Exam 2: Pain Flashcards
1
Q
T/F: Pain affects more Americans than DM, heart disease, and cancer COMBINED
A
True
2
Q
T/F: Over-treatment of pain is a problem defined in literature
A
FALSE - UNDERtreatment is a problem within community, hospital, or nursing homes
3
Q
Pain is a ___ and ___ experience. It is also (objective/subjective)
A
Sensory and emotional experience
It is SUBJECTIVE
4
Q
How do you know if someone is in pain?
A
They say so – it is SUBJECTIVE
5
Q
T/F: Pain is always objective
A
FALSE – it is SUBJECTIVE
Patient’s report of pain is most reliable info available
Pt must be given benefit of doubt of the presence/absence of pain
Deception is counterproductive and polarizes patient-caregiver relationship
6
Q
Consequences of pain
A
Unnecessary suffering
Respond less well to curative medical or surgical treatments
Higher complication rate
Musculoskeletal injuries – further tissue damage
Show more emotional disturbance
Disability and loss of funciton
In some circumstances, die sooner
7
Q
Which pt pops are at higher risk of undertreatment?
A
Elderly and young – inability to communicate or rate their pain
Use changes in behavior and physiologic s/sx (HR) to suggest pain (fussy, inconsolable, changes in eating patterns, crying out, or agitation)
8
Q
Acute pain situations may result in OBJECTIVE data changes associated:
A
HTN, tachycardia, diaphoresis, mydriasis, pallor (but NOT diagnostic)
9
Q
Acute pain duration
A
<3 months
10
Q
Chronic pain duration
A
> 3-6 months
11
Q
Common causes of acute pain
A
Surgery, acute illness (pancreatitis, sickle cell flair), trauma, musculoskeletal injuries, labor, post-op pain, etc.
12
Q
Acute or Chronic?: Follows body injury and generally appears when the body heals, has a well-defined temporal onset, usually nociceptive in nature
A
Acute
13
Q
How does acute pain serve as a warning or protective purpose?
A
It permits us to live in an environment fraught with dangers
Learning comes from the experience
Adaptive
14
Q
Acute pain: Painful, continuous stimulation can induce:
A
Suffering
Neuronal remodeling
May contribute to the development of chronic pain (becoming maladaptive)
15
Q
Acute or Chronic?: Usually defined as pain which lasts beyond the ordinary duration of time that the body needs to heal itself, does not resolve spontaneously, pain persists 3-6month or longer
A
Chronic
16
Q
Chronic pain: Maladaptive pain characteristics
A
May not have well-defined temporal onset
underlying cause may not be treatable
Serves no physiologic roles an dit itself not a symptom, but a disease state (maladaptive)
May last months to years
17
Q
Maladaptive pain results from ____ or _____ of the peripheral nervous system (PNS) and/or central nervous system (CNS)
A
damaging or abnormal functioning
18
Q
Maladaptive pain often mixes causes with which 3 mechanisms present at the same time?
A
Nociceptive
Neuropathic
Centralized
19
Q
Acute or Chronic?: Pathophysiologic pain, disengaged from noxious stimuli or healing
A
Chronic
20
Q
Acute or Chronic?: Pain that persists beyond the normal healing time for an acute injury – post herpetic neuralgia
A
Chronic
21
Q
Acute or Chronic?: Pain related to chronic disease – osteoarthritis, lower back pain
A
Chronic
22
Q
Acute or Chronic?: Pain without identifiable organic cause – fibromyalgia
A
Chronic
23
Q
Acute or Chronic?: Pain associated with cancer
A
Chronic
24
Q
Acute or Chronic: Often associated with s/sx of depression
A
Chronic
25
What can result from untreated chronic pain?
May have profound morbidity associated
Disrupting normal living and degrading functional capacities
```
Immobility
immune system dysfunction
disturbed sleep
Poor appetite and nutrition
Over-dependence on family and other caregivers
Overuse and inappropriate use of healthcare providers
Poor job performance
Isolation from society and family
Anxiety and fear
Hopelessness
Helplessness
Bitterness, frustration, suicide
```
26
Acute or Chronic?: USUALLY obvious source: injury, disease, iatrogenic (surgery)
Acute
27
Acute or Chronic? Intensity generally variable and indicative of underlying condition or situation
Acute
28
Acute or Chronic?: Prolonged functional impairment (physical and psychological)
Chronic
29
Acute or Chronic: Rubbing, moaning, crying
Acute
30
Acute or Chronic?: May or may not be a/w insomnia, anorexia, irritability, depression
Chronic
31
Acute or Chronic?: Often more difficult to manage
Chronic
32
Treatment goal of ACUTE pain
Cure
33
Treatment goal of CHRONIC pain
Funcitonality
34
WHO Step Ladder: Step 1 pain level
1-3 out of 10
35
WHO step ladder: Step 2 pain level
4-6 out of 10
36
WHO Step Ladder: Step 3 pain level
7-10 out of 10
37
Nociceptive pain results from _____
Injury to or inflammation of somatic or visceral tissues
38
T/F: Nociceptive pain is unresponsive to typical analgesics
False - responsive to typical analgesics
39
Examples of nociceptive pain
```
Paper cut
Burn
Arthritis (hands, knees, and hips)
Trauma
Muscle strains or sprains
Tendonitis
```
40
What adjuvants are not typically used for nociceptive pain?
Anti-epileptic-like gabapentinoids (gabapentin and pregabalin)
41
4 Steps of physiologic process of pain
Stimulation
Transmission
Perception
Modulation
42
Stimulation of ____ is the first step in pain sensation
Free nerve endings (nociceptors)
43
_____ can distinguish between safe or harmful stimuli
Nociceptors
44
Nociceptors are found in...
