Search

A STUDY ON ACUTE TOXICITY, LOCAL IRRITATIVE EFFECT OF AND ALLERGIC RESPONSE TO A NOVEL INTRANASAL MEDICATION CONTAINING THE INTERLEUKIN- 1Β RECEPTOR ANTAGONIST (IL-1RA)

Intranasal drug administration is a less invasive method of drug delivery that is easily accessible for adult and pediatric patients. Medications administered by the intranasal route have efficacy comparable to intravenous administration and typically have superior efficacy to subcutaneous or intramuscular routes. The intranasal route is beneficial in emergent situations when the intravenous route is not available. The intranasal route is safe and effective in various indications, and therapeutic systemic concentrations of medication can be attained via this route. As the evidence for and comfort with intranasal administration continue to grow, guidance on correct technique, medications, and dosing is vital for appropriate use. This article reviews the process and practices of appropriate intranasal medication administration.

BACKGROUND Vasoconstrictors and local anesthetics are commonly administered using a squeeze bottle atomizer to the nasal mucosa to reduce edema, limit bleeding, and provide analgesia. Despite widespread use, there are few clinical guidelines that address technical details related to safe administration. The purpose of this study was to quantify, via simulation, the amount of liquid delivered to the nasal mucosa when patients are in the supine and upright positions and administration parameters that would reliably provide the desired amount of medication per spray. METHODS A convenience sample of 10 anesthesia residents was studied. Providers were instructed to use a 25-mL dip and tube nasal squeeze bottle to administer the test solution (sterile water) to a mannequin in the upright (90° elevation) and supine (0° elevation) position. After mannequin testing, additional testing was completed with the spray bottles at 0°, 15°, 30°, 45°, and 90° to determine the relationship between the angles of administration and the amount of liquid dispensed. RESULTS The mean volume delivered per spray was substantially greater when administered in the supine position (0.56 ± 0.22 mL) compared with the upright position (0.041 ± 0.02 mL, difference = 0.52 mL, 95% confidence interval [CI], 0.37-0.67 mL, P < .001). Converting the administered volume to the dose of phenylephrine that would be administered using our standard 0.25% solution, an estimated additional 1300 mcg is delivered per spray in the supine position compared with the upright position (95% CI, 925-1675 mcg, P < .001). Administration with a delivery angle of ≤30° resulted in significantly more volume than when the bottle was oriented at a 90° angle. The volume dispensed at 45° was not different from the volume delivered at 90° (0.032 ± 0.006 mL vs 0.030 ± 0.005 mL, P = .34). CONCLUSIONS We found a 14-fold increase in the volume (ie, dose) delivered per spray when a nasal squeeze bottle was used with a mannequin in the supine position compared with the upright position. Given the reported toxicity from the use of intranasal medication and the inadvertent overdosing that occurs when squeeze bottle atomizers are used in clinical practice, our data suggest that all intranasal drugs should be administered with a precise, metered-dose device. If a metered-dose device is unavailable, the medication should be delivered at an angle of ≥45°; however, we recommend administering the drug with the patient in the sitting position and the bottle at 90° because only a small change in angle below 45° will result in a substantial increase in medication delivered.

The paper presents clinical and laboratory study results of the immune response indicators dynamics in 199 children aged 1 year to 14 years with verified diagnosis of influenza depending on the type of immune response to the treatment with recombinant interferon alpha-2b (IFN) (Grippferon®, nasal drops). A total of 100 people received this medication, whereas 99 patients in the control group received pathogenetic therapy. The immune response type was determined on the basis of the polarisation coefficients (PC) suggested by the authors: PC1 = IL-4/IFN- γ and PC2 = IL-10/IFN- γ obtained by calculating the content ratio in the serum cytokines of IL-4 to IFN- γ and IL-10 to IFN- γ , responsible for the predominant type of immune response to antigen introduction. A good therapeutic efficacy of the intranasal medication of recombinant interferon alfa-2b was established for the treatment of influenza in children, given both the Th1and Th2-type immune response. This allows us to recommend this medication for use in children, regardless of the immune response type.

