ALL endogenous and synthetic opioid agonists Analgesia, euphoria, sedation SUPRASPINAL analgesia (and some spinal) Miosis (pupil constriction) Bradycardia Urinary retention Prolactin release, hypothermia
What acts on Mu-2 receptor? What are the effects?
ALL endogenous and synthetic opioid agonists Hypoventilation (resp depression) Physical dependence SPINAL analgesia Constipation, N/V, urinary retention Bradycardia Miosis Pruritis
What acts on the Kappa receptor? What are the effects?
DYNORPHINS act on kappa receptors SUPRASPINAL and SPINAL analgesia Dysphoria Sedation Miosis Diuresis Psych reactions (hallucinations, delirium)
What acts on the delta receptor? What are the effects?
ENKEPHALINS act on delta receptors SUPRASPINAL and SPINAL analgesia Hypoventilation (resp depression) Physical dependence Constipation Urinary retention Pruritis
Which two receptors (Mu1/2, kappa, or delta) are responsible for physical dependence?
Mu-2 and Delta receptors
What G-coupled reactions occur when an opioid acts on an opioid receptor?
- MAPK cascade -> phospholipase A2 producing prostaglandins and leukotrienes
- K influx
- Ca channel inactivation -> suppression of neurotransmitter (substance P) release
- Dec adenylate cyclase, less cAMP
Are opioids strong or weak, acid or base?
WEAK BASES
Someone acidotic needs ____ (more/less) opioid
MORE
Because more ionization occurs
The higher % unionized, the higher diffusible fraction, and ____ (faster/slower) the onset
The higher unbound, the ____ (faster/slower) the onset
The higher % unionized, the higher diffusible fraction, and FASTER the onset
The higher unbound, the FASTER the onset
Which opioids are highly ionized vs non-ionized?
Morphine, meperidine, fentanyl, sufentanil, alfentanil, remifentanil
Non-ionized: alfentanil 89%, remifentanil 58%
The rest are highly ionized, the percents nonionized is..
Morphine 23%, meperidine 7%, fentanyl 8.5%, sufentanil 20%
List opioids in order of % protein binding.
Morphine, meperidine, fentanyl, sufentanil, alfentanil, remifentanil
Morphine 35% (LOW) Meperidine 70% Fentanyl 84% Alfentanil 92% Remifentanil 66-93% Sufentanil 93%
List opioids in order of clearance.
Morphine, meperidine, fentanyl, sufentanil, alfentanil, remifentanil
Alfentanil 238 mL/min Sufentanil 900 Meperidine 1020 Morphine 1050 Fent 1530 Remi 4000
List opioids in order of volume of distribution.
Morphine, meperidine, fentanyl, sufentanil, alfentanil, remifentanil
Alf 27 Remi 30 Suf 123 Morphine 224 Meperidine 305 Fent 335
What is the partition coefficient (how much it penetrates the tissues)?
(Morphine, meperidine, fentanyl, sufentanil, alfentanil, remifentanil)
Remi (no data) Morphine 1 Meperidine 32 Alfentanil 129 Fent 955 Suf 1727
Do young and old patients need more or less opioids? Why?
LESS
Neonates have dec rate of elimination due to immature CP450
Elderly have more sensitivity to the drug
Are opioids dosed based on current weight or ideal body weight?
Ideal weight (lean body mass) not actual body weight
What area produces spinal analgesic effects?
Receptor activation in the spinal cord and dorsal root ganglia, substantia gelatinosa
What area produces supra spinal analgesia?
Receptor activation in the periaquaductal/periventricular gray matter of the brain
Opioid perioperative CNS effects?
Analgesia, euphoria Drowsy, sleep Miosis Nausea (chemoreceptor trigger zone) Dec CBF, ICP (neuro stability)
Opioid perioperative CV effects?
CV stable
Dose dependent bradycardia, dec CO/BP
Vasodilation
Meredine- tachycardia, myocardial depression
Opioid perioperative ventilatory effects?