Cutaneous structures
Somatic structures
Visceral structures
45
Nociceptors are activated and sensitized by ____, ____, and _____ impulses
mechanical
Thermal
Chemical
46
Stimulation: Injury to tissue causes cell breakdown and release various mediators of inflammation and those that communicate pain. What are some examples of these mediators?
Bradykinins, potassium, prostaglandins, histamine, leukotrienes, serotonin, substance P
47
Stimulation: ____ and ___ can result at this stage
Vasodilation and edema (redness/swelling)
48
T/F: Many of the nerve endings are minimally sensitized and function at their resting state
True
49
Stimulation: Some substances (___ and ___) can cause INCREASED sensitization of the nociceptor resulting in a lower threshold for firing and cause them to generate nerve impulses
Bradykinin and serotonin
50
Stimulation: Receptor activation leads to action potentials that are transmitted to the ____
spinal cord
51
Transmission: Signals created by the nociceptors travel primarily along 2 afferent fiber types to the spinal cord and brain -- ____ and ____
A and C afferent fibers
52
A alpha and beta nerve fibers
Large, fast, and myelinated fibers
53
A delta nerve fibers
Small-diameted myelinated fibeers
54
______ nerve fibers transmit sharp, well-localized pain
A fibers
55
C fibers
Small-diameter unmyelinated fibers
56
___ nerve fibers transmit dull, aching, poorly localized pain
C fibers
57
Transmission: 2 processes must occur from transmission to be complete (for pain to be felt)
From periphery to spinal cord
| Spinal cord to the brain
58
Transmission to the spinal cord: Most neural signals travel to the ___ of the spinal cord
Dorsal horn (DH)
59
Transmission to the spinal cord: The afferent fibers synapse on neuroreceptors in varying layers of the dorsal horn, releasing neurotransmitters like ___
Glutamate, substance P, and calcitonin gene-related peptide
60
Transmission to the spinal cord: These interactions influence pain ___, ___, and ____ to the pain (Gate Control Theory)
Pain sensation, magnitude, and response to the pain
61
___ is when the pain becomes a conscious experience
Preception
62
Perception: Nociceptive info from the DH travels to the brain via the ___ to the ____ where the input is mapped to preserve certain information like location, intensity, and quality
Via thalamus to the contralateral somatosensory cortex
63
Perception: There are at least ___ known ascending spinal cord pathways, ___ tract being the most known
At least 5 are known -- spinothalmic tract is most known
64
After pain info is processed, the response is sent out of the brain via descending pathways from brain to ___ to ___
brain to spinal cord to periphery
65
Modulation: ___ and ___ modulate pain through a number of intricate processes (gate control theory)
Brain and spinal cord
66
Pain transmission: may be facilitated by _____ to make signals stronger and pain more intense
Neurotransmitters like glutamate and substance P
67
Pain transmission can be attenuated/inhibited by descending pathways that consists of ___ __ __ or ___
Endogenous opioids, GABA, NE, or serotonin
68
Modulation: Cognitive and behavioral functions can modify pain: Examples
Relaxation, distraction, meditation, and guided mental imagery may strongly influence pain perception and decrease pain sensation
69
Modulation: ____ often worsens pain
Depression or anxiety
70
Modulation: Neurotransmitters involved
```
Glutamate
Substance P
Endogenous opioids
Serotonin
NE
GABA
Neurotenisn
```
71
Modulation: Cognitive and behavioral functions that may modify pain perception
```
Relaxation
Distraction
Meditation
Guided mental imagery
Stress, anxiety
Depression
```
72
2 important concepts that are involved in nociceptive pain (occur at and adjacent to the site of injury)
Adaptive inflammation
| Central sensitization
73
Adaptive inflammation def
In response to trauma (sprain, surgical wound, traumatic injury) the body will purposefully cause inflammation/swelling
Decreases contact with and minimal movement to injured area (prevents further injury, allows healing to begin)
74
Central sensitization
In response to tissue damage and inflammation in the CNS -- neurotransmitters change composition, transduction, and transmission properties, resulting in enhance excitability/responsiveness and result in ENHANCED pain
75
Changes caused by central sensitization may result in
Hyperalgesia -- an exaggerated pain response
Allodynia - painful response to a normally non-noxious stimuli (pt with gout, breeze can feel painful)
Persistent pain
76
Hyperalgesia def
An exaggerated pain response
77
Allodynia def
Painful response to a normally non-noxious stimuli
78
T/F: Maladaptive inflammation can play a role in chronic pain
True
79
T/F: Central sensitization also plays a role in neuropathic pain, chronic pain, and fibromyalgia
True
80
___ pain is due to damaged or dysfunctional nerves
Neuropathic
81
Neuropathic pain: Nerves that are cut off from input from the periphery (amputation) that may become __active
hyperactive
82
Nociceptive or neuropathic?: "Dully, sharp, cramp, aching"
Nociceptive
83
Nociceptive or neuropathic?: "Burning, radiating, shooting, shock-like, electric, tingling"
Neuropathic
84
Nociceptive or Neuropathic: Responsive to typical analgesics
Nociceptive
85
Nociceptive or neuropathic?: Poorly responsive to typical analgesics
Neuropathic
86
Nociceptive or neuropathic: Peripheral neuropathy (DM, HIV/AIDS, Cancer), post herpetic neuropathy, phantom limp pain
Neuropathic
87
Neuropathic pain syndromes
```
Diabetic neuropathy
Post herpetic neuralgia (shingles)
HIV-associated pain
Phantom limb pain
Post stroke pain
Spinal cord injury
Lower back pain
Multiple sclerosis
```
88
T/F: APAP and NSAIDs are helpful for neuropathic pain
False
89
Which meds are not helpful for neuropathic pain?
