Intranasal adverse effects

The intranasal formulation is the preferred route of administration owing to ease of administration and fewer adverse effects, which mainly are local in nature. Adverse effects associated with the intranasal formulation include rhinitis, nasal irritation, and dryness. Hypersensitivity can develop with either formulation and should be considered before administering to patients with a suspected risk of hypersensitivity. 

Intranasal anticholinergic agents (e.g., ipratropium) reduce the severity and duration of rhinorrhea but have no effect on other nasal symptoms.11,12,21 Ipratropium reduces cholinergic hyperreactivity and cholinergically mediated histamine- and antigen-induced secretion. Intranasal ipratropium acts locally, with only minimal systemic absorption. Clinical trials demonstrated that ipratropium bromide 0.3% reduced rhinorrhea in adults and children with PAR.11,12 Intranasal ipratropium is an option for patients in whom rhinorrhea is refractory to topical intranasal corticosteroids and/or antihistamines.8,12 Intranasal ipratropium is available only by prescription, and the dose is two sprays nasally two to three times daily.15 Adverse effects are minimal, but dry nasal membranes have been reported.11,12... 

Intranasal corticosteroids are the most effective anti-inflammatory agents used in pediatric patients with allergic rhinitis. Although fewer studies have been conducted in children, results demonstrate that intranasal corticosteroids are effective and well tolerated, with an adverse-effect profile similar to placebo. Mometasone is indicated for children as young as 2 years of age, fluticasone is indicated for children 4 years of age and older, and beclomethasone, budesonide, flunisolide, and triamcinolone are indicated for children 6 years and older.15 Because concerns regarding effect of intranasal steroids on growth exist, the growth of pediatric patients prescribed intranasal steroids should be monitored routinely via stadiometry. 

Is the patient taking antihistamines and/or intranasal steroids Is the patient experiencing adverse effects (e.g., sedation from antihistamines or nasal itching, burning, or bleeding from intranasal corticosteroids) ... 

The intranasal dose is 200 units daily, alternating nares every other day. Subcutaneous administration of 100 units daily is available but rarely used because of adverse effects and cost. 

Intranasal butorphanol may provide an alternative to frequent office or emergency department visits for injectable migraine therapies. Onset of analgesia occurs within 15 minutes of administration. Adverse effects include dizziness, nausea, vomiting, drowsiness, and taste perversion. It also a has the potential for dependence and addiction. 

Tolerance to glucocorticoids in this, as in some other respects, varies from individual to individual some patients tolerate 30 mg of prednisone for a long time without developing Cushing s syndrome, while others develop symptoms at 7.5 mg the doses recommended today to avoid Cushing s syndrome in most patients are usually equivalent to hydrocortisone 20 mg. Cushing s syndrome and other systemic adverse effects can occur not only from oral and injected glucocorticoids, but also from topical and intranasal treatment (115) and intrapul-monary or epidural administration (SEDA-19, 376 SEDA-20, 370 116,117). 

Salmon- and eel-derived calcitonins are more potent than the human and porcine forms. Intranasal calcitonin has a systemic availability of only 3% of the subcutaneous form but is associated with fewer adverse effects, probably because of lower systemic availability. Antibodies against calcitonin are often found after prolonged treatment, more commonly with salmon (30-69%) or eel calcitonin than with human calcitonin. Antibodies do not usually affect the clinical effect of calcitonin and have not been reported to cause any harm to the patient. Antibody-mediated resistance is exceptional. 

Intranasal calcitonin is associated with fewer adverse effects than parenteral formulations, probably because of low systemic availability. However, a meta-analysis has confirmed that adverse events are poorly reported in clinical trials (21). The pooled relative risk for rhinitis from four trials (n = 1663) was 1.72, but this did not reach statistical significance. 

The adverse effects of parenteral and intranasal calcitonin have been compared (22). Parenteral salmon calcitonin is commonly associated with flushing of the face, ears, hands, and feet within minutes of the injection. Nausea and vomiting can occur within 30 minutes. The flushing needs to be distinguished from the less common but serious and potentially fatal hypersensitivity reactions that have been reported. The nausea, which is mild, usually abates with continued therapy. Intranasal calcitonin is better tolerated rhinitis of mild or moderate severity is the most frequent adverse effect. 

Intranasal corticosteroids are effective in reducing ocular symptoms as well as nasal symptoms. The mechanism of action is unclear it may partly be due to a systemic effect resulting from local absorption, although system-ically related adverse effects are uncommon. These are used once or twice daily depending on choice and should be used regularly during the hay fever season. 

Intranasal corticosteroids are safe if used correctly. Adverse effects are usually localised and include dryness, irritation and nose bleed (which may require stopping treatment for a period). Rarely, ulceration and nasal septal perforation (usually after nose surgery) can occur. Headaches, smell and taste disturbances, and hypersensitivity reactions have been reported. 

