Acute Pain & Opioid-Free Analgesia (Exam II) Flashcards
1
Q
What types of somatic pain are there?
A
- Superficial: skin, SQ, mucous membranes
- Deep: muscles, bones, tendons
2
Q
What types of visceral pain are there?
A
- Parietal: sharp, localized organ pain.
- Referred: Cutaneous pain from convergence of visceral and somatic afferent input.
3
Q
Is chronic nociceptive pain or neuropathic pain more abnormal?
A
Neuropathic pain
4
Q
What are some possible cardiac consequences of poorly managed pain? 3
A
↑ HR
↑ BP
↑ Cardiac workload
5
Q
What are some possible respiratory consequences of poorly managed pain? 5
A
- Splinting (resp muscle spasm)
- ↓ VC
- Atelectasis
- Hypoxia
- Pulmonary infection risk
6
Q
What are some gastrointestinal consequences of poorly managed pain? 1
A
Ileus
7
Q
What are some possible renal consequences of poorly managed pain? 2
A
- Oliguria
- Urine retention
8
Q
What are some possible coagulative consequences of poorly managed pain? 1
A
↑ clot risk
9
Q
What are some possible immunologic consequences of poorly managed pain? 1
A
Immunosuppression
10
Q
What are some possible musculoskeletal consequences of poorly managed pain? 2
A
- Fatigue & weakness
- Limited mobility = clotting
11
Q
What is the Specificity Theory?
Who came up with it?
A
Specific sensation w/ its own sensory system independent of touch and other senses - Descartes
12
Q
What theory linked pain and emotion?
A
Intensity Theory (Plato)
13
Q
Where is pain attenuated in the CNS according to gate theory?
A
Substantia Gelatinosa
The cells in this area function as a gate regulating transmission of impulses to the central nervous system.
14
Q
What chemicals are released upon tissue injury that mediate pain? 4
A
- Histamine & Inflammatory Mediators:
- Bradykinin (peptide)
- Prostaglandins (lipids)
- Serotonin
15
Q
Give an example of first order neurons.
A
Aδ and C
16
Q
Where do first order Aδ and C fibers synapse at?
A
Dorsal Root of the spinal cord
17
Q
Where do second order neurons synapse at?
A
Thalamus
18
Q
What is the name of the process by which noxious stimuli are converted to action potentials?
A
Transduction
19
Q
What is the name of the process by which an action potential is conducted through the nervous system?
A
Transmission
20
Q
What is the name of the process by which pain transmission is altered along its afferent pathway?
A
Modulation
21
Q
What is the name of the process by which painful input is integrated in the somatosensory and limbic cortices of the brain?
A
Perception
22
Q
Hyperalgesia is the process by which tissue trauma releases _____ _______ ______ that produced augmented sensitivity to stimuli. 1
A
local inflammatory mediators
23
Q
What is primary hyperalgesia?
A
Augmented sensitivity to painful response.
or
Allodynia-style misinterpretation of non-painful stimuli.
24
Q
What is secondary hyperalgesia?
A
Increased neuronal excitability due to glutamate activation of NMDA receptors.
Similar to Remifentanyl where admin without Ketamine (NMDA) will lead to Hyperalgesia
AKA: Medication induced
25
What opioid will potentiate hyperalgesia?
Remifentanil
26
What is the treatment for hyperalgesia that was mentioned in lecture?
Ketamine
27
Differentiate Hyperalgesia and Allodynia.
*In graphical form*.
Note: Stimulus that does not typically evoke pain, evokes pain. (Allodynia)
With chronic pain, a small painful stimulus can be perceived as a large painful stimulus (Hyperalgesia)
Both are considered a Left Shift in the graphical representation of Pain Sensitization
28
What is the hallmark "negative" symptom of neuropathy?
numbness
*Positive s/s can exist as well (pain, sensitivity, etc.*
29
GI blood flow and motility increase as we age. T/F?
False.
30
Gastric acid secretion ______ as we age thus _______ gastric pH.
decreases; increasing
31
What effect does aging have on nutrient absorption in the GI tract?
Minimal
32
What occurs to muscle and fat mass as a patient ages?
Muscle decreases while fat increases
33
A decrease in _______ affects your protein-bound drugs in aging.
albumin
34
What occurs with hepatic function in the aging patient? 3
- ↓ hepatic blood flow
- ↓ liver mass and metabolic activity
35
What occurs with renal function due to aging?
- **↓ GFR**
- ↓ kidney mass & functioning nephrons
36
Do opioids or non-opioid analgesics exhibit a ceiling effect?
Non-opioid analgesics
37
What opioid receptor is responsible for analgesia, respiratory depression, euphoria, and reduced GI motility?
μ receptor
38
What opioid receptor (when agonized) is responsible for analgesia, dysphoria, psychosis, miosis, and respiratory depression?
Κappa receptor
39
What opioid receptor causes analgesia alone when bound by an agonist?
Delta
40
What drug is described by the following organic structure:
Substitution of methyl group for hydroxyl group on #3 carbon of morphine molecule.
