Peak effects

Po adrninistered nifedipine is almost completely absorbed. The onset of action is 20 min and peak effects occur at 1—2 h. The principal route of elimination is through hepatic metaboHsm by oxidation to hydroxycarboxyHc acid and the corresponding lactone. These metaboHtes are pharmacologically inactive. Almost 70—80% of dmg is eliminated in the urine during the first 24 h. About 15% is excreted in the feces. The elimination half-life of nifedipine is about 1—2.5 h (1,98,99). Frequency of occurrence of side effects in patients is about 17% with about 5% requiring discontinuation of therapy (1,98,99). 

When adininistered orally, digoxin bioavailabihty ranges from 40 to 90% depending on the manufacturing process. Peak plasma levels occur within 3 h after oral adininistration peak effects occur 2 h later. The dmg is elkninated primarily through the kidney (114). 

Three rapid-acting insulins have been approved in the United States lispro, aspart, and glulisine. Substitution of one or two amino acids in regular insulin results in the unique pharmacokinetic properties characteristic of these agents. Onset of action of rapid-acting insulins varies from 15 to 30 minutes, with peak effects occurring 1 to 2 hours following administration. 

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... 

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... 

The basal insulin component may be provided by once- or twice-daily NPH or detemir, or once-daily insulin glargine. Most type 1 DM patients require two injections of all insulins except insulin glargine. All of the insulins (with the exception of insulin glargine) have some degree of peak effect that must be considered in planning meals and activity. Insulin glargine or insulin detemir is a feasible basal insulin supplement for most patients. 

With oral opioids, the onset of action usually takes about 45 minutes, and peak effect usually is seen in about 1 to 2 hours. 

Selegiline also increases the peak effects of L-dopa and can worsen preexisting dyskinesias or psychiatric symptoms such as delusions and hallucinations. Other adverse effects include insomnia, jitteriness. 

Ipratropium bromide has a slower onset of action than short-acting /J2-agonists (15 to 20 minutes vs. 5 minutes for albuterol). For this reason, it may be less suitable for as-needed use, but it is often prescribed in this manner. Ipratropium has a more prolonged bronchodilator effect than short-acting /l2-agonists. Its peak effect occurs in 1.5 to 2 hours and its duration is 4 to 6 hours. The recommended dose via MDI is two puffs four times a day with upward titration often to 24 puffs/day. It is also available as a solution for nebulization. The most frequent patient complaints are dry mouth, nausea, and, occasionally, metallic taste. Because it is poorly absorbed systemically, anticholinergic side effects are uncommon (e.g., blurred vision, urinary retention, nausea, and tachycardia). 

Under the Food Quality Protection Act (FQPA), the U.S. EPA evaluates the potential for people to be exposed to more than one pesticide at a time from a group of chemicals with an identified common mechanism of toxicity. As part of the examinations, to clarify whether some or all of the pyrethroids share a common mechanism of toxicity, a comparative FOB (functional observational battery) studies with 12 pyrethroids were carried out under standardized conditions [15]. The FOB was evaluated at peak effect time following oral administration of non-lethal doses of pyrethroids to rats using com oil as vehicle. Four principal components were observed in the FOB data [22], Two of these components described behaviors associated with CS syndrome (lower body temperature, excessive salivation, impaired mobility) and the others described behaviors associated with the T syndrome (elevated body temperature, tremor myoclonus). From the analysis, pyrethroids can be divided into two main groups (Type I T syndrome and Type II CS syndrome) and a third group (Mixed Type) that did not induce a clear typical response. Five other pyrethroids were also classified by an FOB study conducted in the same manner [16]. The results of these classifications are shown in Table 1. The FOB results for all non-cyano pyrethroids were classified as T syndrome, and the results of four ot-cyano pyrethroids were classified as CS syndrome however, three of the ot-cyano pyrethroids, esfenvalerate, cyphenothrin, and fenpropathrin, were classified as Mixed Type. 

