2. Objectives
Identify non-narcotic and narcotic
analgesics by their generic and brand
name
List appropriate clinical applications for
non-narcotic and narcotic analgesics
List the different modalities for pain
management
Write an error free prescription for a non-
narcotic and a narcotic analgesic
3. Quiz question #1
Induction of a conformation change in the
receptor such that the agonist no longer
―recognizes‖ the agonist binding site is
accomplished by which of the following?
1. Non-competitive antagonist
0%
2. Irreversible antagonist
0%
3. Competitive antagonist
0%
4. Partial agonist
0%
5. Inverse agonist
0%
4. Quiz question #2
The concentration of the drug which induces
a specified clinical effect in 50% of subjects
is called the ____________.
1. Lethal Dose 50%
0%
2. Toxic dose 50%
0%
3. Effective dose 50%
0%
4. Therapeutic index
0%
5. Affinity
0%
5. Quiz question #3
Which of the following statements
concerning pharmacodynamics is
incorrect?
In general, as dose increases, concentration of drug at
1.
0% receptor sites increases
The pharmacological response to a drug is proportional
2.
0%
to the number of drug receptor interactions that occur
The concentration of a drug at the receptor sites
3.
0%
determines number of receptors occupied by drug
An antagonist is a drug that occupies and activates a
0% 4.
receptor, thereby producing a cellular response
0% There are a finite number of receptors on the surface
5.
of any given cell
15. Pain
Peripheral terminals of primary
afferent, somatic, and visceral afferent fibers
respond to thermal, mechanical and chemical
stimuli.
– chemical stimulations are associated with
inflammation and tissue injury
In the presence of inflammation and tissue
damage, kinins are produced and act by
stimulating bradykin receptors (B1 and B2)
– B1 receptors are induced in response to the pain
and inflammatory cytokines IL-1β, TNF-α, IL-2 and
IL-9, and to bacterial lipopolysaccharides
16. Pain
Conduction of pain signals from the periphery to
the spinal cord.
– type-Aβ neurons conduct signals rapidly and have a
low stimulus threshold to mechanical stimuli.
– type-Aδ respond to cold, heat and high-intensity
mechanical stimulation and conduct with intermediate
velocity.
– type-C fibers conduct slowly, responding multimodally
(heat, intense mechanical stimuli, or chemical
irritants)
some type-C afferents only become responsive during
inflammation
17. Pain
Descending and local inhibitory regulation in
the spinal cord
– opioid receptors (μ, δ, қ)
μ receptors are targeted for morphine (opioid)
analgesia
– norepinepherine acts on the α2-adrenergic
receptor
Clonidine can be used for pain treatment
At this time, no effective medications are
available to treat the transmission of pain
through the dorsal horn of the spinal cord
18. Pain
Peripheral sensitization:
– lowered activation thresholds
allodynia
– normally innocuous stimuli perceived as painful
hyperalgesia
– high intensity stimuli are perceived as more
painful than usual at the site of injury
– complaints of pain out of proportion to the
stimulus
19. Migraine
Pathophysiologic mechanisms are not
completely understood
Migraine can be considered the acute
manifestation of abnormal intermittent
peripheral and central excitability
The leading theory involves three events:
– 1st :
a region of neural activation followed by deactivation
travels across the cortex
– ―cortical spreading depression”
– correlates with the sensory disturbances of migraine auras
20. Migraine
2nd:
– neuropeptide release occurs in the dural
vasculature
possibly evoked by cortical excitation
3rd:
– trigeminal afferents from dural vasculature are
activated and sensitized by the local release of
neuropeptides
21. Pain Treatment
Depends on the type of pain:
– acute
– chronic
– neuropathic
(ideally) Target the specific receptors on
the specific nerves.
– How?
22.
23.
24. Pharmacologic classes for
treatment of pain
There are three broad categories of
analgesic drugs:
– non-opioid analgesics
– adjuvant analgesics
– opioid analgesics
25. Pharmacologic classes for
treatment of pain
Nonsteroidal anti-inflammatory drugs (NSAIDs)
DMARDs
TCAs
SSRIs/SNRIs
Anticonvulsants
NMDA receptor antagonists
Adrenergic agonists
5HT1 receptor agonists (triptans)
– for acute treatment of migraine
Opioid receptor agonists
27. Acetaminophen
Analgesic and antipyretic
MOA is unknown
– raises pain threshold
As effective as NSAIDs in relieving OA pain
Acetaminophen is metabolized by the liver
Oral dose for adults is 325 to 650 mg every 4 to
6 hours
– maximum daily dose is 4 grams
Pregnancy cat. B
28. NSAIDs
~ equal in terms of pain relief
inhibit both COX-1 and COX-2:
Salicylates
– aspirin, diflunisal (Dolobid), choline magnesium
trisalicylate (Trilisate), and salsalate (Disalcid)
– irreversibly bind to COX isoenzymes
Proprionic acids
– ibuprofen (Motrin), naproxen (Naprosyn), fenoprofen
(Nalfon), ketoprofen (Orudis), flurbiprofen
(Ansaid), and oxaprozin (Daypro)
– relatively lower side effect incidence than salicylates
– high incidence of GI discomfort/PUD
– naproxen has a longer ½-life
29. NSAIDs: Pharmacodynamics
analgesic, anti-inflammatory, antipyretic
Inhibit cyclo-oxygenase isoenzymes:
– COX-1, COX-2
interfere with the production of prostaglandins
– reduce activity threshold at peripheral terminals of
nociceptive primary afferent neurons.
