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PAIN MANAGEMENT Opioids, NSAIDs, Migraine drugs

PAIN MANAGEMENT Opioids, NSAIDs, Migraine drugs. NURS 203, Pharmacology I Dr. Nolan. PAIN. Most common complaint leading people to seek healthcare Can be acute or chronic Acute – less than ~3 months duration Chronic – 3 months or longer. TYPES OF PAIN. ACUTE

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PAIN MANAGEMENT Opioids, NSAIDs, Migraine drugs

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  1. PAIN MANAGEMENTOpioids, NSAIDs, Migraine drugs NURS 203, Pharmacology I Dr. Nolan

  2. PAIN • Most common complaint leading people to seek healthcare • Can be acute or chronic • Acute – less than ~3 months duration • Chronic – 3 months or longer

  3. TYPES OF PAIN • ACUTE • CHRONIC (longer than 3 months) • CANCER PAIN • SOMATIC PAIN • VISCERAL PAIN • NEUROPATHIC PAIN

  4. Types of Pain • Cancer • Can be acute or chronic • Somatic • Localized to a certain area (bone, muscle, skin…) • Can be acute (injury) or chronic (arthritis) • Visceral • Not localized, harder to define • Nociceptors in internal organs are stimulated (hepatitis, pancreatitis…) • Dull, aching, cramping, deep pain

  5. Types of Pain • Neuropathic • Perpheral pain receptors or nerves, damaged or dysfunctional • Excessive excitability in these areas, leading to exaggerated pain response • Diabetic neuropathy, herpes zoster (Shingles, post-herpetic neuralgia) • Not as responsive to normal analgesics

  6. Pain Physiology • Tissue damage stimulates peripheral pain receptors – nociceptors • Signal transmitted to spinal cord (ascending pathway) – hypothalamus – cerebral cortex • A-delta fibers : acute, “fast” pain • C fibers : slow, poorly localized pain • Descending pathway – inhibitory pathway, includes endogenous opioids, norepinephrine and serotonin to suppress nociceptive transmission of pain impulse via substance P

  7. Neural pathways for pain.

  8. Pain Treatment - Analgesics • Opioids • Non Opioids • NSAIDs • Tramadol • Acetaminophen • Antidepressants, antiepileptics • Neuropathic pain • CNS vasoconstrictors • Migraine pain

  9. Review Question • Which of the following drugs does not have a “ceiling” dose? • A) acetaminophen • B) ibuprofen • C) aspirin • D) morphine • E) all of the above have ceiling doses that should not be exceeded

  10. Opioid Analgesics – general characteristics • Relieve moderate to severe pain by inhibiting pain signal transmission from periphery to brain. • Well absorbed with PO, IM, SQ administration. • Metabolizedin liver, metabolites excretedin urine. • Liver or Renal impairment can interfere with metabolism or excretion.

  11. Opioids - widespread pharmacological effects • CNS • Analgesia • CNS depression • Respiratory depression • Pupil constriction • GI • Slowsmotility • Constipation • N/V • Bowel and Biliary spasm

  12. Opioids • Potent analgesics for moderate to severe pain • Acute and chronic pain • best for nociceptive pain • Not generally effective for non-nociceptive pain (neuropathic) • Serious side effects • No ceiling dose • chronic use universally leads to tolerance, physical dependence, may lead to addiction • tolerance leads to high doses in patients treated long term with opioids that could kill opioid naïve patients

  13. Opioids – Mechanism of Action • Stimulate Mu and Kappa receptors • Mu • Analgesia, ↓ gastric motility, sedation, respiratory depression, euphoria, physical dependence • Kappa • Analgesia, ↓ gastric motility, sedation • Mixed agonist/antagonists stimulate one, antagonize the other • Antagonists antagonize both (block opioids from binding to receptor or displace) • naloxone

