Transcript Pharmacological Approaches in Pain Management

Pharmacological Approaches in
Pain Management
Ryan J. Bickel, Pharm.D., BCPS
updated by
David G. Curry, PhD, APRN for
NUR344, Fall, 2009
Used with permission
Learning Objectives
• Review common non-opioid, opioid, and
adjuvant analgesic medications
• Discuss and apply equianalgesic dosing
concepts to selected case studies
WHO Pain Ladder
http://erlewinedesign.com/end-of-life-care/gfx/who_ladder.gif
Non-Opioid Medications
• “Ceiling effect” to
analgesia
• Do not produce
tolerance or physical
dependence
• Exhibit antipyretic
properties
Ref. 1
Acetaminophen (APAP)
• Mechanism of action unclear
• No anti-inflammatory effects
• Causes liver toxicity at high doses
– Max dose: 4 gm/day, if no liver disease
– Newest recommendation 2.6 gm/day
• Decreases opioid requirements
Ref. 1,2
Salicylates
Aspirin (ASA)
• Effective as APAP for
acute pain at similar
doses
• Worse side effect
profile than APAP
Salicylate Salts
• Safer than ASA
• No platelet effects
• Examples:
– Diflunisal (Dolobid)
– Magnesium salicylate
(Doan’s)
Ref. 1,3
NSAIDs
• Efficacy is similar amongst NSAIDs
• Differences in potency, time of onset, &
duration of action
• Side effects:
– GI bleeding
– renal dysfunction
– platelet dysfunction
Ref. 1,3
NSAIDs
Ibuprofen (Motrin)
• initial choice for acute pain due to cost &
safety
• GI safety profile similar to placebo in doses of
<1200 mg/day
• Maximum daily dose ~ 3200 mg/day
• Now available in IV form (Caldolor)
Ketorolac (Toradol)
• first parenteral NSAID available in U.S.
• use limited to <5 days due to side effects
Ref. 2,3
COX-2 Inhibitors
• Selectively inhibit cyclooxygenase-2
– less GI irritation; less platelet effects
– other side effects similar to NSAIDs
• Celecoxib (Celebrex)
– Role: patients with low cardiovascular risk
who require NSAID therapy & are at
increased risk for GI toxicity
Ref. 4
Opioids
• Originally derived from
poppies
• Body possesses
endogenous opioids
– enkephalins
– endorphins
• Opiate Receptors
–
–
–
–
mu ()
delta ()
kappa ()
sigma ()
Papaver somniferum
Ref. 2,5
Pharmacology of Opioids
• 1: inhibit transmission of pain
• 2: respiratory depression, euphoria,
constipation, physical dependence
• : inhibit transmission of pain
• : inhibit transmission of pain
• : autonomic effects, dysphoria,
hallucinations
Ref. 5
Common Side Effects of Opioids
Constipation
• very common, tolerance is unlikely
• stool softeners + stimulant +/metoclopramide
Nausea/Vomiting
• tolerance usually develops
• pretreat with prochlorperazine
Ref. 6
Common Side Effects of Opioids
Urticaria/Pruritis
• due to histamine release
• treat with antihistamine
Sedation
• tolerance usually develops
Delirium
• rare in patients with normal renal
function
Ref. 6
Side Effects of Opioids
Respiratory Depression
• preceded by somnolence
• tolerance develops
• use caution in patients with underlying
pulmonary dysfunction
• if RR <8 bpm, consider naloxone
(Narcan)
Ref. 6
Morphine
•
•
•
•
Gold standard of opioid therapy
Half-life: 1.5 -2 hrs
Duration: 3 - 5 hrs
Metabolized to a renally excreted active
metabolite
– dose adjustment may be needed in renal
failure
Ref. 7
Morphine
• Multiple dosage forms available
– extended-release cap/tab
• Avinza: once daily dosing
• Kadian: daily or q12h dosing
• MSContin, Oramorph SR: q8-12h dosing
– Immediate-release tab
– oral suspension (Roxanol)
– suppository (RMS)
– parenteral injection (Duramorph, Infumorph)
Ref. 7,8
Hydromorphone (Dilaudid)
• Alternative to morphine
– safe in renal failure
– more soluble than morphine
• Good choice when opioid volume is an
issue
– opioid tolerant patients
– cachectic patients
• Forms: parenteral, tab, suppository
Ref. 7,9
Oxymorphone (Opana)
• Highly selective for mu receptor
• More potent than morphine
• Forms:
– immediate release tab
• do not take with meals
– extended-release tab
• do not take with meals or alcohol
– parenteral
Ref. 8,9
Codeine
• Indicated for mild-moderate pain
– weak opioid activity itself
– usually combined with acetaminophen
• Metabolized to morphine by the liver (2D6)
– poor metabolizers (lack 2D6)
– ultra-rapid metabolizers (2D6 gene duplication)
• Side effects limit use
– Primarily nausea/vomiting or constipation
Ref. 2,10
Codeine Derivatives
• Used in moderate-severe pain
• Hydrocodone
– combined with acetaminophen (Lorcet, Lortab,
Norco, Vicodin, Zydone)
– watch amount of acetaminophen (max: 4 gm/day)
• Oxycodone
–
–
–
–
extended-release tabs (OxyContin)
immediate release caps/tabs (OxyIR, Roxicodone)
oral solution (Oxyfast, Roxicodone)
combination products (Percocet, Percodan, Tylox)
Ref. 1,2,8
Meperidine (Demerol)
Not a first line agent!
• Variable oral bioavailability
• Short duration of action
• Relatively low potency
• Neurotoxic metabolites
– Normeperidine has very long half-life!
