12/14/2019
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`Educational links regarding nasal medication delivery
`
`Therapeutic Intranasal
`Drug Delivery
`
`Needleless treatment options for medical
`problems
`
`(Scroll down if the text is missing on your screen)
`
`Home
`
`Concepts:
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`Featured new IN
`medication articles
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`Overview
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`Off-Label-Use
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`Informational Links Related to Intranasal
`medication delivery
`
`CONTACT INFORMATION for specific questions not
`addressed on this web site:
`
`Anatomy-Physiology
`
`E-mail address - info@intranasal.net
`
`Delivery-Techniques
`
`Clinical-Uses:
`
`(Be aware that I am usually busy caring for patients, spending time with my
`kids or climbing mountains and only check this e-mail during the times I update
`the site - about every 4 to 6 weeks. So if you are in a hurry you may be
`disappointed)
`
`Seizure-Therapy
`
`History behind this web site:
`
`Pain-Control
`
`Sedation
`
`Opiate-Overdose
`
`Epistaxis
`
`Topical-Anesthetics
`
`Hypoglycemia
`
`Hospice
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`Miscellaneous
`
`Education:
`
`Protocols
`
`Teaching
`
`Peer Reviewed
`Articles
`
`Bibliography
`
`The primary author of this site, Tim Wolfe MD, is a practicing emergency
`physician with a background in EMS. Some of his physician and paramedic
`colleagues also assist with the writing of this site and many contribute clinical
`insights.
`
`He trained in a medically underserved
`county hospital during the onset of the HIV
`epidemic in the 1980's where he noticed
`that many of his patients were able to
`"safely" self medicate using elicit drugs
`without needles - they used a form of nasal
`drug delivery called snorting. This concept
`led him to test the efficacy of having his
`patients "snort" inexpensive generic
`medicines (by dripping it in their noses) in
`hopes of finding both a safe and a painless
`method of drug delivery for paramedics and
`ER nurses (who at that time were
`seroconverting to HCV and sometime HIV
`simply for doing their jobs). Unfortunately
`his clinical experience was mixed -
`sometimes nasally delivered drugs were very effective, other times not so
`effective. His epiphany occurred in the middle of the night while dripping a
`measured dose of a benzodiazepine into a child's nose - the child spit it back in
`his face. At that moment he realized that he was giving ORAL drugs via the
`nose which probably explained the variable efficacy he had noticed all along. He
`needed to change the mode of delivery. If there was only a way to rapidly
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`intranasal.net/information_links/default.htm
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`1/6
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`Links
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`Educational links regarding nasal medication delivery
`aerosolize an exact dose of the drug into a fine mist that could be delivered
`directly to the nasal mucosal with no loss into the environment (nebulization
`does not achieve these needs since most is not delivered to the nose or to the
`lung, rather is it lost to the environment, takes time to deliver and usually
`requires a compliant patient). Through trial and error using compressed air,
`dual syringes, etc the idea morphed into a very simple syringe driven atomizer.
`He and a friend started a company selling that device (the MAD - mucosal
`atomization device).
`
`A few years ago the company was sold and Dr. Wolfe currently receives no
`royalty nor any money from the MAD, allowing him to write this web site and
`pursue other interests. Dr. Wolfe consults for interested device and
`pharmaceutical companies and occasionally is paid to educate their sales people
`specifically about the MAD device, but he earns no money for any sales of any
`topical drug delivery products or drugs nor does he have shares in these
`companies nor do they have any control of this web site. Never the less an
`author can never completely remove his or her bias from any writings and you
`will find that Dr. Wolfe feels strongly that nasal drug delivery is a valuable drug
`delivery adjunct to providing efficient and effective patient care. Furthermore
`due to his training in a poor, medically underserved community you will find a
`bias towards using inexpensive generic drugs that are proven by the literature
`to be clinically effective (rather than focusing on drug levels and bioavailability
`which do not necessarily translate into clinical effect when applied in the real
`world - case in point the tiny 0.1 ml volumes that supposedly work via the nose
`of compliant patients but are extremely difficult to administer in the ER
`setting). Since the MAD is commonly used in these research studies there is
`also a great deal of literature that involves that product so a bias could be
`suggested here as well.
`
` Because he gets questions from clinicians and patients all over the world and
`because he enjoys teaching about the topic he and some colleagues created
`this site to help provide a place for the curious clinician seeking detailed
`information. He apologizes for the somewhat disorganized look of this site - he
`is just a doctor, not a web master. Someday when he has the time he may re-
`write the site to make it less cluttered. If you personally want to communicate
`with him feel free to do so via the email address above providing your name
`and affiliations and he will eventually respond.
