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: The paper describes 2 case reports of non-medical use of Naphazoline (Naphthyzin). Both demonstrate that the peripherally acting alpha-adrenergic agonist Naphazoline obtains some addictive potential. The drug produces a feeling of euphoria, which resembles the perceived effects of psychostimulants. Both patients and people who consume Naphazoline for intoxication report increased tolerance after repeated use which indicates the addictive potential of the substance. To the best of our knowledge, this is the first examination of non-medical Naphazoline use and the first attempt to describe its addictive potential. Clinical psychiatrists should be aware of this phenomenon when addressing polysubstance use behavior.

Purpose: To investigate whether exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy was associated with an increased risk of malformations in humans., Methods: All women giving live birth between 1997 and 2011 in Denmark were included in this nationwide cohort study. All women redeeming at least one prescription of antazoline-naphazoline eye drops during the first 84 days of pregnancy were identified. Logistic regression was used to estimate the odds ratios of malformations among exposed offspring compared to non-exposed offspring., Results: We identified 977 706 births between 1997 and 2011. A total of 3061 women (0.32%) were exposed to antazoline-naphazoline eye drops in the first trimester of pregnancy. The rate of congenital malformations was 3.0% (n = 93) in exposed offspring and 3.5% (n = 33 594) in unexposed offspring. First-trimester exposure to antazoline-naphazoline was not associated with major congenital malformations overall (odds ratio: 0.88, 95% confidence interval: 0.71-1.09) or with any specific major malformation. The number of redeemed prescriptions was unchanged during all trimesters of pregnancy as compared to before and after pregnancy (p < 0.05)., Conclusion: Exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy appears not to be associated with increased teratogenic risk., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: To observe the process of nasal mucosa injury and repair induced by nasal decongestants in guinea pigs Methods: Sixty-five male guinea pigs were randomly divided into 4groups by digital random method.The guinea pigs in Group A (20 guinea pigs)were treated with 2 sprays of 0.1% Naphazoline 6 times a day for 2 weeks; Group B (20 guinea pigs)with 2 drops of 1% Ephedrine 6 times a day for 2 weeks; Group C(20 guinea pigs) with 2 sprays of Naphazolin hydrochloride and Chlorphenamine Maleate Nasal Spray 8 times a day for 2 weeks.Group D (5guinea pigs)did not do any intervention as a control group.At the end of first and second weekend, 6 guinea pigs randomly selected from each group were observed the morphological changes of the nasal cavity with nasal endoscope and pathological microscope.Two weeks after stopping use of decongestant, 24 animals were grouped.Three guinea pigs were selected randomly from each group to form Group E ( n =9) and Group F ( n =9)respectively. The 6 remaining guinea pigs falled into Group G. Group E received 2 sprays of Mometasone Furoate Nasal Spray once a day for 2 weeks; Group F received 1 ml 2.3% saline to wash the nasal cavities once a day for 2 weeks.Group F was used to show the natural progess without any treatment.At the end of the third and fourth weekend, nasal endoscopic and pathological microscopes were used to observe the nasal cavity structure and the pathological changes of nasal mucosa. Results: Nasal mocusa congestion and edema were observed with nasal endoscopy after 2 weeks of using nasal decongestant. Cell edema, blood vessel expansion, acute and chronic inflammatory cell infiltration, cilium lodging or loss were observed under the pathological microscope in GroupA, B, C. After using MometasoneFuroate Nasal Spray and 2.3% saline for 2 weeks, the above changes were all recovered in Group E and F. No recovery was found in Group G. Conclusions: Short-term and over dose of nasal decongestant can result in the injury of nasal mucosa in guinea pigs, and the injury is much severe as using decongestant last longer.MometasoneFuroate nasal spray and 2.3% saline can repair the injury.

