Flashcards in Opioids Deck (84)
Drugs naturally derived from opium (poppy plant extract) and synthetically produced drugs with opium- or morphine-like properties
Derived from the Greek word meaning "stupor"; used interchangeably with opioid (used less often d/t negative legal connotation)
What are some favorable opioid properties?
-preservation of blood flow autoregualation (CNS, heart, kidneys) (not preserved with inhalation agent)
-minimal cardiac depression (good for peds with cardiac issues for non related surgery)
-blunting of autonomic response to sympathetic stimulation (laryngoscopy, surgical stress)
What is the MOA of opioid agonists?
Bind to opioid receptors at presynaptic and post synaptic sites in CNS (brain, spinal cord) and peripheral sites (primary efferent neurons)
Act like the endogenous peptides that normally activate these receptors (enkephalins, endorphins, dynorphins)
Describe opioid receptor (OR) activation
-binding to specific G protein coupled receptors causes decreased neurotransmission
*closure of voltage gated Ca channels on presynaptic terminals cause reduction of release of neurotransmitters
*opening K+ channels to hyper polarize the cell, this causing inhibition of post synaptic neurons
Why is there an analgesic affect with opioids?
1) directly inhibit the ascending transmission of nociception info from the spinal cord dorsal horn
2) activate pain control pathways that descend from the midbrain, via the rostral ventromedial medulla to the spinal cord dorsal horn
What are the agonists for Mu I receptors?
What effects are caused at Mu I receptors?
-analgesia (spinal and supraspinal)
-bradycardia (Pavulon good NMB with inc. HR)
What are the agonists of Mu II receptors?
What effects are caused by Mu II receptors?
What are the agonists for kappa receptors?
What effects are caused by the kappa receptors?
-analgesia (spinal, supraspinal) *not as strong as Mu receptors
-respiratory depression *less than Mu
What are the agonists of delta receptor?
What effects are caused by Delta receptors?
-analgesia (spinal and supraspinal
Where are spinal opioid receptors located?
-all three present in high concentrations in dorsal horn of the spinal cord
-on spinal cord pain transmission neurons AND on the primary afferents that relay pain message to the them
Where are supraspinal opioid receptors located?
•pain modulating descending pathways
-rostral ventral medulla
-midbrain periaqueductal gray area
•exogenous opioids act on the brain circuits by stimulating release of endogenous opioid peptides
What are opioid effects outside the CNS?
-sites of inflammation are sensitive to peripheral opioid actions
-Mu receptors on peripheral terminals of sensory neurons
*ex: injecting morphing into the knee after arthroscopic knee surgery
What are general effects of opioids?
Describe distribution of opioids.
Rapidly leave the blood compartment and move to highly perfumed tissues such as brain, lungs, liver, kidneys, and spleen
What is general distribution half life of opioids?
All rapid, 5-20 min
What impacts distribution of opioids?
Varying degrees of protein binding and lipid solubility
*low lipid soluble (morphine): slow movement across BBB so slow onset, prolonged duration
*high lipid soluble (fentanyl and sufentanil): rapid onset, short duration
What role do the lungs play in redistribution of opioids?
-significant amount taken up by lungs on first pass uptake
*this can be later returned to circulation
Ex: sufentanil 50% uptake by lungs on injection, 20 min after termination 18% still in lungs
What influences the amount of uptake by the lungs?
-prior accumulation of another drug (decreased)
-inhalation anesthetic administration (decreased)
What terminates the effect of small opioid doses?
What terminates the effect of large opioid doses?
Metabolism: mostly liver
*remifentanil metabolized by ester hydrolysis by plasma esterases (not affected by pseudocholinesterase deficiency)
Clearance of opioids are dependent on what?
Hepatic blood flow
What is morphine metabolized into and how is it excreted?
-conjugated with glucuronic acid to form morphine 3-glucuronide and morphine 6-glucuronide
*morphine 6 is an active metabolite excreted by kidneys and in bile, it produces analgesia and respiratory depression similar to morphine
What is meperidine metabolized to and how is excreted?