`
`Note from a Fellow EMS director, emergency physician:
`
`January 14, 2010
`Dear Tim,
`I am offering this little note to share with you some thoughts regarding the importance of
`mucosal administration in the care of our patients. It is clear to us in the ields of emergency
`medicine and EMS medicine that we have had a long neglected opportunity for care. You have
`brought this advance to the forefront. You saw clearly that through a novel yet simple idea, we
`could garner a new advantage that had long been missing in clinical care. Because of your
`insight, we can now approach many of the long-dealt-with dilemmas in emergency care that
`before often eluded us, indeed caused us to offer in many cases less than optimal care.
`One important example is in the treatment of seizures. Those of us who have dealt with
`pediatric patients suffering from convulsions for example, in the absence of intravenous
`access, have been left with virtually no other alternative than the per rectum administration of
`diazepam to halt the seizure. You gathered the budding information in the literature and
`quickly adapted an invention that could simply, safely treat this dificult problem in a much
`more proper, much less toxic manner. This has been a great advance in the history of
`medicine.
` Another critical area, the dilemma of “excited delirium,” presents a hazard to patient and
`responder alike. These patients must often be sedated to provide safety in therapy and
`management. The intranasal route of administration presents a fast alternative that is much
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`intranasal.net/information_links/default.htm
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`2/6
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`Opiant Exhibit 2148
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
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`Educational links regarding nasal medication delivery
`
`less hazardous for the responding emergency provider as regards the potential for infectious
`disease contamination from the patient, especially in the dificult problem of the spread of
`viruses such as hepatitis C and HIV through needle-stick exposure.
` Finally, we all understand how important the prompt treatment of severe pain is to our
`patients. We now have the capability of prompt administration of fentanyl via the intranasal
`route and thousands of patients will no longer suffer as a result of this important medical
`advance.
` I would close by thanking you for your contributions to medicine, Tim. You have seen clearly
`where others did not. Because of your persistence and your great loving heart, patients
`everywhere – who will never know you – are being treated promptly and humanely, for the
`beneit of all concerned.
` Thank you for your service and dedication.
` With kind regards, I am
`Respectfully,
`Raymond L. Fowler, MD, FACEP
`Professor of Emergency Medicine
`Chief of EMS Operations
`Southwestern Medical Center at Dallas
`Attending Emergency Medicine Faculty
`Parkland Memorial Hospital
`
`
`
`INTERNET DISCUSSIONS regarding IN therapy
`
`Reviews
`
`Synopsis of a review article regarding intranasal medication use in
`children published in the journal Pediatrics Sept 2010 (click here)
`
`Abstract of this article
`
`Pain discussions
`
`Intranasal fentanyl relieves breakthrough cancer pain
`Industry sponsored discussion of intranasal pain medications
`Intranasal fentanyl or intravenous morphine for analgesia in adults - Best
`Bets evidence based topic review.
`Intranasal Fentanyl versus parenteral opiates for acute pain in children -
`Best Bets evidence based topic review.
`Prommer et al, Intranasal fentanyl review article 2011
`Stay on top of kids pain in the ED (use IN fentanyl) - ACEP news
`December 2010
`
`EMS links of interest
`
`The Nose Knows - cost effectiveness of transnasal therapy
`Australian Lay public education regarding treating seizures, calling 112
`and using intranasal midazolam (PDF 0.2 MB)
`New South Wales EMS protocol for pediatric seizures (PDF 0.17 MB)
`Audio interview with Debra Kerr - IN naloxone researcher
`Contra Costa EMS update 2010 (Intranasal naloxone pp 38-50)
`Intranasal fentanyl use in ski resort
`
`intranasal.net/information_links/default.htm
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`3/6
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`Opiant Exhibit 2148
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
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`12/14/2019
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`Educational links regarding nasal medication delivery
`Inhaled methoxyflurane vs intranasal fentanyl for adult visceral pain in an
`ambulance
`Dyer, Snuffing out the overdose: The Boston BLS nasal naloxone program
`slide presentation (11 MB)
`Intranasal Versed usage - Paramedic perception of Utility in urban EMS
`system (Columbus OH)
`Use of IN naloxone by ALS and BLS providers in Boston MA
`National public radio - Overdose rescue kits save lives
`Chris Colwell, MD - The Nose Knows: Intranasal Medications options are
`growing (Gathering of Eagles EMS conference feb 2011)
`Excited Delirium in EMS - treatment with IN midazolam, Emergency
`Medicine News October 2010
`Prepackaged syringes of drug ready for use with an atomizer - cool idea
`Intranasal naloxone as a layperson administered procedure - the
`Massachusetts experience
`Intranasal fentanyl in EMS discussion (Editorial comment - the dose is too
`low - 1.5 to 2 mcg/kg should be used as initial dose. If you only give an
`adult 75 mcg you can expect it to fail so don't make this common error.
`Since this publication, the author has convinced his medical control of the
`right dose and now uses that shown to be effective on this web site.)