Intranasal administration is an attractive option for the delivery of many therapeutic agents especially for the treatment of central nervous system (CNS). In contrast to drugs that require delivery by peripheral injection, which requires blood brain barrier permeability of the injected drug for CNS delivery and may cause anxiety and infection, the intranasal route allows drugs to bypass the BBB due to its highly specialized nasal anatomy and the olfactory pathway. Due to its non-invasive nature and easy procedure, intranasal drug delivery is particularly suited for use in children and may be performed by medical staff or family members. This article will review the use of intranasal medications with a focus on their utility in children. We will provide an overview of the nasal anatomy and its impact on drug delivery, the side effects of drugs specific to intranasal delivery, and a list of the medications which are currently administered intranasally. The most common drug classes for intranasal delivery in pediatrics include sedatives and analgesia, drugs for seizure control, opioid antagonists, and antimigraine medications. In summary, intranasal delivery is a versatile method for drug application with a wide range of clinical utility, and especially effective in the pediatric population.

AVP-825 (sumatriptan nasal powder) is an FDA-approved intranasal medication delivery system containing low-dose sumatriptan powder for acute treatment of migraine with or without aura in adults. AVP-825 utilizes unique nasal anatomy features to avoid limitations of other intranasal delivery methods. Areas covered: Literature search terms: 'AVP-825', 'sumatriptan nasal powder', 'intranasal sumatriptan', 'sumatriptan safety', 'sumatriptan acute migraine'. Pharmacokinetic, Phase 2/3 studies, reviews (AVP-825) and metanalyses/reviews (sumatriptan) were evaluated. Expert opinion: AVP-825 provides a more efficient sumatriptan delivery method versus other formulations. Pharmacokinetics showed that a single dose of AVP-825 (22 mg) delivers 15-16 mg sumatriptan and produces significantly lower exposure than oral or injectable formulations, which may translate into a better safety/tolerability profile. AVP-825 was well tolerated in controlled trials, with the most common adverse events localized at the administration-site (abnormal taste, nasal discomfort); these were mostly mild, leading to only one discontinuation. Compared to 100 mg oral sumatriptan, AVP-825 had a significantly lower rate of atypical sensations across multiple attacks. AVP-825 has the advantage of early efficacy onset associated with faster absorption at a lower delivered dose than liquid nasal spray or oral formulations. AVP-825 provided earlier efficacy (within 30 min) vs. 100 mg oral sumatriptan and similar sustained efficacy. AVP-825 offers the benefits of a non-oral, low-dose, tolerable acute migraine medication.

Intranasal medication administration in the emergency care of children has been reported for at least 20 years and is gaining popularity because of ease of administration, rapid onset of action, and relatively little pain to the patient. The ability to avoid a needle stick is often attractive to practitioners, in addition to children and their parents. In time-critical situations for which emergent administration of medication is needed, the intranasal route may be associated with more rapid medication administration. This article reviews the use of intranasal medications in the emergency care of children. Particular attention will be paid to anatomy and its impact on drug delivery, pharmacodynamics, medications currently administered by this route, delivery devices available, tips for use, and future directions.

Background Intranasal medication delivery for allergic rhinitis (AR) is considered a mainstay of therapy but is hampered by poor compliance. Among reasons given are unpleasant sensations associated with spray penetration into the pharynx. Our objective was to study a novel method of particle delivery to the nose that would abrogate these issues. Methods This was a double-blind, randomized study. Subjects who met study criteria underwent intranasal particle delivery using a novel device (Trivair Nasal Deposition System; Trimel Pharmaceuticals, Toronto, Canada) that delivered anhydrous lactose particles into the nose via a transoral air puff (thus elevating soft palate and blocking the nasopharynx). Subjects had nostrils randomized into 4 groups (particle sizes 5 μm and 50 μm × doses 12.5 mg and 25 mg). Particle deposition was assessed at 1 minute, 10 minutes, and 30 minutes on the inferior turbinate, middle turbinate, and nasopharynx, respectively, using high-definition endoscopic photography. Each image was compared using an expert blinded 2-person panel for percentage particles remaining. Nonparametric data was assessed using the Wilcoxon signed-rank test via Strata software. Results Twelve nostrils in total met study criteria. The results showed no difference in effectiveness of nasal particle retention between the groups based on particle size or dose. No particles entered the nasopharynx or oropharynx. Conclusion This study provides proof-of-principle data that the Trivair Nasal Deposition System is effective at retaining medication in the nose without pharyngeal penetration. Larger studies on this device are warranted.