Respiratory depression (dose dependent)
Decrease compliance in chest wall, constricted pharyngeal and laryngeal muscles (inhibition of GABA, increase in dopamine)
Hypercarbia, hypoxia
Dec RR, inc Vt (dec Vt in high doses)
Dec hypoxic ventilatory drive
Vent response curve reduced and shifted to R
Opioid perioperative renal/GI/liver effects?
Increase peristalsis and tone of ureters Urgency Block catecholamine and cortisol release Sphincter of Oddi spasm (inc biliary pressure) Constipation, dec GI motility Prolonged gastric emptying
When giving neuraxial block, cephalic movement of opioid depends lipid solubility, the more lipid solubility will cause what?
More lipid solubility causes limited migration (fentanyl)
Less lipid solubility causes more cephalad movement in CSF (morphine)
Side effects of neuraxial opioids?
Pruritis
N/V
Urinary retention
Ventilatory depression (delayed in morphine)
Morphine: solubility, protein binding, ionization?
Poor lipid solubility
Low PB 35%
Highly ionized (low nonionization 23%)
Which two opioids are histamine releasers?
Morphine
Meperedine
This may be the mechanism causing pruritus
Morphine peak? DOA?
Peak: 15-30 min
DOA: 4 h
Morphine metabolism?
ACTIVE metabolite: M6G - morphine-6-glucuronide
Metabolized by liver, kidneys also play a role
Meperidine is structurally similar to what drug?
Atropine, giving it muscarinic effects
Also similar to local anesthetics, it blocks Na channels
Meperidine metabolism?
ACTIVE metabolite: normeperidine lasts 3 days, half as potent, can cause seizures
How does hydromorphone compare to morphine?
5x more potent
Derivative of morphine
Q4h dosing needed
More sedation but less euphoria than morphine
Fentanyl is _____x more potent than morphine
100x
Meperidine is ____ as potent as morphine
1/10
Sufentanil is _____x more potent than morphine
1,000x
Sufentanil metabolism?
ACTIVE metabolite: desmethylsufentanil
Rapidly metabolized in liver
Undergoes first pass pulmonary uptake
Alfentanil is ____x more potent than morphine
10-20x
Remifentanil metabolism?
Metabolized by tissue/plasma esterases
Remifentanil is _____x more potent than morphine
100 (similar to fentanyl, but slightly more potent than fentanyl)
List the order of potency of opioids.
Morphine, meperedine, fentanyl, sufentanil, alfentanil, remifentanil, dilaudid
Sufentanil (most potent) Remifentanil Fentanyl Alfentanil Dilaudid Morphine Demerol/meperidine "She ran far away down main drive" From least to most: "Dad made dinner again from ramen soup"
What receptors are opioid Agonist-Antagonists hitting?
Mu- antagonist
Kappa- partial agonist
(Note: kappa receptors may cause dysphoria)
Nalbuphine (nubain) MOA?
Works at kappa and sigma receptors to antagonize opioid induced respiratory depression while maintaining analgesia
Nalbuphine (nubain) pros/cons?
Pro: no adverse CV problems, reverses sphincter of Oddi spasm (used instead of glucagon), analgesic response equal to morphine
Con: dyseuphoria (kappa receptor), hypotension can occur
Butorphenol (stadol) acts as an agonist at ____ receptor and a weak antagonist at ____ receptor and is ____ x more potent than morphine
Agonist at kappa
Weak antagonist at mu
5x more potent than morphine
Naloxone class of drug and MOA?
Opioid antagonist
Competitively blocks receptor sites (mu, kappa, delta) and reverses respiratory depression and analgesia
Naloxone DOA, onset?
Short DOA (less than most opioids) Onset 1-2 min
Naloxone side effects?
Tachycardia, HTN, vent dysrhythmias
Severe pain
Pulmonary edema (due to catecholamine release)
