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Management of Acute Pain, Nausea, and Emesis Joseph Bubalo PharmD, BCPS, BCOP Oncology Clinical Pharmacy Specialist Assistant Professor of Medicine.

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Presentation on theme: "Management of Acute Pain, Nausea, and Emesis Joseph Bubalo PharmD, BCPS, BCOP Oncology Clinical Pharmacy Specialist Assistant Professor of Medicine."— Presentation transcript:

1 Management of Acute Pain, Nausea, and Emesis Joseph Bubalo PharmD, BCPS, BCOP Oncology Clinical Pharmacy Specialist Assistant Professor of Medicine

2 Acute Pain and Nausea Management Overview Assessment Therapeutic options Monitoring/management

3 Pain Assessment History of past pain medication use as well as history of recreational or substance abuse activity, including alcohol. List of current medications (RX and OTC) and supplements (herbal, nutritional, homeopathic, etc) Allergy/sensitivity History

4 Pain Assessment Location – find all locations and intensity at each. Get an overall pain score. Character – sharp, dull, aching, constant, intermittent, burning, etc. Frequency and pattern. Severity. Has it changed or what makes it better/worse? Known etiology?

5 Pain Assessment What have they tried (pharmacologic and non- pharmacologic) and what were the results? –Therapy, dose, duration, how results were evaluated. What are the patients expectations/goals? Initial evaluation and follow-up must be done a bedside Follow-up over time – is a change new pain as opposed to not enough drug?

6 Opioid Agonists DrugOnset (min) Peak (h) Duration (h) Half- life(h) Dose Interval(h) CodeineIM PO FentanylIM 7-15 IV Hydrocodone Hydromorphone PO MethadonePO IV Acute 4-6 Chronic > MorphinePO IV <5 PO IV OxycodonePO

7 Equianalgesic Interchange AgentIM/IV/SQOral Morphine1030(60) OxycodoneN/A30 Hydromorphone Methadone Fentanyl0.1N/A-Actiq* HydrocodoneN/A30 Codeine Meperidine75300

8 Routes of Administration Oral Rectal Transdermal Sublingual/Buccal Intramuscular Intravenous Subcutaneous Spinal

9 PRN IV Opioid Equivalents Morphine 4 mg Hydromorphone 0.5 mg Fentanyl 40 mcg Meperidine – no longer used at OHSU

10 PRN Oral Opioid Equivalents Morphine mg Oxycodone mg Lortab ® tabs Lortab ® tabs Hydromorphone 2-4 mg Codeine mg

11 Analgesic Therapeutics Start at normal dose Base frequency on severity of pain, patient tolerance, pharmacokinetics If chronic analgesics minimum of 25-30% of chronic dose for breakthrough to achieve efficacy Titrate to therapeutic dose and lengthen interval as analgesia occurs Consider adjuvants and co-analgesics

12 Duration of Therapy Based upon etiology …the expected duration of pain will vary –Somatic, abdominal, neuropathic Fixed pain course? Acute pain – Subsides over an expected period of time Acute exacerbation of chronic pain –Return to baseline or titrate to new baseline

13 Renal and Hepatically Impaired Patient Choose agent with fewest active metabolites Dose to effect than titrate slowly at increased intervals Agents of choice - hydromorphone, oxycodone, and fentanyl Contraindicated agents – meperidine, propoxyphene

14 The Opioid Naive Assess type and duration of pain Analgesic doses used thus far and response/side effects PCA OK, but no basal Frequent reassessment Most at risk: small, elderly, organ compromised

15 Opioid Tolerant Chronic pain patient Recreational user Figure 24 hour usage Base rescue dosing at 10% of 24 hour use or 25-30% of incremental dose at the normal interval Assess bowel function

16 PCA Guide Initial basal may be used to replace chronic dosing otherwise leave off during initial assessment period Breakthrough frequency generally 6, 10, or 15 minutes Choices – Morphine 1 mg = hydromorphone 0.2 mg = fentanyl 10 mcg Give range to allow titration for more effective dosing Naloxone part of protocol orders

