Pharmacology of Chronic Pain Management Flashcards
1
Q
Hydrocodone MAO
A
Full opioid agonists
2
Q
Hydrocodone Indications
A
Relief of moderate pain. As an antitussive when used
in combination with other Nrespiratory agents
(expectants/decongestants/ antihistamines)
3
Q
Hydrocodone Dosage
A
Equianalgesic Dose: (PO): 30
5-10mg every 4-6h
4
Q
Hydrocodone Duration and Half life
A
Duration: 4-8h
Half-life: 3.3- 4.5h
5
Q
Hydrocodone formulation
A
Weak opioid only available in combination with nonopioid analgesic (acetaminophen or ibuprofen)
6
Q
Hydrocodone compared to Hydromorphone
A
Hydrocodone is the methyl ether of hydromorphone, but is much weaker an analgesic than hydromorphone.
7
Q
Hydrocodone Metabolism
A
Undergoes-O-demethylation to dihydromorphine and its
major metabolites excreted into urine are dihydrocodeine
and nordihydrocodeine
8
Q
Hydromorphone MOA
(Dilaudid)
A
Full opioid agonists
9
Q
Hydromorphone Indications
(Dilaudid)
A
Immediate – release: relief of moderate to severe pain due to conditions such as biliary/renal, colic burns,
cancer, myocardial infarction, surgery, and trauma
Long-acting: relief of moderate to severe pain in
patients requiring continuous, around the clock analgesia
10
Q
Hydromorphone Dosage
(Dilaudid)
A
Equianalgesic Dose
Hydromorphone (IV/IM/SC): 1.5
Hydromorphone (PO): 7.5
Immediate Release: 2-4mg q 4-6h (tablets), 2.5- 10mg q3-6h (solution)
Titrated by response; higher doses may be needed for severe pain
SR preparation (exalgo)
For breakthrough pain: 5-15% of total daily dose may be given every 2h prn
Dosing interval for long acting formulation: 24h
11
Q
Hydromorphone Duration and Half Life
(Dilaudid)
A
Duration: 4-5h
Half-life: 2-3h
12
Q
Hydromorphone Metabolism and Excretion
(Dilaudid)
A
Hydromorphone is preferred over morphine in patients
with renal dysfunction due to less accumulation of active
metabolites compared to morphine
Renal excretion
13
Q
Meperidine (Demerol) MAO
A
Meperidine binds to opioid receptors, particularly
μ receptors. It also binds well to κ receptors
Meperidine cab block voltage dependent sodium channels.
Meperidine also has agonist activity at the alpha 2B adrenoreceptor subtype.
Inhibit serotonin and norepinephrine reuptake
14
Q
Meperidine (Demerol) Indications
A
Not used for chronic pain because of short duration of
action and toxicities associated with chronic use
The use of meperidine should be limited to 1 to 2
days for acute pain and should be avoided in chronic
pain management
Relief of moderate to severe pain
15
Q
Meperidine (Demerol) Side Effects
A
Seizures and central nervous system effects have been
associated with high doses or prolonged use because of
accumulation of the metabolite Normeperidine. Especially in elderly and pts with renal dysfunction not affected by naloxone
Meperidine similar to Atropine may elevate the heart rate
interactions of Meperidine and MAOIs are combined,
severe respiratory depression or excitation, arrhythmias,
delusions, hyperpyrexia, seizures and coma can be seen.
Meperidine has cardiac (hypotension and myocardial
depression), local anesthetic, and anticholinergic
properties
16
Q
Meperidine (Demerol) Dosage
A
Meperidine (IV/IM/SC): 75
Meperidine (PO): 300
50-150mg q 3-4 prn
17
Q
Meperidine (Demerol) Duration and Half Life
A
Duration: 2-4h
Half-life: 3-4h
18
Q
Morphine (Roxanol, Contin, Oramorph, Kadian, Avinza) MAO
A
Morphine acts at κ receptors in laminae I and II of
the dorsal horn of the spinal cord, and it
decreases the release of substance P, which
modulates pain perception
19
Q
Morphine Indications
A
Immediate- release: relief of moderate to severe pain
Long-acting: relief of moderate to severe pain in
patients requiring continuous around the clock analgesia
Morphine has greater potency but slower speed of
onset and offset in women
20
Q
Morphine Side Effects
A
Morphine and other opioids produce seizures at HIGH doses due to inhibition of release of GABA at synaptic levels.
Therapeutic doses of morphine decrease
Minute Ventilation by decreasing Respiratory Rate (as oppose to tidal volume).
Opioids acting in μ- and κ- receptors constrict
the pupil by exciting the Edinger Westphal nucleus (parasympathetic)
Long-term opioid use can produce tolerance to miotic effects of opioids
21
Q
Morphine dosing
A
Morphine (IV/IM/SC): 10 Morphine (acute PO): 60 Morphine (chronic PO): 30 Immediate Release formulation: 5- 30mg every 4h, titrated by response Dosing intervals for long acting formulations: 8-12h for MS Contin and Oramorph SR, 12h for Kadian, 24h for Avinza
22
Q
Morphine Metabolism and Excretion
A
Hepatic metabolism, renal excretion
Morphine is metabolized by the liver to morphine-6-glucuronide which is more potent than morphine itself
and has a longer half-life, resulting in additional analgesia. Morphine is also metabolized to morphine-3-
glucuronide which causes adverse effects and is inactive according to others.
Renal dysfunction can produce accumulation of morphine-6- glucuronide, with subsequent opioid effects, including respiratory depression, so morphine should be used with care in renal dysfunction.
Patients with liver failure can tolerate morphine (even in hepatic precoma), because glucuronidation is rarely impaired
23
Q
Morphine and Respiratory Depression
A
Delayed respiratory depression is likely to occur with
larger dose of epidural opioids, particularly morphine that
is hydrophilic and therefore subject to spread in the CSF,
reaching the respiratory center in the brainstem. Morphine in the epidural space produces a biphasic respiratory depression pattern. One portion
of the initial bolus is absorbed systemically, accounting for the initial phase, which usually occurs within 2 hours of the bolus dose. The second phase occurs 6 to 12 hours later owing to the slow rostral spread of the remaining drug as it reaches the brainstem. Pts should be monitored 24hrs after administration epidurally.
Intrathecal doses of morphine produce only a uniphasic
pattern of respiratory depression.
Neurotoxic metabolites cause hyperalgesia, myoclonus,
and seizures
24
Q
Morphine Duration, Half-life, Bioavailability
A
Duration: 3-7 h
Half-life: 1.5- 2h
Oral Bioavailability: 25-35%
25
```
Oxycodone MOA
(OxyContin)
```
.
26
Oxycodone Indication
Immediate- release: relief of moderate to severe pain
Long-acting: relief of moderate to severe pain in
patients requiring continuous around the clock analgesia
27
Oxycodone Dosage
Oxycodone (PO): 20
Oxycodone has been typically used in combination with nonopioids (acetaminophen, aspirin)
Immediate release: 10-30mg q4h, titrated by response
5mg capsules and oral concentrate 5mg q6h, titrated by response Dosing intervals for long acting formulations: 12h
28
Oxycodone Duration and Half Life
| Bioavailability
Duration: 4-6h
Half-life: N/A
Higher bioavailability than that of morphine (approximately 60%).
