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An evidence-based review of the pharmacology of inpatient pain management with focus on opioid therapy. Geared towards advance medical students and housestaff.
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Kyle P. Edmonds, MD
Doris A. Howell Palliative Care Consult Service
UC San Diego Health System
PAIN PEARLS & PET PEEVES
2
DR. DORIS A. HOWELL PALLIATIVE CARE CONSULT
SERVICEDr. Doris Howell, pediatric
oncologist.Multi-disciplinary teamFor those with life-threatening disordersComplex CommunicationExpert symptom mgmtClarifying goals of care
OBJECTIVESDescribe the concept of the pain ‘elevator.’List the principles for dosing constant and breakthrough pain.
Name the most common unwanted effect of opioid therapy.
Describe the principle for titration of drips.
International Association for the Study of Pain ( IASP ):
“An unpleasant sensory and emotional experience
associated withactual or potential tissue damage.”
PAIN
5
PEEVE: THE PROCEDURE WASN’T EVEN THAT BAD!
BASIC STEPS: PAIN PROCESSING
TransductionTransmissionPerceptionModulation
7
“TOTAL PAIN”
Pain
Disease Mgmt
Physical
Psych
SocialSpiritual
Practical
EOL Worry
8
PEARL: EXPERIENCES MODULATE PAIN PERCEPTION
9
PEEVE: THEY’RE ON ‘NARCOTICS.’
PAIN MANAGEMENT: DEFINITIONS
Opioid: anything that binds the opioid receptor
Opiate: derived from the opium poppy (Papaver somniferum)
Narcotic: archaic term, associated with illicit use
10
11
PEARL: WE SOUND SMARTER WHEN WE SAY “OPIOID.”
12
PEARL: MEDS ARE CHOSEN BASED UPON LEVEL (AND TYPE) OF PAIN.
GUIDING THERAPY
DiagnosisAssessmentEfficacySafety / tolerabilityEase of useCost
WHO LADDER ELEVATOR
1, Pain 1 – 3
2, Pain 4 – 6
3, Pain 7 – 10
Morphine
Hydromorphone
Fentanyl
OxycodoneMethadone
± Adjuvants
Tramadol
A / Hydrocodone
A / Oxycodone
± AdjuvantsAcetaminophen
NSAID’s
± Adjuvants
WHO. Geneva, 1996.
OPIOID ADVERSE EFFECTS
CommonConstipation
Dry mouthNauseaSedationSweats
UncommonBad dreams / hallucinations
DeliriumMyoclonus / seizurePruritis / urticarialRespiratory depressionUrinary retention
Pla
sma
Co
nce
ntr
atio
n
0 Time
STAGES OF RESPIRATORY DEPRESSION
Sedation
Bradypnea
Death
Awake & in Pain
17
PEARL: RESPIRATORY DEPRESSION IS UNCOMMON IF DOSED PROPERLY.
18
PEEVE: MORPHINE IS TOO STRONG SO I GAVE THEM TWO PERCOCET.
EQUIANALGESIC DOSES
Oral/Rectal Analgesic IV/SC/IM
15 Hydrocodone --
15 Morphine 5
10 Oxycodone --
3 Hydromorphone 1
19
20
PEARL: OPIOID FORMULATIONS DIFFER IN POTENCY.
PAIN MANAGEMENT PRINCIPLES
Don’t delay control Unmanaged pain
nervous system changes
Treat underlying cause
22
BRACE YOURSELVES FOR PHARMACOLOGY.