NSAIDS/APAP
Steroid injections
Hyaluronic acid injections
90
Centralized pain is also known as
functional pain
91
T/F: Nerve injury and inflammation exists for centralized (functional) pain
FALSE -- NO nerve injury or inflammation exists
92
Centralized (functional) pain: Disturbances in pain processing within the nervous system that leads to pain hypersensitivity and subsequently spontaneous pain
Fibromyalgia
Irritable bowel syndrome (IBS)
Temporomandibular joint disorder
Chronic tension headaches.
93
____ is a result of an abnormal operation of the nervous system
Centralized (functional) pain
94
Explain Centralized (functional) pain pathophysiology
Caused by abnormal signal processing in the peripheral or CNS -- nerve injury causing lower level of activation energy for action potential firing
Enhancement of NE, serotonin inhibition resulting in overall excitement of DH which manifests as mechanical hypersensitivity and allodynia or spontaneous pain
Nerve damage or persistent stimulation may cause pain circuits to rewire themselves both anatomically and biochemically
95
Describe fibromyalgia
A disorder of chronic, widespread pain and tenderness
Considered a rheumatoid disease (syndrome)
Etiology is unknown, typically presents in young or middle aged women but can affect either sex at any age
96
T/F: In fibromyalgia, painful muscles are accompanied by inflammation and body damage/deformity
FALSE - Painful muscles are NOT accompanied by inflammation and despite potentially disabling body pain, pts do not develop body damage or deformity
97
Fibromyalgia: Studies suggest that the CNS may be somehow ___-sensitized
super sensitized
98
Which meds are not used for centralized(functional) pain?
Steroid injections
Hyaluronic acid injections
(non-opioids, weak opioids, opioids are not THAT effective but still can be used)
99
Non-opioid analgesics (APAP/NSAIDs) primary indication
Pain relief for pts who do not respond to non-pharmacologic interventions
100
APAP or NSAIDs: Anti-inflammatory mechanism of pain relief
NSAIDs only
101
APAP or NSAIDs?: Can be used monotherapy or in combo
BOTH
102
APAP or NSAIDs: Can be combined with opioids
BOTH
103
APAP or NSAIDs?: Fever reducing properties
BOTH
104
APAP or NSAIDs?: Central acting mechanism of pain relief
BOTH
105
APAP effective in what type of pain?
Mild
Mild-moderate
NOT effective for chronic low back pain
106
T/F: APAP is effective in chronic low back pain
FALSE - it is NOT effective in chronic low back pain
107
NSAID effective in what type of pain?
Mild
Moderate
Severe
108
APAP Rx or OTC?
OTC, dosing based on safety
109
NSAIDs Rx or OTC?
Rx and OTC
| Max dosing based on if Rx or OTC
110
APAP or NSAIDs?: Considered 1st line oral agent due to safety profile (particularly if tx is long term or in high safety risk individuals)
APAP -- safer than NSAIDs hence why it is 1st line but it may not be as effective
111
NSAIDs: Are oral or topical agents considered to be safer?
Topical -- but more expensive (2nd line or alt therapy)
112
NSAIDs safety profile matters
GI risk (can be minimized with PPI use)
Renal
CV
Concomitant med use (HTN, warfarin)
113
When to use non-opioid analgesics (APAP/NSAIDs) prn examples
```
Headache
Dysmenorrhea
Short lived muscle pain – strain or sprain
Short lived knee pain - injury
Fever
Tendonitis
Bursitis
Osteoarthritis
Rheumatoid arthritis
Post-op from surgery
Trauma
Cancer-related pain
```
114
When to use non-opioid analgesics (APAP/NSAIDs) Long term use
```
Osteoarthritis
Rheumatoid arthritis
Severe sprain
Chronic back pain
Cancer-related pain
```
114
When to use non-opioid analgesics (APAP/NSAIDs) Long term use examples
```
Osteoarthritis
Rheumatoid arthritis
Severe sprain
Chronic back pain
Cancer-related pain
```
115
APAP: Dosage forms
Tablet, capsule, liquid, rectal supp (rectal bioavailability 50-60% of that achieved by oral administration), IV
116
APAP onset of pain or fever relief
30 min
117
APAP duration
about 4 hrs
| Increased to 6-8 hrs with ER formulations
118
APAP renal dosing
CrCl 10-50 give q6h
| CrCl <10 give q8h
119
APAP Side effects
Well tolerated
If using other products that contain APAP - Be mindful of total daily APAP dose
Overdose
Liver toxicity *be careful of high doses!
Uncommon SE: GI (> 2 g/day) and nephrotoxicity (high dose, chronic use)
120
APAP DDI
Warfarin (increase INR)
Alcohol (hepatotoxicity, 3+ drinks/day)
CBZ, phenytoin, rifampin, (induces metabolism and increases toxic metabolite, hepatotoxicity -- limit APAP to 2g/day)
Black cohosh (actaea racemosa, hepatotoxicity if used long term with high dose APAP)
Kava (piper methysticum, hepatotoxicity if used long term with high dose APAP)
Milk thistle (decreased APAP efficacy)
121
APAP Overdose
```
Delayed sx (N, V, drowsiness, confusion, abdominal pain)
Manifestations of hepatotoxicity begins 2-4 days post ingestion (jaundice, increased LFTs, etc..)