29
Oxycodone Metabolism and Excretion
Metabolite via 3-0 demethylation is Oxymorphone. Must
be converted to oxymorphone by CYP2D6 to be effective
Renal excretion
30
Oxymorphone MOA
| Opana
.
31
Oxymorphone Indications
| Opana
Immediate- release: relief of moderate to severe acute
pain
Long-acting: relief of moderate to severe pain in
patients requiring continuous around the clock analgesia
32
Oxymorphone Dosage
Oxymorphone (IV/IM/SC): 1.0
Oxymorphone (PO): 10
Immediate- release formulation: 10- 20mg q4-6h; titrated by response
Dosing intervals for long acting formulations: 12h
33
Oxymorphone Duration and Half-life
Duration: 3-6h
| Half-life: N/A
34
Oxymorphone metabolism
Active metabolite of oxycodone
35
Fentanyl (Actiq, Duragesic, Fentora, Onsoild) MOA
Full opioid agonists
Fentanyl is a potent mu agonist, with high lipid
solubility, low molecular weight and high potency,
making it an ideal drug for transdermal and
transmucosal administration 92% of fentanyl delivered transdermally reaches the circulation as unchanged fentanyl.
Transmucosal route at the buccal and sublingual
mucosa skips the first pass effect and overall
bioavailability is 50%.
For opioid rotation when tolerance to opioid
develops. Do not reduce the dose but maintain
the equianalgesic dose.
36
Fentanyl Indications
Transdermal patches: relief of moderate to severe
chronic pain in patients requiring continuous around
the clock analgesia when other analgesia have failed
Oral formulations (sublingual, lozenges, buccal
tablets/films): management of breakthrough cancer pain
in patients on or tolerant to opioid therapy
37
Fentanyl Side Effects
Causes less constipation than sustained-release morphine
38
Fentanyl Dosage
Equianalgesic Dose: Fentanyl is 80
times as potent as morphine
Fentanyl (IM/IV): 0.1
Fentanyl (Transdermal): 0.2
39
Fentanyl (Transdermal)
92% of fentanyl delivered transdermally reaches systemic circulation as unchanged fentanyl
Peak plasma concentration after application is 12 to 24 hours and a residual depot remains in subcutaneous tissues for about 24 hours after removal of the patc
40
Advantages of Fentanyl Patch
Low MW, High Lipid Solubility; this allows it to be administered by the transdermal route. It interacts
primarily with mu receptors, 80X more potent than morphine, and low abuse potential which is a
property of the delivery system not opioid itself.
41
Fentanyl Duration and Half Life
Duration: 1-2h
Half-life: 1.5-6 h
Time of onset of IM: 7-15 mins
42
Fentanyl Characteristics
Fentanyl is both lipophilic and highly protein bound.
Fentanyl
also distributes to fat tissue and redistributes slowly from
there into the systemic circulation
43
Fentanyl Metabolism
Fentanyl is metabolized to inactive metabolites by the
CYP450 3A4 system mainly in the Liver and minor extent
in CNS, Kidneys, lung, placenta
Best given in patient with Chronic Kidney Disease and
Liver Disease
44
Oral transmucosal fentanyl citrate (OTFC)
Applied against the buccal mucosa. 25% of total dose is absorbed from GI tract but escapes hepatic and intestinal first pass elimination. Total apparent bioavailability: 50%
45
Actiq lollipop
25% absorbed transmucosally, 75% GI, 2/3
of which is inactivated. Net = ½ the dose is available for
analgesia
46
Codeine MOA
Full opioid agonists
Metabolized to Morphine
The analgesic actions of codeine derive from its
conversion to morphine by the CYP450 2D6
enzyme system
47
Codeine Indications
Relief of mild-mod pain.
As an antitussive when used in combination with other
respiratory agents (expectants/decongestants/
antihistamines)
48
Codeine Side Effects
avoid in renal insufficiency
49
Codeine Dosage
Equianalgesic Dose:
Codeine (IM/IV): 120
Codeine (PO): 200
15-60mg every 4-6h
50
Codeine Duration and Half life
Duration: 4-6h
Half-life: 3h
Weak opioid only available in combination with nonopioid
analgesic (acetaminophen or Ibuprofen)
51
Codeine in Caucasians
10% ineffective as an analgesic in the Caucasian with
genetic polymorphisms in CYP2D6 (enzyme necessary to
O methylate codeine to morphine)
52
Methadone (Dolophine) MOA
Mediated by μ- agonist (pure) and agonist, NMDA
inhibitor, inhibitor of serotonin and norepinephrine
reuptake
In addition, methadone is an antagonist of NMDA receptor, which is useful in the treatment of neurogenic pain.
Addition of an NMDA antagonist is a strategy
available for opioid rotation when tolerance to
opioid develops. Reduce the dose by 75-90%
53
Methadone Indications
Methadone is used as an analgesic in nociceptive and
neurogenic pain as well as in the controlled withdrawal of dependent abusers from heroin and morphine
because withdrawal symptoms tend to be less severe than morphine’s, this and its long duration of action, good oral bioavailability, and high potency
54
Methadone Dosage
Methadone (acute IV): 5.0
Methadone (acute PO): 10
2.5-10mg every 8-12h, slowly
titrated by response
55
Methadone Titration
Rapid titration is not possible, making this drug more useful for stable type of pain
56
Methadone Formulation
Methadone is the only opioid with prolonged activity not achieved by controlled release formulation.
Can be used in a intrathecal pump
57
Methadone Excretion
Excreted exclusively in the feces and can be given in patient with renal dysfunction
58
Methadone Duration and Half-life
Duration: 4-6h
| Half-life: 15- 30h
59
Methadone Metabolism
Methadone unlike morphine is metabolized through N-demethylation by the liver cytochrome P-450 enzyme (CYP1A2) caution in patients receiving multiple medications
Safe in liver and renal disease
60
Methadone Elimination
Methadone has biphasic elimination. β-elimination phase (ranges from 30 to 60 hours) producing sedation and respiratory depression can outlast the analgesic action which equates the α-elimination phase (6-8 hours).
61
Levorphanol MOA
Full opioid agonists
62
Levorphanol Indications
Relief of moderate to severe
pain
As a preoperative medication
63
Levorphanol Dose
Equianalgesic Dose
Levorphanol (acute PO): 4.0
Levorphanol (chronic PO): 1.0
2mg every 6-8h
64
Levorphanol Duration and Half Life
Duration: 6-8h
Half-life: 12-16h
Long half life may lead to accumulation with chronic use
65
Buprenorphine (Buprenex, Subutex) MOA
A partial agonist at the μ-receptor and very little
activity at the κ- and δ-receptors. It has high
affinity but low intrinsic activity at the μ-receptor
and has a pharmacologic ceiling owing to its
partial agonist activity.