17 PCA Safety Issues PCA by proxy Patient education –For appropriate analgesia –To prevent oversedation –Videogame thumb Monitoring –Pain, alertness, vitals Q 4H-rate/quality of respirations first hours. Product selection

18 Adjuvants/Coanalgesics Laxatives NSAIDs Anti-anxiety Antiemetics Hypnotics Muscle relaxants Local anesthetics Consider additive side effects and potential to exacerbate co-morbidities

19 Opioid Side Effects Respiratory depression – titration rate based on analgesic need, reduce dose if cause of pain relieved. Rare after 3-4 days. Constipation Itching – Antihistamines or change agent. True allergy rare Nausea – Antiemetics, take with food, change agent or route Hallucinations – Change agent or route Sedation – Rule out other causes, change agent, add stimulant Urinary retention – Change agent or add bethanacol

20 General Management of Nausea and Vomiting Ralph Hurl Spew Blow Chunks Emesis Upset Stomach Barf Spit Up Retching Hyperemesis Puke Disgorgement Regurgitation Expulsion Vomito Sick Throw up Heave OH Gag Upchuck Honk Ow

21 The First Emesis?

22 Assessment of N/V GI status – Obstructed or not Frequency – nausea/emesis Volume – emesis and contents Timing – Proximate cause, worse in AM/PM? Hydration status?

23 Assessment Associated Factors –Undigested food –Neurologic signs/headache –Electrolyte abnormalities –New medications (include OTC, supplements, etc) –Therapy – drugs, radiation, chemo, –Phobias, anxieties, anticipatory habits –Patient expectations


25 Blood brain Barrier Chemoreceptor Trigger Zone (area postrema) 5HT 3, D 2, M, NK 1 Memory, fear, dread Motion/space H 1, M, 5HT 1a Inner ear Nucleus tractus solitarious (NTS) 5HT 3, D 2, M, H 1, NK 1 Cerebrum GI tract 5HT3, SP Blood born toxins Local irritants Vagal and sympathetic afferents Pharynx CNS Periphery Sensory input (pain, smell, sight) Emetic center

26 Etiologies Drug/treatment Induced –Opioids, supplements, antibiotics, cytotoxics, NSAIDs, SSRI, radiation (to GI, CNS) Disease related –Gastric irritation/obstruction, constipation, electrolyte/metabolic factors, increased intracranial pressure, vestibular disturbances Psychological Factors –Anxiety, fears, phobias, sights, odors

27 Therapy/Drug Selection Issues Drug affinity for probable cause (receptors, pharmacodynamics, etc) Available routes of administration Side effect profile Patient Contraindications Treat underlying condition if possible

28 Major Antiemetic Drug Classes Serotonin (5-HT 3 ) receptor antagonists Dopamine (D 2 ) receptor antagonists Neurokinin 1 antagonists (NK 1 a) Substituted benzamides (metoclopramide) Steroids Benzodiazepines (BZ) Cannabinoids Histamine (H 1 ) receptor antagonists Muscarinic receptor antagonists

29 Agents and Issues Metoclopramide – GI stasis or lower sedation level needed Dexamethasone – inflammatory component, cerebral edema, additive effect needed Octreotide - Bowel obstruction in terminal disease or those who fail anticholinergics Benzodiazepines – anxiety, phobias, learned behaviors

30 Agents and Issues Phenothiazines – Broadly active, especially in combination Haloperidol, droperidol – similar to phenothiazines in spectrum of activity Meclizine, dimenhydrinate, scopolamine – vestibular component Hyoscyamine – for nausea secondary to excess bronchial or gastric secretions Serotonin antagonists – Drug of last resort

