Timing of Onset and Duration

If a carbonic anhydrase inhibitor is being given for absence or nonlocalized epileptic seizures, the nurse assesses the patient at frequent intervals for the occurrence of seizures, especially early in therapy and in patients known to experience seizures at frequent intervals. If a seizure does occur, the nurse records a description of the seizure in the patient s chart, including time of onset and duration. Accurate descriptions of the pattern and the number of seizures occurring each day helps the primary health care provider plan future therapy and adjust drug dosages as needed. 

In Vitro Mediator Release. Although no pulmonary effects have been demonstrable in guinea pigs following inhalation of bract extract (104), contraction of isolated guinea pig ileum by extracts (105,106) has been reported. Aqueous extracts of cotton, jute, flax, and hemp cause contractions of isolated guinea pig ileirni or tracheal muscle preparations which are similar in time of onset and duration to those produced by... 

Commercial insulin preparations differ in a number of ways, such as differences in the recombinant DNA production techniques, amino acid sequence, concentration, solubility, and the time of onset and duration of their biologic action. 

HMR1964 (INN insulin glulisine) is a human insulin analogue for the treatment of Type I and Type II patients with diabetes mellitus. Combinations of insulin preparations that differ both in their time of onset and duration of action are used optimally to control blood glucose in patients with diabetes mellitus. The most commonly used insulin regimens include a long-acting in-... 

Much of the present day safety evaluation follows precepts (Table VI) which were promulgated by FDA for new drugs. This requires that therapeutic and toxic doses be studied for all toxic effects, site of action, mechanism of action, rates of absorption, distribution in the body, metabolism, excretion, time of onset and duration of effects. 

The loop diuretics usually possess a much greater diuretic profile in comparison to the thiazides and are observed to be even more potent and effective in a situation having electrolyte as well as acid-base disturbances concurrently. Besides, the time of onset and duration of action of the high-ceiling diuretics are emuch shorter than those with the thiazides. 

V 1 1 Inh Ons < 15m, Dur 3-4h PO Ons < 30m, Dur 4-8h. Time of onset and duration are most important points of distinction between these drugs. MAO inhibitors, tricyclic antidepressants and other sympathomimetics enhance sympathomimetic effects, may induce toxicity. P-blockers inhibit activity. Bronchodilator efficacy is severely reduced in hypoxic and acidotic patients. 

Administration of a local anesthetic in a carbonic acid-carbon dioxide aqueous solution rather than the usual solution of a hydrochloride salt appreciably improves the time of onset and duration of action. This change in solution form is apparently not associated with local or systemic toxicity. 

Relating the Time-Course of Plasma Concentrations to the Time-Course of Effect A critical decision to be made after the first human study is whether the compound s speed of onset and duration of action are likely to be consistent with the desired clinical response. Speed of onset is clearly of interest for treatments which are taken intermittently for symptoms rehef, for example, acute treatments for migraine, analgesics, or antihistamines for hay fever. Duration of action phase I is particularly important when the therapeutic effect needs to be sustained continuously, such as for anticonvulsants. The first information on the probable time course of action often comes from the plasma pharmacokinetic profile. However, it has become increasingly evident that the kinetic profile alone may be misleading, with the concentration-time and the effect-time curves being substantially different. Some reasons for this, with examples, include... 

Some of the more frequently used barbiturates are described briefly in the following sections. For the structures, the usual dosages required to produce sedation and hypnosis, the times of onset, and the duration of action, see Table 14-2,... 

Malnutrition during the early life of animals and humans alters the number of brain colls, brain coll size and/or other biochemical parameters, depending upon the time of onset and the duration of the malnutrition. 

Most ACE inhibitors are prodrugs, with the exceptions of captopril, lisinopril, and ceranapril. Prodrugs exert improved oral bioavailability, but need to be converted to active compounds in the liver, kidney, and/or intestinal tract. In effect, converting enzyme inhibitors have quite different kinetic profiles with regard to half time, onset and duration of action, or tissue penetration. 

The Army, however, was now attempting for the first time to develop trustworthy estimates of how various doses of a given drug would affect populations, rather than single individuals. This required the establishment of parameters - numbers that would define the most probable quantitative clinical effects across a spectrum of subjects. Commanders would need to know not only the typical but also the probable range of response values for such important attributes as potency, time of onset, duration and other important aspects of drug action. Such precision is rarely called for in civilian settings (except in, e.g., cancer therapy). 

While the individual drugs in the benzodiazepine group differ in potency, all benzodiazepines in common use have anxiolytic, sedative-hypnotic, anticonvulsant and muscle-relaxant activity in ascending order of dose. The main clinical difference between the individual drugs lies in the time of onset of their therapeutic effect, and the intensity and duration of their clinical activity. 

What toxic effects are induced following a single exposure to a substance, their time of onset, duration, and severity (all to be related to dose)... 

The first-generation sulfonylureas are not frequently used in the modem management of diabetes mellitus because of their relatively low specificity of action, delay in time of onset, occasional long duration of action, and a variety of side effects. They also tend to have more adverse drug interactions than the second-generation sulfonylureas. They are occasionally used in patients who have achieved previous adequate control with these agents. 

Some 25 anxiolytics and hypnotics are marketed at present the best known of these are listed in Table 1.10. Here, again., there are striking differences between the doses of these products, which can be explained m the same way as for antipsychotics. The benzodiazepine derivatives and related compounds show few qualitative differences nevertheless, the time effect features, i.e. the timing of onset of action and peak action as well as duration of action, mean that it is sensible to use different products for different purposes. 

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