Exam 2 - Acute Pain & Opioid-Free Analgesia (Grayson's) Flashcards
What are the 2 types of somatic pain?
- Superficial: skin, SQ, mucous membranes
- Deep: muscles, bones, tendons
Visceral pain can be: select 2.
A. localized to area around organ
B. from tendons, bones, and joints
C. referred cutaneous pain like radiating left shoulder pain from cardiac ischemia
D. from an accidental cut on a finger from a knife
A. localized to area around organ
C. referred cutaneous pain like radiating left shoulder pain from cardiac ischemia
- Parietal: sharp, localized organ pain.
- Referred: Cutaneous pain from convergence of visceral and somatic afferent input.
Which pain is more abnormal: chronic nociceptive pain or neuropathic pain?
Neuropathic pain
What is the Specificity Theory?
Who came up with it?
intensity of pain is directly related to amount and degree of pain assoc. with tissue injury - Descartes
What theory linked pain with emotion, rather than with sensory?
A. intensity
B. specificity
C. gate-control
D. none of these
A. Intensity Theory (Plato)
According to the gate-control theory, where is pain transmission regulated in the CNS?
A. reticular activating system
B. nucleus marginalis
C. substantia gelatinosa
D. thalamus
C. Substantia Gelatinosa (lamina II)
Surgical incision (aka trauma) produces tissue injury, causing release of namely what 4 inflammatory mediators?
- Histamine
- Bradykinin (peptide)
- Prostaglandins (lipids)
- Serotonin (neurotransmitter)
Where do first order neuronas (Aδ and C fibers) synapse with second order neurons?
A. postcentral gyrus
B. thalamus
C. dorsal horn
D. ventral horn
C. Dorsal horn of the spinal cord
After the proximal axon synapses with 2nd order neurons in dorsal horn, what 2 things happen?
A. crosses to the contralateral side of spinal cord
B. crosses to the contralateral side of medulla
C. ascends in DCML tracts to thalamus
D. ascends in spinothalamic tracts to thalamus
A. crosses to the contralateral side of spinal cord
D. ascends in spinothalamic tracts to thalamus
in this order ^
2nd order neurons synapse with third order neurons in the:
A. thalamus
B. pons
C. medulla
D. dorsal column
A. thalamus
Third order neurons in thalamus project through the internal capsule and to the ____. select 2.
A. precentral gyrus of cerebral cortex
B. postcentral gyrus of cerebral cortex
C. primary sematosensory cortex
D. primary motor cortex
B. postcentral gyrus of cerebral cortex
C. primary sematosensory cortex
just 2 different ways to call it
What is the name of the process by which noxious stimuli are converted to action potentials?
A. perception
B. modulation
C. transmission
D. transduction
D. transduction
What is the name of the process by which an action potential is conducted through the nervous system?
A. perception
B. modulation
C. transmission
D. transduction
C. transmission
What is the name of the process by which pain transmission is altered along its afferent pathway?
A. perception
B. modulation
C. transmission
D. transduction
B. modulation
What is the name of the process by which painful input is integrated in the somatosensory and limbic cortices of the brain?
A. perception
B. modulation
C. transmission
D. transduction
A. perception
Hyperalgesia is the process by which tissue trauma releases local inflammatory mediators that can produce:
A. augmented sensitivity to stimuli
B. depressed sensitivity to stimuli
C. pain from a stimulus that doesnt normally evoke pain
D. numbness
A. augmented sensitivity to stimuli
What is primary hyperalgesia? select 2.
A. augmented sensitivity to painful response
B. Increased excitability of neurons in the CNS d/t glutamate activation of NMDA-R
C. allodynia-style misinterpretation of non-painful stimuli.
D. decreased excitability of neurons in the CNS d/t glutamate activation of NMDA-R
A. augmented sensitivity to painful response
C. allodynia-style misinterpretation of non-painful stimuli.
What is secondary hyperalgesia?
A. augmented sensitivity to painful response
B. Increased excitability of neurons in the CNS d/t glutamate activation of NMDA-R
C. allodynia-style misinterpretation of non-painful stimuli.
D. decreased excitability of neurons in the CNS d/t glutamate activation of NMDA-R
B. Increased excitability of neurons in the CNS d/t glutamate activation of NMDA-R
What opioid can be a cause of hyperalgesia?
A. hydromorphone
B. sufentanil
C. morphine
D. remifentanil
D. remifentanil - should never be used without ketamine
Differentiate Hyperalgesia and Allodynia.
In chart form.
What is the hallmark negative symptom of neuropathic pain?