  14. Opioids – Mechanism of Action • Binding to Mu and Kappa receptors slows the transmission of pain impulses between cells in the periphery, spine, and brain • Stimulating Mu and Kappa receptors activates the endogenous analgesia system • Endorphins, etc. act on receptors same as exogenous (narcotic) agents

  15. Opioids –Effects • Analgesia • Sedation, CNS depression (life threatening) • Respiratory depression (life threatening) • Constipation • Euphoria • Nausea/vomiting • Dependence • Tolerance • Miosis

  16. Opioids - widespread pharmacological effects • CNS • Analgesia • CNS depression • Respiratory depression • miosis • GI • Slowsmotility • Constipation • N/V • Bowel and Biliary spasm

  17. Opioids - Pharmacokinetics • Well absorbed orally, and via SQ, IM, and IV • Metabolized hepatically • Excreted via urine • Liver or renal disease can inhibit clearance or efficacy • T1/2 can range from minutes (IV) to days (fentanyl patch)

  18. Opioids – indications • Before, during, after surgery • To provide pain relief, sedation, ↓anxiety • Acute and chronic pain control, outpatient • there is limited data on the safety and efficacy of treating chronic pain with opioids • significant safety concerns • Pain/anxiety reduction for various procedures

  19. Opioids – contraindications/cautions • Respiratory depression, lung disease • Hepatic/renal dysfunction • Increased intracranial pressure • Allergy (true allergy)

  20. Morphine • Opioid agonist (primarily acts on Mu receptor) • Named after the Greek God of dreams, Morpheus • Prototype opioid analgesic • DEA Schedule II (DEA CII) • Given PO, SL, PR, TD, SC, IM, IV, IT, PCA pump

  21. Morphine • Maximal analgesia and resp depression within: • 10-20 min IV • 30 min IM • 60-90 min SC • 60 min orally (IR). ER forms are QD or BID • Duration is 5-7 hours (PO ER ~ 12-24 hours)

  22. Morphine - Pharmacokinetics • T1/2 is about 7 hours • Metabolites accumulate in pts with renal/hepatic dysfunction, must reduce dose • 30% bound to plasma proteins, extensive first pass metabolism • So PO doses considerably higher than Inj doses

  23. Morphine – Some specific uses • moderate to severe pain • procedure related anxiety/pain • MI related pain • Pulmonary edema • why?

  24. Morphine – Some cautions • head trauma – increased intracranial pressure • long acting agents with short acting procedures • respiratory depression can manifest after procedure

  25. Morphine – Side Effects • Profound sedation/CNS depression • Constipation, N/V • at least 41% incidence of constipation with chronic opioids • in 2000 study, 95% of patients interviewed by nurses in a hospital oncology unit reported constipation as the major side effect of their pain therapy • Resp depression, decreased breath sounds • Encourage deep breathing, coughing • Hypotension • Physical dependence • Paradoxical CMS stimulation and insomnia

  26. Morphine – availability • 24 hour controlled release • Kadian, Avinza • BID-TID controlled release • MS Contin, Oramorph • Q4-6h immediate release • MSIR • Liquid • MS oral solution, 10mg/5ml, 20mg/5ml, 100mg/5ml (concentrated) • Embeda (morphine/naltrexone) • naltrexone inactive unless crushed

  27. Morphine administration • Embeda, Kadian, Avinza caps can be opened and sprinkled immed. prior to oral admin. • DON’T chew the pellets! • IM vs. SQ for repeated doses to reduce tissue irritation • Don’t administer IV too quickly to avoid excessive sedation and RR depression • 2.5mg to 15mg over 5 minutes • PO vs parenteral doses • TYPICAL DOSE: • ORAL 30mg Q4h • IV/IM 5-10mg q4h

  28. Morphine important points • Breakthrough pain • Continuous infusion or SR forms will need short acting bolus or tablets for breakthrough pain • HIGH ALERT • periodically monitor RR, BP • caution if RR<10 • Placebo effect • Explain the therapeutic effect to the patient • Suggestions of efficacy are often very effective in increasing analgesia • Don’t let pain get severe • opioids are more effective in maintaining analgesia if pain doesn’t become severe