31 Agents and Doses Metoclopramide mg IM/IV/PO Q 4H PRN ( mg/day on average) Droperidol mg IV/IM Q 4H PRN Haloperidol mg Q 6 H PRN Prochlorperazine mg IV/IM/PO Q 4H PRN* Promethazine mg IV/IM/PO/PR Q 4H PRN Chlorpromazine mg IV/PO Q 4H PRN * Also have PR Option

32 Additional Agents Dexamethasone 4-8 mg IV/PO QD to QID Scopolamine patch 1.5 mg (up to 8 hours for effect) Dimenhydrinate mg IV or mg PO Q 4H PRN Meclizine mg q 8 H PRN Trimethobenzamide 200 mg IM/PR Q 6H PRN

33 Serotonin(5HT 3 ) Antagonists for General N/V Ondansetron – 4 mg IV or 8 mg PO Granisetron – mg IV/PO Dolasetron – mg IV or 50 mg PO All dosed one to two times daily

34 Additional Routes Sub Q –Metoclopramide, octreotide, haloperidol, dexamethasone, scopolamine Dont give Sub-Q (cause irritation and erosions) –Chlorpromazine, diazepam, prochlorperazine, promethazine, hydroxyzine Sublingual –Lorazepam, hyoscyamine, haloperidol

35 Is Droperidol Evil? 03/01 UKs Medicine Control Agency reviews QT issues and Janssen Dcs Droleptan ® and injectable droperidol after risk benefit assessment FDA reviews drug and receives 273 reports for 11/97-12/01 with many being duplicates Majority of events occurred at doses > 10 mg 10 deaths, 18 cardiac arrests, 6 cases of QTc prolongation and 3 of torsades de pointes reported at doses < 2.5mg in 30 years 10 Serious case reports at doses < 1.25 mg, none of which showed a causal relationship Horowitz BZ, et al Academy of Emergency Medicine 2002;9(6);615-8

36 Droperidol Effects Normal QTc is 440 msec males and 450 msec females Prolonging QTc more than 500 msec or 60 msec increases the risk for dysrhythmia QT prolongation fatal arrhythmia/ cardiac arrest 0.1, 0.175, and 0.25 mg/kg doses equivalent in a 70 kg adult to 7, 12.25, and 17.5 mg caused a 37, 44, and 59 msec QTc prolongation respectively. Before 2001 warning for doses > 25 mg causing sudden death if at risk for cardiac dysrythmias Lischke V, et al Anesthesia and Analgesia 1994;79:983-6

37 Droperidol May be evil … However Droperidol is associated with QTc prolongation This temporal and dose dependent association has not been proven to be related to torsades de pointes in any type of randomized or controlled setting Case reports suggest that rare cardiac events may be associated with droperidol administration but none are causally associated with its use Analogous situations exist with other medications including haloperidol, cyclobenzaprine, and 5HT 3 antagonists

38 Droperidol Recommendations Ongoing safety monitoring should occur Avoid use with other agents which prolong the QT interval, change target drug metabolism, or in patients with known cardiac dysrhythmias Consider ECG monitoring if elevated doses are required or use is indicated in a patient with known risk factors Use the minimum effective dose Consider alternative agents if doses > 5mg are indicated Kao LW et al Annals of Emergency Medicine 2003;41:546-58

39 Combinations D 2 Antagonist –Metoclopramide –Prochlorperazine –Haloperidol –Droperidol –Promethazine 5HT 3 Antagonist –Ondansetron Other –Dexamethasone –Lorazepam –Dronabinol –Dimenhydrinate –Diphenhydramine –Meclizine –Scopolamine –Hyoscyamine –Trimethobenzamide

40 NonPharmacologic Approaches Decrease Milk products Clear liquid diet Bland diet Decrease sources of smell (cold and room temperature food) Manage anxiety Distraction techniques, guided imagery NG tube

41 Other Issues Multiple agents common Ginger, Peppermint oil Hydration Acupressure Marijuana

42 Results Are the Bottom Line

43 Thank you!

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