Undesirable effects of the application of the intransal vasoconstricting medications are a frequent occurrence in the pediatric practice. The objective of the present study was to evaluate the role of the intranasal vasoconstricting medications in the structure of the means and methods currently available for the treatment of toxicological pathologies based at a multi-field clinical hospital. The retrospective analysis of the medical histories of the patients admitted to the toxicological department and annual reports for the period from 2015 to 2016 was undertaken. The study has demonstrated that intoxication associated with the use of the intranasal vasoconstricting medications was the most common cause of hospitalization of the children in the toxicological departments. Intoxication of this origin accounted for 15-20% of the total number of toxicological pathologies among the children. The cases of intoxication are most frequently documented in the group of children at the age between 1 and 3 years. The risk of the undesirable serious complications is especially high after the application of naphazoline-based intranasal vasoconstricting medications (71.7-77.4% of all the cases of intoxication with these products). It is concluded that the use of intranasal vasoconstricting medications in the pediatric practice should be carried out under the strict control, with the naphazoline-based preparations being totally excluded from the application.

Cutaneous squamous cell carcinoma (cSCC) is a frequent side-effect of vemurafenib treatment. The main aim of this study was to identify the clinical risk factors associated with the development of cSCC in melanoma patients treated with vemurafenib. We carried out a retrospective study, including 63 consecutive melanoma patients treated with vemurafenib for BRAF-mutant metastatic melanoma in an oncodermatological department. Clinical and follow-up data were collected and analysed, and a comparison of the subgroups who did and did not develop cSCC was performed. A total of 42.9% of patients (n=27) treated with vemurafenib developed one or more cSCC. Patients with cSCC were significantly older (P=0.01). Clear eyes were also associated with a higher risk of developing cSCC (odds ratio=3.50; 95% confidence interval: 1.08-12.43). Three patients developed cSCC more than 1 year after the initiation of treatment (12, 16 and 18 months, respectively). Clinicians should be vigilant in older patients undergoing vemurafenib therapy as well as patients with clear eyes as they seem to be at increased risk of developing cSCC, even late after the initiation of treatment.

Introduction: Vasoconstrictors, widely prescribed in the congestive states during acute rhinitis, are responsible for many cases of drug-related iatrogenic disease., Case Report: We report the case of a 40-year-old man, who presented with an episode of malignant hypertensive crisis associated with life-threatening congestive heart decompensation. The patient interview revealed consumption to supra-therapeutic dosage of an association of naphazoline and prednisolone nasal sprays. The diagnostic work-up allowed to rule out disease-related causes of secondary hypertension. The drug-related disease was thus retained., Conclusion: The results of the literature review showed many cases of vasoconstrictor poisoning responsible for central nervous system and cardiovascular involvement, especially in young children. This first case of heart failure related to nasal decongestant administration increases the scope of potentially serious risks of these drugs and demonstrates the outreach needs for health professionals and patients about their proper use., (Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Objective: The aim of this study was to analyze the causes and perinatal outcome related to fetal ductus arteriosus constriction or closure at a single center over a 26-year period., Methods: This was a retrospective analysis of 45 consecutive cases of constriction (n = 41) and closure (n = 4) from 1987 through 2013. Patients were divided into Group A (maternal use of non-steroidal anti-inflammatory drugs (NSAID), n = 29), Group B (idiopathic, n = 8), and Group C (other drugs not previously described, n = 8)., Results: The median gestational age at diagnosis was 34 weeks (range, 27-38), mean systolic and diastolic velocity in the ductus arteriosus was 2.01 ± 0.66 m/s and 0.71 ± 0.46 m/s, respectively. Among the 29 cases of NSAIDs, 27.5% (8/29) have taken a single day use and 75% multiple days/doses. Right ventricular dilatation was present in 82.2% of the fetuses, tricuspid insufficiency in 86.6%, and heart failure in 22.2%. Neonatal persistent pulmonary hypertension occurred in 17.7% of the patients. Late follow-up showed all 43 survivors alive and healthy with only two deaths from unrelated causes., Conclusions: The results of this study indicate that clinically significant ductal constriction may follow maternal exposure to single doses of NSAIDs. Unknown causes or other new substances were also described, such as naphazoline, fluoxetine, isoxsuprine, caffeine and pesticides. Echocardiographic diagnosis of ductal constriction led to an active medical approach that resulted in low morbidity of this group of patients.

