Tachyphylaxis

Another potential complication can occur if the responsiveness of the receptor system changes temporally. This can happen if the receptor (or host system, or both) demonstrates desensitization (tachyphylaxis) to drug stimulation (see Chapter 2). There are numerous systems where constant stimulation with a drug does not lead to a constant steady-state response. Rather, a fade of the response occurs. This can be due to depletion of a cofactor in the system producing the cellular response or a conformational change in the receptor protein. Such phenomena protect against overactive stimulation of... 

Tachyphylaxis is a loss of drug efficiency which develops in minutes or hours. Transmitter depletion and receptor desensitization are the basic mechanisms of this phenomenon. 

Tachyphylaxis develops with repeat doses. Activity may return after a 3-d drug-free period... 

If an inadequate response is observed after 1-2 d, may increase the dose to eight units/kg SQ every 12 h ° Tachyphylaxis may develop (limit use to 48 h)... 

Continuous infusions of nitroglycerin should be initiated at a dose of 5 to 10 mcg/minute and increased every 5 to 10 minutes until symptomatic or hemodynamic improvement. Effective doses range from 35 to 200 mcg/minute. The most common adverse events reported are headache, dose-related hypotension, and tachycardia. A limitation to nitroglycerin s use is the development of tachyphylaxis, or tolerance to its effects,... 

Desmopressin (DDAVP) increases the release of factor VIII (von Willebrand factor) from endothelial tissue in the vessel wall. Bleeding time is promptly reduced, within 1 hour of administration, and is sustained for 4 to 8 hours.42 Doses used for uremic bleeding are 0.3 to 0.4 mcg/kg intravenously over 20 to 30 minutes, 0.3 mcg/kg subcutaneously, or 2 to 3 mcg/kg intranasally. Repeated doses can cause tachyphylaxis by... 

A loading dose of 0.2 mg/kg (repeated up to a maximum of 2 mg/kg) followed by a continuous infusion of 0.05 to 2 mg/kg per hour is recommended in RSE.29-31 The dose must be adjusted during prolonged infusions, especially in patients with renal impairment, as the active metabolite can accumulate.32 Breakthrough seizures are common with midazolam infusions and usually respond to a bolus and a 20% increase in the rate. Despite this, tachyphylaxis can occur and the patient should be switched to another agent if seizure activity continues. 

Topical P-blockers are typically administered twice daily. A gel-forming solution of timolol (Timoptic-XE) can be administered once daily. Tachyphylaxis may occur in 20% to 50% of patients on monotherapy with a P-blocker, resulting in the need for a different agent or combination therapy. Patients on concurrent systemic P-blockers may experience less IOP reduction than patients only on topical P-blockers.10,38... 

Topical intranasal decongestants (e.g., oxymetolazine, xylome-tolazine, phenylephrine, and naphazoline) are OTC options that provide prompt relief of nasal congestion. Nasal decongestants are dosed multiple times daily.15 Tachyphylaxis, rebound congestion, and rhinitis medicamentosa may occur with chronic use therefore, use should be limited to 3 to 5 days.8,12 These may be used 5 to 10 minutes before administration of intranasal corticosteroids in patients with blocked nasal passages.15... 

Vitamin D analogues (calcipotriol, calcitriol, and tacalcitol) are also frequently selected as initial pharmacotherapy in the management of mild to moderate psoriasis.2 These inhibit keratinocyte differentiation and proliferation and maybe antiinflammatory.2 Unlike corticosteroids, tachyphylaxis does not occur with prolonged use. Clearance of lesions should occur after 4 to 6 weeks of treatment.2 Lack of response by 8 weeks... 

Primary therapy is based on disease severity and type of hemorrhage.7 Most patients with mild to moderate disease and a minor bleeding episode can be treated with l-desamino-8-D-arginine vasopressin [desmopressin acetate (DDAVP)], a synthetic analog of the antidiuretic hormone vasopressin. DDAVP causes release of von Willebrand factor (vWF) and factor VIII from endogenous storage sites. This formulation increases plasma factor VIII levels by three- to fivefold within 30 minutes. The recommended dose is 0.3 mcg/kg intravenously (in 50 mL normal saline infused over 15 to 30 minutes) or subcutaneously or 300 meg intranasally via concentrated nasal spray every 12 hours. Peak effect with intranasal administration occurs 60 to 90 minutes after administration, which is somewhat later than with intravenous administration. Desmopressin infusion may be administered daily for up to 2 to 3 days. Tachyphylaxis, an attenuated response with repeated administration, may occur after several doses.8... 

Tachyphylaxis Rapidly decreasing response to a drug or other physiologically active agent after a few doses. 

Decreased sensitivity to a drug, or tolerance, is seen with some drugs such as opiates and usually requires repeated administration of the drug. Tachyphylaxis, in contrast, is tolerance that develops rapidly, often after a single injection of a drug. In some cases, this may be due to what is termed as the dawn regulation of a drug receptor, in which the number of receptors becomes decreased. 

Midazolam has been suggested by some practitioners as the first-line treatment for refractory GCSE. Most patients respond within 1 hour, but the infusion rate should be increased every 15 minutes in those who do not. Tachyphylaxis can develop, and dosing should be guided by EEG response. 

Patients should be monitored for tachyphylaxis, especially with / -blockers or apraclonidine. Treatment can be temporarily discontinued to monitor its benefit. 

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. 

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