A. burning
B. deep, dull ache
C. numbness
D. sharp
E. shooting
C. numbness
All others listed are positive signs of neuropathic pain
Gastric acid secretion ____ (decreases or increases) as we age thus ____ (decreases or increases) gastric pH.
decreases; increases
Answer this with increases or decreases
With normal aging, what happens to a patient’s:
muscle and fat mass?
proportion of body fat?
total body water?
albumin?
muscle and fat mass: decreases
proportion of body fat: increases
total body water: decreases (crucial for water soluble drugs)
albumin: decreases (crucial for protein bound drugs)
Answer this with increases or decreases
With the aging patient, what occurs to their:
hepatic blood flow?
liver mass and metabolic activity?
hepatic blood flow: decreases
liver mass and metabolic activity: decreases
this is important b/c our liver converts substances believed to be harmful into a form that can easily be eliminated.
so maybe more harmful substances floating around longer in an aging patient
Which of the following is the most important renal change that occurs with aging?
A. decreased blood flow
B. decreased kidney mass
C. decreased GFR
D. decreased functioning nephrons
C. decreased GFR
T/F: Opioid and non-opioid analgesics both have a ceiling effect.
False.
Opioids DO NOT have a ceiling effect (reason why we can just keep giving more and more)
Non-opioids DO have a ceiling effect (increase in dose only increases side effects, not analgesia)
The Mu opioid receptor is responsible for:
A. dysphoria
B. bradycardia
C. only analgesia
D. diuresis
B. bradycardia - this one is a differential from other receptors!!
but also responsible for:
analgesia, resp dep, euphoria, reduced GI motility
The kappa opioid receptor is responsible for: select all that apply.
A. dysphoria
B. constipation
C. urinary retention
D. miosis
A. dysphoria
D. miosis
as well as:
analgesia, psychosis, delusion/delirium, resp dep
What opioid receptor causes only analgesia when bound by an agonist?
Delta
What drug is described by the following organic structure:
Substitution of methyl group for hydroxyl group on #3 carbon of morphine molecule.
A. tramadol
B. hydromorphone
C. codeine
D. hydrocodone
C. Codeine
____ is more reliably absorbed orally than morphine.
A. tramadol
B. codeine
C. hydromorphone
D. methadone
B. Codeine
Children less than 12 lack maturity of enzyme to metabolize which drug?
A. codeine
B. morphine
C. oxycodoone
D. fentanyl
A. Codeine - can experience side effects without the analgesia :/
What two CYPs metabolize codeine?
CYP2D6 → morphine (10% of admin dose)
CYP3A4 → norcodeine (remainder becomes this which is inactive)
Codeine metabolism is variable due to more than 50 polymorphisms resulting in analgesic variability.
About what % of the population is resistant to codeine’s analgesic effect?
10%
What is the adult dose and max for codeine?
15 - 60 mg q4h
max: 360mg per day
What is the pediatric dose and max of codeine?
0.5 - 1 mg/kg/dose
60mg max per day
60mg of codeine (max analgesia) is equivalent to how much aspirin?
650mg
What drug is described by the following?
“Synthetic 4-phenylpiperidine analogue of morphine and codeine which is composed of a racemic mixture of two enantiomers + and – “
A. methadone
B. oxycodone
C. hydromorphone
D. tramadol
D. Tramadol
The (+) enantiomer of tramadol is a centrally acting opioid agonist with moderate affinity at ____ receptors.
A. delta
B. mu
C. kappa
D. serotonin
B. mu = moderate affinity
kappa and delta = weak affinity
ALSO: (+) enantiomer opposes serotonin reuptake!
The (-) entantiomer of tramadol inhibits ____ reuptake and stimulates ____ receptors.
A. serotonin; beta
B. serotonin; alpha1
C. norepinephrine; alpha1
D. norepinephrine; alpha2
E. norepinephrine; beta1&2
D. norepinephrine; alpha2
The (-) entantiomer of tramadol inhibits norepinephrine reuptake and stimulates alpha2 receptors.
What is tramadol metabolized into and what is the relevance of its metabolite?
Tramadol → CYP3A4 & 2D6 → O-desmethyltramadol (2-4x more potent)
What is tramadol’s potency compared to morphine?
1/5 to 1/10
When is tramadol contraindicated?
A. renal insufficiency
B. hypoalbuminemia
C. seizure disorders
D. with other opioids
C. Seizure Disorders!
and maybe also PONV since high incidence of n/v already
What are the benefits of tramadol vs other opioids?
