Lecture 2 Flashcards
(189 cards)
1
Q
Types of pain
A
Nociceptive
Neuropathic/functional
2
Q
Nociceptive pain
A
Caused by damage to body tissue, secondary to noxious stimuli
3
Q
Neuropathic/functional pain
A
Disengaged from noxious stimuli or healing; Described in terms of chronic pain, result of nerve damage or abnormal operation of nervous system
4
Q
Postherpetic neuralgia - pain type?
A
Neuropathic/functional pain
5
Q
Diabetic neuropathy - type of pain?
A
Neuropathic/functional
6
Q
Neuropathic pain
A
Result of nerve damage
7
Q
Pain regulated by -
A
Excitatory & inhibitory neurotransmitters in response to stimuli
8
Q
Perception of pain - 3 systems?
A
- Afferent pathways
- CNS
- Efferent pathways
9
Q
Afferent pathway
A
send signals to spinal cord
10
Q
CNS system involvement in pain pathway
A
discriminate & localize pain, arouse & alert (fight/flight), motivational factors
11
Q
Efferent pathway
A
Modulate pain sensation
12
Q
Pathophysiology - 4 stages of pain
A
- Stimulation
- Transmission
- Perception
- Modulation
13
Q
Pain - Stimulation pathophysiology
A
Involves stimulation of free nerve endings - nociceptors
14
Q
Pain - Transmission pathophysiology
A
Afferent fibers synapse into various layers of the spinal cords dorsal horn - pain impulses transmitted to brain stem — thalamus via ascending pathways — then finally to CNS
15
Q
Ascending transmission pathway
A
Peripheral pain receptors to spinal cord to medulla to brain stem to midbrain to cortex
16
Q
Pain - perception pathophysiology
A
The point at which pain becomes a conscious experience
17
Q
Pain - modulation
A
Initiation of the anti-nociceptive system
Endogenous opiate system in CNS releases “endorphins”
18
Q
Location of pain modulation
A
Descending system - inhibits pain transmission at dorsal horn
19
Q
Neuropathic pain
A
Rewiring of pain circuits - anatomically and biochemically
20
Q
The goal of managing pain
A
Reduce peripheral sensation (the cause) and decrease central stimulation
21
Q
Pain severity vs. therapy measurement
A
Numerical assessment unless cognitive deficit or children - use face scale
22
Q
Mild pain scale
A
1-3
23
Q
Mild pain treatment
A
APAP, aspirin, NSAID, COX-2 inhibitors
24
Q
Moderate pain scale
A
4-7
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Moderate pain treatment
NSAID, opioid + APAP, tramadol
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Severe pain scale
8-10
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Severe pain treatment
Opioids
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Reason for combination therapy (opioid + another Rx)
1. Take advantage of the synergistic effect on pain
| 2. To limit the dose
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Benefits of non-opioids
Availability, additive therapy when combined with opioids, inexpensive, low abuse
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Only true “pain killers”
NSAIDs - decreasing inflammation (large cause of pain)
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Disadvantages of non-opioids
Effects are “capped”, not effective at a certain pain level, side effects - can be toxic, limited parenteral availability
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APAP
Tylenol
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Tylenol - MOA
Believed to inhibit synthesis of prostaglandins in CNS; work peripherally to block pain impulse generation
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Tylenol Dose
325-650 mg Q4H or 1000 mg q6h
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Maximum dose of Tylenol/day
4 grams/day
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Maximum Tylenol dose for liver impairment/alcoholism
2grams/day
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Dosage forms of Tylenol
PO, PR, IV ($$$)
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Tylenol black box warning
Hepatotoxicity and failure with excessive doses (>4g/day)
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COX
Enzyme - cycle-oxygenase
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COX binds to
Arachidonic acid
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Arachidonic acid
Inflammatory mediator released in setting of tissue injury
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COX-1 and COX-2
Isoenzymes
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COX-1 pathway
Generates cytoprotective prostaglandins and thromboxane
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COX-1 pathway location
GI, kidney, lung
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COX-1 pathway effects
Platelet aggregation, vasoconstriction
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COX-2 pathway
Inflammatory prostaglandins and prostacyclin
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COX-2 effects
Inflammation, pain, antiplatelet, vasodilation
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What pathway is blocked from NSAIDs?