– reduce inflammatory hyperalgesia and allodynia.
– reduce recruitment of leukocytes which produce other
inflammatory mediators.
prostaglandins act as pain-producing
neuromodulators in the dorsal horn of the spinal
cord.
30. NSAIDs: Pharmacokinetics
absorption
– 80% absorbed from GI tract
distribution
– highly protein bound
metabolism
– biotransformation in the liver
excretion
– excreted primarily in the urine
– Some biliary excretion
32. NSAIDs: Precautions & Contraindications
Precautions:
– GI, hepatic, renal disease
– dehydration
– pregnancy cat. B & C
Contraindications:
– sensitivity to ASA
– 3rd trimester of pregnancy
– recent CABG
33. NSAIDs: Adverse Reactions
non-selective COX inhibitors cause injury to gastric
mucosa and the kidneys
– the longer the patient uses the medication the greater the
potential for adverse side-effects
– certain medications have higher incidence of side effects
GI upset (nausea)
PUD
GI bleeding
Rash
Risk of cardiovascular events
Liver failure
36. NSAIDs
COX-2 selective inhibitors
– COX-2 is selectively expressed in inflammation
– the criteria used to determine if a medication is
COX-2 selective is its thromboxane activity
– 50% less incidence of PUD (GI
perforation, ulceration, bleed) than ibuprofen
– 12-hour pain relief
– celecoxib (Celebrex) 100mg BID
39. Antidepressants
Most are analgesics
Can relieve chronic pain even if the
patient has no coexisting depression
Anti-depressant effects are also
important in alleviating chronic
depression
Potentially capable of relieving all types
of pain
42. Anticonvulsants
Gabapentin (Neurontin)
– most commonly used
– side effects:
dizziness, somnolence, ataxia, confusion
– lowest effective dosing is 900mg / day
start with 100mg/day
titrate up over several weeks to avoid side effects
43. Adjuvant analgesics
DMARDs
GABA agonists:
– Baclofen interacts with the brain receptor for GABA
– used for many years as a treatment for neuropathic
pain and trigeminal neuralgia
– also used as an SMR
NMDA (n-methyl-D-aspartate) receptor
antagonists
– very important in the treatment of neuropathic pain
– dextromethorphan
– amantadine (Symmetrel)
– Ketamine
44. Adjuvant analgesics
Corticosteroids:
– Pharmacodynamics:
anti-inflammatory & immunosuppressant
stimulates the synthesis of enzymes
needed to decrease the inflammatory
response
suppresses the immune system by reducing
activity and volume in the lymphatic system
causing lymphocytopenia
45. Adjuvant analgesics
Corticosteroids:
– Pharmacokinetics:
absorption
– most are readily absorbed with peak onset is 1-2 hours
distribution
– extensively bound to plasma proteins
– only the unbound portion is active
– distributed into breast milk and through the placenta
metabolism
– by the liver into inactive metabolites
excretion
– excreted in the urine and feces as metabolites and
unchanged drug
46. Adjuvant analgesics
Corticosteroids:
– have the same effects as hormones produced by the
adrenal glands
– contraindicated in patients with systemic fungal
disease (numerous precautions)
– adverse reactions: (dosing or duration dependent)
GI irritation, increased appetite weight gain
arrhythmias, thromboembolism, heart failure
seizures
– the adverse effects from these drugs worsen with the
duration of treatment
– Pregnancy cat. C
– acute renal insufficiency may occur with
increased stress (i.e. infection, surgery, trauma)
or abrupt withdrawal after prolonged therapy
48. Adjuvant analgesics
Corticosteroids:
– methylprednisolone (Medrol)
Tabs: 2mg, 4mg, 8mg, 16mg, 24mg, 32mg
dosing: 2-60mg QD
– methylprednisolone acetate (Depo-Medrol)
Suspension: 20mg/ml, 40mg/ml, 80mg/ml
dosing: 10-80mg IV QD
– methylprednisolone sodium succinate (Solu-Medrol)
Solution (per vial): 40mg, 125mg, 500mg, 1000mg, 2000mg
dosing: 10-250mg IM or IV q4h
– dexamethasone sodium phosphate (Decadron)
commonly used to treat/prevent cerebral edema
also used intra-articular and intra-lesional injection
Solution: 4mg/ml, 10mg/ml, 20mg/ml, 24mg/ml
dosing: 10mg IV, then 4mg IM q4h x3-4 days then taper
49. Adjuvant analgesics
Muscle Relaxants:
– marketed as pain relievers for musculoskeletal pain
problems
– orphenadrine citrate (Norgesic, Norflex)
Pharmacodynamics:
– atropine-like action on the cerebral motor centers
Pharmacokinetics:
– ½-life of ~14hours
dosing: 100mg po or 60mg IV/IM q12h
– cyclobenzaprine (Flexeril)
Pharmacodynamics:
– unknown MOA but it is a CNS depressant
– potentiates the effects of norepinephrine (NE)
– exhibits anticholinergic effects similar to TCAs
Pharmacokinetics:
– ½-life of 1-3 days
dosing: 10 - 20mg BID
51. Adjuvant analgesics
Local Anesthetic Drugs:
– when injected close to a nerve, a local
anesthetic produces regional anesthesia
in the distribution of the nerve
– when taken orally or intravenously, a
local anesthetic drug can provide pain
relief
oral agents
– include mexiletine, tocainide and flecainide
IV or SC infusion of lidocaine
– used to treat neuropathic pain
52. Adjuvant analgesics
Topical Agents:
– local anesthetics are commonly used in this
way
– lidocaine (Lidoderm patch) is approved in the
U.S. for the treatment of postherpetic
neuralgia and is now being used for a variety
of other pain problems
– lidocaine and prilocaine (EMLA)
– capsaicin (Zostrix)
– ? analgesic effects from topical
antidepressants (i.e. doxepin)
– Topical NSAIDs
53. Opioid receptor agonists
Used for moderate to severe pain (7-10)
Morphine is the standard for comparing narcotic
effectiveness
All are Schedule II, III, or IV controlled substances
Pharmacodynamics:
– bind on μ receptors located in:
brain and brainstem
spinal cord
GI tract
primary afferent peripheral terminals
54.