N-demethylated to normeperidine
*active metabolite is CNS stimulant (delirium, hallucinations, seizures with toxic levels)
*excreted by kidneys
*larger, multi doses and renal failure
What are fentanyl class drugs eliminated?
Inactive metabolites excreted by kidneys and in bile
How does propofol use affect metabolism of alfentanil and sufentanil?
When used in conjunction for TIVA, clinical doses of propofol inhibit degradation of alfentanil and sufentanil by 50-60% and up to 90% with higher doses of propofol
*intial doses of opioids shouldn't be altered but may need to reduce infusion rates required for maintenance
What is the equilibration time of morphine?
What is the duration of morphine?
By how much can morphine decrease MAC?
Up to 65%
What are good indications for morphine use?
-pre op for cardiac cases (longer case and still on vent post op so long duration ok)
-orthopedic cases (bug post op pain)
How is morphine's effect different in women?
-greater analgesic potency
-slower onset and offset
-no effect on apneic threshold
-decreased hypoxic sensitivity (lower PaO2 needed for drive to kick in)
What drug is meperidine similar to?
Atropine- cause increased HR
*some large airway bronchodilation
*can cause myocardial depression at doses above 2 mg/kg
What are exaggerated effects of meperidine?
Sensitized the labyrinthine apparatus causing dizziness, orthodontic hypotension, and increased N/V
*don't give if patient likely to be up and moving
What are indications for meperidine?
-supplemental anesthesia in pediatrics
-suppress post op shivering (works on kappa receptors to reset shivering threshold)
What's the duration of meperidine?
2-4 hrs typically
*1 hr and 25 min with 100 mg IM
What effect does meperidine have when combined with a MAOI?
Serotonin syndrome (check med list)
-neuromuscular changes (hyperreflexia)
*severe: coma, seizures, coagulopathy, metabolic acidosis
What is the elimination half life of normeperidine?
15 hrs (>30 hrs in neonates)
What is the distribution 1/2 time of fentanyl?
< 28 min
How does the potency of fentanyl compare to morphine?
100x more potent
How does the potency of meperidine compare to morphine?
1/10th as potent
How does dose affect duration of fentanyl?
-smaller doses have shorter duration (20-40 min) due to redistribution
-larger doses have longer duration due to accumulation
How much of the initial dose of fentanyl is taken up by the lungs?
*repeated doses accumulate in muscle and fat to be gradually released causing prolonged duration
How does infusion time affect context sensitive half time of fentanyl?
Infusions > 2 hrs cause the context sensitive half time of fentanyl to jump higher than sufentanil
*sufentanil is the better choice for longer infusions
How is fentanyl metabolized?
-by liver in to inactive metabolites excreted by kidneys
* <10% unchanged fentanyl excreted by kidneys
What is the elimination half life of fentanyl?
3.1-6.6 hrs (about 8) (longer than morphine d/t larger volume of distribution)
How much of fentanyl is protein bound?
When is fentanyl prolonged?
-elderly (less hepatic blood flow, less microsomal enzymes, less albumin)
*give decreased dose
-abdominal aortic surgery with infrarenal aortic cross clamping (blocks renal blood flow; may be d/t 10% excreted unchanged renally)
**not prolonged with liver cirrhosis
What is MAC reduction with fentanyl?
Large doses (50-150 mcg/kg): up to 80%
Small doses (1 mcg/kg): about 40 %
What are some advantages of fentanyl?
-no direct myocardial depression (changes in SVR and preload not d/t contractility)
-no histamine release
-suppresses stress response r/t surgery
what are some disadvantages of fentanyl?
-sympathetic stimulation in response to pain (not an issue with balanced anesthesia)
-post op resp depression (re narcatization)
What is the drug interaction of fentanyl with benzos?
Synergistic effect increasing sedation and respiratory depression
*don't give both in holding, give the one that is needed most (pain or anxiety?)
What are some unique side effects of fentanyl?
-more decrease in HR
-reflex coughing (pre op?)
-myoclonus w/o EEG change (depression of inhibitory neurons)
-changes SSEP (nerve study) with doses of 30mg/kg
-increased ICP w/o change in CO2
*hyperventilate to drop CO2 and ICP then give
*remifentanil best with neuro cases
What is the most potent opioid in use?