Codeine
41
______ is much more reliably absorbed than morphine.
Codeine
*More reliably absorbed orally than morphine*
42
What drug exhibits side effects (without concurrent analgesia) in children?
Why is this?
Codeine
*Children lack enzymatic maturity needed to properly break down codeine*.
43
What CYPs metabolize codeine?
CYP2D6 → morphine
CYP3A4 → norcodeine
44
Codeine metabolism is variable due to more than ____ polymorphisms resulting in analgesic variability.
50
45
What is the adult dose and max of codeine?
15 - 60 mg q4
360mg max per day
46
What is the pediatric dose and max of codeine?
0.5 - 1 mg/kg/dose
60mg max per day *<— what? Literally 1 adult dose.*
47
60mg of codeine (maximal dose) is equivalent to how much aspirin?
650mg
48
What drugs does codeine have interactions with? 3
Opioids, EtOH, and Anticholinergics
49
What drug is described by the following?
Tramadol
50
Where does the + enantiomer of tramadol have affinity and what does it do? 4
Centrally acting opioid agonist:
- μ → moderate affinity
- K & δ → weak affinity
- Opposes serotonin reuptake
51
What does the - entantiomer of tramadol do? 2
- Inhibits NE reuptake
- Stimulates α2 receptors
52
What is tramadol metabolized into and what is the relevance of its metabolite?
Tramadol → *CYP3A4 & 2D6* → O-desmethyltramadol (2-4 times more potent as the OG compound).
53
What is tramadol's potency compared to morphine?
1/5 to 1/10
54
What is the oral onset for tramadol?
1-2 hours
55
What is the half life of tramadol?
6.3 hours
56
When is tramadol contraindicated?
- **Seizure Disorders**
- PONV
*this is definitely going to be a question*
57
What are the benefits of tramadol vs other opioids? 3
- Minimal respiratory depression
- Minimal-none addiction
- Minimal constipation
58
Oral morphine dose is ____ times the IM or IV route.
3
59
What receptors are primary affected by morphine?
μ-1 and μ-2
60
What are the two principle active metabolites of morphine? (also list effects)
- Morphine-6-glucuronide → analgesia
- Morphine-3-glucuronide → neurotoxicity & hyperalgesia
*bad things come in 3’s*
61
How is morphine metabolized?
- Hepatic → conjugation w/ glucuronic acid
- Kidneys
62
What factors contribute to morphine's minimal CNS absorption?
- ↓ lipid solubility
- ↑ protein binding
- ↑ Ionization at normal bodily pH
63
What is the IV/IM onset and peak of action for morphine?
Onset: 15-30 min
Peak: 45-90 min
64
What differences does morphine exhibit in women vs men?
In women:
↑ potency
↓ speed of offset
65
What is the protein binding of morphine?
What about the half-time?
35% protein binding
1.7 - 3.3 hours
66
What is released from morphine administration?
What is the result?
Histamine → vasodilation and hypotension
67
Morphine should be avoided in patients with ____ impairment as the metabolite morphine--6-glucuronide can accumulate and lead to _________ ________.
Renal impairment : respiratory depression
68
What drug is a synthetic derivative of thebaine?
Oxycodone
69
What are the metabolites of oxycodone?
Oxymorphone (active)
Noroxycodone (inactive)
*Oxycodone is primary a prodrug*.
70
What is the site of action of oxycodone?
μ and κ receptors of the CNS
71
What are the two types of PO oxycodone?
IR = Immediate release
CR = Controlled release
72
What is the dose of oxycodone? And compared to morphine?
10 - 15mg is equal to 10mg Morphine
1:1 equivalence with morphine
73
What is the onset of action of oxycodone?
< 1 hour
74
Opioids (in general) exhibit an ____ effect with other drugs that are CNS depressants
additive
75
Why is methadone used for opioid addiction maintenance? 3
- 60-90% oral bioavailability
- High potency
- Long duration of action
76
What should be known about methadone's half life?
Very long and unpredictable (up to 36 hours)
Can accumulate w/ repeated doses
77
What various receptors affinities does methadone have? 4
- Weak noncompetitive NMDA antagonist
- Serotonin reuptake inhibitor
- Monoamine reuptake inhibitor
- High μ receptor affinity
78
What would occur with concurrent methadone and carbamazepine use?
Carbamazepine is a CYP450 inducer thus methadone will be **metabolized faster.**
79
What agents can inhibit the metabolism of methadone?
CYP450 Inhibitors:
- Antiretrovirals
- Grapefruit juice
80
How much is methadone clearance affected by hepatic and renal impairment?
Not much
81
What is the dose of methadone?
2.5 - 10 mg PO/IM/SC q4-12 hours
82
Why are standardized simple dosing guidelines unachievable for methadone?
High variable half life (8-80 hours)
83
What is the worst med interaction associated with methadone?
MAOI's
84
What drugs are known to increase the concentration/effects of methadone?