55. Opioid receptor agonists
Interactions:
– potentiation with ETOH, CNS depressants, MAOIs, TCAs, &
anticholinergics
Common side effects:
– respiratory depression
– constipation (often a persistent problem)
– nausea and vomiting (occurs at onset but resolves quickly)
– somnolence (sedation) and fatigue
– dizziness and confusion
– pruritus
– urinary retention
– dry mouth
– sexual dysfunction
– euphoria
– hepatotoxicity
56. Opioid receptor agonists
Morphine sulfate
– oral and parenteral forms
– controlled release oral preparations provide
extended pain control over 12 24 hours
– Patient Controlled Analgesic (PCA) devices are
used for post operative, cancer, trauma, sickle
cell crisis and burn treatment
– epidural administration delivers high
concentrations in the dorsal horn of the spinal
cord resulting in much longer duration of action
– indicated for moderate to severe pain
57. Morphine sulfate
Pharmacodynamics
– Degree of effects are dosing dependent
– CNS
analgesia, respiratory depression, sedation, cough
suppression
– GI
decreased gastric, biliary, and pancreatic
secretions
decreased peristalsis
– Cardiovascular
peripheral vasodilation orthostatic hypotension
58. Morphine sulfate
Pharmacokinetics
– absorption
varies according to route of administration
onset of analgesia within 15-60 minutes
– distribution
– metabolism
primarily by the liver
– excretion
excreted in the urine and bile
Contraindications:
– impaired respiration
– paralytic ileus
59. Morphine sulfate
Precautions:
– head injury or increased ICP
– impaired renal, hepatic, thyroid, pulmonary, or
adrenal function
– elderly & debilitated
– Pregnancy cat. C
Interactions:
– potentiated by ETOH and CNS depressants
– do not use within 14 days of MAOIs
Adverse reactions:
– sedation
– constipation
– urinary retention
– respiratory depression
– orthostatic hypotension
60. Morphine sulfate
MS Contin
– Sustained release
– Tabs: 15mg, 30mg, 60mg, 100mg, 200mg
– dosing = q12h
– MS CONTIN TABLETS ARE TO BE TAKEN
WHOLE, AND ARE NOT TO BE
BROKEN, CHEWED, OR CRUSHED
TAKING BROKEN, CHEWED, OR CRUSHED MS CONTIN
TABLETS COULD LEAD TO THE RAPID RELEASE AND
absorption OF A POTENTIALLY TOXIC dosing
MSIR
– Liquid: 15mg, 30mg, 10mg/5ml, 20mg/5ml
– dosing = 5-30mg q4h
61. Opioid receptor agonists
meperidine (Demerol)
– pharmacodynamics are similar to MS
– pharmacokinetics
absorption
– varies according to route of administration
– oral is only half as effective as parenteral
distribution
– 60-80% bound to plasma proteins
metabolism
– primarily by hydrolysis in the liver
excretion
– excreted in the urine as metabolites and unchanged drug
– Tabs: 50mg, 100mg
– Liquid: 50mg/5ml
– Parenteral:
10mg/ml, 25mg/ml, 50mg/ml, 75mg/ml, 100mg/ml
– dosing: 50-150mg (po, IM, SC, IV) q3-4h
may cause convulsions with large dosings
62. Opioid receptor agonists
hydromorphone (Dilaudid)
– pharmacodynamics
acts directly on the cough center of the medulla
similar to MS
– pharmacokinetics
absorption
– varies according to route of administration
distribution
metabolism
– primarily by the liver
excretion
– excreted in the urine as metabolites and unchanged drug
– Tabs: 1mg, 2mg, 3mg, 4mg, 8mg
– Liquid: 5mg/ml
– parenteral: 1mg/ml, 2mg/ml, 4mg/ml, 10mg/ml
– Supp = 3mg
– dosing:
oral: 2 - 4mg q4-6h
parenteral: 1 - 2mg SC or IM q4-6h
63. Opioid receptor agonists
Codeine sulfate or phosphate
– much less effective for pain control then other opioids
– also used as antitussive and antidiarrheal
– pharmacokinetics
absorption
– peak analgesic effect in 30-60 minutes with a 4-6 hour duration
distribution