How does sufentanil potency compare to morphine and fentanyl?
10x more potent than fentanyl
1000x more potent than morphine
Compare sufentanil to fentanyl
-more lipid soluble
-greater protein binding (causing smaller volume of distribution and shorter elimination t 1/2 life)
-more intense, longer lasting analgesia with less respiratory depression
(Greater affinity for opioid receptors; estivated avg 20 min sooner)
How much sufentanil is taken up by the lungs?
What is the elimination t1/2 life of sufentanil?
What is the MAC reduction of sufentanil?
up to 70% (more than equipotent dose of fentanyl)
What are some guidelines with sufentanil infusions?
-turn off 30-45 min prior to emergence
-if using an inhalation agent, turn it off early to ensure none remains when trying to wake up
-use of benzos may need a decrease in infusion rate
-adjust loading dose to age and health
How does infusion time affect context sensitive 1/2 life of sufentanil when compared to fentanyl and alfentanil?
After 3 hr infusion, sufentanil will decrease 80% faster and after 8 hr infusion, will decrease 50% faster
What are some unique effects of sufentanil?
-preinduction dose may cause apnea without loss of consciousness
*must instruct to breathe
-stuff chest common with 10-15 mcg dose prior to induction
*seen more with elderly and in ortho and cardiac cases
-difficult ventilation d/t stiff chest and glottic obstruction
-OD difficult to determine since BP doesn't change much with minimal effective dose and 5x that dose
What is an indication for sufentanil?
Extreme post op pain (ortho) since analgesic effect 10x that of fentanyl
Compare alfentanil to fentanyl.
-1/5th as potent
-lower lipid solubility and more protein binding so much smaller volume of distribution (4-6x smaller)
-shorter elimination t1/2 life
*more rapid onset since only 10% is ionized at physiologic pH
*lower incidence of N/V than fentanyl and sufentanil
*more liable to produce stiff chest
What is the elimination t1/2 life of alfentanil?
1.1- 1.6 hrs
When does the alfentanil infusion need to be stopped?
15-25 min prior to emergence
(Small volume of distribution keeps alfentanil from distributing peripherally which keeps plasma concentration up.....reason context sensitive half time is longer)
How is alfentanil metabolized?
By the liver via 2 pathways
-96% cleared within 60 min of administration
When is alfentanil indicated?
For a single, brief stimulus
What can happen of alfentanil is given after the painful stimulus?
A drop in BP
Compare potency of Remifentanil to fentanyl
5x more potent on a mg per mg basis
What's the elimination t1/2 for Remifentanil?
*no point in giving a bolus, just start the infusion
How is Remifentanil metabolized?
By plasma and tissue esterases to inactive metabolites that are excreted by the kidneys
*hypothermia slows clearance by 20% (bypass)
*99.8% eliminated within within elimination t1/2 (6.3 min)
**not good for post op pain
What is the distribution t1/2 of Remifentanil?
What is the context sensitive 1/2 time of Remifentanil?
Approx 4 min
-independent of infusion time
*must give a longer acting opioid to ensure analgesia when patient awakens
How does effect site concentration of Remifentanil decrease compare to other fentanyls?
Decrease by 50% in less than 4 minutes
-sufentanil: 34 min
-alfentanil: 58 min
-fentanyl: 262 min
Compare Remifentanil to fentanyl
-greater incidence of hypotension
*30% drop in SBP 2 min after admin
-smallest volume of distribution of all fentanyls
What are some clinical uses of Remifentanil?
-laryngoscopy (esp with aortic aneurysms)
-labor and delivery (crosses placenta but metabolized quickly)
-desire for rapid recovery
*craniotomy (need to do neuro checks)
**good when intense intra op analgesic needed but little post op pain
What is the onset and duration of hydromorphone?
Onset: 5 min
Duration: 4-5 hrs (1/2 life 2-3 hrs)
How does hydromorphone potency compare to morphine and fentanyl?
1.5 mg equals 10 mg morphine or 100 mcg fentanyl
What are indications for hydromorphone?
-moderate to severe pain
-terminally ill patients (increased potency with minimal side effects)