- Cipro
- Diazepam
- Acute EtOH
85
What drugs are known to decrease concentration/effects of methadone? 5
- Anti-retrovirals
- Phenobarbital
- Phenytoin
- Rifampin
- MAOI's
86
What cardiac complication can occur in rare cases with methadone usage?
Pause dependent dysrhythmia
87
What drug is fentanyl structurally similar to?
Meperidine
88
Fentanyl has ____ potency, ____ onset of action and _____ duration of action.
High potency
Rapid onset
Short duration
89
What is the priniciple metabolite of fentanyl?
Norfentanyl
*Detectable in urine up to 72 hours after single dose*.
90
Why is elimination of fentanyl slightly prolonged despite very short duration of action?
Lungs serve as large inactive reservoir (up to 75% of initial dose undergoes first pass pulmonary uptake).
91
Why is fentanyl more potent and rapid than morphine?
Greater lipid solubility
92
What is responsible for fentanyl's short duration of action?
Rapid redistribution to fat and muscle
93
What is the protein binding of fentanyl?
84%
94
What is hydromorphone and how is it formed?
Hydrogenated ketone of morphine formed by N-demethylation of hydrocodone
95
Hydromorphone is ______ times as potent as morphine when administered orally.
3 - 5 times
96
Hydromorphone is ______ times as potent as morphine when administered parenterally.
8.5 times
97
What is hydromorphone's primary metabolite?
Hydromorphone-3-glucuronide
98
What should be known about Hydromorphone-3-glucuronide?
- Lacks analgesic effects
- May potentiate neurotoxic effects (allodynia, myoclonus, seizures).
99
When is Hydromorphone-3-glucuronide's neurotoxic side effects an actual concern?
Patients with renal insufficiency
100
What is the typical dose of parenteral Hydromorphone?
0.2 - 2 mg
101
What is the typical oral dose of hydromorphone?
2 - 8 mg
102
What is the duration of action of hydromorphone?
3 - 4 hours
103
What is hydrocodone derived from?
Codeine
104
How does the potency of hydrocodone and codeine compare?
Hydrocodone is 6 - 8 x more potent
105
What are the two most abused opioids?
1st = Oxycodone
2ⁿᵈ = Hydrocodone
106
What are the two metabolites of hydrocodone metabolism?
- Hydromorphone (via CYP2D6)
- Norhydrocodone (inactive) via CYP3A4
107
What is the morphine equivalent of hydrocodone?
1 mg morphine = 3 mg hydrocodone
108
What is typical hydrocodone dosing?
2.5 - 10mg w/ 300 - 750mg acetaminophen q4-6hours
109
What receptors does buprenorphine have affinity to?
μ - partial agonist (strong)
κ - antagonist (strong)
δ - agonist (weak)
110
What benefits does buprenorphine provide? 4
- ↓ respiratory depression
- ↓ immune suppression
- ↓ constipation
- No accumulation in renal patients
111
What is the primary metabolite of buprenorphine?
Norbuprenorphine
112
What should be known about norbuprenorphine?
- 1/50th analgesic activity of buprenorphine
- ↑↑↑ Respiratory depression
113
What is the IV/IM buprenorphine dose equivalence for morphine?
0.3mg IM buprenorphine = 10mg morphine
114
What is the half life of buprenorphine?
Long
20 - 73 hours
115
Should buprenorphine be avoided in patients with renal impairment?
No. Hepatic elimination primarily
116
What are the side effects and drug interactions of buprenorphine?
Resistant to Narcan & can develop Pulmonary edema.
Slower dependence
Dysphoria unlikely
117
What receptors do NSAIDs bind to?
Trick question. NSAIDs inhibition COX as their method of pain modulation.
118
What is the recommended dose for celecoxib?
100mg daily
119
What is the recommended dose for diclofenac?
50 mg BID
120
How might antidepressants work as pain medication adjuvants?
Modulation of spinal cord transmission to reduce pain signaling
121
Whats the IV dose of fentanyl for pain?
20 - 50 mcg
122
What anticonvulsants are used as adjuvant medication to relieve pain?
* Gabapentin (watch for sedation/ respiratory depression in older patients)
* Phenytoin
* Carbamazepine
* Topiramate
123
What skeletal muscle relaxants are used as adjuvant medication to relieve pain? 5
* Baclofen (Lioresal®)
* Carisoprodol (Soma®)
* Cyclobenzaprine (Flexeril®)
* Methocarbamol (Robaxin®)
* Tizanidine (Zanaflex®)
124
What is Opioid Free Anesthesia?
* Technique where no intra-operative systemic, neuraxial, or intracavitary opioid is administered during the anesthetic.
125
Opioids acting on the Mu receptor will produce these unwanted effects.
* Respiratory depression
* Decrease GI motility/ constipation
* Urinary retention
* Prurititis
* Physical dependence
126
Opioids acting on the Kappa receptor will produce these unwanted effects.
* Respiratory depression
* Dysphoria
127
Opioids acting on the Delta receptor will produce these unwanted effects.
* Respiratory depression
* Urinary retention
* Prurititis
* Physical dependence
128
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.
