2 nd Cancer Pain Symposium Opiate Related Side Effects: Focus on
Constipation Lydia Mis, PharmD, BCOP Clinical Oncology Pharmacist
June 6, 2008 Duke University Hospital School of Nursing Slide 2
Objectives List the common toxicities associated with opioid
analgesic use Understand the mechanisms associated with opioid
toxicity Describe pharmacologic and non- pharmacologic means by
which to treat and prevent opioid associated toxicities Slide 3
Opioid Induced Nausea Pathophysiology Circulating blood opiates
activate receptors in the chemoreceptor trigger zone located
outside of the blood brain barrier This transmits a signal to the
vomiting center, located in the medulla of the brain Implications
Tolerance to the nauseating effects may occur Slow titration to a
therapeutic dose may decrease likelihood of developing nausea Slide
4 Opiate Induced Nausea Prevention Make antiemetics available with
opioid prescription and slowly titrate up on doses Assessment of
alternate causes Constipation, CNS pathology, chemotherapy,
radiation therapy, GI obstruction Treatment Consider non-opiates
adjuncts as alternatives Antiemetic therapy Slide 5 Opioid Induced
Nausea Nausea persistent for > 1 week Reassess cause and
severity of nausea Change opioid (rotation) Refractory nausea
Persists after above has been tried Reassess cause and severity of
nausea Consider neuroaxial analgesia or neuroablative techniques to
potentially reduce opiate dose NCCN Practice Guidelines in Oncology
- v.1.2007 Adult Cancer Pain Slide 6 Opioid Induced Sedation
Preventive measures Initiate opioids at lowest possible doses
tailored for patient opioid history and clinical status If dose
needs to be increased, do so by 25-50% Counsel pts - dose sedation
x 24-72 hrs Persistent sedation > 1 week after initiation of
opioids Evaluate for other causes of sedation CNS pathology, other
sedating medications, hypercalcemia, dehydration, sepsis, hypoxia
Slide 7 Opioid Induced Sedation Persistent sedation > 1 wk after
start Consider of opioid or dose to lowest possible Consider
adjuvant analgesics Consider lower dose more frequently to peaks
Consider CNS stimulants Caffeine, methylphenidate,
dextroamphetamine, modafinil Refractory sedation Reassess cause and
severity & consider neuroaxial analgesia or neuroablative
techniques NCCN Adult Cancer Pain v.1.2007 Slide 8 Opioid Induced
Delirium Assess for other causes of delirium Hypercalcemia, CNS
pathology, brain metastasis, other psychoactive medications
Consider change opiate or adjuvant analgesic to decrease dose
Consider neuroleptic agent Antipsychotics: haloperidol,
risperidone, etc NCCN Practice Guidelines in Oncology Adult Cancer
Pain v.1.2007 Slide 9 Opioid Induced Motor and Cognitive
Dysfunction Stable dose of opioids > 2 weeks are not likely to
interfere with psychomotor and cognitive function Monitor closely
during analgesic administration and titration Patients should not
drive during initial titration and should be counseled not to drive
x 48 hours after dose increase NCCN Practice Guidelines in Oncology
Adult Cancer Pain v.1.2007 Slide 10 Opioid Toxicity Syndrome Use of
extremely high doses of opioids (> 100 mg/hr morphine or
equivalent) Hyperalgesia, myoclonic jerks, AMS Dose of opioid pain
not analgesia Associated with dehydration, renal impairment,
debilitated patients with advanced disease Treatment: opioid
rotation and NMDA antagonists (methadone or ketamine) NCCN Practice
Guidelines Adult Cancer Pain v1.2007 J Clin Oncol
2007;25(28):4497-4498 Slide 11 Opioid Induced Respiratory
Depression Use reversal agents sparingly If respiratory problems or
acute MS Naloxone Intravenous Administration 0.4 mg diluted in 10
mls NS Give 1 ml (0.04mg) Q 30-60 seconds until improvement in
symptoms is noted x 10 minutes Note: half-life of opioid
>>> half-life of naloxone If no response, consider
alternative causes of respiratory depression NCCN Adult Cancer Pain
v.1.2007 Slide 12 Opioid Induced Constipation WD is a 44 yo female
admitted to the inpatient 9300 service with abdominal pain
Metastatic gastric cancer (liver, bone) with delays in chemotherapy
d/t increased abdominal pain unresponsive to current pain regimen
of OxyContin 40 mg TID and prn oxycodone Slide 13 Opioid Induced
Constipation Other meds on admission included Protonix, ativan,
cipro/augmentin, ritalin, zofran, neurontin Senna 1 tab BID,
colace, lactulose, fleets Patient states maintaining hydration
& urination, no BM x 7 days PTA CT abdomen ordered Chemistries
notable for Ca 2+ 12.3 Slide 14 Opioid Induced Constipation Slide
15 Slide 16 Patient CT Scan/KUB suggestive of severe hypercalcemia
or opioid induced constipation Aggressively managed with enemas,
oral laxatives, stool softeners, osmotic agents, IV hydration and
zometa Discharged home on same opioid dose and aggressive bowel
regimen with instructions Slide 17 Opioid Induced Constipation
Cause Dehydration, electrolyte abnormalities Opioid analgesics
directly acting on opioid receptors in the gut Ondansetron &
other agents causing constipation Chemotherapy agents known to
affect nerve conduction in the gut Prevention Hydration/fluids,
exercise Stool softener Sorbitol, lactulose, docusate, miralax,
SMOG enemas Stimulant laxatives Bisacodyl, senna Saline laxatives
MOM, fleets, mag citrate Prokinetic agents Metoclopramide Slide 18
Opioid Induced Constipation Evaluation Patient history Listen for
bowel sounds R/O obstruction - Scans Rectal exam Impaction? R/O
organic causes Hypercalcemia, treatment related constipation,
hydration, hypothyroidism Peritoneal carcinomatosis Abdominal
adenopathy Treatment Sorbitol/lactulose 30 ml Q3h x 3 then prn
Bisacodyl 10-15 mg PO or 10 mg PR daily Docusate 200 mg BID or
Miralax 17 gm po BID Senna-S 2 tab po BID Fiber + Opiate = Brick
NCCN v.1.2007, J Pain Symptom Manage 2008;35(1):103-113 Slide 19
Opioid Induced Constipation Methylnaltrexone (naloxone derivative)
New kid on the block for treatment and prevention of opioid induced
constipation Peripherally-acting mu-opioid receptor antagonist for
use in patients with advanced illness receiving palliative care
Does not reverse analgesia Contraindicated if patient has bowel
obstruction Typically dosed 8-12 mg (wt based) SQ every other day
(up to Q 24 hours) http://www.wyeth.com/hcp/relistor/landing,
accessed 5/08 Slide 20 Opioid Induced Constipation Causes intense
laxation within 30 minutes of dose Close proximity to proper
facilities needed DC for severe or persistent diarrhea or if need
for systemic opioids are eliminated