- Minimal respiratory depression :)
- low incidence of addiction
- Minimal constipation :)
Oral dose requirement of morphine is ____ times the IM or IV route.
three
PO 3X > IV or IM
What are morphine’s primary receptors?
μ-1 and μ-2
What are the two metabolites of morphine? and what are their effects?
- Morphine-6-glucuronide → analgesia
- Morphine-3-glucuronide → neurotoxicity & hyperalgesia
maybe use ketamine to help w the hyperalgesia and target different receptors
How is morphine metabolized?
- Hepatic → conjugation w/ glucuronic acid
- Kidneys
What factors contribute to morphine’s minimal CNS absorption? select 2.
A. increased lipid solubility
B. increased protein binding
C. decreased lipid solubility
D. decreased protein binding
B. increased protein binding
C. decreased lipid solubility
- also: ↑ Ionization at normal bodily pH
What differences does morphine exhibit in women?
hint: has to do with potency and speed of offset
- greater analgesic potency
- slower speed of offset!
What is released in response to morphine administration?
which results in?
Histamine! → vasodilation and hypotension
Morphine should be avoided in patients with ____ as the metabolite morphine–6-glucuronide can accumulate and lead to respiratory depression.
A. liver failure
B. renal impairment
C. COPD
D. CHF
B. Renal impairment
What drug is a synthetic derivative of thebaine and is the most used opioid worldwide?
A. MSContin
B. fentanyl
C. OxyContin
D. Dilaudid
C. Oxycodone (OxyContin)
What are the metabolites of oxycodone?
Oxymorphone (active)
Noroxycodone (inactive)
Oxycodone is primary a prodrug so extensive first pass effect!.
What is the site of action of oxycodone?
A. mu
B. kappa
C. delta
D. all of the above
E. mu and kappa
F. mu and delta
E. mu and kappa receptors in CNS
What are the two types of PO oxycodone?
IR = Immediate release
CR = Controlled release
What is the dose of oxycodone?
10 - 15mg (equivalent to 10 mg morphine)
What is the onset of oxycodone?
DOA?
onset: < 1 hour
DOA: IR = 3-4 hrs /// CR = 12 hrs
this is good b/c pts get to steady state and stay there easier than with other opioids
Why is methadone used for opioid addiction maintenance?
- 60-90% oral bioavailability
- High potency
- Long duration of action
What should be known about methadone’s half life?
Very long and unpredictable (up to 36 hours)
Can accumulate w/ repeated doses
What would occur with concurrent methadone and carbamazepine use?
Carbamazepine is a CYP450 inducer thus methadone will be metabolized faster. = shorter DOA
What agents can inhibit the metabolism of methadone?
CYP450 Inhibitors:
- Antiretrovirals
- Grapefruit juice
What is the dose of methadone?
2.5 - 10 mg PO/IM/SQ q4-12 hours
What is the worst med interaction associated with methadone?
A. EtOH
B. diazepam
C. valproic acid
D. MAOIs
D. MAOI’s
What (3) drugs are known to increase the concentration/effects of methadone?
A. ciprofloxacin
B. acute EtOH
C. diazepam
D. phenytoin
E. rifampin
F. phenobarb
A. ciprofloxacin
B. acute EtOH
C. diazepam
What drugs are known to decrease concentration/effects of methadone? select 3.
A. gentamycin
B. MAOIs
C. diazepam
D. phenytoin
E. rifampin
F. phenobarb
D. phenytoin
E. rifampin
F. phenobarb
and amprenavir (antiretroviral)!!
What drug is fentanyl structurally similar to?
Meperidine
Fentanyl has high potency, ____ onset, and ____ duration of action.
A. slow; short
B. rapid; long
C. slow; long
D. rapid; short
D. Rapid onset and Short duration
What is the priniciple metabolite of fentanyl?
Norfentanyl
Detectable in urine up to 72 hours after single dose.
Why is elimination of fentanyl slightly prolonged despite very short duration of action?
A. liver unable to metabolize as easily
B. lungs act as large inactive reservoir
C. kidneys keep it in circulation longer
D. liver takes large first pass uptake
B. Lungs serve as large inactive reservoir!
(75% first pass pulmonary uptake).
Why is fentanyl more potent and rapid than morphine?
Greater lipid solubility
What is responsible for fentanyl’s short duration of action?
Rapid redistribution to fat and muscle = Vd is 335L !!
Hydromorphone is ____ times as potent as morphine when administered orally.
PO dilaudid 3 - 5X more potent than morphine
Hydromorphone is ____ times as potent as morphine when administered IV.