It acts like morphine in naive patients, but it can
also precipitate withdrawal in morphine users
66
Buprenorphine Indications
A partial agonist at the μ-receptor and very little
activity at the κ- and δ-receptors. It has high
affinity but low intrinsic activity at the μ-receptor
and has a pharmacologic ceiling owing to its
partial agonist activity.
It acts like morphine in naive patients, but it can
also precipitate withdrawal in morphine users.
The tablets are indicated for the treatment of opioid
dependence and are available in buprenorphine alone
(Subutex) and also in a combination product containing
buprenorphine and naloxone (Suboxone). Naloxone was
added to buprenorphine to prevent the abuse of
buprenorphine via IV administration
67
Buprenorphine Dosage
Equianalgesic Dose: (IM/IV): 0.4
Opioid Naïve patients: 5mcg/h transdermal patch initially, titrated at intervals of 72h up to maximum of 20mcg/h transdermal patch
Nonopioid naïve patients: Taper current opioid dose for up to 7 days to no more than morphine 30mg/d; patients originally requiring < 30mg/d of morphine (or equivalent)
can be started on a 5mcg /h patch.
Patients originally requiring 30-80mg/d of morphine (or equivalent) can be started on a 10mcg /h patch
68
Buprenorphine Transdermal
Each transdermal patch should be worn for 7 days
Transdermal patch: relief of moderate to severe chronic
pain in patients requiring continuous, around the clock
analgesia
69
Buprenorphine Sublingual
Sublingual: treatment of opioid dependence
70
Butorphanol (Stadol) MOA
Mixed Opioid agonists/ antagonist
71
Butorphanol (Stadol) Dosage
Equianalgesic Dose: (IM/IV): 2.0
1-2mg intranasally; may be repeated in 3-4h, if needed
If a 1mg dose is used initially, a 2nd 1 mg dose may be
given 60-90min later if pain relief is not adequate
72
Nalbuphine (Nubain)
.
73
Pentazocine (Talwin) MOA
Mixed Opioid agonists/ antagonist
Acts as an agonist on κ receptors and is a weak
antagonist at μ and δ receptors
74
Pentazocine (Talwin) Indications
Pentazocine promotes analgesia by activating
receptors in the spinal cord, and it is used to relieve
Moderate pain
75
Pentazocine (Talwin) Dosage
25-50mg every 3-4h
76
Pentazocine (Talwin)
Weak opioid only available in combination with a
nonopioid analgesic (acetaminophen) or an opioid
anatagonist (naloxone)
77
Suboxone (Buprenorphine/naloxone) MOA
.
78
Suboxone (Buprenorphine/naloxone) Indications
Used to maintain addicts, requires special license
| Good option for addicts with true pain
79
Suboxone (Buprenorphine/naloxone) Side Effects
GI absorption of naloxone is negligible
80
Suboxone (Buprenorphine/naloxone) characteristics
Can’t be abused due to naloxone administration if taken
| parenterally
81
Naloxone (Narcan) Antagonist
Antagonist
Competitive antagonist at μ, κ, and δ, receptors,
with a tenfold higher affinity for μ than for κ
receptors
82
Naloxone (Narcan) Indications
Used to reverse the coma and respiratory depression of
opioid overdose. It rapidly displaces all receptor-bound
opioid molecules and, therefore, is able to reverse
the effect of a morphine overdose
83
Naloxone (Narcan) Half life
Half-life of 30 to 81 minutes
84
Tramadol (Ultram) Schedule
Schedule II controlled
| substance
85
Tramadol (Ultram) MOA
Acts through monoceminergic (like TCA) and
opioid (central) mechanism to block pain
perception
Weak mu opioid receptor agonist and SSNRI
Weak inhibitor of norepinephrine and serotonin
reuptake
A centrally acting analgesic that binds to the μ- opioid receptor. The drug undergoes extensive
metabolism via CYP450 2D6, leading to an active
metabolite that has a much higher affinity for the
μ receptor than the parent compound.
In addition, it weakly inhibits reuptake of
norepinephrine and serotonin. Major mechanism,
which is thought to account for
86
Tramadol (Ultram) Indications
Used to manage moderate to moderately severe pain
Neuropathic pain
Fibromyalgia
Immediate release: relief of moderate to moderately
severe pain
Extended release: relief of moderate to moderately severe
chronic pain in patients requiring continuous around the
clock analgesia
87
Tramadol (Ultram) Side Effects
Nausea, Sedation, Constipation,
Seizures, Headache, Tremor, Dry
mouth Urinary retention, increase risk suicide
Fewer side effects than morphine. The risk of respiratory depression is lower at equianalgesic doses; the risk of fatal respiratory depression is minimal at appropriate
oral dosing, and limited essentially to patients
with severe renal failure.
Tramadol has a low abuse potential,however,
Nausea and vomiting occur at the same rate as with other opioids
Tramadol should also be avoided in patients taking
MAOIs.
Serotonin syndrome (caution with MAOI’s, TCA’s and
SSRI’s
88
Tramadol (Ultram) Dosage
50-100mg 4x daily
25mg/d initially, titrated to 25mg 4x daily over 3d, then to 50-100mg every 4-6h; maximum dose of 400mg/d
Extended release tablets can be started at dose of 100mg/d and slowly titrated to a maximum of
300mg/d
89
Tramadol (Ultram) Metabolism and Excretion
Metabolized with one pharmacologically active metabolite, M1
Reduce dose in pts with hepatic dysfunction and in older
patients
Adjust dose for hepatic, renal disease and elderly
90
Tapentadol MOA
a centrally acting analgesic that binds the μ- opioid receptor and is also a norepinephrine
reuptake inhibitor that is believed to create an
additive effect to the opioid actions
91
Tapentadol Indications
Used to manage moderate to severe pain, both chronic
| and acute.
92
Tapentadol Avoided in what patients
Tapentadol should be avoided in patients currently taking MAOIs and those who have taken MAOIs within the last 14 days
93
Tricyclic Antidepressants (TCA) MOA
Theorized that the analgesic properties are
associated with their action as SNRI
TCAs with the greatest effect upon serotonin
seem to have the greatest analgesic effect.
Inhibit NE and 5-HT reuptake leading to increased
descending inhibition of pain pathways
Also block sodium channels, alpha-adrenergic,
muscarinic (cholinergic), and histaminergic
pathways
94
Tricyclic Antidepressants compared to SSRI
| Onset
Analgesic effect (superior to SSRIs)
- Independent of their effect on clinical depression
- Onset of analgesia with TCA ranges from 3-7 days
- Analgesia tends to occur at lower doses and plasma
levels than that needed for antidepressant effects
95
TCA Side Effects
Sedation (1-3hrs after ingestion)
Contraindicated in patients with severe cardiac disease, particularly conduction disturbances, obtain a
pretreatment ECG
Avoid in pts w/ GI dysfunction
Orthostatic hypotension, anticholinergic effects, weight gain, sexual dysfunction, restlessness
96
Signs of TCA Toxicity
Hyperthermia, Tachycardia, Seizures
97
TCA Metabolism and Excretion
Metabolized via CYP2D6 isoenzyme
| Excreted in urine
98
Tricyclic side effects
.
