Exam 2 - Acute Pain & Opioid-Free Analgesia (Grayson's) Flashcards by Levi Juarez

What are the 2 types of somatic pain?

Superficial: skin, SQ, mucous membranes
Deep: muscles, bones, tendons

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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.

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Which pain is more abnormal: chronic nociceptive pain or neuropathic pain?

Neuropathic pain

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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

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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)

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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)

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Surgical incision (aka trauma) produces tissue injury, causing release of namely what 4 inflammatory mediators?

Histamine
Bradykinin (peptide)
Prostaglandins (lipids)
Serotonin (neurotransmitter)

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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

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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 ^

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2nd order neurons synapse with third order neurons in the:
A. thalamus
B. pons
C. medulla
D. dorsal column

A. thalamus

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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

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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

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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

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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

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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

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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

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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.

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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

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What opioid can be a cause of hyperalgesia?
A. hydromorphone
B. sufentanil
C. morphine
D. remifentanil

D. remifentanil - should never be used without ketamine

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Differentiate Hyperalgesia and Allodynia.

In chart form.

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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

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Gastric acid secretion ____ (decreases or increases) as we age thus ____ (decreases or increases) gastric pH.

decreases; increases

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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)

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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

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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! ## Footnote *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 ## Footnote *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 ## Footnote *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 ## Footnote 2nd most abused opioid... after oxy (#1)

What is typical dose of hydrocodone?

2.5 - 10mg w/ 300 - 750mg acetaminophen q4-6hrs ## Footnote **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* ## Footnote *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 ## Footnote Reduces pain intensity up to 20 -25% and analgesic comsumption up to 30 – 50% **up to 48 hrs after surgery**