Delayed onset effect

Latent effects occur either only after there has been a significant period free of toxic signs following exposure, or after resolution of acutely toxic effects which appeared immediately following exposure. They are also referred to as delayed-onset effects. 

Meyer A, Seidler FJ, Slotkin TA (2004) Developmental effects of chlorpyrifos extend beyond neurotoxicity Critical periods for immediate and delayed onset effects on cardiac and hepatic cell signaling. Environ Health Perspect, 112(2) 170-178. 

The delayed onset effect was discovered experimentally by Ederer [180] in 1964 in the photoionisation spectrum of Xe gas. A more recent compilation of results for the same spectrum is presented in fig. 5.1. If one considers the ionisation continuum of H, then just above the ionisation threshold, there is a maximum in the cross section, which is followed by a monotonic decline with increasing energy. Such situations are illustrated in fig. 4.1 until the observations of Ederer, it had been believed that this would be the most general behaviour of continuum cross sections and that, apart from the Seaton-Cooper minima discussed in section 4.4, or the local influence of interchannel perturbations, revealed in spectra such as that of fig. 4.3, unperturbed continuum cross sections would usually follow a monotonic course of declining intensity comparable to that of H. 

The delayed onset effect was soon explained in terms of a centrifugal... 

Fig. 5.1. The spectrum of Xe above the 4d thresholds, showing the delayed onset effect. The dots are experimental results from [181], the open circles are from [182] and the triangles from [183], while the theoretical curves (Hartree-Fock length and velocity approximations - see equation (5.31)) are due to [184]. Note the logarithmic scales.

Another scientific argument for evaluating safety pharmacology effects on repeat-dosing is the phenomenon of delayed-onset effects that may be missed if just assessing the effects of a single administratiOTi. Mechanisms for delayed effects... 

The threshold limit value—time integrated average, TLV—TWA, of chlorine dioxide is 0.1 ppm, and the threshold limit value—short-term exposure limit, STEL, is 0.3 ppm or 0.9 mg /m of air concentration (87,88). Chlorine dioxide is a severe respiratory and eye irritant. Symptoms of exposure by inhalation include eye and throat irritation, headache, nausea, nasal discharge, coughing, wheezing, bronchitis, and delayed onset of pulmonary edema. Delayed deaths occurred in animals after exposure to 150—200 ppm for less than one hour. Rats repeatedly exposed to 10 ppm died after 10 to 13 days of exposure. Exposure of a worker to 19 ppm for an unspecified time was fatal. The ingested systemic effects of low concentration chlorine dioxide solutions are similar to that of chlorite. 

The controlled-release (CR) formulation is more slowly absorbed and longer acting than immediate-release tablets. Patients need to increase the total daily dose by 30%, as it is not as bioavailable as the immediate-release levodopa/carbidopa. The CR formulation has a delayed onset (45 to 60 minutes) compared to the standard formulation (15 to 30 minutes). Thus, patients may also need to take immediate-release tablets or even a liquid formulation when they want a quicker onset of effect, such as with the first morning dose.1,8,25... 

Imipramine3 10-25 75-250 cardiovascular effects delayed onset of action may precipitate mania sexual side effects toxic in overdose weight gain... 

Antidepressants have a delayed onset of antipanic effect, typically 4 weeks, with optimal response at 6 to 12 weeks. Reduction of anticipatory anxiety and phobic avoidance generally follows improvement in panic symptoms. PD patients are more likely to experience stimulant-like side effects than patients with depression, and they should be initiated on lower doses (Table 37-6) of antidepressant than those that are used for depression or other... 

For patients with moderate to severe symptoms, the patient is usually offered drug treatment first. a-Adrenergic antagonists are preferred over 5a-reductase inhibitors because the former have a faster onset of action (days to a few weeks) and improve symptoms independent of prostate size. 5a-reductase inhibitors have a delayed onset of action (i.e., peak effect may... 

It is considered a second-line agent for GAD because of inconsistent reports of efficacy, delayed onset of effect, and lack of efficacy for comorbid depressive and anxiety disorders (e.g., panic disorder or SAD). It is the agent of choice in patients who fail other anxiolytic therapies or in patients with a history of alcohol or substance abuse. It is not useful for situations requiring rapid antianxiety effects or as-needed therapy. 

Since the introduction of the first approved SSRI, fluoxetine (1) in 1987 [9], a number of SSRIs have been developed for the treatment of depression [2], Currently, the five most commonly prescribed SSRIs are fluoxetine, escitalopram (2, S-enantiomer of citalopram), sertraline (3), paroxetine (4) and fluvoxamine (5). Recent effort in the clinical development of new SSRIs has focused on the treatment of premature ejaculation (PE) by taking advantage of the ejaculation-delaying side effects of SSRIs [10]. Although SSRIs have been prescribed off-label to treat this condition, an SSRI with rapid onset of action and rapid clearance could be preferred for on-demand treatment of PE [11,12]. Dapoxetine (LY210448, 6), an... 

Like the MAOIs, TCAs are hindered by a delayed onset of action that can be especially intolerable for those with frequent and severe panic attacks. When starting treatment, TCAs, like SSRIs, may also produce a transient nervousness that is especially uncomfortable for those with panic disorder. When this occurs, the starting dose should be reduced by half, and the pace of subsequent dose increases should be even slower than usual. Because they produce prominent side effects and can be dangerous in overdose, TCAs are also now reserved for patients unresponsive to other treatments. Refer to Chapter 3 for a more extensive discussion of the TCAs. 

Buspirone (Buspar). The first nonsedating, nonbenzodiazepine specifically introduced as an anxiolytic, buspirone is FDA approved for the treatment of GAD. This medication acts as a partial agonist at the postsynaptic serotonin (5HT)-1A receptor. Like the antidepressants, buspirone has a delayed onset of action and effectively relieves the intrapsychic symptoms of GAD. Devoid of the muscle-relaxing properties of benzodiazepines, buspirone does not as effectively relieve the physical symptoms of GAD. Buspirone is not effective in the treatment of depression. Furthermore, its utility for the treatment of anxiety disorders other than GAD appears to be limited. 

Buspirone (Buspar). Buspirone is a nonbenzodiazepine anxiety-reducing medication. It can be an effective treatment for demented patients with chronic anxiety. Buspirone is not sedating like the benzodiazepines and in fact probably has the fewest side effects of any available psychiatric medication. Buspirone does have a delayed onset of action therefore, it is not useful for acute treatment of anxiety or agitation. 

The LCso in mice for 60 minutes was 150 ppm effects were irritation of the eyes and nose and the delayed onset of labored breathing and lethargy autopsy findings included marked pulmonary congestion and hemorrhage. Mice exposed to sublethal concentrations had pulmonary irritation and delayed development of focal necrosis in the liver and kidneys. ... 

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