• Multiple drug interactions
Ref. 11,12
Meperidine
• Borgess Usage Guidelines
– Do not use for over 48 hrs
– Maximum dose: 600 mg/24 hr period
– Avoid in patients with renal dysfunction or a
history of seizures
• Oral use discouraged
Fentanyl
• Highly lipophilic
• Causes less histamine release than other
opioids
• Unique dosage forms/delivery devices
– buccal tablet (Fentora)
– lozenge (Actiq)
– transmucosal film (Onsolis) – restricted use
in US at the present time
– transdermal patch (Duragesic)
Ref. 7-9
Fentanyl Transdermal Patch
Advantages:
– sustained-release opioid
– good in patients with poor compliance
– good choice if concerned about drug abuse
Disadvantages
– delay in onset
– residual activity after patch removed – must
remove old patch!!
– expensive
Note: Heat increases rate of release from patch
Ref. 2,13
Methadone (Dolophine)
• Not a first-line opioid
• Non-opioid actions provide additional
analgesia
• Half-life: 22 hrs
• Duration: 3-6 hrs (initial) ;8-12 hrs (chronic)
• Pros: cheap; good for refractory pain
• Cons: unpredictable; difficult to dose; drug
interactions
Ref. 12,14
Propoxyphene (Darvon)
•
•
•
•
Not a first line agent!
Neurotoxic metabolite
Long half-life
Propoxyphene-APAP (Darvocet)
– not much more efficacious
than APAP alone
Ref. 2,3
Mixed Agonist-Antagonists
• Not a first line agent
– causes withdrawal in
patients on opioids
– ceiling effect on
analgesia
– psychotomimetic
adverse effects
Examples:
• Butorphanol (Stadol)
• Pentazocine (Talwin,
Talwin NX)
• Buprenorphine
(Buprenex)
• Lower abuse
potential
Ref. 7
Tramadol (Ultram)
•
•
•
•
Dual mechanism of action
Used for moderate pain
Less respiratory depression than opioids
May enhance risk of seizures
– max dose: 400 mg/24 hrs
– decrease dose in elderly & renally impaired
Ref. 5,8
Adjuvant Pain Medications
“drugs that are used
primarily for treating
conditions other than
pain, but may be
analgesic in selected
circumstances”
-AMA
Ref. 1
Common Adjuvant Medications
•
•
•
•
•
•
Antidepressants
Anticonvulsants
Corticosteroids
Topical Anesthetics
Calcitonin
Bisphosphonates
Ref. 1
Pharmacokinetics of Routes
Ref. 6
Equianalgesic Table
Opioid
IM/IV
Oral
(mg)
(mg)
10
30
Not Available
20
1
10
Hydromorphone
1.5
7.5
Fentanyl
0.1
Not Available
Meperidine
75
300
Not Available
20
120
200
Morphine
Oxycodone
Oxymorphone
Hydrocodone
Codeine
Ref. 8,15
Equianalgesic Dosing
Methodology
• Total the 24-hour dose of current opioid
usage including prn doses
• Convert for drug & route using table
• Reduce calculated dosage 30-50%
• Calculate breakthrough pain dose, if
converting long-acting opioids
– 5 – 15% of total daily opioid dose
Ref. 15,16
Equianalgesic Case 1
MJ is a 56 YOM with prostate cancer
admitted to hospital for pain control. He
was started on a morphine PCA. In the
last 24 hours the patient has received 34
mg and his pain has been adequately
control. The physician discontinued the
PCA and started the patient on MSContin
30 mg PO BID. Is this an equivalent
regimen?
Equianalgesic Case 1
Table IV dose
Table PO dose
=
Pt 24 hr IV dose
X amount of PO
Equianalgesic Case 1
Opioid
IM/IV
Oral
(mg)
(mg)
10
30
Not Available
20
1
10
Hydromorphone
1.5
7.5
Fentanyl
0.1
Not Available
Meperidine
75
300
Not Available
20
120
200
Morphine
Oxycodone
Oxymorphone
Hydrocodone
Codeine
Ref. 8,15
Equianalgesic Case 1
Set up proportion
10 mg IV
34 mg IV
Cross multiply
10 mg IV
34 mg IV
=
30 mg PO
X
=
30 mg PO
X
Equianalgesic Case 1
10X = 1020
Divide each side by the number in front of X:
10X
=
10
1020
10
X = 102
Select Reasonable Regimen
MS Contin 45 mg PO BID
Equianalgesic Case 1
Calculate the oral morphine dose needed
for breakthrough pain
Answer: Morphine 5 – 15 mg PO every 4
hours prn pain
Equinalagesic Case 2
PJ is a 47 YO female who is receiving
morphine 2-6 mg IV q2h prn post-op. In
the last 24 hours, the patient has
received 24 mg IV morphine. Surgery
just dc’d the morphine & ordered Lortab
5/500 mg 1-2 tabs PO q6h PRN pain.
What do you think of this regimen?
Equinalagesic Case 2
Convert to oral morphine:
10 mg IV
30 mg PO
=
24 mg IV
X
10X = 720
X = 72 mg PO morphine
Equinalagesic Case 2
Convert to hydrocodone:
30 mg MS
20 mg HC
=
72 mg MS
X
30X = 1440
X = 48 mg hydrocodone
Equinalagesic Case 2
Dose Reduction
– Suggested daily hydrocodone dose for BR
24 – 36 mg/day
Assessment
– BR’s current hydrocodone dose if given
q6h scheduled = 20 – 40 mg
Questions
References
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