Treatment of allergic diseases of eyelids and conjunctiva (conjunctivites and blepharoconjunctivites) often presents difficulties due to peculiarities of their pathogenesis - allergic and vascular reactions, disorder of lacrimal production, meibomian gland dysfunction, and possible bacterial contamination. It has been suggested to use Ocumethyl, which contains zinc sulfate (binding, drying, anti-inflammatory, and antiseptic effect), diphenhydamine hydrochloride (an Н1-antihistamine that decreases capillary permeability and helps resolve conjunctival and eyelid edema), naphazoline hydrochloride (a sympathomimetic notable for its strong, rapid, and long-lasting vasoconstrictive effect), and methylene blue (antiseptic effect, disintoxication, and antioxidant activity). A total of 80 patients with chronic allergic conjunctivitis, blepharoconjuntivitis, or giant papillary conjunctivitis associated with contact lens wearing were treated with Ocumethyl instillations (3 times daily for 15-30 days). A clinically significant effect was obtained in 77-91% of patients depending on the disease entity.

Diagnosing Horner Syndrome can be difficult in the setting of an incomplete triad. A 27-year-old man presented with unilateral eyelid droop and intermittent ipsilateral headaches, having already seen 7 physicians. Physical examination revealed unilateral ptosis but no pupillary miosis or facial anhidrosis. Inspection of his clinical photographs revealed elevation of the ipsilateral lower eyelid, suggesting sympathetic dysfunction. On further questioning, he admitted to naphazoline dependence. Reexamination after ceasing the naphazoline unveiled the anisocoria. Vascular imaging subsequently revealed carotid dissection, and the patient was started on anticoagulant and antiplatelet therapy. The ptosis persisted after conjunctival Müllerectomy. External levator resection was recommended, but patient declined. This case underscores the importance of clinical photography, meticulous medical record review, and complete medication history including over-the-counter preparations. Clinicians should meticulously inspect the lower eyelid in cases of atypical blepharoptosis and consider the effects of eye drops when inspecting pupils for miosis.

Ten percent of all strokes are due to spontaneous cerebral hemorrhages. They are associated to drugs (licit and illicit) in 9.5% of all cases in young adults. This is a case report of a 44-year-old man, without previous morbidities, who presented a sudden onset headache and arterial hypertension 24 hours after use of naphazoline as nasal decongestant. Cranial tomography showed right thalamus hemorrhage. Cerebral angiography showed no aneurisms, vascular malformations or vasculitis. No other risk factors were found during investigation in this patient and the stroke was attributed to naphazoline exposition.

Objective: Imidazoline derivatives like naphazoline have a firm place in diagnostics and therapy of otorhinolaryngology because of their vasoconstrictive and decongestive properties. Their alpha-adrenergic potential could induce not only local but also systemic side effects like hypertension and tachycardia which can increase a life-threatening intoxication. Signs of imidazoline intoxication are excessive systolic and diastolic hypertension and hypotension, bradycardia with arrhythmia, respiratory depression, excitation or severe CNS depression., Patients: The typical course of an intoxication and its sufficient therapy is reported by means of two cases of intraoperative application of naphazoline for hemostasis., Results: In case of overdosage or intoxication, symptomatic drug therapy with intravenous administration of 5 mg phentolamine for adults and 1 mg phentolamine for infants has to be done. Phentolamine, an alpha-adrenoceptor antagonist, acting against peripheral and central side effects has to be used because no specific antidote is available., Conclusions: Especially pediatric otorhinolaryngologists have to know about symptoms and therapy of an intoxication after application of naphazoline. Particularly with children, a narrow therapeutic to toxic window can be observed in this frequently used drug.