– crosses the placenta and enters breast milk
metabolism
– primarily by the liver through demethylation or conjugation
excretion
– excreted in the urine as metabolites and free or conjugated morphine
– pregnancy Cat. C
– numerous interactions
64. Opioid receptor agonists
Codeine sulfate or phosphate
– Tabs: 15mg, 30mg, 60mg
– Sol: 15mg/5ml (phosphate)
– Inj: 15mg/ml, 30mg/ml, 60mg/ml (phosphate)
– typically in combination with 300mg of
acetaminophen (C III)
#3 = 30mg of codeine
#4 = 60mg of codeine
elixir = 12mg codeine + 120mg acetaminophen (C IV)
dosing = 1-2 tablets q4h
– children 3-6y = 5ml
– children 7-12y = 10ml
65. Opioid receptor agonists
Oxycodone
– semisynthetic
– high potential for abuse/addiction
more effective for acute pain than chronic pain
– several active metabolites
– pharmacodynamics are similar to morphine
– pharmacokinetics
absorption
– onset of effect in 15-30 minutes with peak effect in 1 hour and 6 hour
duration
distribution
metabolism
– primarily by the liver
excretion
– excreted in the urine as metabolites and unchanged drug
67. Opioid receptor agonists
Hydrocodone
– semisynthetic
– high potential for abuse/addiction
– pharmacodynamics and pharmacokinetics are similar
to oxycodone
– Interactions:
ETOH, MAOIs, TCAs, anticholinergics
– + acetaminophen
Lortab: 2.5/500, 5/500, 7.5/500, 10/500, 7.5/500/5ml
Vicodin: 5/500, ES = 7.5/750, HP = 10/660
dosing: 1 tablet q4-6h
– + ibuprofen (Vicoprofen)
7.5/200
dosing: 1 tablet q4-6h
68. Opioid receptor agonists
methadone HCl (Dolophine)
– qualitatively similar to that of morphine
onset of action is slower but more prolonged
side effects are less severe
– indications:
treatment of moderate to severe pain not responsive to non-narcotic analgesics
detoxification treatment of opioid addiction (heroin or other morphine-like drugs)
maintenance treatment of opioid addiction (heroin or other morphine-like
drugs), in conjunction with appropriate social and medical services
– pharmacokinetics
absorption
– peak effect in 1-7 hours
metabolism
– primarily by the liver
excretion
– excreted in the urine and feces as metabolites and unchanged drug
– 35-hour ½-life
– precautions: avoid grapefruit
– dosing: 10 - 225mg QD
69. Synthetic opioid receptor agonists
Fentanyl
– significantly more potent than morphine
– short-acting
– indicated for patients with chronic/breakthrough
cancer pain
– pharmacokinetics
absorption
– varies according to route of administration
metabolism
– primarily by the liver
excretion
– excreted in the urine as metabolites and unchanged drug
72. Synthetic opioid receptor agonists
propoxyphene HCl (Darvon)
propoxyphene napsylate (Darvon N)
+ acetaminophen (Davocet, Darvocet N)
– C IV
– considered a ―mild‖ analgesic and a ―bad
drug‖
73. Synthetic opioid receptor agonists
tramadol (Ultram)
– not chemically related to opiate buts binds to opioid receptors
– inhibits reuptake of NE and 5-HT
– use to treat moderate to moderately severe pain
– pharmacokinetics
absorption
– 75% obsorption
distribution
– ~20% bound to plasma proteins
– can cross the blood-brain barrier
metabolism
– extensive
excretion
– excreted in the urine as metabolites (60%) and unchanged drug (30%)
– precautions: renal insufficiency (CrCl < 30ml/min)
– Tabs: 50mg
– + acetaminophen (Ultracet) – 37.5/325
indicated for short-term treatment of acute pain
dosing: 1-2 tabs q4-6h
74. Opioid receptor agonists
Butorphanol (Stadol)
– (occasional) competitive antagonist
– (occasional) partial μ receptor agonist
– available as a nasal spray
– pharmacokinetics
absorption
– IM - onset in <10 min; peaks in 30-60 min.
