Long-term tachyphylaxis

The long-term toxicities of concern are opportunistic infections, lymphoproli-ferative disorders, and immunogenicity, manifesting as tachyphylaxis and/or allergic reactions. Preclinical approaches which serve to identify these as potential hazards to humans of a biologic drug moiety are thus needed. 

Geriatric Considerations - Summary Systemic absorption of ophthalmic drugs may occur and cause adverse effects in older adults. Since betaxolol is beta-selective, cardiovascular, respiratory and CNS adverse effects occur less frequently than with beta-nonselective topical opthalmics. These effects may still occur therefore close monitoring for systemic side effects is warranted. Betaxolol maybe less effective than the nonselective topical beta-blockers with an average lOP reduction of 18%-26%. Tachyphylaxis may occur after long-term therapy. 

Tachyphylaxis can develop after treatment with ophthalmic beta-blockers (366). There are two forms, short-term escape, which occurs over a few days, and long-term drift, which occurs over months and years. 

Billups KL. Re Long-term efficacy of sildenafil and tachyphylaxis effect. J Urol 2002 168(l) 204-5. 

Skill Pimecrolimus and tacrolimus can be used for prolonged periods, avoiding the adverse effects that are related to long-term use of topical glucocorticoids. Although atrophy, telangiectasia, and tachyphylaxis have not been described, topical tacrolimus... 

No tachyphylaxis has been observed in any species at repeated administration. In dogs the effects on acid secretion of daily oral administration have been recorded at intervals for 7 years without any significant change over the years [3]. Thus, these studies are well suited to answer questions about consequences of long-term acid inhibition in animals. The highest doses used in these studies render the test animals almost anacidic for the entire treatment period. 

As tachyphylaxis due to angiotensin can be prevented when the time between injections is sufficiently long in duration (14) or when the dissociation of the complex receptor - peptide is acdele-rated (20), it may be concluded that tachyphylaxis is due to resi-dually bound peptide. We therefore prefer the term auto-inhibition as the reduction of response is due to angiotensin itself and not to a persistent modification of muscular tissue. It must be noted that angiotensin tachyphylaxis on guinea-pig ileum is partially specific in that angiotensin renders the smooth muscle insensitive to itself but furthermore reduces its sensitivity to brady-kinin and in a lower extent to histamine in these conditions, action of acetylcholine is potentiated. 

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