Introduction. Opioid overdose is an ever-increasing problem globally. Recent studies have demonstrated that intranasal (IN) naloxone is a safe and effective alternative to traditional routes of naloxone administration for reversal of opioid overdose.Aims. This randomised controlled trial aimed to compare the time taken to deliver intranasal medication with that of intravenous (IV) medication by advanced paramedic trainees.Methods. 18 advanced paramedic trainees administered either an IN or IV medication to a mannequin model in a classroom-based setting. The time taken for medication delivery was compared. End-user satisfaction was assessed using a 5-point questionnaire regarding ease of use and safety for both routes.Results. The mean time taken for the IN and IV group was 87.1 seconds and 178.2 seconds respectively. The difference in mean time taken was 91.1 seconds (95% confidence interval 55.2 seconds to 126.9 seconds,P≤0.0001). 89% of advanced paramedic trainees reported that the IN route was easier and safer to use than the IV route.Conclusion. This study demonstrates that, amongst advanced paramedic trainees, the IN route of medication administration is significantly faster, better accepted and perceived to be safer than using the IV route. Thus, IN medication administration could be considered more frequently when administering emergency medications in a pre-hospital setting.

With the exception of oral medications, most traditional forms of drug delivery outside the operating suite require an injection with a needle—a process that is painful and anxiety-provoking, risks needle stick injury, and consumes valuable staff time. In addition, intravenous access in pediatrics may be difficult for inexperienced providers. Intranasal medication delivery offers an alternative method of drug delivery that is often as fast in onset as intravenous medication, usually painless, inexpensive, easy to deliver, and effective in a variety of acute pediatric medical conditions. This article briefly reviews the most common uses for intranasal medication delivery in pediatrics: pain control, anxiolysis, and seizure control.

Intranasal medication for eustachian tube dysfunction (ETD) is an established practice in otolaryngology through the effects of steroids, decongestants, antihistamines or a combination of the above in reducing tubal oedema. The author has previously argued that a double-blind, randomised control trial would be helpful in determining effectiveness of treatment, if a standardised head position, chiefly Mygind or Ragan, was adopted to maximise intranasal drop delivery into the eustachian tube orifice. One recent paper suggests that intranasal treatment is not very effective, but ultimately does not state whether a standardised head position was adopted. Although a large body of evidence supports the hypothesis that the nasal passages are the route to middle ear disease, there is as yet no paper that has been published that has specifically addressed this issue, therefore the author must conclude that evidence to support intranasal treatment for ETD is still lacking and further research is desirable.

For analgesia and sedation in the paediatric setting, intranasal medication is favourable for several reasons, in particular ease of administration and rapid onset of action. A survey was conducted of all Emergency Departments in England and Wales regarding their use of intranasal medication in children. Approximately 50% use intranasal medication, commonly intranasal diamorphine with sporadic use of other opiates. Intranasal midazolam is used for sedation but is less well tolerated than when administered orally. Intranasal diamorphine, however, is safe and effective in the management of pain in the paediatric emergency setting and its ease of administration makes it ideal for use in the already traumatised child.

SummaryScopolamine in small doses (0.3-0.4 mg) given intranasally by spray 30 minutes prior to exposure, exerted significant protection against swing sickness. During actual flight testing, addition of a surface active agent (sodium lauryl sulfate-Duponal C) increased its effectiveness. Nasal instillation to subjects 15-20 minutes after take-off sharply reduced the incidence of vomiting from airsickness during subsequent 40-45 minutes. Oral and sublingual administration under these conditions were ineffective. Considerable variations in the drug instilled resulted when given by spray. The use of nose drops allowed more accurate medication. The significance of this mode of administration for treating motion sickness is discussed.