– nasal – onset in <15min
distribution
– crosses the placenta
metabolism
– primarily by the liver (hydroxylation) into inactive metabolites
excretion
– excreted in the urine and feces as metabolites
– adverse effects
may increase ICP
– dosing
IM = 1-4mg q3-4h
IV = 0.5-2mg q3-4h
nasal = one spray in one nostril
75. Opioid receptor agonist-antagonist
Nalbuphine (Nubain)
– acts on Қ agonist with μ antagonist in CNS
– use to treat moderate to severe pain
– pharmacokinetics
absorption
– onset <15 minutes
distribution
– not protein bound
metabolism
– primarily by the liver
excretion
– excreted in the urine and bile
– dosing = 10-20mg (IV, IM, or SC) q3-6h (NMT
160mg/day)
76. Naloxone
naloxone (Narcan)
– μ antagonist
– Pregnancy cat. B
– pharmacodynamics
MOA is unknown (? competitive antagonism of 1+
opioid receptors)
– pharmacokinetics
absorption
– onset of action in 1-2 minutes IV and 2-5 minutes IM
metabolism
– primarily by the liver (conjugation)
excretion
– excreted in the urine as metabolites and unchanged drug
77. Naloxone
naloxone (Narcan)
– adverse reactions:
v. fib
cardiac arrest
– indications:
used to reverse side effects of opioids
adjunct in the management of opioid overdosing
– shorter half-life than morphine
– dosing:
adult: 0.4 – 2mg (IV, IM, SC) q2-3min (NMT 10mg)
child: 0.01mg/kg IV
78. Migraine
Various treatment options
– acetaminophen
– NSAIDs
– opioid analgesics
– ergotamine
– triptans
– antiemetics
– anticonvulsants
– adjuncts
Mg sulfate
caffeine
Combination therapies work best after the
headache has started
79. Ergotamines
Nonselective 5HT1D agonist
Affinity for dopaminergic, cholinergic, and alpha-
/beta-adrenergic receptors
Adverse effects:
– vascular occlusion
– toxicity
– rebound headaches
– pregnancy cat. X
Typically combined with
phenobarbital, belladonna, and caffeine
(Cafergot)
dosing:
– 2mg SL or po, then 1-2mg q30min (NMT 6mg/24 or
10mg/wk)
80. dihydroergotamine mesylate
(DHE 45)
Used to prevent, treat, and abort migraines
Pharmacodynamics:
– vasoconstrictor (peripheral)
– alpha-adrenergic blocker
– inhibits NE reuptake
– 5-hydroxytriptamine (5HT)1D receptor agonist
Pharmacokinetics:
– absorption
onset <5min IV and 15-30min IM
– distribution
90% protein bound
– metabolism
primarily by the liver
– excretion
excreted in the urine and feces as metabolites
81. dihydroergotamine mesylate
(DHE 45)
Contraindications:
– do NOT take in conjunction with
MAOIs, ergotamines, or triptans
– elderly
– ischemic HD, angina, uncontrolled HTN
– Pregnancy Cat X
dosing:
– 1mg IM or IV qh x3 (x2 IV)
– NMT 6mg in one week
Works best when combined with an
antiemetic
82. Migraine treatments: Triptans
5HT1 receptor agonists
– 5HT1B receptors on the vascular smooth muscle of
menigeal, dural, and cerebral arteries
– 5HT1B/1D receptors in the central trigeminal nerve
terminals
prevent the release of sensory neurotransmitters
Considered an abortive therapy
– must be take early in the headache cycle (<90 min.)
work best at maximum dosing
– approximately ½ of all patients treated require repeat
dosing within 24 hours
– use long-acting preparations for:
delayed intensity, menstrual migraines, frequent recurrence
83. Migraine treatments: Triptans
Not recommended for anyone <18 years old
Pregnancy cat. C
Do not use more than 6-8x per month
Adverse effects:
– warmth/flushing
– ―burning‖ or ―tightness‖ in the chest, face, or limbs
Contraindications:
– ischemic HD
– cerebral or peripheral vascular disease
– uncontrolled HTN
– concomitant MAOIs or ergotamines
No association between triptans and CVA, CV
events, and death
84. Triptans
Pharmacodynamics
– vasoconstriction of the cranial blood vessels
– inhibition of pro-inflammatory neuropeptide release
Pharmacokinetics
– absorption
varies according to route of administration
– distribution
~ 15 - 25% protein bound
– metabolism
primarily by the liver
– excretion
excreted in the urine and feces as metabolites
85. Triptans
sumatriptan (Imitrex)
– binds to 5HT1B receptors
– 2 hour ½-life
– oral, nasal, and parenteral preparations
– efficacy is 50-85% at 2 hours
– interactions:
ergots & MAOIs
– adverse reactions:
a. fib; v. fib; v. tach; MI
– dosing: 6mg SC (can repeat after 1 hour prn)
86. Triptans
zolmitriptan (Zomig)
– high affinity binding to 5HT1B and 5HT1D receptors
– 2 hour ½-life
– prodrug: converted into active N-demethyl metabolite
maximum concentration achieved in 2-3 hours
– oral and nasal preparations
– efficacy is 60-70% at 2 hours
– interactions:
cimetidine doubles the ½-life
SSRIs may cause weakness, hyperreflexia, incoordination
MAOIs increase plasma concentration
– dosing: 2.5mg po (can repeat after 2 hours prn)
87. Migraine
naratriptan (Amerge)
– high affinity binding to 5HT1B and 5HT1D receptors
– 6 hour ½-life
– oral form only
– efficacy is 40-50% at 2 hours
– adverse reactions:
abnormal ECG changes
– prolonged PR and QT intervals
– ST/T wave changes
– a. flutter; a. fib; PVCs
– dosing: 1 - 2.5mg po (can repeat after 4 hours)
88. Triptans
rizatriptan (Maxalt)
– high affinity binding to 5HT1B and 5HT1D receptors
– 2 hour ½-life
– pharmacodynamics/–kinetics are similar to
zolmitriptan
– oral preparations only (completely absorbed)
mean absolute bioavailability is about 45%
mean peak plasma concentrations are reached in ~ 1 - 1.5
hours
efficacy is 60-75% at 2 hours
– dosing: 5 - 10mg po (can repeat after 2 hours)
89. Triptans
almotriptan (Axert)
frovatriptan (Frova)
26 hour ½-life
eletriptan (Relpax)
high affinity binding to 5HT1B/5HT1D/5HT1F
receptors
oral preparations only
– well absorbed with peak plasma levels after ~1.5 hours
– mean absolute bioavailability is ~ 50%
90% non-renal clearance
dosing: 20 – 40mg po (can repeat after 2 hours)
90. Migraine treatments
Other agents:
– butalbital, acetaminophen & caffeine
50/325/40 (Fioricet, Esgesic)
50/500/40 (Esgesic-plus)
– butalbital, aspirin & caffeine
50/325/40 (Fiorinal)
CIII
– dosing: 1 or 2 po q4h
– isometheptene 65mg, dichloralphenazone
100mg, acetaminophen 325mg (Midrin)
indicated for tension & vascular headaches
contraindications:
– glaucoma
– severe cardiac, renal, or hepatic disease
– uncontrolled HTN
– concomitant MAOIs
dosing: 2 po stat, then 1 qh prn x3 (NMT 5 per 12 hours)
91. Migraine
Other options:
– Botox
– trigger point injections
– occipital nerve block
– sphenopalatine ganglion block
– olanzapine (Zyprexa)
―rescue‖ drug
thienobenzodiazepine derivative
DA1-4 and 5HT2A/2C agonist
95. Quiz question #4
A 19-year-old male arrives to the ED via EMS. He is
unconscious but responds to painful stimuli. His pupils are
constricted and respirations are depressed. You not
several needle marks on his arms. Which of the following
medications should you order?