The imidazoline derivative naphazoline, an alpha(2)-adrenergic agonist, is used as non-prescription eye and nasal preparation because of its vasoconstrictive and decongestive properties. Especially in children, overdose and/or systemic side effects due to absorption can quickly cause severe central nervous system depression and cardiovascular adverse effects. In a 7-year-old boy was diagnosed a naphazoline intoxication by toxicological analysis. The case was also of forensic interest, because the naphazoline mixture was prepared in a pharmacy in a concentration 80 times above the adequate dosage for children. In general, physicians, pharmacists and the public should be educated about the toxicity of over-the-counter preparations.

During neurosurgery for hypophysary adenoma under general anaesthesia in a prone position, a 34 year-old-women received accidental 6 ml intramucosal injection of lidocaine with naphazoline. The patient presented a severe bradycardia associated with a major increase in arterial blood pression followed by a brief cardiac arrest. She also presented a prolonged awakening and a pulmonary oedema, which lead to mechanical ventilation. The patient rapidly recovered a normal clinical state.

Background: As potent alpha-adrenergic agonists imidazoline derivatives like naphazoline are frequently used drugs because of their vasoconstrictive and decongestant properties. Beside their well-known local side effects also rare systemic ones like hypertension, excitability and nausea are possible. In case of intoxication this can enhance to ischemia of vital organs, bradycardia with arrhythmia, respiratory depression, hypothermia, excitation or marked sedation., Patients: Two cases of intoxication after application of naphazoline for haemostasis under the operation, the postoperative course and therapy are reported., Results: No specific antidote is available but a symptomatic drug therapy with intravenous administration of 5 mg phentolamine, an alpha-adrenoceptor antagonist acts against the vasoconstrictive side effects., Conclusions: Because of the serious side effects and the narrow therapeutic to toxic window of naphazoline a strict observance of guidelines and contradictions, such as maximum dose, is necessary.

Implications: Naphazoline intoxication by intrabronchial overdose caused prolonged unconsciousness of an 18-mo-old child after general anesthesia for tracheal rigid bronchoscopy. The leading symptoms were side effects involving the cardiovascular, pulmonary, and central nervous systems. Intensive care unit admission with the need for mechanical ventilation was necessary. Recovery was uneventful.

Background: Vasoconstricting nasal drops are applied frequently. Especially early ultrastructural alterations of the vessels were not examined up to now in animal models. Our goal was the systematic investigation of the submucosal vessels and the epithelium after topic application of naphazoline nitrate (Privin) in an animal model., Methods: Three times daily over 6 days 3 ml of 0.1% naphazoline nitrate solution (Privin) were instilled into the right nasal cavity of 5 rabbits. At the 7th and 14th day an incisional biopsy of the lower nasal turbinate was carried out in ketamine/rompun anesthesia., Results: In the naphazoline group the capillaries showed an edematous endothelium with narrowed lumina. Thrombosis of the arterioles were frequently observed. The more cubic epithelial cells had deciliated areas with microvilli. Venules, submucosal glands and the surrounding connective tissue was normally configurated. Analogous findings were also observed after 2 weeks., Conclusions: The disturbance of the microcirculation shows impressive endothelial alterations. These structural changes can result in nonreversible mucosal damages. A regeneration time of more than 1 week is assumable. Our results should be considered critically in order to prevent damages of the nasal mucosa.

In this study, oxime and oxime ether derivatives of anticonvulsant nafimidone [1-(2-naphthyl)-2-(imidozole-1-yl)ethanone] were prepared as potential anticonvulsant compounds. Nafimidone oxime was synthesized by the reaction of nafimidone and hydroxylamine hydrochloride. O-Alkylation of the oxime by various alkyl halides gave the oxime ether derivatives. Anticonvulsant activity of the compounds was determined by maximal electroshock (MES) and subcutaneous metrazole (scMet) tests in mice and rats according to procedures of the Antiepileptic Drug Development (ADD) program of the National Institutes of Health (NIH). In addition to anticonvulsant evaluation, compounds were also screened for possible antibacterial and antifungal activities because of the structural resemblance to the azole antifungals, especially to oxiconazole. All compounds were evaluated against three human pathogenic fungi and four bacteria using the microdilution method. Most of the compounds exhibited both anticonvulsant and antimicrobial activities; the O-alkyl substituted compounds (2, 3, 4 and 5) were found to be more active than the O-arylalkyl substituted compounds in both screening paradigms.

