Presentation on theme: "Advances in pain management:"— Presentation transcript:
1Advances in pain management: Atomized intra-nasal opiate and sedative drug delivery:A Novel method of pain and anxiety control.
2End of life pain and anxiety control: Problems Pain medication requirements increase in final days.Hinkka, Support care cancer 2001.Breakthrough pain, requiring immediate-release analgesics is common and difficult to control.Miller, Am Fam physician 2001.Fine, J Pain Symtom Manage 1998Portenoy, Pain 1990
3End of life pain and anxiety control: Problems Pain and anxiety medications are increasingly difficult to deliver:Oral medications ineffective or too slow.Patients often can’t swallow, have N/V or GI obstruction eliminating oral drug delivery option.Letizia, Hosp J 2000.Takala, Acta Anaesthesiol Scand 1997.
4End of life pain and anxiety medication delivery: Options OralAppropriate for baseline pain control.Often too slow for breakthrough pain.Ineffective once patient cannot swallow.TransdermalToo slow for breakthrough pain.RectalRelatively slow for breakthrough pain.Socially unacceptable to many patients and families.
5End of life pain and anxiety medication delivery: Options Subcutaneous/Intramuscular –.Suboptimal/inappropriate for baseline pain control over long periods.OK for breakthrough pain, but delivery method is painful.Slower onset than IV or Transmucosal.Invasive.Slight infection risk.Difficult for family members to manage.Needle stick risks.
6End of life pain and anxiety medication delivery: Options Intravenous therapy.Gold standard for severe pain control.Appropriate for baseline as well as breakthrough pain management.Invasive.Mild to moderate infection risk.Difficult for family members to manage.Needle stick risks.
7End of life pain and anxiety medication delivery: Options Transmucosal (Nasal, sublingual, buccal).Appropriate for baseline as well as breakthrough pain management.Titratable.Non-invasive.No infection risk.Easy for family members to manage.No needle stick risks.No need to swallow.
8Transmucosal medication delivery Is this really a novel idea?Commercially available transmucosal drugs:Actiq oral (transmucosal fentanyl lollipop)Nitroglycerin – Sublingual.Stadol (butorphanol) - Intranasal opiate.Fentora - Transmucosal fentanyl tabletDDAVP - Intranasal delivery route.Migraine medications - Intranasal meds available.Influenza Vaccine - Intranasal system on the horizon.Active area of pharm research
9Transmucosal Drug Delivery Many IV medications, including analgesics and sedatives, can be delivered transmucosally, though not available for that indication commercially:Large literature base to support their use.No need to wait for R&D of new forms.In some cases, generic drugs are available, cutting costs significantly.
10Intranasal Medication Administration Needleless: Intranasal Medication administration offers a truly “Needleless” solution to drug delivery.Superior: Intranasal medication administration generally results in superior drug delivery to the blood stream compared to other transmucosal routes.The remainder of this slide show will surround the topic of intranasal drug delivery issues.
11Nasal Drug Delivery for Analgesia and Sedation: What Medications? Drugs of interest in end of life care:Analgesics: Intranasal OpiatesFentanylSufentanilOthersSedatives: Intranasal BenzodiazepinesMidazolam (Versed)Diazepam (Valium)Lorazepam (Ativan)
12Intranasal Opiates: Literature support Zeppetella, J Pain Symptom Manage 2000.Assessed IN fentanyl (20 µg total) in 12 hospice cancer patients with breakthrough pain.Results:Two thirds had pain relief in 10 minutes or less.Three quarters wanted to continue use.One-quarter (that did not have good experience) had higher opiate baseline needs.Conclusion: Dosing studies needed.
13Intranasal Opiates: Literature support Zeppetella, J Pain Symptom Manage 2000.Problems:Dose - Too low when compared to other similar studies in post-operative pain patients and recommend IV doses.Manufactured recommended dosing for acute pain: µ/kg/hr infusion IV.Effective intranasal fentanyl post-op pain dose: 1.5 µg/kgOpiate dependent patients - may need even higher doses than post-operative patients.No titration- Due to rapid onset of action intranasal pain meds can be titrated to effect. The single dose given in this study is inadequate.Sample size - makes any conclusions difficult.
14Intranasal Opiates: Literature support Jackson, J Pain Symptom Manage 2002Sufentanil PCINA (Patient Controlled Intra-nasal analgesia) for breakthrough pain.Dose: 4.5 µg to 36 µg q 10 minutes up to 3 doses per event (dose titrated up daily if needed, sufentanil is 8 times more potent than fentanyl)Preliminary data“Patients who achieved good pain relief rated IN sufentanil as much better than their usual opioid breakthrough, both in speed of onset and efficacy.”