1. Propoxyphene
0%
2. Naloxone
0%
3. Tramadol
0%
4. Carbamazepine
0%
5. Nalbuphine
0%
96. Quiz question #5
After administering the Naloxone the patient
immediately regains consciousness. This
medication was effective because _____.
1. The patient was suffering from a cocaine
0%
overdose
2. Naloxone binds to the opiate and inactivates
0%
it
3. Naloxone is a CNS stimulant
0%
4. Naloxone antagonizes opiates at the receptor
0%
site
5. Naloxone immediately activtes μ, κ, and δ
0%
receptors
97. Quiz question #6
NSAIDs act primarily by which of
the following mechanisms?
1. They inhibit cyclooxygenase
0%
2. They antagonize μ receptors
0%
3. They reduce prostoglandin synthesis
0%
4. They block neurotransmission
0%
5. They produce vasodilatation
0%
98. Case Study #1
45-year-old female with a long-standing history of
chronic pain walks into your emergency department
in ―severe‖ generalized pain (10+/10). She denies
any trauma or other reason for the exacerbation of
her chronic symptoms. She has taken 1-2 Percocet
every 4 hours for the past two days without relief.
She is a 1½ ppd smoker and consumes moderate
quantities of EtOH. She denies other drug use.
VSS. Every place you palpate is tender but she
has no obvious signs of injury. The remainder of
your exam is unremarkable. She demands IV
narcotics.
What factors are influencing this pt’s pain control?
What do you prescribe?
99. Case Study #2
23-year-old female college student presents with
her ―worst headache ever‖ (10/10) that started this
morning. She has associated nausea &
photophobia. PMH is significant for periodic
migraine headaches which have been the same as
this headache but not as severe. She is under a lot
of stress at school and from her fiance’. Non-
smoker and rare EtOH. VSS. PERRLA with
moderate photophobia. CN II-XII are grossly intact.
Equal strength bilaterally.
What is your Dx?
What is your next recommendation?
100. Which of the following medications
would be the best first line treatment for
this patient (Case #2)?
1. Ibuprofen 600mg orally
0%
2. Sumatriptan 6mg SC
0%
3. Sertraline 50mg orally
0%
4. Zolmitriptan 2.5mg orally
0%
5. Meperidine 50mg IM
0%
101. Case #3
A 32-year-old woman complains of daily headaches. The
headaches vary in severity, but she usually has severe
headaches (8/10 on a visual analog scale) once or twice a
week; she describes the latter as severe throbbing or
pounding pain on the top of the head but also involving the
occipital and frontal areas—and occasionally one or the
other temple. These episodes, which are usually associated
with some nausea and sensitivity to bright light and loud
noises, typically last up to 48 hours if untreated.
The patient also has headaches that are not nearly as
severe (3-4/10 on the VAS) but are almost constant. She
describes them as mild to moderate, dull, pressure-like pain
located primarily on the top of her head and occipital area
bilaterally. She is able to function with these headaches
more easily than with the severe ones, although she
sometimes needs to use over-the-counter (OTC)
medications to lessen the intensity of the pain.
102. Case Study #3
She started having severe episodic headaches in her early
20s; these became progressively more frequent. In addition
to the increasingly frequent severe headaches, about 5
years ago, she began having milder headaches as well.
These also became gradually more frequent—and
eventually occurred daily. She has had daily headaches for
about 2 years.
She has been using oral sumatriptan, 100 mg, for her
severe headaches and notes that this reduces the severity
of the pain significantly within 1 to 2 hours when she is able
to take the medication shortly after pain onset.
However, she seldom takes it early enough to have this
effect. She uses OTC acetaminophen or ibuprofen for her
milder headaches once or twice a day, about 2 days a
week.
Results of physical and neurologic examinations and MRI
and CT scans of the head are all normal.
104. Case Study #4
26-year-old male presents via EMS in full spinal
immobilization secondary to a high-speed MVA.
He is obtunded but responds to verbal stimuli. He
had a brief LOC at the scene. He ―hurts all over‖
(8-9/10) but sensory and motor function are intact.