99
Tricyclic Guidelines
.
100
Amitriptyline (Elavil)
Tertiary amine
101
Amitriptyline (Elavil) Side Effect
Has the most Anticholinergic side effects (dry mouth, orthostatic hypotension, constipation, urinary retention, Insomnia, restlessness)
102
Amitriptyline (Elavil) Dosage
100-150mg/day (25-150mg/day)
Neuropathic pain: initial dose of 10- 25mg at bedtime titrated by 10-25mg per week until response or a
maximum of 150mg/day
Anticholinergic SE reduce by starting low doses qhs and slowly titrated to higher dose or using
secondary amine
103
Tertiary amine TCA
Imipramine , Tripramine, Clomipramine, Doxepin, Amitriptyline
104
Secondary amine TCA
Desipramine, Nortriptyline, Protriptyline, Amoxapine
105
Desipramine Side Effect
Fewer anticholinergic side effects Lower sedating effect
106
Desipramine Dosage
200-250mg/day (10-150mg/day) Neuropathic pain: initial dose of 10- 25mg at bedtime titrated by 10-25
mg per week until response or a
maximum of 150mg/day
Time to Effect: 6 week
Safe in older pts but starting dose reduced by ½
107
Nortriptyline Side Effect
Fewer side effects
108
Nortriptyline Dosage
100-150mg/day (30-150mg/day) Neuropathic pain: initial dose of 10-25mg at bedtime titrated by 10-25
mg per week until response or a
maximum of 150mg/day
Time to Effect: 6 week
Fewer anticholinergic side effects
Safe in older pts but starting dose reduced by ½
109
Trazadone MOA
Inhibits serotonin uptake and blocks serotonin
| 5HT2 receptors, Alpha-1-receptor antagonist
110
Trazadone Indications
At low dose, it is used as an
| adjunct for insomnia
111
Trazadone Side Effect
Sedation
| Orthostatic Hypotension
112
Duloxetine (Cymbalta) MOA
NE and 5-HT reuptake inhibitor
113
Duloxetine (Cymbalta) Indications
```
Chronic Musculoskeletal Pain
(Discomfort from Chronic Low Back Pain and Osteoarthritis)
Diabetic Peripheral Neuropathy
Fibromyalgia
DM and depression
```
114
Duloxetine (Cymbalta) Side Effects
Nausea, Dry mouth, Insomia, Drowsiness, Constipation, Fatigue, Dizziness
SIADH(rare)
Sucide
Hepatoxicity
SEs are reduced by administering 30mg daily for one week before increasing to 60mg daily
duloxetine does not cause QTc interval prolongation,
115
Duloxetine (Cymbalta) Dose
20 to 60 mg daily or bid
60-120mg/day (Reduce dose if CrCl< 30 ml/min)
Chronic Musculoskeletal Pain: 30mg/day for 1 week to target of 60mg/day
Diabetic Peripheral Neuropathy: the initial and target dose is 60mg/day
Fibromyalgia: 30mg/day for 1 week to a target dose of 60mg/day
Time to Effect: 4 week
116
Duloxetine (Cymbalta) Metabolism and Excretion
Liver metabolism and excreted in urine/feces (70/30)
Associated with transaminase elevation
Avoid in: MAOI’s or phenothiazine use, narrow-angle glaucoma, alcohol use
Avoided in patients with hepatic or severe renal insufficiency
117
Milnacipran (Savella) MOA
,
118
Milnacipran (Savella) Indication
Fibromyalgia
119
Milnacipran (Savella) Dose
```
Fibromyalgia: dose titrated as follow
Day 1: 12.5 mg
Day 2 -3: 12.5mg twice daily
Day 4-7: 25mg twice daily
Target dose is 50mg twice daily
```
120
Venlafaxine (Effexor) MOA
NE and 5-HT reuptake inhibitor
121
Venlafaxine (Effexor) Indication
Painful Diabetic Peripheral Neuropathy
| Painful polyneuropathies of different origin but NOT Post Herpetic Neuralgia
122
Venlafaxine (Effexor) Side Effect
Prescribe with caution in patients with cardiac disease
Nausea, headache, somnolence, insomnia
Suicidality, seizures, SIADH, HTN, mania, arrhythmia, serotonin syndrome, blood dyscrasia’s
Monitor EKG though less concerning than TCA
Avoid with MAOI’s
123
Venlafaxine (Effexor) Dose
150-225mg/day (37.5- 225 mg/day)
25mg daily and titrate
Neuropathic Pain: initial doses of 37.5mg once or twice daily titrated by 75mg weekly to response or a maximum dose of 225mg/day
Time to Effect: 4-6 week
124
Venlafaxine (Effexor) Metabolism and Excretion
Liver metabolism, urine excretion
| Reduce the dose by 25-50% in patients with mild to moderate renal impairment and 50% in hepatic impairment
125
Fluoxetine (Prozac) MOA
Serotonin Reuptake Inhibitor
126
Fluoxetine (Prozac) Indications
Fibromyalgia
Peripheral Neuropathy
Not preferred for neuropathic pain
127
Fluoxetine (Prozac) Side Effect
,
128
Fluoxetine (Prozac) Dose
Fibromyalgia: usual dose is 20-80mg/day
| Peripheral Neuropathy: usual dose is 20-40 mg/day
129
Paroxetine (Paxil)
.
130
Paroxetine (Paxil)
.
131
Paroxetine (Paxil)
.
132
Paroxetine (Paxil)
.
133
Paroxetine (Paxil)
.
134
Carbamazepine (Carbatrol, Tegretol) MOA
Blocking sodium channels
135
Carbamazepine (Carbatrol, Tegretol) Indications
Trigeminal neuralgia and bipolar disorder.
136
Carbamazepine (Carbatrol, Tegretol) Side Effects
Hyponatremia, drowsiness, fatigue, dizziness, and blurred vision. Drug use has also been associated with Stevens-Johnson syndrome. Blood dyscrasias: neutropenia,
leukopenia, thrombocytopenia, pancytopenia, and anemias
Cause bone marrow suppression or hepatotoxicity. A CBC and LFT should be obtained at baseline
Use with caution in patients with hepatic impairment
137
Carbamazepine (Carbatrol, Tegretol) Dose
200mg tid
Neuropathic pain: 100mg 2x daily titrated slowly to response or a maximum of 1200mg/day
Time to Effect: 4 week
138
Carbamazepine (Carbatrol, Tegretol) Excretion and Metabolism
CYP3A4 system, urine/feces (70/30)
139
Carbamazepine (Carbatrol, Tegretol) effects on drugs
Induces metabolism of many drugs (warfarin, CCB’s, OCP’s, HIV, azoles, other AEDs, etc)
Mycins, cimetidine, and propoxyphene increase CBZ levels
140
Carbamazepine (Carbatrol, Tegretol) and Bicuculline
Bicuculline antagonizes its antinociceptive effect
141
Oxcarbazepine (Trileptal) MOA
Blocks Na+ channels
| an analogue of carbamazepine
142
Oxcarbazepine (Trileptal) Indications
.