```
122
When to use APAP
Mild - moderate pain syndromes
Fever reducer
Safer in long term pain control
```
Safer for:
Pregnancy / breastfeeding / elderly
Taking anticoagulants
Dz states:
CV dz, HTN, renal dz, GI disorders
```
Commercially available opioid combo products
Tylenol #3 (codeine + APAP)
Vicodin (hydrocodone + APAP)
Percocet (oxycodone + APAP)
123
APAP is considered safer for...
pregnancy/breastfeeding/elderly
Taking anticoags
Disease states - CV, HTN, renal, GI
124
APAP Combo products
Tylenol #3 (codeine + APAP)
Vicodin (hydrocodone + APAP)
Percocet (oxycodone + APAP)
125
Tylenol #3 is combo with ___ and ___
codeine and APAP
126
Vicodin is combo product with __ and __
Hydrocodone and APAP
127
Percocet is combo product with __ and __
Oxycodone and APAP
128
When to NOT use APAP
Significant liver disease
Significant alc use (≥3 drinks/day)
Achieving pain relief only at high doses
129
APAP liver failure -- chronic use of ___g/day can lead to increased LFTs after > ___ days (does not necessarily suggest progression to liver failure)
4g/day
after >4 days
130
APAP max dosing (Rx and OTC)
4000mg/day OTC (No Rx APAP -- prescriptions written so it is covered by insurance but it is same as OTC)
131
Ibuprofen max dosing (Rx and OTC)
3200mg/day Rx
| 1200mg/day OTC
132
Naproxen max dosing (Rx and OTC)
1500mg/day Rx
| 600mg/day OTC
133
Naproxen sodium max dose (Rx and OTC)
1375-1650mg/day Rx
| 660mg/day OTC
134
Ketoprofen max dose (Rx and OTC)
300mg/day Rx
| 75mg/day OTC
135
APAP IV formulation name
Ofirmev
136
APAP IV (Ofirmev) approved for ages ___ and up
2yo and up
137
APAP IV (Ofirmev) approved for
mild-moderate pain and moderate-severe pain with opioids
| Fever reduction
138
APAP IV (Ofirmev) dosing
Weight based
650mg IV q6h prn pain
15min infusion
139
APAP IV (Ofirmev) common ADRs
N/V
HA
Insomnia
140
APAP IV (Ofirmev) Cautions
```
Hepatic impairment or active liver disease
Alcoholism (≥3 drinks/day)
Chronic malnutirition
Severe hypovolemia
Severe renal impariment
```
141
NSAIDs MOA
Relieves pain through peripheral inhibition of COX and subsequent inhibition of prostaglandin synthesis
142
Prostaglandin effects on the stomach
Inhibits gastric acid secretion
| Stimulates synthesis of GI mucous
143
Prostaglandin Effect on renal
Maintains renal blood flow
144
Prostaglandin Effect on blood
Enhances platelet aggregation -- increases clotting (vasoconstriction)
145
Prostaglandins inflammatory effect
Inflammation -- pain, fever, edema (vasodilation)
146
COX 1 inhibition effects
GI -- epigastric distress, ulceration, hemorrhage
Renal -- Na, H2O retention, edema, interstitial nephritis
Anti-coagulant effects
147
COX 2 inhibition effects
Anti-inflammatory
Analgesic
Anti-pyretic
148
COX 1 effects which parts
GI, Renal, Platelets
149
COX 2 effects which parts
Inflammation -- pain, fever, edema (vasodilation)
150
T/F: NSAIDs have a class effect -- if one doesn't work, all the NSAIDs options probably don't work
FALSE -- they do not have a class effect, if ibuprofen doesn't work, try naproxen
Little literature substantiates that one agent is more effective than another
Patients who do not tolerate or is ineffective to one particular agent, may do well with another
151
NSAIDs formulation types
```
PO
Topical
Rectal
IM
IV
```
152
NSAIDs onset of action
30min
153
NSAIDs duration for Naproxen
12h
154
NSAIDs duration of action for ibuprofen
6-8 hours
155
Which NSAID is used in acute settings due to availability as injectable?
Ketorolac -- available as IM/IV/PO (Limit to 5 days of use total to avoid ADEs)
156
Ketorolac limit use to ___ days
5 days
157
NSAIDs: Avoid oral diclofenac due to increased
CV events, causes more liver toxicity, more GI toxicity
Topical diclofenac is less risky due to low absorption
158
Naproxen sodium (OTC) strength and directions
220mg q8-12hours
First dose you can take 2 caps within first hours
Do not exceed 2 caps in any 8 to 12 hour period
Do not exceed 3 caps in 24hr period
Do not take more than directed, use smallest effective dose
If taken with food, may take longer before it works
159
Ibuprofen (OTC) strength and directions
200mg 1 tab q4-6 hours
Do not take more than directed, use smallest effective dose
If pain does not respond to 1 tab, then take 2 tabs
Max 6 tabs/24hr period
160
Naproxen sodium (Rx) strength
IR - 275, 550mg
| ER- 375, 500mg
161
Ibuprofen (Rx) strength
400, 600, 800mg
162
NSAIDs safety profile considerations: Kidney disease
Avoid if renal insufficiency -- CrCl <30ml/min
163
NSAIDs safety profile considerations: HTN
NSAIDs promote water retention can increase about 5 mmHg and make anti-HTN meds less effective
164
NSAIDs safety profile considerations: CAD
Risk of MI, stroke based in PG inhibition
| Contraindicated in the setting of CABG surgery
165
NSAIDs safety profile considerations: HF
NSAIDs promote water retention, increased risk of HF exacerbation and CV event (MI or stroke)
166
NSAIDs safety profile considerations: Severe liver disease
Bleeding risk due to anti-platelet effects and direct stomach irritation (people with severe liver disease have compromised clotting factor synthesis)
167
NSAIDs safety profile considerations: GI disorder
Bleeding risk due to anti-platelet effects and direct stomach irritation
168
NSAIDs safety profile considerations: Pregnancy
Category C, lactation: Possibly unsafe (naproxen)
| Category B, lactation: safe (ibuprofen)
169
NSAIDs safety profile considerations: Elderly
Greater risk for GI adverse effects and other side effects based on age or other comorbidities
170
NSAIDs safety profile considerations: Pediatrics
Weight based dosing - look it up
| Self-care: can use IBU for ≥6 months of age and naproxen >12yo
171
NSAIDs safety profile considerations: Veterinary
Don't give IBU or naproxen to cats or dogs ever?? apparently
172
NSAIDs ADEs
GI - dyspepsia, ulcer, bleeding (dyspepsia due to direct irritation to stomach, not COX)
CV - thrombotic events
Renal - sodium and fluid retention, acute renal failure
173
NSAIDs ADE: explain GI ADEs
Dyspepsia due to direct irritation to the stomach
Ulcers - COX inhibition decreases mucous production and causes ulcers
Bleeding - COX inhibition causes inhibition of platelet agg and increases risk of bleeding
174
NSAIDs: Moderate risk factors for GI bleeding
60yo and up
Current high dose of NSAID
Uncomplicated peptic ulcer history
Concomitant use of ASA, anticoags, or corticosteroids
175
NSAIDs: High risk factors for GI bleeding
Hx of previous complicated/bleeding ulcer
| Multiple (>2) risk factors
176
NSAIDs: Other risk factors for GI bleeding
H. pylori infection
cigarette smoking
alcohol use
Chronic debilitating disorders (esp. CV)
177
NSAIDs: GI ADEs: How to protect from dyspepsia
Take with food
Antacids, H2 blockers, PPI
Enteric coated, buffered, SR, or PR dosage forms
178
NSAIDs: GI ADEs: How to protect from Ulcer/bleeding
Choose COX2 selective NSAID
| Enteric coating, buffering, sustained-release DO NOT protect from bleed risk!!!