COX-1 and COX-2
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Salicylates
Aspirin
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Aspirin MOA
Irreversibly binds to COX-1 and COX-2 enzymes
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Aspirin properties
Analgesia, anti-inflammatory, antipyretic, antiplatelet
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Aspirin - harmful
Antiplatelet - irreversible. Prevents synthesis of thromboxane A
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Thromboxane A
Vasoconstrictor & inducer of platelet aggregation
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Aspirin onset
15-20 min
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Aspirin peak
1-3 hours
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Aspirin duration
3-6 hours
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Aspirin half life
3 hours
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Aspirin elimination
Urine and liver
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Aspirin adverse events
GI irritation and bleeding (ulcers), dizziness, deafness, tinnitus (salicylism) with high doses, Reye’s syndrome
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Reye’s syndrome
Liver disorder and encephalopathy - occurs in children with viral infections
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Aspirin - unique adverse effect
Asthamtics - increase risk of bronchospasm, urticaria, angioedema
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Aspirin contraindication
Active peptic ulcer, history of GI bleed, hypersensitivity to aspirin or NSAID
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Aspirin safety
Avoid use with recent surgery
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NSAIDs general properties
Same as aspirin: analgesic, anti-inflammatory, antipyretic, antiplatelet (reversible)
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Different property in general NSAID vs. aspirin
General NSAID: antiplatelet (reversible)
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Ibuprofen maximum dosage/day
2400 mg
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Indomethacin max dose/day
200 mg
68
Ketorolac max dose/day
120 mg
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Naproxen max dose/day
600 mg
70
Common NSAIDs
Ibuprofen, indomethacin, ketorolac, naproxen
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NSAID adverse effects - cardio
Fluid retention, hypertension, edema
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NSAID - adverse effects - GI
Irritation, ulcers, bleeding, perforation
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NSAIDs adverse effects - respiratory
Bronchospasm
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NSAIDs adverse effects - skin
Rash
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NSAIDs adverse effects - renal
Insufficiency or failure
76
NSAIDs - avoid with?
Other nephrotoxic drugs
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Nephrotoxic drugs
Diuretics - furosemide, hydrochlorothiazide; Ace inhibitors
78
Black box warnings - NSAIDs
Potential adverse CV thrombotic events (MI and stroke), GI ulceration/bleeding/perforation, Tx of periop pain in setting of CABG
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Toradol
Ketorolac
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Ketorolac indication
Short-term management of moderate to severe pain
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Routes - ketorolac
Parenteral (IV/IM) or PO
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Ketorolac adverse events
Severe bleeding post-op, renal failure
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Maximum length of therapy for toradol
5 days
84
COX-2 Inhibitor
Celecoxib
85
Celebrex
Celecoxib
86
Advantage of Celebrex
Minimal GI side effects, no effect on platelet aggregation
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Disadvantages of Celebrex
Renal dysfunction, avoid with “sulfa-allergy”, CARDIOVASCULAR EVENTS
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NSAID selectivity, most to least
Celecoxib, meloxicam/diclofenac, ibuprofen/naproxen, aspirin
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All NSAIDs increase the risk of
Major Adverse Cardiac Events
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Dose dependent
Dose-effect of NSAIDs...try to take as little as possible to minimize cardiac adverse effects
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Phenanthrenes
Morphine, hydromorphone, levorphenol, oxymorphone, codeine, hydrocodone, oxycodone
92
Phenylpiperidines
Meperidine, fentanyl, sufentanil, alfentanyl, remifentanyl
93
Phenylheptanes
Methadone
94
Morphine is eliminated how?
Renal —— KNOW THIS
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Morphine routes of administration
PO, PR, IV, IM, SubQ, epidural, intro the cal
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Morphine PO Dosing
15-30 q4h PRN
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Morphine dosing IV
2-4 mg q4h PRN
98
Active metabolites of Morphine
1. 6-glucuronide: active analgesia
| 2. 3-glucuronide: myoclonus, confusion, hallucinations
99
Histamine release
Hypotension, Pruritis
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Unique morphine related effect
Histamine release
101
Histamine Release
Hypotension, Pruritis
102
Hydromorphone formulations
PO, PR, IV, IM, SubQ, epidural
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Hydromorphone formulations
PO, PR, IV, IM, SubQ, epidural
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Hydromorphone half life
2-3 hours
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Hydromorphone metabolism
Primarily non-renal, no active metabolites
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Alternative agent for morphine in patient with advanced CKD, concerned of accumulation of morphine in the setting of lack of renal elimination
Hydromorphone
107
Hydromorphone dosing PO
2-4 mg q4-q6 PRN
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Hydromorphone dosing IV
0.2-1 mg q2-3h PRN
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Methadone - used for?
Chronic Pain
110
Reason Methadone is used for withdrawal
Long analgesic half life, even longer occupation of opiate receptor/preventing cravings
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Methadone Route of administration
PO, IV, IM, SubQ
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Methadone Dosing PO
2.5 mg q8-12h
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Methadone Dosing IV
2.5-10 mg q8-12h
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Methadone metabolism
Renally cleared
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Unique feature of Methadone
Prolong QTc - hold or reduce dose if QTc greater than or equal to 500
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When should caution be used when prescribing methadone?
In combination with other medications that could cause prolongation of QTc interval
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Methadone Cautions
Lowers threshold of seizures - use caution in patients with history; serotoninergic effects
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Methadone Metabolism
Biphasic elimination - analgesic half life: 8-12h; terminal half-life: 24-36h
119
Meperidine routes of administration
PO, IV, IM, SubQ
120
Meperidine Dose
IV: 50-150 mg q4-q6h
121
Meperidine Metabolism
Renal
122
Meperidine Metabolite
Active metabolite: normeperidine
123
Side effect of normeperidine
Anxiety, seizures, tremors
124
Increased risk of active metabolite when?