The use of topical ocular antihistamine/decongestant combinations to treat symptoms associated with allergic conjunctivitis is widespread, effective, and generally without adverse effects. Recently, these medications have become available without a prescription, possibly leading patients to the erroneous assumption that they are void of side effects. Likewise, patients may use these drugs for many ocular therapies for which they are unintended, possibly resulting in ocular complications. One significant adverse effect of these antihistamine/decongestant combinations when used inappropriately is pupillary dilation with associated blurry vision. Continued emphasis of the possible deleterious side effects by the clinician is recommended to circumvent these problems.

Objective: To describe patterns of conjunctivitis caused by ophthalmic decongestants., Design: Case series., Setting: Outpatient eye clinic., Patients: We selected patients with conjunctival inflammation who were using nonprescription decongestant eyedrops, who had no other cause for conjunctivitis, and whose conditions improved after discontinuing the incriminated preparations., Main Outcome Measures: Clinical characteristics of conjunctival inflammation and time to resolution of symptoms and signs after discontinuing the use of eyedrops., Results: Seventy patients (137 eyes) were identified. Preparations containing the vasoconstrictors naphazoline, tetrahydrozoline, or phenylephrine were associated with 3 clinical patterns of conjunctivitis: conjunctival hyperemia (50 cases), follicular conjunctivitis (17 cases), and eczematoid blepharoconjunctivitis (3 cases). Decongestants were used daily for a median of 3 years (range, 8 hours to 20 years) prior to presentation. The median time to resolution of symptoms and signs was 4 weeks (range, 1-24 weeks), and patients remained asymptomatic for a median follow-up of 6 months (range, 0-12 years)., Conclusion: Nonprescription decongestant eyedrops can produce acute and chronic forms of conjunctivitis by pharmacological, toxic, and allergic mechanisms. Once recognized, conjunctival inflammation often takes several weeks to resolve.

Nasal mucous membrane of patients with rhinitis medicamentosa caused by prolonged use of decongestants (privine) was studied by measurement of nasal mucus clearance time and observation of pathological changes under both optical and electron microscopes. It was found that privine destroyed the nasal cilia and mitochondria of epithelial cells, and disturbed their function so that they were damaged and dropped. Pathologically, the nasal epithelia were swollen, the arterioles dilated, and the glands proliferated. Twenty-two patients with rhinitis medicamentosa were treated by topical dexamethasone or triamcinolon in normal saline for 1-2 weeks followed by normal saline as regular nasal drops. Eight patients were treated effectively by oral ATP 20mg tid. The results were evaluated by nasal mucus clearance time measurement and rhinomanometry.

Nafimidone is a potential new antiepileptic drug with a therapeutic profile in experimental animal seizure models similar to that of phenytoin (PHT). We report here the first clinical trial of nafimidone in epileptic patients. Twelve adult male patients with a mean of four or more medically intractable seizures per month were enrolled in a 14-week pilot study. Patients were stabilized on therapeutic levels of PHT and carbamazepine (CBZ) (nine patients) or on PHT alone (three patients) before entering a 4-week baseline period. Nafimidone, to a maximum dose of 600 mg/day, was added during 2 weeks in hospital. Patients were then evaluated weekly for 8 weeks. Eight patients experienced 33-98% improvement in seizure control. Three others did not show significant change in seizure frequency but experienced sufficient subjective improvement that they continued into long-term follow-up. One patient, who had a 63% improvement in mean weekly seizures during the pilot study, declined to continue. Thus, 10 patients entered long-term follow-up. Six of the 10 sustained 53 to greater than 99% improvement in seizure control compared with baseline over the course of 46-53 weeks of follow-up. Nafimidone had a marked inhibitory effect on the clearance of CBZ and PHT, resulting in higher plasma levels in nine patients. The possible role of the elevated CBZ levels in the apparent efficacy of nafimidone is discussed.