179
Selective NSAID example
Celecoxib
180
Celecoxib Max dosing
200mg/day
181
Which NSAID is safest for GI SE
Celecoxib
182
If pt is at high risk of GI ADEs, add on ____
PPI, misoprostol, or high dose H2 blocker
183
Out of non-selective NSAIDs, which is more likely to be safe for GI risk?
Ibuprogen
184
When to stop celecoxib for procedure with risk of bleeding (colonoscopy)
1 day before (no antiplatelet effects)
185
When to stop non-selective NSAIDs prior procedure with bleeding risk?
7 days prior (ASA has longer anti-platelet effects than other non-selective NSAIDs)
186
NSAID issue for CV risks
Renal effect - sodium, water retention, edema, interstitial nephritis -- affects BP, preload, etc. !!
Vasoconstriction/dilation balance
187
Which non-selective NSAID increases cardiac risk (MI or stroke)?
ALL -- naproxen is likely safer for CV risk
188
Which COX 2 inhibitor increases CV risk (MI or stroke)?
Vioxx -- risky at low doses, starts shortly after starting drug (taken off the market)
Celecoxib (Celebrex) -- increased risk over 200mg/day
189
High CV Risk considerations with NSAIDs
Hx of CV event, DM, HTN, HLD, obesity
190
Administering NSAID ___ ASA may diminish the antiplatelet effect/cardiac benefit of ASA
BEFORE -- do not take NSAID within 2hrs
191
NSAIDs: concurrent drugs that increase bleeding risk
Anticoags, steroids, SSRIs
192
NSAIDs: Drug interactions (renal)
Diuretics
ACEi/ARBs
All anti-HTN meds (reduces HTN med efficacy)
May increase the toxicity of lithium and methotrexate
193
Which NSAID should you avoid use in G6PD deficiency
ASA
194
How many weeks does it take to fully evaluate NSAID efficacy?
2-4 weeks
195
When do you stop NSAID and call doctor
Sx of bleeding (black/tarry stool)
Pain worsens or lasts longer than 7-10 days
Fever worsens or lasts longer than 3 days
Any new sx appear
196
Topical NSAIDs exampels
Diclofenac -- Voltaren gel, Pennsaid solution, Flector patch
197
Potential advantages of TOPICAL agents over systemic agents
```
delivery at site
Lower rates of systemic absorption (lower risk of systemic ADEs but higher derm side effects)
Similar efficacy to oral NSAID
Pt preference
Recommended in older patients (>75yo)
```
198
T/F: Systemic side effects are impossible with topical NSAIDs
FALSE -- systemic conc can be achieved and systemic SE are possible, CV and GI warnings are in all topical package inserts
199
T/F: You can combine NSAID topicals with oral agents
FALSE -- do NOT combine
200
Voltaren gel strength and approved uses
Voltaren gel 1% for OA
| Voltaren gel 3% for Actinic keratosis
201
Important counseling notes to know for voltaren gel
of joints matter! -- dose limits for a single joint and total daily amount for all joints used (look it up when counseling)
Don't use it on open skin wounds/infections/rash/burns
Do not cover treated skin or expose to heat (can increase absorption and cause harmful effects)
Wash hands after (don't wear gloves until 10min after)
After applying, wait 10min before dressing and at least 1 hr before showering
Do not use oral NSAIDs in combo
202
Flector Patch dosing
1 patch q12 hours
No advantage in efficacy or safety than topical gel -- more expenisve
203
Pennsaid important notes
It's good for s/sx of OA of knees
| 40 drops per knee, 4 times/day
204
Opioids work on which receptors?