143
Oxcarbazepine (Trileptal) Side Effect
Nausea, rash, hyponatremia, headache, sedation, dizziness, vertigo, ataxia, and
Diplopia, weight gain and edema, GI symptoms, fatigue, allergic rxn
May cause hyponatremia; monitoring of serum sodium levels may be necessary
144
Oxcarbazepine (Trileptal) Doses
Diabetic Neuropathy: 150-300 mg/day titrated to response or a maximum dose of 1800mg/day; the usual effective dose is 900-1200mg/day. Start 75-150mg BID and titrate weekly as tolerated to effect, max 1200 BID
Neuralgia: 300mg 2or 3 times daily titrated to response or a maximum of 2000mg/day
145
Oxcarbazepine (Trileptal) Metabolism and Excretion
Dose adjusted in patients with renal impairment
146
Gabapentin (Neurontin) MOA
Unknown MAO
Thought to inhibit voltage dependent calcium channels at the alpha 2- delta subunit and inhibit neurotransmitter release
An analog of GABA. However, it does not act at GABA receptors, and it neither enhances GABA actions nor is converted to GABA.
147
Gabapentin (Neurontin) Indications
Neuropathic pain conditions
Postherpetic Neuralgia
Diabetic Neuropathy
First-line drug for treatment of PHN and PDN
148
Gabapentin (Neurontin) Side Effects
Mild drowsiness, dizziness, ataxia, weight gain, and diarrhea. Few drug interactions.
149
Gabapentin (Neurontin) Dose
2400-3600mg/day (dose 3 or 4 times daily)
Reduce dose if CrCl < 60ml/min
Neuropathic Pain: 100-300mg at bedtime titrated weekly in increments of 300mg/day to response or a maximum dose of 3600mg/day divided 3 times daily
Fibromylagia: 300mg at bedtime titrated slowly to 1200mg/day
Time to Effect: 4 week
150
Gabapentin (Neurontin)
Dose must be adjusted in patients with renal impairment
Excreted in urine unchanged
Lower dose in renal insufficiency
151
Lamotrigine (Lamictal) MOA
Blocks sodium channels as well as high voltage–dependent calcium channels
152
Lamotrigine (Lamictal) Indications
Reduce the symptoms of complex regional pain syndrome (type 1), with the sudomotor changes seen in this condition being alleviated along with pain and allodynia.
153
Lamotrigine (Lamictal) Side Effects
Nausea, drowsiness, dizziness, headache, and diplopia. Rash (Stevens-Johnson syndrome—potentially life-threatening). Broad spectrum of antiseizure activity.
Lamotrigine is associated with rare but serious skin reactions
Rapid titration to high serum concentrations of lamotrigine have been reported to cause a rash, which in some patients may progress to a serious, life-threatening reaction
Caution with OCP’s
154
Lamotrigine (Lamictal) Dosage
100-200 mg bid
(Use reduce dose in significant renal impairment)
Neuropathic pain: 50mg/day for 2 weeks followed by 50 mg twice daily for 2 weeks then titrate by 100mg/day every week to response or a maximum dose of 600mg/day (the immediate release formulation is administered in 2 divided doses)
Time to Effect: 6-8 week
155
Lamotrigine (Lamictal) Metabolism and Excretion
Dose should be reduced and titrated carefully in patients with impaired hepatic or renal function
156
Pregabalin (Lyrica) Schedule
Schedule V
157
Pregabalin (Lyrica) MOA
Binds to the α2 -δ site, an auxiliary subunit of voltage-gated calcium channels in the CNS, inhibiting excitatory neurotransmitter release.
A lipophilic GABA analog to facilitate diffusion across the blood brain barrier
158
Pregabalin (Lyrica) Indications
Diabetic peripheral neuropathy,
| Postherpetic Neuralgia, Fibromyalgia.
159
Pregabalin (Lyrica) Side Effect
Common: Constipation, Dizziness, Blurred vision, Dry mouth, Sedation
Weight gain, somnolence, , headache, weight gain, diplopia, and ataxia.
One hundred percent renal elimination.
rhabdomyolysis (rarely)
160
Pregabalin (Lyrica) Dosage
300-600 mg/day (dose 2 or 3 x daily)
Reduced dose if CrCl < 60ml/min
Fibromyalgia: initial dose of 150mg/day divided twice daily may be increased to 300mg/day within 1 week and titrated to a maximum dose of 450mg/day
Diabetic Peripheral Neuropathy: initial dose of 150mg/day divided 3 times daily may be increased to a maximum dose of 300mg/day within 1 week. Maximum dose of 600mg/day
Time to Effect: 4-6 week
Postherpetic Neuralgia: initial dose of 150mg/day divided 2-3x daily may be increased to 300mg/day within 1 week and titrated to a maximum dose of 600mg/day
161
Pregabalin (Lyrica) Dosage Metabolism and Excretion
Reduce doe in patients with renal dysfunction
| Renal excretion, no liver metabolism
162
Topiramate MOA
Blocks voltage-dependent sodium channels, and it has been shown to
increase the frequency of chloride channel opening by binding to the
GABA-A receptor agonist. High-voltage calcium currents (L type) are reduced by topiramate . It is a carbonic anhydrase inhibitor and may act at glutamate (NMDA) sites
163
Topiramate Indications
Migraine.
164
Topiramate Side Effects
Paresthesia, weight loss, nervousness, depression, anorexia, anxiety, tremor,
cognitive complaints, headache, and oligohidrosis. Few drug interactions.
Broad spectrum of antiseizure activity.
Interacts with OCP’s, DM meds, AED’s
165
Topiramate Dosage
150-200mg bid
Reduced dose if CrCl < 70ml/min
25mg daily, titrate weekly to max 200mg/d
Time to Effect: 12 week
166
Topiramate Metabolism and Excretion
Minimal liver metabolism, urine excretion
167
Valproate (Depakote) MOA
sodium channel blockade, blockade of GABA transaminase, and action at the T-type calcium channels.
168
Valproate (Depakote) Indications
Anti-epileptic
169
Valproate (Depakote) Side Effects
Weight gain, easy bruising, nausea, tremor, hair loss, weight gain, GI upset, liver damage, alopecia, and sedation. Hepatic failure, pancreatitis, and teratogenic effects have been observed. Broad spectrum of antiseizure activity.