Column temperature (T) Increased temperature decreased retention time Increased temperature sharper peaks effect on N difficult to define check maximum and minimum temperature before using column... 

The effect may be delayed with respect to plasma concentration because of slow uptake into the target tissue from the plasma. A well-known example is digoxin, where there is a delay of several hours between peak plasma concentration and peak effect. 

A surface peak effect has been observed during Rb and Sr diffusion in vitreous silica (13). Such large near-surface concentrations are postulated to result from the exposure at the glass surface of a greater number of interstices or defects over which diffusion can occur. This would lead to steep penetration curves observed in some XPS profiles of glass. 

A methodologically controlled study of valerian in sleep was published that utilized both double-blind and placebo controls, as well as randomization (Gessner and Klasser 1984). Also employed were two doses of valerian (60 and 120 mg), computerized EEG power spectral analysis and psychometric mood questionnaires. Valerian increased sleep stages 1, 2, and 3 and reduced stage 4 and REM. Dose-dependent effects were noted, where the 120 mg dose produced greater sedative effects. Peak effects occurred 2-3 hours after administration. Mood ratings did not differ, positively or negatively, between the experimental and control conditions. 

Both THC and ethanol increase reaction time, and produce decrements in standing steadiness and psychomotor coordination (Belgrave et al. 1979). Whereas the peak effects of ethanol appeared quickly and wore off quickly (after 280 minutes), THC s effects were slower in onset and longer in duration. The effects of combined THC and ethanol are additive and not synergistic, and THC did not alter blood-ethanol levels. Other studies have shown an interaction between ethanol and THC on psychomotor skills necessaiy for driving, although there were no interactions on the subjective "high," heart rate acceleration, or THC plasma concentration (Perez-Reyes et al. 1988). 

The IDso of 302196 produces essentially the same effect on performance, whether given by the intramuscular or the intravenous route (Fig. 51). Peak effects occur early, with a Tonso of abut 10 minutes. Partial recovery occurs at less than 4 hours and full recovery at about 10 hours. By both routes, the onset is very rapid and short dived. 

TABLE V. ON PEAK EFFECT OF INJECTION CONCENTRATION HEIGHT AND RETENTION VOLUME OF D2O ... 

The duration and degree of reversal of benzodiazepine effects are related to the dose and plasma concentrations of flumazenil. The onset of reversal is usually evident within 1 to 2 minutes after the injection is completed. Within 3 minutes, 80% response will be reached, with the peak effect occurring at 6 to 10 minutes. Pharmacokinetics After IV administration, flumazenil has an initial distribution half-life of 7 to 15 minutes and a terminal half-life of 41 to 79 minutes. Peak concentrations of flumazenil are proportional to dose, with an apparent initial volume of distribution of 0.5 L/kg. After redistribution the apparent volume of distribution ranges from 0.77 to 1.6 L/kg. Protein binding is approximately 50%. 

Extended-release - When administered at bedtime, office evaluation of blood pressure (BP) during morning and early afternoon hours is essentially a measure of peak effect. The usual evaluation of trough effect would be just prior to bedtime. Swallow whole do not chew, break, or crush the tablets. 

Oral The peak effects of single oral doses occur within 2 to 4 hours and lasts 8 to 12 hours. The maximum, steady-state BP response upon oral, twice-a-day dosing occurs within 24 to 72 hours. 

Visuai disturbances Single oral doses of phosphodiesterase inhibitors have demonstrated transient, dose-related impairment of color discrimination (blue/green), with peak effects near the time of peak plasma levels. The findings were most evident 1 hour after administration, diminishing but still present 6 hours after administration. 

SR Administer one-half the patient s total daily oral morphine dose as Kadian every 12 hours or by administering the total daily oral morphine dose as Kadian every 24 hours. Kadian should not be given more frequently than every 12 hours. The first dose of Kadian may be taken with the last dose of any IR opioid medication because of the long delay until the peak effect after administration of Kadian. 

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