VS: B/P – 108/70 mmHg; P – 96bpm, regular;
R – 20, shallow; T – 98.9 F orally;
SpO2 – 96% RA
PE reveals a fracture of the right femur, 2
fractured ribs, and a dislocation of the left
shoulder.
What is your recommendation for pain
management?
105. A 24-year-old female G1P0 at 36 weeks gestation complains of
back pain (3-4/10) and generalized muscle aches. She admits
that she ―over did it‖ yesterday working around the house. She
has taken two 650mg doses of acetaminophen without relief.
She denies any problems with her pregnancy and has had
regular pre-natal checkups. VSS. P.E. is unremarkable except
for some mild paravertebral tenderness in the L4-S1 region.
Which of the following treatments should you prescribe to
control her pain?
Acetaminophen 1000mg every four hours prn pain
1.
0%
Ibuprofen 600mg every six hours prn pain
2.
0%
Tylenol w/ codeine #3 two every six hours prn pain
3.
0%
Orphenadrine citrate 100mg one every 12 hours
4.
0%
Methylprednisolone 8mg daily
5.
0%
Vicodin one every fours hours prn pain
6.
0%
106. Case Study #5
Bob is a 52-year-old salesman at Lowe’s.
He has mild, generalized osteoarthritis.
He has been previously evaluated on a
couple of occasions, but you don't remember the full
details, apart from him having had back pain. When you
arrive in the exam room, Mr Jones is lying supine on the
exam table with his knees bent.
He states he was changing the TV channel when he felt
a ―click‖ in his back and was immediately unable to
move. He is currently experiencing lumbosacral back
pain, spreading up into his dorsal region and down into
his buttocks.
He takes 600mg of Ibuprofen BID for his OA
NKDA
107. Case Study #5
VSS
On examination he lies stiff and motionless and
he is anxious and diaphoretic. Neurological
examination of his lower extremities reveals
slightly diminished strength (5+)
bilaterally, normal sensation, and severe back
pain on straight leg raising. Reflexes are 2+
bilaterally.
Next step?
Rx?
108. If you were going to give him
painkillers, what might you consider?
1. Acetaminophen
0%
2. NSAIDs
0%
3. COX-2 inhibitors
0%
4. Tramadol (Ultram)
0%
5. Opioids
0%
6. None of the above
0%
109. If you were going to give her
painkillers, what else might you
consider?
1. Anticonvulsants
0%
2. Amitriptyline (Elavil)
0%
3. Hypnotics
0%
4. Skeletal muscle relaxants
0%
5. None of the above
0%
110. Case Study #6
Julie Smith is a 45-year-old female with a long history of
mild chronic low back pain. She is in the clinic today
because it has got a lot worse in the last 6 months. Past
medical history is significant for irritable bowel
syndrome, a sero-negative arthritis, and chronic
headaches. In the past she has suffered from alcoholic
abuse and was also addicted to Diazepam.
However, she has been successfully weaned off both
alcohol and Diazepam.
The back pain is now debilitating and she cannot do
some of her household jobs and cannot drive for more
than 5 minutes. There is no radiation into the legs. She is
stiff in the morning when she wakes and the pain then
gets worse over the day with activity. It remains
throughout the night, and keeps her awake.
111. Case Study #6
She weighs 192 pounds and is 66‖ tall.
On examination she has marked tenderness
throughout the back, her paravertebral muscles
are extremely tight and tense, and she has a
mild scoliosis to the left.
Pain is present on axial loading and on straight
leg raising to 45 degrees bilaterally but she can
sit to 90 degrees. She puffs and pants
throughout the examination.
Next step?
112. Case Study #6
A straight X-ray of her lumbar spine shows
disc degeneration at L4/5 and L5/S1.
ESR is normal. She has a mild iron
deficiency anemia. Other bloodwork is
normal.
Next step?
– does she require further investigation?
MR scan shows disc bulging at S1 without
neural encroachment.
113. What is your primary
management of this patient?
1. Tell her to ―work through the pain‖
0%
2. Tell her to lose weight
0%
3. Prescribe analgesics
0%
4. Refer her to a neurosurgeon
0%
5. Refer her for physiotherapy for TENS
0%
6. Get a psychological opinion
0%
7. Carry out a nerve block
0%
114. If you were going to give her
painkillers, what would you prescribe?
1. Acetaminophen
0%
2. NSAIDs
0%
3. COX-2 inhibitors
0%
4. Tramadol (Ultram)
0%
5. Opioids
0%
6. None of the above
0%
115. If you were going to give her
painkillers, what else might you
consider?
1. Anticonvulsants
0%
2. Amitriptyline (Elavil)
0%
3. Hypnotics
0%
4. Skeletal muscle relaxants
0%
5. None of the above
0%
116. Case Study #7
Barbie Dawl is a 35-year-old female who presents to a walk-
in clinic with ―severe‖ (8/10) neck pain. She is in ―good‖
general health. At the clinic, Miss Dawl was observed lying
on the bed, grimacing in pain, and looking very stiff. She
states that she was involved in a minor car accident two
days earlier when she was driving home from work. She did
not seek treatment and was fine until yesterday morning
when her neck pain began and continued to get worse
throughout the day. The pain is now spreading up into the
back of the head and over the eyes and is both constant
and severe. She feels dizzy when she tries to get up to go to
the bathroom, and has pains shooting down the left arm and
into the ring and little finger.