Pla
sma
Co
nce
ntr
atio
n
0 Time
AbsorptionExcretion
First Order KineticsWhen biological effect
follows plasma concentration
Pla
sma
Co
nce
ntr
atio
n
0
Maximum Concentration ( Cmax )
20
10
= maximum concentration during the dosage interval
Cmax
Time ( hours )
Pla
sma
Co
nce
ntr
atio
n
0 Time ( hours )
Time to MaximumConcentration ( t Cmax )
20
10
1
= time it takes to get to maximum concentration
Cmax MorphinePO / PR
Cmax = 1 hour
Pla
sma
Con
cen
trat
ion
0 Half-life (t1/2) Time
IV
PO / PR
SC / IM
60min
Time to MaximumConcentration ( t Cmax )
30min
10min
Pla
sma
Co
nce
ntr
atio
n
0
Half-Life ( t ½ )
Morphineall routes
t ½ = 4 hours
20
10
= time it takes for the body to excrete half the dose
Time ( hours )4
Pla
sma
Co
nce
ntr
atio
n
0
Dosing every half-life ( t ½ )Oral morphine = 4 hours
164 8 12Time ( hours )20 24
50%75%
87.5%93.75%
97%100%
Pla
sma
Co
nce
ntr
atio
n
0 Time
Steady state after 5 half-livesMorphine ≈ 20 hours
Peak
TroughConcentration
needed to control pain
Concentration where side-effects
start to occur
CONSTANT PAIN DOSING
31
PEARL: FOR CONSTANT PAIN, DOSE MEDICATION EVERY HALF LIFE
32
PEEVE: TITRATING CONTINUOUS DRIPS (OR LONG-ACTING MEDS) TO SYMPTOMS!
Pla
sma
Co
nce
ntr
atio
n
0
Time to Drip Steady State
164 8 12Time ( hours )20 24
50%75%
87.5%93.75%
97%100%
Pain Control
Change GTT
Pla
sma
Co
nce
ntr
atio
n
…20 Time
Steady state forMorphine ≈ 20 hours
Concentration needed to
control pain
Concentration where side-effects
start to occur
35
PEARL: WITH BREAKTHROUGH PAIN, DOSE EVERY C-MAX
Pla
sma
Con
cen
trat
ion
0 Time
Cmax
Breakthrough Pain
PO / PR≈ 1 hr
37
PEARL: SYMPTOMS GUIDE BOLUS DOSING, BOLUS DOSING GUIDES CONTINUOUS DRIP TITRATION.
38
PEEVE: BAD CARTOONS BETWEEN SLIDES
XKCD.COM/1195/
39
PEEVE: THEY DON’T LOOK LIKE THEY’RE IN PAIN!
CHRONIC PAIN
PersistentMay have no obvious cause
Prolonged functional impairment
No sympathetic response
41
PEARL: CHRONIC PAIN LOOKS DIFFERENT THAN ACUTE PAIN.
42
PEEVE: SHE NEEDS MORE AND MORE OPIOID, “SHE IS GETTING ADDICTED.”
43
ABERRANT DRUG-TAKING BEHAVIOR
Desperation over sxsAggressively complainingRequesting specific drugBuying opioids on streetDoctor shoppingPrescription forgery
Passik et al. JClinPain. 2006.
DDX: ABERRANT DRUG TAKING BEHAVIOR
TolerancePhysiologic DependenceDrug DiversionPseudo-addictionAddiction
ADDICTION: HALLMARK
Continued use of drugs in spite of harm
Rare outcome of pain management
46
PEARL: ADDICTION IS NOT A WORD TO BE USED CARELESSLY.
47 BEWARE: MATH AHEAD.
EQUIANALGESIC CONVERSIONS
Metastatic colorectal CA
Stable on OP regimenHere for tune-up prior to AM procedure
EQUIANALGESIC DOSES
Oral/Rectal Analgesic IV/SC/IM
15 Hydrocodone --
15 Morphine 5
10 Oxycodone --
3 Hydromorphone 1
49
SUMMARYMedication choice is driven by severity and type of pain.
It takes 20 hours of constant dosing to reach steady state.
Breakthrough pain dosing should occur on the Cmax.
Around-the-clock dosing should occur on the half-life.
Titrate drips to number and amount of bolus dosing; titrate bolus dosing to symptoms.
50
PAIN PEARLS & PET PEEVES
Kyle P. Edmonds, MDM: 928.853.1483O: 619.471.9424P: 619.290.1212