  29. Morphine important points • Watch the concentration • DON’T confuse 20mg/5mL with 20mg/mL • 20mg/mL liquid should be given via oral syringe • Bowel function • Bowel habits should be documented before beginning opioid therapy • assess periodically, daily if constipation. • Administer docusate and stimulant laxatives (senna, bisacodyl) on a regular basis if tx exceeds a few days • bulk forming may lead to impaction, especially in palliative care • watch for confounding drugs (anticholinergics) and dehydration

  30. Morphine important points • Don’t crush, break, chew, or dissolve sustained release (SR), controlled release (CR), or extended release (ER) dosage forms! • rapid release of entire day’s dose an result in opioid overdose

  31. Fentanyl • CII, Potent opioid agonist • Available as IV, patch, SL tablet & film • IM/IV • Used pre, during, post surgery • analgesic supplement for general anesthesia • Same cautions apply as for morphine • head trauma • profound sedation, RR depression… • Dosed in micrograms (mcg), caution!

  32. Fentanyl • Patch • Duragesic (fentanyl patch) for chronic pain in opioid tolerant pts • NOT for post-op pain, intermittent pain, or short term pain • 92% absorbed through skin • Dosed every 72 hours • take about 20 hours for the serum conc to reach one half after removal of patch • steady state and maximal analgesia reached by end of second patch application • Comes as mcg/hr patches (eg. 50mcg/hr)

  33. Fentanyl • transmucosal • short acting, for breakthrough cancer pain in opioid tolerant pts (Actiq, Fentora) • opioid tolerant means equivalent of 60mg/day morphine • Buccal film • about half absorbed through muscoa, the other half swallowed • swallowed fentanyl is ~20% bioavailable • Transmucosaltablets, lozenge (lollipop), and nasal spray also available • these products are NOT interchangeable on a per dose basis • Exercise extreme caution if children in the household! • rapidly fatal • watch for partially used discarded “pops”

  34. Other opioids • Embeda (morphine/naltrexone) • intended use is to prevent abuse • combines microencapsulated naltrexone core to morphine sulfate beads inside capsule • only crushing, chewing, or dissolving will release the naltrexone to attenuate the euphoric effects of the morphine • very expensive compared to morphine sulfate

  35. Other opioids • Oxycodone (OxyContin) – CII • IR and CR dosage forms • “Oxy’s” became a common street drug, selling for over $100 per tablet • Can be combined with APAP (Percocet) or ASA (Percodan) • Hydrocodone (Vicodin) – CIII • Similar to codeine in use and efficacy • Combined with APAP

  36. Other opioids • Hydromorphone (Dilaudid, Exalgo) - CII • PO, PR, SC, IM, IV • More potent than morphine, ↑efficacy PO vs morphine • Oxymorphone (Opana) • Derivative of morphine, similar characteristics • Methadone (Dolophine) • Synthetic form of morphine • longer DOA (T1/2 30h +)

  37. Other opioids • Propoxyphene (Darvon, Darvocet) - CIV • Least effective opioid out there • No more effective than APAP, but causes sedation and resp depression like other opiates • Toxic metabolite (norpropoxyphene) can accumulate and cause arrhythmias, pulmonary edema, apnea, and CV events. • Often used in suicides • Should be avoided in kids, older adults • Banned in Britain and many other countries but continues to be prescribed in U.S. • UPDATE: FDA just asked for withdrawal of propoxyphene from US market

  38. Review question • Proper administration of an ordered narcotic • A) can lead to addiction • B) should be done promptly to prevent increased pain and the need for larger doses • C) would include holding the drug as long as possible until the patient really needs it • D) should rely on the patient’s request for medication