170
Valproate (Depakote) Dosage
1000- 1200 mg/day (dose 2 or 3 x daily)
125mg QD-TID, max 500 TID
Reduce starting dose; max dose= 60 mg/kg/day
Diabetic Neuropathy: usual dose of 500mg to 1200mg/day
Time to Effect: 4 week
171
Valproate (Depakote) Metabolism and Excretion
Use with caution in patients with hepatic impairment
CYP2C9 inhibitor, urine excretion mostly
Interacts with other meds via CYP450 system and protein binding (aspirin/warfarin)
172
Clonazepam (Klonopin) MOA
Benzodiazepine—which
| binds to the GABAB receptor
173
Clonazepam (Klonopin) Indication
Utilized to treat various neuropathic pain syndrome and lower extremity muscle conditions. Useful effect in treatment of the shooting pain associated with phantom limb pain
Useful in pts w/ anxiolysis
It belongs to the benzodiazepine group of drugs,
anxiolysis and muscle relaxation may also be
produced by its use
174
Clonazepam (Klonopin) Side Effect
Somnolence is a predominant side effect, and with this drug’s long half-life, daytime sedation may complicate use.
175
Clonazepam (Klonopin) Dosage
,
176
Clonazepam (Klonopin) Metabolism and Excretion
.
177
Muscle Relaxants --> Sedatives
```
Carisoprodol (Soma)
Methacarbamol (Robaxin)
Orphenadrine (Norflex)
Metaxalone (Skelaxin)
Cyclobenzaprine (Flexeril)
```
178
Muscle Relaxants actually relaxes muscles
```
Baclofen
Benzodiazepines
Tizanidine
Dantrolene
Botox
```
179
Baclofen MOA
a muscle relaxant that is believed to affect GABA receptors at the level of the spinal cord.
the ρ-chlorophenyl derivative of
GABA. Baclofen is a GABAB agonist
180
Baclofen Indications
used for muscle spasms and spasticity, neuropathic pain
181
Baclofen Side Effects
Sedation, weakness, and confusion.
| Abrupt cessation may cause a withdrawal syndrome, such as hallucinations, anxiety, tachycardia,or seizures
182
Baclofen Dosage
Spasticity/ Pain: Initial dose of 5mg 3x daily increased in 5mg dose increments every 3 days to response or a maximum dose of 80mg/day
used intra-thecally
183
Baclofen Metabolism and Excretion
Use with caution in patient with renal dysfunction; dosage reduction may be necessary
184
Baclofen Contraindicated in patients
with history of seizures
185
Cyclobenzaprine (Flexeril) MOA
structurally similar to
TCAs and, as such, demonstrates significant
anticholinergic side effects
Centrally acting
186
Cyclobenzaprine (Flexeril) Indications
Nocturnal Muscle spasm
187
Cyclobenzaprine (Flexeril) Side Effects
anticholinergic side effects, including
lethargy and agitation, although it usually
does not appear to produce significant dysrhythmias beyond sinus tachycardia. Elderly patients seem to tolerate cyclobenzaprine less well and may develop hallucinations as well as significant anticholinergic side effects, such as sedation.
```
Side effects: Drowsiness , Cardiac dysrhythmias
– Anticholinergic
» Dry mouth
» Blurred vision
» Urine retention
» Constipation
» Increased intraocular pressure
```
188
Cyclobenzaprine (Flexeril) Dosage
Spasm: Initial dose of 5mg 3x daily increased to 7.5- 10mg 3x/day; the
Extended release capsule should be initiated at 15mg/day and may be increased to 30mg/day
Fibromyalgia: 10-30 mg at bedtime
189
Cyclobenzaprine (Flexeril) Metabolism and Excretion
Use with caution in patients with hepatic impairment; do not use the extended release capsule formulation in theses patients
190
Carisoprodol (Soma) MOA
Act as indirect agonists at the GABAA receptor, yielding CNS chloride ion channel conduction effects similar to benzodiazepines. Therefore, flumazenil may be a potentially useful antidote to carisoprodol toxicity.
Precursor of meprobamate – an anxiolytic
Centrally active
191
Carisoprodol (Soma) Indications
Useful for the short-term treatment of acute musculoskeletal disorders,
especially in combination with acetaminophen, aspirin, or NSAIDs.
192
Carisoprodol (Soma) Side Effects
Poor metabolizers of mephenytoin have a diminished ability to metabolize carisoprodol
and therefore may be at increased risk of
developing concentration-dependent side effects (eg, drowsiness, hypotension, CNS depression) at “usual” adult doses.
Side effects:
– Sedation, drowsiness, dependence
– Withdrawal like any other CNS depressant w/d
Addictive, please avoid. Junkies love to combine with hydrocodone
193
Carisoprodol (Soma) Dosage
350mg three times daily
194
Carisoprodol (Soma) Metabolism and Excretion
Carisoprodol is primarily metabolized in the liver to several metabolites, including meprobamate by N-dealkylation via CYP2C19.
195
Methocarbamol (Robaxin) MOA
Centrally active general CNS depressant
196
Methocarbamol (Robaxin) Indications
MS
Clinical effects:
Reduction of muscle spasms
197
Methocarbamol (Robaxin) Side Effects
drowsiness
198
Methocarbamol (Robaxin) Dosage
1000- 1500mg four times daily
199
Metaxalone (Skelaxin) MOA
.
200
Metaxalone (Skelaxin) Indications
Reduction in muscle spasm through CNS depression
201
Metaxalone (Skelaxin) Side Effects
Nausea
Drowsiness
Dizziness
202
Metaxalone (Skelaxin) Dosage
Daily dosage: 400-800 mg tid
203
Orphenadrine (Norflex) MOA
Analog of diphenhydramine
| Thought to work through central atropine like effects
204
Orphenadrine (Norflex) Indications
Given IV for antispasticity trials
205
Orphenadrine (Norflex) Side Effects
Anticholinergic
| Rare aplastic anemia
206
Orphenadrine (Norflex) Dosage
Daily dosage: 100 mg bid
207
Dantrolene MOA
Suppresses excitation contraction coupling by binding the ryanodine receptor and decreases intracellular calcium
208
Dantrolene Indications
treatment for NMS, MH, SS
209
Dantrolene Side Effects
sedation, hypersensitivity, pleural effusion and pericarditis, liver toxicity, seizures
210
Dantrolene Dosage
Start 25mg daily and titrate to effect as tolerated in 7 day intervals
211
Clonidine MOA
Reduces neurotransmitter release and sympathetic tone, decreases BP
212
Clonidine Indications
Best indication in sympathetically mediated pain
| Complex regional pain syndrome, cancer pain, headaches, postherpetic neuralgia, peripheral neuropathy
213
Clonidine Side Effects
.
214
Clonidine Dosage
Available in oral, transdermal, and epidural or intrathecal use form.
For pain, start 0.05mg daily to BID and titrate as tolerated
215
Tizanidine (Zanaflex) MOA
Agonist at the α2- adrenoreceptor.
| imidazoline derivative that is structurally related to clonidine
216
Tizanidine (Zanaflex) Indications
Useful for painful consitions involving Muscle Spasticity
| neuropathic pain
217
Tizanidine (Zanaflex) Side Effects
Somnolence, dry mouth, dizziness, asthenia
| Hepatotoxicity, hypotension, hallucinations
218
Tizanidine (Zanaflex) Dosage
Spasticity: Initial dose of 4mg/day increased in 2-4 mg dose increments
over 2-4 weeks; the usual dose is 8 mg every 6-8 hours with a maximum dose of 36mg/day
219
Tizanidine (Zanaflex) Metabolism and Excretion
Metabolism of tizanidine occurs primarily in the liver through oxidative processes, and
metabolites of the parent compound have no activity. Excretion of tizanidine and its metabolites occurs primarily
via the kidneys (53%-66%).