`Callopy and Snyder, Intranasal drug delivery in EMS. EMS today May
`2011
`
`Hospice links of interest
`
`Palliative info web site by Mike Harlos, MD
`Lecture slides by Dr. Portenoy (Beth Isreal) regarding breakthrough Pain
`in hospice patients
`www.palliativedrugs.com
`
`Sedation discussions
`
`Another very detailed link discussing IN Precedex for pediatric sedation in
`multiple settings in the hospital
`Excited Delirium in EMS - treatment with IN midazolam, Emergency
`Medicine News October 2010
`
`POSTED INTERNET ARTICLES (to go to peer reviewed
`articles for more PDF and web linked articles - click here)
`
`Nose Brain Pathway articles
`
`Pain Articles
`
`Industry sponsored articles in nasal pain medications
`Borland, IN fentanyl vs IV morphine for fractures in children randomized
`controlled trial, Ann Emerg Med 2007
`Sitte, IN fentanyl for episodic breathlessness, J pain sym manage 2008
`Rickard, IN fentanyl vs IV morphine for fractures in the prehospital
`setting, 2008
`Heshmati, IN sufentanil for postoperative pain, IJPT 2006
`Wilson, IN diamorphine for pediatric analgesia, J Accid EM 1998
`
`Sedation articles
`
`intranasal.net/information_links/default.htm
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`4/6
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`Opiant Exhibit 2148
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
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`12/14/2019
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`Educational links regarding nasal medication delivery
`Bkakta, IN midazolam for preoperative sedation, Ind J Anaesth 2007
`Mathai, Preanesthetic sedation of preschool children: Comparison of
`intranasal midazolam versus oral promethazine. Anesth Essays Res 2011.
`
`Seizure articles
`
`Lahat, IN midazolam vs IV diazepam for pediatric seizures, BMJ 2000
`Ma, Clinical Guidelines on Management of Prolonged Seizures, HK J
`Paediatrics 2010
`Klein-Kremer, IN midazolam for treating seizures in children in the
`emergency setting. Is J Med 2007
`French JA.. Benzo vs Benzo: And the winner is.. Epilepsy Curr
`2011;11(5):143-144.
`
`Intranasal Naloxone articles
`
`Barton, IN naloxone as a needleless alternative to treatment of opioid
`overdose in the prehospital setting, J Emerg Med 2005
`MMWR Feb 17 2012 - Community based opioid overdose prevention
`programs providing naloxone - United States 2010
`Time Magazine - Lifesaving Overdose antidote should be made more
`widely available 2012 article
`Time Magazine - Lifesaving Overdose antidote should be made more
`widely available 2012 editorial
`
`McDermott, C. and N. C. Collins (2012). "Prehospital medication
`administration: a randomised study comparing intranasal and intravenous
`routes." Emerg Med Int 2012: 476161.
`
`RehabCenter.net Naloxone rescue kit downloadable protocol
`
`The PDF file downloaded from their site (click here)
`
`Topical anesthetic articles
`
`A guidance for the use of topical anesthetics for nasal/oropharyngeal and
`laryngotracheal procedures
`Chan, Lidocaine spray prior to NGT placement, Hong Kong Medical
`Journal 2010
`Whit Fisher, MD Procedurettes - how to create a NGT frozen curve to
`enhance passage through nose - link to video
`
`Pediatric reviews
`
`INTRANASAL DRUG DELIVERY REVIEWS AND MISC
`
`References for incident pain and incident dyspnea protocol
`Pires, Intranasal drug delivery - How, why, what for -extensive review, J
`Pharm Pharmaceut Sci 2009
`Mercus, Influence of head position and anatomy on nasal drug
`deposition, Rhinology 2006.pdf
`
`INTERNET PROTOCOLS
`
`Intranasal diamorphine dosing table
`Palliative care incident pain and dyspnea protocol
`Sunshine Hospital emergency department pediatric IN fentanyl protocol
`
`intranasal.net/information_links/default.htm
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`5/6
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`Opiant Exhibit 2148
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
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`12/14/2019
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`Educational links regarding nasal medication delivery
`Princess Margaret Hospital educational information for parents after
`administration of IN fentanyl in the operating theatre
`Royal Children's Hospital Melbourne Australia intranasal pain treatment
`clinical practice guideline
`
`Nasal Drug Compounding Pharmacies
`
`Hospice links
`
`Palliative care incident pain and dyspnea protocol
`
`Palliativedrugs.com
`
`OTHER SITES OF INTEREST
`
`Everest ER (Medical care in extreme mountain environment - including IN
`medications due to difficulty with IV access and safety)
`
`Carpuject - here is an idea that allows the end user to purchase the drug
`in an already packaged format and simply attach an atomizer at the time
`needed and deliver the drug. No need to aspirate the drug from the vial
`first.
`
`World wide science organization listing of ongoing or recent research
`related to intranasal medication delivery of all types.
`
`How insulin works - https://scribeschool.net/how-insulin-works.html
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`Home | Overview | Off-label | Anatomy | Delivery | Protocols | Teaching | Bibliography | Links
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`intranasal.net/information_links/default.htm
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`6/6
`
`Opiant Exhibit 2148
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
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`Page 6
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