  39. Other opioids • Meperidine (Demerol) - CII • Synthetic derivative of morphine • Despite some opinions, meperidine has not shown any benefit beyond other opioids for biliary colic, pancreatitis, labor, or migraine. • Does help with drug induced rigors, anesthesia related shivering • Toxic metabolite, normeperidine, limits it’s use • Accumulates with chronic use (>2 days), renal dysfunction • Very long T1/2, not reversible with naloxone • Causes seizures, hallucinations, agitation • Naloxone will reverse effects of meperidine, leaving normeperidine unopposed – risk of seizures! • Use > 2 days not appropriate

  40. Other opioids • Meperidine (Demerol) - CII • Drug interactions • serotonin syndrome • increased risk of MAO-I interactions and any serotonergic drug, including triptans • serotonin reuptake inhibition

  41. Other opioids • Nucynta (tapentadol) • CII • MOA • Opioid agonist (not as potent as morphine) • Norepinephrine reuptake inhibitor (NRI) • acts on decending pathway • Dosing • IR and ER forms available • 600mg max daily dose. Why? • Monitoring • CNS/RR depression • seizures, tachycardia, BP changes especially in patients taking antidepressants • Side effects • same as other opioids, but ~20% reduced incidence of GI S/E • NOT totally reversed by naloxone

  42. Other opioids • Tramadol (Ultram, Ultracet, Ryzolt) • Not related to opioids chemically • About as effective as Tyl#3 (codeine + APAP) • MOA: binds to Mu receptor, SNRI • Very little resp. depression, risk of dependence • Well tolerated, good for older folks

  43. Opioid antagonists • Block binding to opioid receptors, and can displace opioids bound there • Used for quick reversal of opioid toxicity/overdose • Reverses analgesia and CNS/resp. depression • Naloxone (Narcan), naltrexone (ReVia, Vivitrol) • Naloxone works within minutes of injection (SC, IM, IV) • Short DOA (1-2h), may need to be repeated

  44. Naloxone (Narcan) • For suspected narcotic OD • Give IVP over 10-15 sec • 0.4mg – 2mg • Repeat q 2-3 min if needed, up to total 10mg • If no effect at 10mg, probably not narcotic OD • No effect in the absence of opioids in system • Caution if suspected chronic opioid user, will precipitate immediate withdrawal

  45. Naloxone vs. Naltrexone • Naloxone • short acting competitive opioid antagonis • given parenterally, only 2% bioavailable PO • Used exclusively to reverse opioid intoxication • Naltrexone • given PO (Revia) and IM (Vivitrol) to treat alcohol dependence (main use) and opioid dependence (not very effective) • Vivitrol - monthly IM injection • Revia – PO QD

  46. Opioid withdrawal • Withdrawal • unlike withdrawal of benzodiazepines and barbiturates, opioid withdrawal is not life threatening • in otherwise neurologically and cardiovascularly healthy patients • Stage I – drug craving, anxiety (~5-15 hrs) • Stage II – yawning, perspiration, crying, rhinorrhea (~ 18 hrs) • Stage III – mydriasis, continuation of Stage II, hyperreflexia, hot/cold flashes, cramping (16-24 hrs) • Stage IV – continuation and worsening of Stage III, severe cramping, involuntary leg movements, diarrhea, HBP, ↑ body temp, ↑ RR, tachycardia, nausea (24 – 36hrs)

  47. Opioids withdrawal • Withdrawal • stage V – ↑ severity of earlier stages, fetal position, diarrhea, nausea, significant weight loss, leukocytosis, profuse sweating • stage VI – appetite returns, bowel function normalizes, beginning of psychological withdrawal symptoms, ↑ sensitivity to pain, GI symptoms • may see chronic withdrawal symptoms, both psychological and physical, after the post-acute withdrawal symptoms subside

  48. Opioids - NURSING CARE • Obtain baseline vital signs • Have naloxone available and know how to give it • Consider need for fixed schedule for patients experiencing chronic pain • Do not crush or break ER capsules/tablets

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