Commercial preparations of two topical ophthalmic vasoconstrictors were evaluated for whitening ability, duration of action, tolerance, and rebound vasodilation in 11 normal volunteers. Both 0.02% naphazoline HCI and 0.05% tetrahydrozoline HCI significantly reduced baseline redness after a single use (Part I); however, naphazoline produced significantly more whitening than did tetrahydrozoline. Only naphazoline retained its whitening ability after ten days (Part II). The level of redness remained significantly below baseline for eight hours after a single use of either vasoconstrictor and for six hours after multiple use of naphazoline. The diminished effectiveness of tetrahydrozoline after the ten-day test period may encourage its overuse. Neither vasoconstrictor produced rebound vasodilation after discontinuation of use.

This is the report of two patients, who used eye drops containing adrenergic agents for a relatively long period of time because of conjunctival troubles. The eye drops contained phenylephrine or tetryzoline or naphazoline. As a consequence of the vasoconstriction, the treatment led to an epithelial xerosis in the region of the caruncula and of the neighbouring eyelid edges. The keratinisation resulted in a closure and disappearance of the puncta lacrimalia. Therefore, the application of vasoconstrictive eye drops for a longer period of time is discouraged. Moreover, eye drops with a low concentration of the sympathomimetic agent should be preferred.

A 24-year-old woman was referred to our clinic because of severe hypocalemic hypertension and latent myocardial insufficiency. Plasma renin activity and plasma aldosterone concentration were lowered. Plasma cortisol concentrations and the urinary excretion of vanillin mandelic acid were found within normal range. Some efforts to identify a specific adrenal enzymatic defect were unsuccessful. By combined therapy with spironolactone, methyldopa and clonidine, the blood pressure was significantly lowered, but not normalized. Triamterene had also an expressed hypotensive effect and induced orthostatic phenomena. After six months of hypotensive drug therapy, the patient's mother reported that her daughter consumed for more than seven years high doses of special nasal drops containing, beside ephedrine and naphazoline, the potent mineralocorticoid 9-alpha-fluoroprednisolone. A strong drug-dependence to the naphazoline component could be evaluated. The application of the mineralocorticoid was stopped, and only a slight low-sodium diet had to be added to restore the long-standing elevated blood pressure to normal

Vasoconstrictors such as phenylephrine and naphazoline are used in ophthalmology to decrease hyperemia associated with allergic conjunctivitis and contact lens wear. There is a suspicion, however, that chronic use of these agents can produce dry-eye symptoms in some patients. The purpose of this study was to determine whether vasoconstrictor use interferes with tear film adequacy by decreasing mucin-secreting goblet cells. Cellulose acetate filter strip impressions were taken from the bulbar conjunctiva of rabbit eyes treated with vasoconstrictors or artificial tears for varying periods of time, and the number of goblet cells per light microscopic field counted. There was no significant difference between the number of goblet cells in control and vasoconstrictor-treated animals within each time period. These results indicate that conjunctival goblet cell density is not significantly affected by topical vasoconstrictor use.

We describe six patients who demonstrated a spectrum of adverse ocular reactions following the use of a nonprescription topical medication composed of methylene blue, naphazoline hydrochloride or nitrate, and amylocaine hydrochloride. This preparation has been commonly sold in Quebec and France for various complaints of ocular discomfort and redness. The ocular complications included asymptomatic blue discoloration of the conjunctiva, follicular and papillary conjunctivitis and varying degrees of cicatrization of the conjunctiva and cornea. The most severe reaction, progressive bilateral ocular pseudopemphigoid, occurred in a 73-year-old woman, presumably due to at least one of the ingredients of this medication.