Despite the warnings that have appeared occasionally in the literature, many otolaryngologists still deny the danger of the production of generalized argyria from the use of silver-containing intranasal medication. This heedless attitude is abetted by the advertisements of certain manufacturers of such medications. One of them states quite consistently in the advertising pages of medical publications that the solution is "non-toxic, definitely bacteriostatic, and above all, it is markedly soothing to inflamed tissues." The physician who has seen even a single victim of full-blown argyrosis, with its typical generalized pigmentation of the skin, giving the patient a bronzed blue or slate color which has been described aptly as the appearance of a corpse suddenly come to life, must necessarily have been impressed with the importance of preventing such a condition. Prevention is actually the only treatment, for, although Stillians 1 and others have shown that by painstaking and multitudinous injections of

Is the intranasal administration of a medicated oil within the limits of normal therapeutic dosage necessarily a dangerous clinical procedure? Since the first description, by Laughlen, 1 in 1925, of lipoid pneumonia following the aspiration of nasal oil drops cautious physicians have been asking themselves this question, with few precise scientific data available from which to draw a reliable conclusion. Doubtless the widespread abuse of intranasal oils by the public, with the inevitable tendency toward overdosage and too prolonged treatment, has contributed largely to the cloud of suspicion that has developed. An editorial in The Journal of the American Medical Association 2 called attention to this consideration with the observation, "There is unanimity of opinion among investigators as to the dangers of intranasal medication with oils, particularly as is seen in the uncontrolled use by the public of the various preparations of liquid petrolatum." While such self medication cannot be condemned too

Summary Beclomethasone dipropionate as a pressurized aerosol is effective in nasal polyposis, but the efficacy is only moderate. In these partly-blocked noses, it seems possible that the insufflated drug in powder form is better distributed over the mucous membrane than the pressurized aerosol. To test this hypothesis, we treated forty-two patients with nasal polyposis with intranasal beclomethasone dipropionate as a powder and as a pressurized aerosol in a double-dummy, cross-over design. There was no difference between the treatments in sixteen patients, while in twelve cases there was a preference for beclomethasone dipropionate as aerosol, and in fourteen, for the powder form. Fourteen found the aerosol most irritating and nineteen, the powder. Thus, in a group of polyp patients there were no significant differences between the two application forms, but possibly there is a need for both aerosol and powder, as there appeared to be differences in the individual responsiveness to the two types of intranasal medication;. Blind microscopy of wiped nasal-smears before and after beclomethasone dipropionate treatment showed a reduction of basophilic cells, and counting of sneezes after medication demonstrated a reduction in the number of sneezes. These results suggest that a reduction of epithelial mediator-cells and of irritant receptor-sensitivity are of importance for the efficacy of topical steroids in rhinitis.

Six rhinovirus serotypes showed in vitro susceptibility to two analogues (SK&F 21687 and SK&F 30097) of 3-substituted triazinoindole compounds. The intranasal SK&F 21687 medication

Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (IN) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+IN) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (IV) drug injection is employed, FUS was also applied after IV injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within the targeted region compared with that achieved by IN only. Despite the fact that the IN route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+IN was not significantly different from that of FUS+IV. As a new drug delivery platform, the FUS+IN technique is potentially useful for treating CNS diseases.

The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)- enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.

To the Editor:— Pity the persons today having what is termed the common cold. Especially unfortunate are infants and children. No sooner does a child have a sniffle than the mother, who may have been instructed by a physician or local druggist, begins flushing the nose with various popular nose remedies. A timely report by W. J. Kerr (The Common Cold,The Journal, Aug. 1, 1936, p. 323) asks: "Since it is apparent that no rational means are available to prevent or treat a common cold on the basis of the hypothesis of infectious origin, isn't it urgent to go back to fundamentals and start anew?" It is well to recall that a few decades ago the physician in treating a cold prescribed the usual supportive measures, letting the nose "run" at will. Who can question the rationale of permitting natural drainage? Little is known concerning the function of the