Topical adverse effects

Pharmaceutical powder aerosols have more stringent requirements placed upon the formulation regarding moisture, particle size, and the valve. For metered-dose inhalers, the dispensed product must be deflvered as a spray having a relatively small (3—6 -lm) particle size so that the particles can be deposited at the proper site in the respiratory system. On the other hand, topical powders must be formulated to minimize the number of particles in the 3—6-p.m range because of the adverse effects on the body if these materials are accidently inhaled. 

Along with increasing evidence of health benefits from consumption of vitamins at levels much higher than RE) A recommendations comes concern over potential toxicity. This topic has been reviewed (19). Like all chemical substances, a toxic level does exist for each vitarnin. Traditionally it has been assumed that all water-soluble vitamins are safe at any level of intake and all fat-soluble vitamins are toxic, especially at intakes more than 10 times the recommended allowances. These assumptions are now known to be incorrect. Very high doses of some water-soluble vitamins, especially niacin and vitamin B, are associated with adverse effects. In contrast, evidence indicates that some fat-soluble micronutrients, especially vitamin E, are safe at doses many times higher than recommended levels of intake. Chronic intakes above the RDA for vitamins A and D especially are to be avoided, however. 

Corticosteroids, while effective for rapidly inducing remission, are not effective for maintenance therapy and are associated with significant adverse effects with long-term use. Therefore, systemic or topical corticosteroids should not be used for maintaining remission in patients with IBD. Unfortunately up to 50% of patients treated acutely with corticosteroids become dependent on them to prevent symptoms.2... 

Evaluate for adverse effects and drug interactions. For patients on topical therapy, evaluate for local adverse effects. For patients on acetaminophen or NSAIDs, inquire about alcohol use. 

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... 

Avoiding or minimizing adverse effects from topical or systemic treatments used. 

It is important to remember that adverse effects of topical corticosteroids may be systemic in nature and hypothalamic-pituitary-adrenal axis suppression can occur, especially when high-potency corticosteroids are used. Infants and small children may be more susceptible due to their increased skin sur-face body mass ratio.18 Topical corticosteroids may also cause striae, skin atrophy, acne, telangiectasias, and rosacea.2,10,18 Atrophy can result in thin, fragile, easily lacerated skin. Striae are caused by tearing of dermal connective tissue and are irreversible.18 Due to their significant adverse-effect profile, it has been recommended that no topical corticosteroid be used regularly for more than 4 weeks without review and reassessment.2... 

Adverse effects are likely with the use of topical retinoids. Although transient, erythema, irritation, dryness, and peeling at the site of application are all common effects. Photosensitivity can also occur with retinoid use, causing increased skin irritation and redness.14... 

Adverse effects are generally mild and include dryness, erythema, and itching.18 Although rare and seen most often with oral therapy, pseudomembranous colitis can occur with the use of topical clindamycin.19 As with any antibacterial agent, the possibility of resistance exists with the use of topical erythromycin. However, co-administration of erythromycin and benzoyl peroxide has been shown to decrease the incidence of resistance, as well as to improve symptoms of mild to moderate inflammatory acne.20... 

Adverse effects from topical steroids are usually related to the potency of the steroid used, frequency of application, duration of therapy, and the site of application. Skin atrophy, hypopigmentation, striae, and steroid-induced acne are all possible side effects associated with long-term use.32,33... 

Adverse effects of fenvalerate on survival of terrestrial arthropods were observed at 0.002 to 0.015 pg whole-body topical application, O.llkg/ha aerial application, 5.4 mg/kg in the soil, 50 mg/kg in the diet, and 1.4 g/ant mound (Table 20.4). Synthetic pyrethroids are more effective in biological systems at low temperatures. The relative sensitivity of insects when compared with mammals is attributed in part to this negative temperature coefficient. Thus, warm-blooded animals are less affected than insects and other poikilotherms (Klaassen etal. 1986). Fenvalerate, for example, showed a negative correlation between temperature and toxicity to crickets (Acheta pennsylvanicus), being up to 1.9 times more toxic at 15°C than at 32°C (Harris etal. 1981). A similar case is made for honey bees (Apis mellifera) (Mayer et al. 1987) and for many species of aquatic invertebrates and fish (Mayer 1987). 

Tazarotene (Tazorac) is a synthetic retinoid that is hydrolyzed to its active metabolite, tazarotenic acid, which modulates keratinocyte proliferation and differentiation. It is available as a 0.05% or 0.1% gel and cream and is applied once daily (usually in the evening) for mild to moderate plaque psoriasis. Adverse effects are dose- and frequency related and include mild to moderate pruritus, burning, stinging, and erythema. Application of the gel to eczematous skin or to more than 20% of body surface area is not recommended because this may lead to extensive systemic absorption. Tazarotene is often used with topical corticosteroids to decrease local adverse effects and increase efficacy. 

Methotrexate, an antimetabolite, is indicated for moderate to severe psoriasis. It is particularly beneficial for psoriatic arthritis. It is also indicated for patients refractory to topical or UV therapy. Methotrexate can be administered orally, subcutaneously, or intramuscularly. The starting dose is 7.5 to 15 mg per week, increased incrementally by 2.5 mg every 2 to 4 weeks until response maximal doses are approximately 25 mg/wk. Adverse effects include nausea, vomiting, mucosal ulceration, stomatitis, malaise, headache, macrocytic anemia, and hepatic and pulmonary toxicity. Nausea and macrocytic anemia can be ameliorated by giving oral folic acid 1 to 5 mg/day. Methotrexate should be avoided in patients with active infections and in those with liver disease. It is contraindicated in pregnancy because it is teratogenic. 

The topical immunomodulators tacrolimus (Protopic) and pimecrolimus (Elidel) inhibit calcineurin, which normally initiatives T-cell activation. These agents can be used on all parts of the body for prolonged periods without producing corticosteroid-induced adverse effects. Tacrolimus ointment 0.03% and 0.1% is applied twice daily the lower strength is preferred in children with moderate to severe atopic dermatitis. The most common adverse effect is transient itching and burning at the site of application. Pimecrolimus cream 1% is applied twice daily for mild to moderate atopic dermatitis in adults and children older than age 2. 

Other adverse effects of topical decongestants include burning, stinging, sneezing, and dryness of the nasal mucosa. 

---