A divorced mother of two, she has a part time checkout job
at a local supermarket. Her stress levels are ―fairly high‖
particularly in association with her unsatisfactory marriage
and her financial difficulties since the divorce.
117. Case Study #7
Meds: None
Allergies: Tylenol #3, Penicillin, Aspirin
VSS
Examination reveals a very stiff neck but she
can be coaxed into moving it. The pupils are
equal, round, and react to light. Range of motion
is decreased in BUE but seems restricted only
by pain. Muscle strength in the LUE is 4+ and in
the RUE is 5+. Reflexes are 2+ bilaterally.
Next step?
118. What is the management of this
patient? Do you:
1. Tell her to ―work through the pain‖
0%
2. Send her for X-rays of the neck
0%
3. Prescribe analgesics
0%
4. Refer her to a neurosurgeon
0%
5. Refer her for physiotherapy for TENS
0%
6. Get a psychological opinion
0%
7. Carry out a nerve block
0%
119. Case Study #7
She is sent to your Emergency
department by ambulance.
X-rays are taken of her cervical spine
which are read as normal.
After three or four hours waiting for an
assessment and X-rays, her pain has
begun to settle somewhat.
Next step?
120. If you are going to give her painkillers,
what would you prescribe?
1. Acetaminophen
0%
2. NSAIDs
0%
3. COX-2 inhibitors
0%
4. Tramadol (Ultram)
0%
5. Opioids
0%
6. None of the above
0%
121. If you are going to give her
painkillers, what else might you
consider?
1. Anticonvulsants
0%
2. Amitriptyline (Elavil)
0%
3. Hypnotics
0%
4. Skeletal muscle relaxants
0%
5. None of the above
0%
122. Case Study #7
She is given a cervical collar and
analgesics, and advised to go home and
rest for two days.
Miss Dawl comes back to the walk-in clinic
to see you a week later, complaining of
ongoing neck pain, headache, and a
heavy feeling in the left arm. She is
continuing to use the collar and asks for
more pain killers and a release from work.
Next step?
123. What is the management of this
patient? Do you:
1. Tell her to ―work through the pain‖
0%
2. Prescribe analgesics
0%
3. Refer her to a neurosurgeon
0%
4. Refer her for physiotherapy for TENS
0%
5. Get a psychological opinion
0%
6. Carry out a nerve block
0%
124. If you are going to give her
painkillers, what would you prescribe?
1. Acetaminophen
0%
2. NSAIDs
0%
3. COX 2 inhibitors
0%
4. Tramadol (Ultram)
0%
5. Opioids
0%
6. None of the above
0%
125. Case Study #8
An 88-year-old retired lawyer comes to see you
complaining of severe (6/10) lower back pain spreading
down the back of his legs to his feet when he walks. He
denies any trauma but notes that the pain began after
playing in a golf tournament. He denies urinary or fecal
incontinence.
In the last 3 weeks, he has been unable to play even 9
holes and the pain is now so severe that he has to drive
a golf cart instead of walking the course. He is a very
keen golfer who plays and lives locally. He tells you that
he lives for his golf, and he wants to get back to it, and if
this is impossible his life really isn’t worth continuing on
with. There is no quality to his life as all of his interests
revolve around golf, including his social circle.
126. Case Study #8
He was widowed 10 years ago, but is of sound
mind and in ―good‖ general health.
PMH is significant for HTN, OA, cirrhosis, and
CRI (CrCl = 40ml/min).
He is 6 months S/P 3-vsl CABG.
Ex-smoker. 3-4 alcoholic beverages QD.
Meds:
– Vaseretic 10-25 one QAM
– Excedrin two tablets QAM
– MVI
NKDA
127. Case Study #8
VS: B/P = 108/60mmHg RUE, sitting; P = 60 bpm; R = 12
breaths/min
On examination he moves stiffly. Spine is midline but he
has mild kyphosis. Paravertebral tenderness is present at
L4-S1. Neurological examination of his lower extremities
reveals diminished strength (4+) bilaterally, normal
sensation, and severe back pain on straight leg raising.
Reflexes are 1+ bilaterally.
Next step?
Rx?
128. If you choose pain-relieving techniques,
what do you think would be appropriate?
1. TENS or acupuncture
0%
2. NSAIDs
0%
3. Cox-2 inhibitors
0%
4. Acetaminophen
0%
5. Opioids
0%
6. Nerve block
0%
7. Surgery
0%
129. You decide to prescribe non-narcotic
analgesics. Which of the following should you
choose?
Ibuprofen 800mg three times daily
1.
0%
Celecoxib 200mg twice daily
2.
0%
Diclofenac 50mg three times daily
3.
0%
Tramadol 100mg every morning
4.
0%
Acetaminophen 1000mg four times daily
5.
0%
None of the above
0% 6.
130. You decide to prescribe a narcotic analgesic.
Which of the following would you choose?
Darvocet N-100 one every four hours prn
1.
0%
Meperidine 50mg one every four hours prn
2.
0%
Fentanyl 75mcg/hr transdermal Q3D
3.
0%
Percocet 5/325 one every six hours prn
4.
0%
Vicodin 7.5 one every six hours prn
5.
0%
Tylenol #3 two every six hours prn
6.
0%
131.
132. Thought for the day…
If you have a lot of tension and
you get a headache, do what it
says on the aspirin bottle:
―Take two aspirin‖
and
―Keep away from children.‖
--Author Unknown