Intranasal diamorphine has been evaluated in a multicenter, randomized, controlled trial as an alternative to intramuscular morphine in 404 patients aged 3-16 years with suspected limb fractures (i.e. in acute pain of moderate to severe intensity) (60). They were randomized to either intramuscular morphine sulfate 0.2 mg/kg (n = 200) or intranasal diamorphine hydrochloride 0.1 mg/kg (n = 204). Intranasal diamorphine was significantly better tolerated 80% had no obvious discomfort compared with only 9% of those given morphine. There were no serious adverse effects of diamorphine, but the lack of blinding may have introduced bias. 

Intranasal diamorphine is as effective as intramuscular morphine and is much better tolerated by children, with no apparent increased risk of adverse effects (61,62). In a multicenter, randomized, controlled study, 404 children aged 3-16 years with a fracture of an arm or leg were given either nasal diamorphine 0.1 mg/kg or intramuscular morphine 0.2 mg/kg. The onset of pain relief was faster with nasal diamorphine, and there were no serious adverse effects. The frequencies of opioid-related mild adverse effects were similar in the two groups. 

Desmopressin (DDAVP) (see p. 712) 0.3-0.4 micrograms/kg body weight i.v. (also available in a concentrated intranasal form) increases factor VIII and von Willebrand factor levels by 3-5 times baseline in mild to moderate haemophilia A its use may render transfusion unnecessary after minor procedures such as dental extraction. It is cdso effective in mild to moderate t5q)e 1 von Willebrand s disease for which DDAVP offers nontransfusional treatment. Tachyphylaxis occurs with repeated dosage but stores are repleted after an interval of 2-4 days. Patients with severe deficiency of either factor and patients with any form of haemophilia B do not respond to DDAVP. Adverse effects include flushing, headache, tachycardia, mild h)q)ertension and hyponatraemia. 

Apomorphine, a very potent non-selective dopamine agonist, which acts on both Di and D2 receptors, has been nsed with some snccess in Parkinson s disease, particn-larly in patients with severe long-term adverse effects of levodopa. Because of first-pass metabohsm it has to be used subcutaneously, sublingually, or intranasally. Its adverse effects resemble those of levodopa. 

Intranasal midazolam 0.2 mg/kg and intravenous diazepam 0.3 mg/kg have been compared in a prospective randomized study in 47 children (aged 6 months to 5 years) with prolonged (over 10 minutes) febrile seizures (55). Intranasal midazolam controlled seizures significantly earlier than intravenous diazepam. None of the children had respiratory distress, bradycardia, or other adverse effects. Electrocardiography, blood pressure, and pulse... 

A 65-year-old woman, who had previously tolerated calcitonin nasal spray, developed eye and nose congestion, an itchy nose, and sneezing minutes after using intranasal salmon calcitonin (17). She was later given intramuscular salmon calcitonin and developed generalized urticaria and nasal itching within minutes. Skin testing was positive with eel and salmon calcitonins but not human calcitonin, and she was treated with human calcitonin without adverse effects. 

The adverse effects of interferon alfa have mostly been reported after systemic administration, as intranasal use was not associated with more frequent adverse effects than placebo (13). Almost aU patients treated with interferon alfa have experienced adverse effects, most of which are mild to moderate in intensity and easily manageable without withdrawal of treatment (14). The incidence and profile of adverse effects reported with the available tjfpes... 

Perennial rhinitis is common in both adults and children and is usually treated with intranasal corticosteroids, intranasal ipratropium bromide, antihistamines, intranasal cromones, and decongestants. Treatment-related adverse effects are common and monotherapy is often inadequate. There are few published studies of the comparative efficacy of rhinitis treatments. 

Intranasal 4% lidocaine has been used for migraine and cluster headaches with success and few serious adverse effects a bitter taste was common and some patients complained of nasal burning and oropharyngeal numbness (SEDA-20,127). 

Zanamivir has poor oral systemic availability. Intranasal administration slightly increases its availability, but in mice strongly reduced viral replication (4). In vitro, zanamivir does not significantly inhibit human lysosomal neuraminidases, and so the potential for severe adverse effects is low (5). 

Airway administration of liposome complexes was used for the treatment of pulmonary diseases including cystic fibrosis. Cationic liposome/DNA complex showed no adverse effect towards airway epithelial integrity (190) therefore, the cationic lipid-based delivery system proved to be appropriate for use in human trials for cystic fibrosis (CF). A series of pre-clinical trials were done in CF patients with intranasal instillation to evaluate the risk factors associated with the treatment (191-193). Because there was no apparent toxicity associated with lipoplexes as was seen from these trials, progress had been made in delivering the complexes to the entire lung by aerosol in CF patients (192,194,195). By nebulization, the DNA-liposome complex was delivered into the airways of mutant mice to obtain human cystic fibrosis transmem-... 

Limited studies suggest a role for intranasal lidocaine in the treatment of acute migraine headache. " Intranasal lidocaine provides rapid pain relief within 15 minutes of administration, but headache recurrence is common. Adverse effects generally are limited to local irritation of the nose or eye, an unpleasant taste, and numbness of the throat. 

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