Mu, kappa, delta
205
Opioids that are STRONG agonists on mu, kappa, delta receptors
```
Morphine
Hydromorphone
Methadone
Meperidine
Fentanyl
Oxycodone
```
206
Opioids that are MILD to MODERATE agonists on mu, kappa, delta receptors
Codeine
| Hydrocodone
207
Opioids that are PARTIAL agonists on mu, kappa, delta receptors
Buprenorphine
208
ANTAGONISTS of mu, kappa, delta receptors
Naloxone
209
Recommendation for opioid in acute pain
3-7 day supply (try to use it less for acute pain)
210
Avoid chronic pain dosing ≥ ____mg/day morphine equivalents (MME)
50mg/day MME
211
50mg/day MME is about ___mg/day of hydrocodone
50mg/day
212
50mg/day MME is about ___mg/day of oxycodone
30
213
___ should be co-prescribed with chronic opioids
Naloxone
esp if hx of OD, substance use disorder, taking 50mg/day MME, concurrent benzodiazepine use
214
Avoid opioid use with ___ or ___
benzodiazepines or muscle relaxants
215
Opioids: Avoid or careful dosing considerations for:
Renal/hepatic dysfunction
Elderly ≥65yo
Pregnant
Other diseases (severe COPD, sleep apnea)
Other meds with CNS ADEs (benzo or msucle relaxants)
LOWER DOSES
216
When to use IR opioids
Used PRN when pain is severe an duration of pain is expected to be short or infrequent
217
Why should you NOT use IR opioids for scheduled basis for chronic pain
Shorter duration of effect -- increasing pain at the end of dosing interval, needs multiple doses per day (creates pain cycles)
Pill burden
Higher risk of abuse
218
When to use ER opioids
Usually starts with IR prn and then switch to appropriate ER dosing (oral or patch)
Prevents pain cycle
219
When should you NOT use ER opioids
In opioid naive patients
| on a prn basis
220
Scheduled dosing for ER opioids - oral
every 12 hours (sometimes 8 hrs)
221
Scheduled dosing for ER opioids - patch
Fentanyl patch every 72hrs (3 days)
222
Most common IR opioid examples
```
Morphine
Oxycodone
Oxycodone + APAP (percocet)
Hydrocodone + APAP (Vicodin)
Hydromorphone (dilaudid)
```
223
Most common ER opioids use
Morphine (Contin, Roxanol, Kadian)
Oxycodone (OxyContin)
Fentanyl (Duragesic Patch)
Hydrocodone (Zohydro ER)
224
Opioids: IR to ER calculations
Add up total daily dose of IR in 24 hour period
| Divide by 2 (q12h dosing )
225
ER opioids + prn IR opioids is reserved for ____
SEVERE pain situations, cancer pain, or end of life pain situations
NOT for typical chronic pain syndromes like OA, low back pain
226
Breakthrough dose for severe chronic pain calculations
Add up total daily dose in 24hr period
| 10-15% of total every 4-6hours prn of IR formulation of same med of ER formulation
227
NEW ER + IR breakthrough pain dose calculations
Add up total dose (ER + IR)
Divide by 2 for ER dosing q12h
10-15% of total daily dose q4-6 hours for IR dosing
228
Switching from one opioid to another calculations
Add up total daily dose in 24hr period
Use conversion table
Reduce by 50% to help offset incomplete cross-tolerance
Divide daily dose based on duration of actions of drug/dosage form
Consider if a breakthrough regimen is needed and monitor
229
Patient counseling for opioids
Do not increase dose w/o calling prescriber
Explain PRN meaning
Do not drive while using med
Do not use alcohol or sedatives unless approved by prescriber
When switching opioids, dosing must be titrated to response (different per person)
ADEs
Disposal of leftover pills
230
Opioids ADEs
Constipation (need to treat)
Urinary retention (tolerance may develop)
N/V (may resolve after 48-72hrs)
Pruritis (histamine release, common with morphine, less with fentanyl, using antihistamine may be helpful)
Sedation, confusion, hallucinations, nightmares, dysphoria, euphoria, inability to concentrate
Accumulation - restlessness, agitation, tremor, myoclonus, seizure (meperidine, not with methadone)
Respiratory depression
DDI - additive CNS SE, serotonin syndrome with SSRI (tramadol, methadone)
231
Opioids OD treatment
Naloxone -- Injection (IV/IM/SC) or intranasal
232
Opioid addiction treatment
Methadone
Buprenorphine +/- naloxone (Subutex or Suboxone)
Naltrexone (IM monthly injection, Vivitrol)
233
Subutex generic
Buprenorphine
234
Suboxone generic
Buprenorphine + naloxone
235
Opioid true allergies: Morphine like agonist (Phananthrenes) examples
```
Morphine
Hydromorphone
Hydrocodone
Codeine
Oxycodone
```
236
Opioid true allergies: Meperidine like agonist (Phenylpiperidines) examples
Meperidine (Demeral)
| Fentanyl (Duragesic)
237
Methadone-like agonist (Diphenylheptanes)
Methadone
238
Morphine Schedule
CII
239
Morphine use
Excellent and cost effective first choice for severe acute and chronic pain management
Used in pain control associated with MI (decrease myocardial oxygen demand in ischemic cardiac pts)
240
Oxycodone schedule
CII
241
T/F: Oxycodone is superior than other opioids
FALSE - not more effective than other opioids
242
Hydromorphone (Dilaudid) Schedule
CII
243
Hydromorphone is ___ potent than morphine
MORE
244
Which opioid is the gold standard
Morphine
245
Hydrocodone schedule
CII
246
Hydrocodone IR availability
Not available alone as IR but in combo with APAP (Vicodin)
247
Hydrocodone ER options
Zohydro ER, Hysingla ER
Dosed q12hrs, alt to morphine and oxycodone use in chronic pain
248
Vicodin schedule
CII
249
Codeine schedule
Alone (CII)
with APAP or ASA (CIII)
Cough syrups (CIII or CV)
250
Codeine is ___ potent than morphine
LESS
251
T/F: Codeine is used for moderate pain
True
252
Tylenol #2 has __mg codeine
15mg
253
Tylenol #3 has ___ mg codeine
30mg
254
Tylenol #4 has ___mg codeine
60mg
255
Codeine: Many pts c/o ___
GI upset (not an allergy)
256
Describe metabolism of codeine
Codeine is prodrug that is metabolized to morphine by CYP2D6
Ultra rapid metabolizers may develop toxic blood levels (converts faster and more completely)
Hydrocodone and oxycodone also metabolized to active metabolites by CYP2D6 (be careful)
Morphine not metabolized to active metabolites by CYP2D6
257
Describe metabolism of codeine
Codeine is prodrug that is metabolized to morphine by CYP2D6
Ultra rapid metabolizers may develop toxic blood levels (converts faster and more completely)
Hydrocodone and oxycodone also metabolized to active metabolites by CYP2D6 (be careful)
Morphine not metabolized to active metabolites by CYP2D6
258
Which opioids are metabolized into active metabolites?