IV Dilaudid 8.5X more potent than morphine
What is hydromorphone’s primary metabolite?
Hydromorphone-3-glucuronide
What should be known about Hydromorphone-3-glucuronide?
A. has neurotoxic effects
B. 10% are resistant to analgesic
C. causes dysphoria
D. can cause QT prolongation
A. May potentiate neurotoxic effects (allodynia, myoclonus, seizures). especially in those w/ renal insufficiency
and Lacks analgesic effects
What is the typical IV dose of Hydromorphone?
PO dose?
IV: 0.2 - 2 mg q3-5 min
PO: 2-8 mg
slower onset than fentanyl so chill and don’t expect effect super fast
Hydrocodone is a codeine derivative but it is ____ times more potent than codeine.
Hydrocodone is 6 - 8 x more potent
2nd most abused opioid… after oxy (#1)
What is typical dose of hydrocodone?
2.5 - 10mg w/ 300 - 750mg acetaminophen q4-6hrs
but rmbr max of tylenol: 4G
What medication will give hydrocodone an increased opioid effect? select 2.
A. IV mag
B. carbamazepine
C. CCB
D. dexmedetomidine
A. IV mag
C. CCB
What receptors does buprenorphine have affinity to?
μ - partial agonist (strong)
κ - antagonist (strong)
δ - agonist (weak)
What benefits does buprenorphine provide?
- ↓ respiratory depression
- ↓ immune suppression
- ↓ constipation
- No accumulation in renal patients
What is the IV/IM buprenorphine dose equivalence for morphine?
0.3mg IM buprenorphine = 10mg morphine
What is the recommended dose for celecoxib?
100mg daily
What is the recommended dose for diclofenac?
50 mg BID
How might antidepressants work as pain medication adjuvants?
Modulation of spinal cord transmission to reduce pain signaling
Whats the IV dose of fentanyl for pain?
20 - 50 mcg
What anticonvulsants are used as adjuvant medication to relieve pain?
- Gabapentin (watch for sedation/ respiratory depression in older patients)
- Phenytoin (Dilantin)
- Carbamazepine (Tegretol)
- Topiramate (Topamax)
What skeletal muscle relaxants are used as adjuvant medication to relieve pain?
- Baclofen (Lioresal®)
- Carisoprodol (Soma®)
- Cyclobenzaprine (Flexeril®)
- Methocarbamol (Robaxin®)
- Tizanidine (Zanaflex®)
Opioids acting on the Kappa receptor will produce these unwanted effects.
- Respiratory depression
- Dysphoria
Opioids acting on the Delta receptor will produce these unwanted effects.
- Respiratory depression
- Urinary retention
- Prurititis
- Physical dependence
What is opioid-induced hyperalgesia (OIH)?
- State of nociceptive sensitization caused by exposure to opioids.
- The condition is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain might actually become more sensitive to certain painful stimuli.
Opioid tolerance to analgesia can occur:
A. after repeated doses
B. after a patient has used a PCA pump
C. after two doses
D. after a single dose
D. after a single dose.
Desensitization (acute tolerance) involves:
A. administration of an antagonist
B. a patient becoming more sensitive to certain painful stimuli
C. internalization of the opioid receptor
D. non-opioids helping the clearance of opioids
C. internalization of the opioid receptor
and/or phosphorylation of receptors resulting in an uncoupling of receptor from its G protein
so pts start to require more opioids either mins to hours after receiving first dose
OFA toolbox:
What is the lidocaine dose for induction?
for maintanence?
induction: 1.5 mg/kg (100 mg max)
maintanence: 1-3 mcg/kg/hr
Anti-inflammatory agents before surgery:
Dexamethasone dose:
Diclofenac dose:
Dexamethasone dose: 10 mg
Diclofenac dose: 75-150 mg
What’s the OFA maintanence dose for IV tylenol?
1000 mg
Opioid-Free anesthesia toolbox:
What is the dose of gabapentin that provides analgesic ceiling effect?
600 mg
Opioid-Free anesthesia toolbox:
What is the dose of dexmedetomidine for sympathetic block 10 mins before induction?
What about as maintanence dose?
10 mins before induction: 20-30 mcg
maintanence: 0.5-1mcg/kg/hr
Opioid-Free anesthesia toolbox:
What is the dose of ketamine that reduces postop analgesic needs, especially in opioid-tolerant patients?
< 0.5 mg/kg
Reduces pain intensity up to 20 -25% and analgesic comsumption up to 30 – 50% up to 48 hrs after surgery