Reduced dose in patients with renal dysfunction
Use with caution in patients with hepatic impairment
Caution with SSRI’s (inhibit metabolism), especially fluvoxamine (Luvox), and ciprofloxacin
Metabolized by the liver, excretion in urine and feces
220
Glutamate is the major excitatory neurotransmitter and works via several receptors
– NMDA
– AMPA/kainate
– Metabotropic receptors (G protein and kinase cascade)
221
NMDA felt to be involved in neuroplastic changes
of developing chronic pain states
222
NMDA antagonists
– Dextromethorphan
– Memantine and Amantadine
– Methadone and Propoxyphene
– Ketamine
223
Dextromethorphan
A synthetic cough depressant that has relatively
no analgesic action and a relatively low potential for
abuse in usual antitussive doses
224
Capsacin MOA
Alkaloid Active components of chili peppers.
A member of the vanilloid family that binds to the
TRPV1 receptor
Depletes presynaptic substance P
225
Capsacin Indications
```
Chronic musculoskeletal or
neuropathic pain
Postherpetic Neuralgia
HIV neuropathy
Diabetic neuropathy
```
226
Capsacin Side Effects
Burning
Stinging
Erythema
227
Capsacin Dosage
```
Commercially available in 0.025%
and 0.075% concentration. Higher
concentration patch (8%)
Patch administered as a single 60
mins application
Cream must be applied 3-4x per
day over the entire painful area for
up to 6-8 wks before optimal pain
relief can be achieved
```
228
Capsacin Applications
Apply to painful area with gloves and avoid application to
anywhere else especially the eyes and mucous
membranes
May be useful in combination with local anesthetics by
increasing intra-neuronal access for the LA
229
Lidocaine Patch (5%) Indications
Postherpetic Neuralgia
Allodynia
Peripheral Neuropathic pain
230
Lidocaine Patch (5%) MOA
.
231
Lidocaine Patch (5%) Side Effect
Edema, erythema, abnormal
| sensation, exfoliation
232
Lidocaine Patch (5%) Dosage
Its used 12 hours ON and 12 hours OFF.
233
Botulinum Toxin
Botulinum Toxin Type A
| Potent neutotoxin
234
Botulinum Toxin
Postherpetic Neuralgia
235
NSAIDS MOA
NSAIDs are weak organic acids, consisting in one or two aromatic rings connected to an acidic functional group.
Inhibits the prostaglandin G/H synthase enzymes (COX), therefore inhibiting the synthesis of prostaglandin E, prostacyclin, and thromboxane.
Inhibit COX-1 inhibit the synthesis of TXA2
inhibit platelets prolonged bleeding time mild
below the upper limits of normal.
Inhibit COX-1 NSAIDs act mainly in the periphery, but they may have a central effect.
COX-2 induction within the spinal cord may play an important role in central sensitization.
The acute antihyperalgesic action of NSAIDs has been show to be mediated by the inhibition of constitutive spinal COX-2, which has been found to be upregulated
in response to inflammation
Act as antipyretic, analgesic, and anti inflammatory
236
NSAIDS Indications
```
Nociceptive Pain
Indicated for mild to
moderate pain, particularly of
somatic origin.
Used for soft tissue injury,
strains, sprains, headaches,
and arthritis
```
237
NSAIDS Side Effects
Main SEs: Inhibition of platelets, GI insult (dyspepsia and gastric ulceration, food helps), renal insult, and CV effects. In the kidney, prostaglandins help to maintain GFR and blood flow. They also contribute to the
modulation of renin release, excretion of water, and tubular ion transport. NSAIDs may
decrease rapidly the GFR, release of renin, which can progress to renal failure. Sodium, water retention, hyperkalemia, hypertension, acute papillary necrosis, chronic interstitial nephritis, and nephrotic syndrome can also occur. Nephrotoxcity includes reversible renal insufficiency due to renal vasoconstriction, acute interstitial nephritis , ATN in pt with low renal perfusion
NSAIDs rarely cause potentially fatal hepatic necrosis and notable
increases (ALT) or (AST) 3x. Rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis, and hepatic failure (some with fatal outcome
238
NSAIDS
.
239
NSAIDS
.
240
NSAIDS
.
241
COX-2 inhibitors (Coxibs).
.
242
COX-2 inhibitors (Coxibs) Indications
A good choice if there is any history of GI symptoms.
Coxibs are associated with less GI toxicity than standard
NSAIDs, since they do not inhibit the constitutive
COX-1 and therefore the production of the
cytoprotective PGI2 in the stomach mucosa.
243
COX-2 inhibitors (Coxibs) Side Effects
There is a possible increased risk of MI and thrombotic stroke events associated with the continuosly long-term use of coxibs. (rofecoxib and valdecoxib being withdrawn from the market). Coxibs (COX-2 inhibitors) have similar renal effects to NSAIDs. Increase serum warfarin levels
Associated with less GI toxicity than standard NSAIDs but they are more expensive
COX-2 is not present in platetelets, and coxibs are not associated with platelet dysfunction.
Celecoxib and valdecoxib are contraindicated in patients allergic to sulfonamides
244
COX-2 inhibitors (Coxibs) Dosage
Unlike ibuprofen, naproxen, and ketorolac, celecoxib does not interfere with the inhibition of platelet COX-1
activity and function by aspirin. Doses above 200mg per day have been associated with increase cardiovascular risk. high doses of celecoxib (400mg/day or more) should be avoided.
245
COX-2 inhibitors (Coxibs)
.
246
Ketorolac (Tordadol) Indications
Has been used as a short term alternative (less than 5 days) to opioids, for moderate to severe pain.