Codeine, hydrocodone, and oxycodone metabolized to active metabolites by CYP2D6
Morphine NOT metabolized to active metabolites by CYP2D6
259
Codeine Contraindications
All kids <12yo
Kids <18 after tonsilectomy or adenoidectomy
Do not use in kids 12-18 who are obese or have sleep apnea
Avoid in breastfeeding women -- may be ultra rapid CYP2D6 metabolizer and cause toxicity to infant
260
Methadone schedule
CII
261
Methadone MOA
Opioid agonist, NMDA receptor antagonists, SNRI activity
262
Methadone use
Used for opioid dependence and analgesic (chronic pain (nociceptive or cancer pain) and neuropathic pain (4th line, there's better options)
263
Methadone has ___ half-life and duration of action compared to other opioids and has ___ risk of accidental OD
LONGER half life
| HIGHER risk
264
Methadone DDI
Increases QT interval (antidepressants, antipsychotics, antiarrhythmic, macrolides, etc.)
Increase methadone levels (clarithromycine, erythromycin, azoles, fluoxetine, verapamil, etc.)
Decrease methadone levels (CBZ, phenytoin, rifampin, etc.)
Sedation (BDZ, Z-drugs, sedating antihistamines, ETOH)
HIV antivirals may increase or decrease levels (depends)
265
Meperidine (Demeral) schedule
CII
266
Meperidine is __ dosing only
Acute
Short acting -- 3-4hrs
267
Meperidine: When nor-metabolite accumulates what can occur?
Psychosis, tremos, muscle twitching, seizures
268
Meperidine: Caution and avoid in
AVOID in renal insufficiency
Caution in elderly and hepatic impairment
No real adv to use with alt available
269
Fentanyl schedule
CII
270
Fentanyl formulations
IM, IV, transdermal patch, transmucosal
271
Fentanyl may be used in pts with true allergy to ___
morphine
272
___ may cause less pruritus and constipation than traditional opioids
Fentanyl
273
Converting from other opioids to fentanyl patch
Calculate 24hr total daily dose (ER and IR)
| Use table to get patch dose
274
When can you use fentanyl patch
For chronic pain and for already opioid tolerant patients!!
275
Can you cut/trim fentanyl patch
No
276
Fentanyl patches are dependent on ____ and it will increase release of medication from patch
TEMPERATURE -- high fever, heating pad, electric blanket, sauna/hot tub
277
What to do when you DISCONTINUE fentanyl
Remove patch and titrate dose to a new analgesic based on pt report of pain
278
___ hours or more are required for a 50% decrease in serum fentanyl conc
17
279
How to dispose of fentanyl patches
Fold in half (adhesive folds to itself)
| FLUSH down toilet (don't put in trash-- caution for children and pets)
280
Fentanyl transdermal patch only indicated for pts
requiring continuous ATC opioid for an extended period of time
281
Tramadol schedule
CIV
282
Tramadol is effective for ___ nociceptive pain and neuropathic pain
Mild to moderate
Ultracet (tramadol + APAP) used for short term, mod acute pain
283
Ultracet generic
Tramadol + APAP
284
Tramadol brand name
Ultram, Ultram ER, Ryzolt
285
Explain how tramadol is effective for neuropathic pain
Metabolite binds to mu receptor
| Inhibits reuptake of serotonin and NE
286
Tramadol ADEs
Nausea
Constipation
Drowsiness
(Less than other opioids)
287
Tramadol efficacy is similar to ____
Tylenol #3
Less risk for respiratory depression
Risk for dependence
Limited to 5 refill on prescription
288
tramadol refills are limited to only ___ refills
5
289
Tramadol DDI
Serotonin syndrome risk with antidepressants that effect 5HT, triptans, lithium
Lowers seizure threshold (avoid in risk pts)
Others:
- Hx of seizure, alc abuse, head trauma, taking bupropion, antidepressants (TCA), antipsychotics
- increase levels of other drugs - warfarin dig
- Other opioids - increase risk of adverse effects
- CYP3A4 inducers: carbamazepine
290
Tramadol metabolism
Prodrug
| Converted to active metabolite by CYP2D6 (also 3A4)
291
Tramadol contraindications
All kids <12yo
Kids <18yo after tonsilectomy and adenoidectomy
12-18 with sleep apnea
Breastfeeding women
292
Tramadol place in thearpy
Acute, moderate pain (nociceptive or neuropathic)
Alt to stronger opioids in select pts for chronic pain (third alt after APAP or NSAIDs)
Fibromyalgia (3rd line behind anticonvulsants and antidepressants)
293
First line agents for neuropathic pain
Anti-convulsants: Pregabalin, gapapentin
Antidepressants (SNRI): duloxetine, venlafaxine
Antidepressants (TCA): nortriptyline, desipramine (secondary amine for better SE profile)
Topicals: Lidocaine, capsaicin
294
If there is no clinically meaningful effect after using first line agents for neuropathic pain what should yoou do next?