Renal dysfunction, preexisting CNS dysfunction, prolonged use > 48h, high cumulative doses
125
Meperidine alternative uses
Post-op shivering
126
Side effects of meperidine
Serotoninergic effects
127
Codeine route of administration
PO
128
Codeine dosage
15-60 mg q4h PRN
129
Codeine metabolism
Converted to morphine (active metabolite)
130
Codeine Metabolism Route
Major CYP 2D6 substrate (metabolizer variants)
131
Codeine side effects
Antitussive
132
Codeine tolerance
Weak agonist - low risk for abuse
133
Hydrocodone route of administration
PO
134
Hydrocodone dosage
5-10 mg q4-q6h PRN
135
Hydrocodone metabolism
Metabolized to hydromorphine
136
Hydrocodone metabolized via which route
CYP2D6
137
Hydrocodone is used when?
Acute moderate to severe pain in patients with limited opioid use
138
Hydrocodone is available as?
Immediate release combination product with APAP (Vicodin), ibuprofen (vicoprofen), OR extended release (Zohydro ER, Hysingla ER)
139
Fentanyl route of administration
Transdermal, IV, lozenge, buccal, intranasal, sublingual, epidural
140
Fentanyl dosage IV
25-50 mcg q2-3h
141
Fentanyl Metabolism
Via CYP3A4
142
Preferred agent for pain in liver failure
Fentanyl
143
Why does fentanyl have a rapid onset?
High potency, lipid solubility
144
Adverse effects of fentanyl
Bradycardia, chest wall rigidity
145
Antagonists
Naloxone, naltrexone, methylnaltrexone
146
Naloxone is used to?
Reverse toxic effects of agonists and agonists-antagonists
147
Naloxone dosage
Repeated dosing maybe necessary based upon half-life of agonist
148
Naloxone metabolism
Poor systemic bioavailability d/t extensive first pass
149
Oral Naloxone
May be used to prevent opioid induced constipation
150
Naltrexone uses
Not for acute reversal of toxic effects
151
Naltrexone routes of administration
IM depot and PO (opioid dependence)
152
Naltrexone brand name
Vivitrol
153
Naltrexone side effects
Hepatotoxic
154
Methylnaltrexone Brand Name
Relistor
155
Methylnaltrexone route of administration
SubQ
156
Methylnaltrexone is not used for?
Acute reversal of toxic effects
157
Methylnaltrexone is used for?
To treat opioid induced constipation with chronic opioid use
158
Methylnaltrexone metabolism
Renally eliminated
159
Methylnaltrexone risk of?
GI perforation
160
Methylnaltrexone acts on?
Peripheral mu receptors - GI tract; does NOT cross BBB
161
Opioid conversion - Morphine 10 IV
30 PO
162
Opioid conversion - Hydromorphone 1.5 IV
7.5 PO
163
Tramadol MOA
Weak opiate mu receptor binding, inhibition of norepinephrine and serotonin reuptake
164
Tramadol route of administration
PO
165
Tramadol dosage
25-100 mg q4-q6h PRN
166
Tramadol Metabolism Route
CYP 2D6
167
Tramadol is cleared by?
Renal and hepatic
168
Advantages of tramadol
Less respiratory depression, GI dysmotility
169
Tramadol adverse effects
Decreases seizure threshold, drug intxn (CYP, serotonin)
170
Opioid Adverse Effects
Respiratory Depression, sedation, constipation
171
Less serious adverse effects of opioids
Itching
172
Which adverse effect of opioids is persistent?
Constipation
173
Because of respiratory depression from opioids, what is an increased risk?
Cardiac insult
174
Tolerance of opioids
Dose increase required to maintain similar analgesia
175
Tolerance Development
High/Moderate/None
176
Chronic pain regimen
Long acting opioid with a short acting opioid for breakthrough pain
177
Short acting opioid for breakthrough pain (chronic pain regimen) - calculated how?
10-15% of total daily dose of regularly scheduled opioid & offer immediate release formulation q2-4h PRN
178
When would you increase the long-acting dose opioid for someone on a chronic pain regimen?
If patient uses greater than or equal to 3 doses of break thru Rx per day
179
Which drug would you avoid in the elderly?
Morphine
180
A patient with liver disease will react how to Codeine?
Activity of codeine may be decreased due to decreased conversion
181
What is the preferred medication for pain in liver disease patients?
Fentanyl
182
Which drug would you avoid in patients with kidney disease?
Morphine and codeine
183
Treatment strategy for neuropathic pain?
SSNRI, tricyclics antidepressants, calcium channel a2 “something” ligand
184
SSNRI
duloxetine, venlafaxine
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Tricyclic antidepressants
Nortriptyline, despiramine
186
Calcium channel a2 Ligands
Gabapentin, pregabalin
187
How do you start therapy for patients beginning gapabentin or pregabalin?
Start slow and titrate to effect
188
Adverse effects of gabapentin or pregabalin?
CNS depression, dizziness, somnolence, abnormal gait
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Who should you be wary of while taking gabapentin or pregabalin?
Accumulation in renally impaired patients