15Intranasal Opiates: Literature support Striebel, Anesth Analg 1996Toussaint, Can J Anaesth 2000Schwagmeier, Anaesthesist 1996Compared IV Fentanyl PCA to Fentanyl PCINA (Patient controlled intranasal analgesia)Prospective, Randomized trialsResults:No difference in pain intensityPCINA provided relief of postoperative pain as effectively as IV PCASimilar Patient satisfaction
16Intranasal Opiates: Literature support Striebel, J Clin Anesth 1996Schwagmeier, Anaesthesist 1996Compared Fentanyl PCINA (25 µg, lock out 6 minutes) to customary ward-provided pain control therapy.Prospective, Randomized trials.Results:PCINA provided better pain controlPCINA provided much higher patient satisfaction
17Intranasal Opiates: Literature support Kendall, BMJ 2001Compared nasal diamorphine to IM morphine in 404 ER patients with bony fractures.Compared to IM morphine, the nasal medication had the advantages ofFaster onset of pain reliefNo discomfort with administrationMore acceptable
18IN Fentanyl Borland, Ann Emerg Med, 2007. IN fentanyl versus IV morphine for treatment of pediatric orthopedic fractures - Randomized, double blind, placebo controlled trialResults:Pain scores identical for IV morphine and IN fentanyl at 5, 10, 20 and 30 minutesLess time to delivery of medication via nasal routeConclusion: IN fentanyl is as effective as IV morphine for treating pain associated with broken extremities
19Intranasal Opiates: Literature support Manjushree, Can J Anesth 2002:IN fentanyl (mean dose 1.43 µg/kg) provides good pain relief postoperatively.Hallett, Anaesthesia 2000:IN diamorphine provides good pain relieve post operatively.Wilson, J Accid Emerg Med 1997:IN diamorphine equivalent to IM morphine
20Intranasal Opiates: Literature support Striebel, Can J Anaesth 1995:IN meperidine (Demerol) better than SQ meperidine for post-op pain.Strieble, Anaesthesia 1993:IN fentanyl equivalent to IV fentanyl for post-op pain
21Intranasal Opiates: Web based support Sublingual/IN sufentanil protocol for breakthrough pain:Pain Management abstracted references:
22IN Opiate Bioavailability Morphine: 10%Morphine plus Chitosan: %Diamorphine: HighFentanyl: 70-80% - very lipid solubleSufentanil: 78% - very lipid solubleAlfentanil: 65%Oxycodone: 46%
23Intranasal Sedatives: Literature support Benzodiazepines represent the most commonly studied intranasal sedatives.Intra-nasal benzodiazepines studied:Midazolam (Versed®): Huge literature baseLorazepam (Ativan®): Small literature baseDiazepam (Valium®): Small literature base
24IN Midazolam for sedation Hollenhorst, AJR 2001: IN midazolam for MR imaging in adultsResulted in “sizable reduction in MR imaging related anxiety and improved MR image quality”Lloyd, Br J OMFS 2000: IN midazolam prior to oral and maxillofacial surgery“Intranasal midazolam is a safe and effective alternative to general anesthesia in the definitive treatment of children with oral and maxillofacial injuries”
25IN Midazolam for sedation Bjorkman, Br J Anaesth: Pharmacokinetics of IN midazolam in adult surgical patients“Uptake of Midazolam was rapid and bioavailability was 83%”.Weber, J Nurse Care Qual: IN midazolam prior to radiographic procedures.In midazolam as followup agent for failure to sedate with chloral hydrate was 82% effective.Yealy, Am J Emerg Med 1992:“Intranasal midazolam is a safe and effective for sedative for laceration repair.”
26IN Midazolam for sedation Fukuta, J Clin Pediatr Dent 1993: IN midazolam for highly combative, mentally disabled dental patientsPatients “showed a marked improvement in behavioral patterns after administration of intranasal midazolam.”Malinovsky, Br J Anaesth 1993:IN midazolam peaked sooner and 3 times higher than rectal midazolam.Sedation occurred sooner with IN meds (7.7min vs min rectal)
27IN Benzodiazepine Pharmacokinetics MidazolamBioavailability: 60% (drops) to 85% (Atomized)Clinical onset of action: 5-10 minutesPeaks: minutesOffset: minutesLorazepam: 77% bioavailable, single studyDiazepam: 34% to 50% bioavailable, few studies
28Conclusions Medications: Dosing: Titration: Multiple Opiates, Benzodiazepines and other drugs designed for IV administration are highly bioavailable via the nasal mucosal membranes.Dosing:Needs to be higher than IV formsTitration:Due to the rapid CNS and serum penetration, adequate pain control and/or sedation can be rapidly achieved.
29Conclusions Research data: Currently available data for IN analgesics and sedatives in the hospice setting is limited.Data from other settings (post-operative, anesthesia, emergency, radiology and dental) is more extensive.Randomized controlled trials to determine the optimal dosing and quantify any unknown problems are warranted in hospice setting.