Try another one
Combo
Or add tramadol if trying another one or combining doesn't work
295
Pregabalin and gabapentin MOA
Selectively binds to voltage-gated CA channels – reduces calcium current and modulates excitatory neurotransmitters (glutamate, norepinephrine, substance P)
296
Pregabalin brand name
Lyrica
297
Pregabalin is FDA approved for
Diabetic peripheral neuropathy
Postherpetic neuralgia
Fibromyalgia
298
Pregabalin can be used in combo with
Lidocaine, capsaicin, TCA, SNRI
299
Pregabalin side effects
Dizziness, nausea, somnolence, peripheral edema, weight gain, confusion
CAUTION in elderly
300
Pregabalin DDI
No clinically sig DDIs -- additive CNS effects with other agents with CNS effects
301
Pregabalin schedule
CV
302
Pregabalin ___mg dose ratings of "good drug effect" "high" and "liking" similar to 30mg of diazepam
450mg
303
Pregabalin dosing frequency/adjustments
BID or TID
Dose titration needed to tolerate ADEs
Renal adj
304
Pregabalin onset usually within ___
a week
305
Pregabalin caution in
elderly and pts with substance abuse hx
306
Pregabalin must be tapered over ___ week when d/c
>1 week
307
Gabapentin IR brand
Neurontin
308
Gabapentin enacarbil ER brand name
Horizant
309
Gabapentin has enhanced efficacy when used in combo with ___
nortriptyline
310
Gabapentin can be in combination with
lidocaine
capsaicin
TCA
SNRI
311
Gabapentin FDA approved for
Post herpetic neuralgia
| Gabapentin enacarbil ER (Horizant) for Restless Leg Syndrome (RLS)
312
Gabapentin is effective in
```
DM neuropathic pain
Post herpetic neuralgia
Trigeminal neuralgia
Restless leg syndrome (RLS)
Hot flashes
ETOH dependence
Fibromyalgia
```
313
T/F: Only pregabalin (not gabapentin) has to be tapered with d/c
FALSE - both should be tapered when D/C
314
T/F: Only gabapentin (not pregabalin) should be titrated to avoid ADEs
FALSE -- both are titrated
315
Gabapentin onset should be within __
a week
316
Gabapentin for restless leg syndrome dosing frequency
Once daily
317
Gabapentin dosing adjustments?
Renal insufficiency
318
Gabapentin DDIs
Chelation with calcium, iron, antacids (2 hr separation)
Additive CNS effects with other agents with CNS effects
319
Pregabalin or Gabapentin: which has higher risk of dependence?
Pregabalin
320
Duloxetine (Cymbalta) can be used in combo with
Anticonvulsants or topicals
BUT NOT with other antidepressants
321
Duloxetine ADEs
Nausea, dizziness, somnolence, fatigue
Take on full stomach
322
Duloxetine FDA approved for
DM neuropathy
Fibromyalgia
LBP/OA
323
Duloxetine onset within
a wekk
324
Duloxetine brand name
Cymbalta
325
Duloxetine dosing
60mg daily (start 30mg daily x1 week, then increase dose)
326
Duloxetine DDIs
```
CYP1A2 substrate
CYP2D6 substrate
CYP2D6 inhibitor, moderate
Antiplatelet effects
CNS depression
Hyponatremia
Lowers seizure threshold
Strong serotonergic effects – combining with other agents modulating serotonin can cause serotonin syndrome
```
327
SNRI are likely effective for neuropathic pain because of modulation of ___ more than ___ modulation
NE (not serotonin)
328
SNRI Examples for neuropathic pain
Duloxetine
| Venlafaxine
329
___ is as effective as imipramine for polyneuropathies
Venlafaxine
330
Venlafaxine ADEs
Nausea, somnolence, HA, insomnia
HTN
cardiac rhythm change
331
T/F: Venlafaxine low doses are just as effective as high
FALSE - low doses are inaffective
332
Venlafaxine doses
150-225mg daily
333
TCA has no FDA indication for pain but useful in pain stated for ___
those with or w/o depression
334
Difference in efficacy between TCA
No diff -- all are effective but amitriptyline most studied
335
T/F: TCA lower doses are effective for pain
True - lower doses than antidepressant effects/doses
336
Can use TCA in combo with
Anticonvulsants or topicals
337
TCA sedation onset
1-3 hrs
338
When to take TCA
10-12hrs before awake time (rather than "bedtime"
Start low dose to minimize ADEs
339
Amitriptyline dosing
50-150 mg HS
340
Nortriptyline dosing
50-150mg HS
341
Imipramine dosing
100mg QD
342
Despramine dosing
100mg QD
343
TCA ADEs
```
Sedation
Anticholinergic SE (dry mouth, constipation, urinary retention, blurred vision, tachycardia) -- caution elderly BPH
Interaction characteristics (CNS depression, CYP2D6 substrate, hyponatremia, lowers seizure threshold, serotonin effects, prolonged QT interval
```
344
Avoid using TCA in
Second or third-degree heart block, arrhythmias, prolonged QT interval, severe liver disease, recent MI
345
SSRI for neuropathic pain
Inferior to TCAs but better SE profile
Partially effective for DM neuropathy
Fluoxetine generally NOT effective
346
Fibromyalgia non-drug approaches
Exercise
Reduce stress
Sleep hygiene
Cognitive behavioral therapy
347
Fibromyalgia FDA approved agents
Duloxetine (Cymbalta)
Milnacipran (Savella)
Pregabalin (Lyrica)
348
Fibromyalgia non-FDA approved agents
Gabapentin
Tramadol
TCA
Cyclobenzaprine
349
Agents to avoid in Fibromyalgia bc lack of benefit
NSAIDs
Capsaicin
Opioids
350
Cancer pain def
Pain syndromes associated with malignant pain or cancer pain
| Can be pain caused by the disease itself, or by painful diagnostic procedures or treatments
351
Why does cancer pain have its own classification?
Has both acute and chronic components
Often has multiple etiologies
Hard to classify based on duration/pathology
Although there is a distinct pain syndrome called Cancer Pain, many clinicians will diagnose a patient with cancer with either acute or chronic pain
352
What is bone pain and how is it described?
Pain resulting from bone disruption bc of a malignant tumor is growing on the bone
"sore" "aching"
353
Bone pain treatment options
NSAID, radiopharmaceuticals, opioids -- tumors active nociceptors by pressure, ischemia, or secretion of locally acting algesic substance (prostaglandin E2)
Bisphosphonate therapy - imbalance between bone formation and resorption resulting in an imbalance and bone destruction