247
Ketorolac (Tordadol) MOA
potent analgesic, poor anti-inflammatory
248
Non-acetylated salicylates (Salsalate and Choline
| magnesium trisalicylate) MOA
Nonacidic prodrug metabolized to a structural analogue of naproxen
249
Non-acetylated salicylates (Salsalate and Choline
| magnesium trisalicylate) Side Effects
Minimally toxic to the GI tract, and it is the choice when GI side effects are a special concern
250
Acetaminophen MOA
An aniline derivative Induced analgesia is centrally mediated but has peripheral mechanism of action NOT anti-inflammatory
251
Acetaminophen Indications
Drug of choice for relieving mild to moderate
| musculoskeletal pain. Hip or knee osteoarthritis
252
Acetaminophen Side Effects
The liver receives the major insult from acetaminophen toxicity, with the predominant lesion being acute centrilobular hepatic necrosis. Relative contraindications: liver disease or heavy alcohol use. Max dose in these patients is 2g per day
253
Acetaminophen Dosage
OTC FDA lists the maximum daily dose
to be 4g per day but manufactures uses maximum daily dose to 3 to 3.25g per day Caution with narcotic combos
Acetaminophen overdose can lead to severe
hepatotoxicity
254
Acetaminophen Metabolism and Excretion
It is suggested the use of the glutathione precursor of N-acetylcysteine for the treatment of acetaminophen intoxication in efforts to maintain hepatic reduced
glutathione concentrations and adrenergic agonists may lower hepatic glutathione
significantly
255
Aspirin MOA
Covalently acetylates COX-1 and COX-2,
irreversibly inhibiting COX activity
Irreversibly inhibit platelet aggregation for lifetime of the platelet (4-7 days) Inhibition of platelet COX-1 (COX-2 is expressed only in
megakaryocytes) last for the lifetime of the
platelet, 8 to 12 days (10 days average) after
therapy has been stopped.
256
Aspirin Indications
.
257
Aspirin Side Effects
ASA and other salicylates are contraindicated in children and young adults (younger than 20 years) with fever associated with viral illness, owing to the association with Reye syndrome. Sensitivity of platelets to inhibition by low doses of aspirin, as low as 30 mg/d is related to their presystemic inhibition in the portal circulation before aspirin is deacetylated to salicylate on first pass through the liver. Patient allergic to ASA may also be allergic to other NSAIDs
258
Aspirin Dosage
Aspirin because of its irreversible antiplatelet effect should be stopped 10 days before elective surgery.
259
Diflunisal MOA
a difluorophenyl derivative of salicylic acid, more potent than aspirin
260
Diflunisal Indications
Used primarily as analgesic in osteoarthritis and musculoskeletal sprains, where is 3 to 4 times more potent than ASA
261
Diflunisal Side Effects
It also produces fewer and less intense GI and antiplatelet effects than ASA.
262
Indomethacin Indications
Reserve for challenging patients or those with known disease, ie gout, RA, etc
263
Indomethacin Side Effects
Intolerance limits its dosing to short-term. It also may have a direct, COX-independent vasoconstrictor effect. increased risk of MI and stroke, Very potent and worse side effect profile
264
Indomethacin Dosage
10 to 40 times more
| potent inhibitor of COX than ASA
265
Diclofenac Side Effects
Diclofenac is available in combination with
misoprostol, retaining the efficacy of diclofenac while reducing the frequency of GI toxicity; higher incidence of hepatotoxicity
266
Diclofenac Dosage
```
Topical gel (voltaren 1%) and patch (flector)
more potent than ASA; its potency against COX-2 is substantially greater than that of indomethacin, naproxen, or several other NSAIDs.
```
267
Calcitonin Indications
Used as an adjuvant drugs for Phantom limb pain, Sympathetically maintained pain, Cancer bone pain, Osteoporosis pain
268
Ziconotide MOA
non-opioid and non-NSAID analgesic
A synthetic drug with an amino acid sequence
derived from marine sea snail venom (a conopeptide), binds to a neutral N-type Ca channels
269
Ziconotide Indications
Intrathecal analgesic therapy reserved for intractable severe pain
270
Ziconotide Side Effects
Black Box warning of neurologic impairment and psychiatric symptoms
271
Ziconotide Dosage
Effective when given IV or orally
272
Botulinum MOA
two clinically available botulinum toxins in the United States are botulinum toxin type A and botulinum toxin type B.
Most evident mechanism of botulinum toxin-induced analgesia is via reduction of muscle spasm by cholinergic chemodenervation
at motor end plates and by inhibition of gamma motor endings in muscle spindles
273
Botulinum Indications
Diminished pain in patients with painful muscle spasms or cervical dystonia by
diminishing muscle tone, it is also felt that botulinum toxin may itself possess analgesic
properties
274
Botulinum
.
275
Corticosteroids (glucocorticoids) MOA
.
276
Corticosteroids (glucocorticoids) Indications
Most effective in nociceptive syndromes
277
Corticosteroids (glucocorticoids) Side Effects
```
Corticosteroids increase the risk of glaucoma by raising the intraocular pressure (IOP) when administered exogenously. ESIs were noted to cause a significant increase in the blood
glucose levels in diabetics, Mania/anxiety, Adrenal suppression, Exacerbation of
myasthenia gravis, Glaucoma
Side Effects
Kaposi’s sarcoma
Myopathy
Psychiatric disturbances
Adrenal suppression
Bronchospasm
Delayed wound healing
Immunosuppression
Osteoporosis
AVN
Fluid retention
Hypertension
Hyperglycemia
GI ulceration
exacerbation of MG
Increased IOP
Cushings
Tissue atrophy
Anaphylaxis
```
278
Corticosteroids (glucocorticoids) Dosage
For epidural injection, a crystalline depot for is used to allow for prolonged release of the
medication over time. These particles can occlude blood vessels and lead to cord infarction and stroke, especially with cervical
transforaminals . Also can cause arachnoiditis
279
Calcitonin/bisphosphonates indications
helpful in reducing pain due to bony metastases helpful in chronic neuropathic
pain states – CRPS, phantom pain
280
Pharmacological Treatment of Fibromyalgia
```
Gabapentin
Duloxetine- less effective
Amitriptyline- less effective
Pregabalin- CCB
Cyclobenzaprine
Tizanidine
TPI - less effective
```
281
Treatment of CRPS
Amitriptyline 10–75 mg/day Once a day (at night) Sedation, anticholinergic effects
Nortriptyline 10–75 mg Once a day (at night) Sedation, anticholinergic effects
Desipramine 10–75 mg/day Once a day (at night) Least sedative/anticholinergic effects
Venlafaxine 37.5–340 mg/day BID–TID
282
Anticholinergic Effects Mnemonic
Hot as a hare, blind as a bat, dry as a bone, red as a beet, mad as a hatter.
Hot as a hare: increased body temperature
Blind as a bat: mydriasis (dilated pupils)
Dry as a bone: dry mouth, dry eyes, decreased sweat
Red as a beet: flushed face
Mad as a hatter: delirium
283
Diabetic Neuropathy Treatment
Duloxetine
Gabapentin and pregabalin effective in diabetic neuropathy and postherpetic
neuralgia (PHN)
284
Anticonvulsants for CRPS
Gabapentin 900–3600 mg/day TID Somnolence, memory impairment,
tremors
Pregabalin 150–600 mg/day BID–TID Dizziness, somnolence, peripheral
edema
Carbamazepine 100–1000 mg/day BID–QID Ataxia, sedation, nausea, liver
damage, skin rash, bone marrow
285
Opioid for CRPS
Morphine (extended release) 15–60 mg BID–TID Nausea, vomiting, constipation,
sedation, pruritus
Oxycodone (extended release) 10–60 mg BID–TID Nausea, vomiting, constipation,
sedation, pruritus
Methadone 5–20 mg BID–TID Nausea, vomiting, constipation, sedation, pruritus
