Тиопентал в опытах!!!
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#3
13.10.2005, 20:45
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#4
13.10.2005, 22:39
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А вот и неверно, существует видовая чувствительность и формулы для перерасчета дозы. А вообще для типентала все уже давно известно. Так на ком работаете. Дя и еще скобрезный вопрос, откуда тиопентал для опытов?
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#5
13.10.2005, 22:55
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#7
13.10.2005, 23:17
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#8
13.10.2005, 23:26
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#9
13.10.2005, 23:35
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#11
13.10.2005, 23:55
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#13
14.10.2005, 00:23
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#14
14.10.2005, 04:59
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Цитата:
•Absorption Following IV administration of usual induction doses of thiopental sodium (2.5–5 mg/kg) in adults, onset of action (hypnosis or unconsciousness) reportedly occurs rapidly, within 10–40 seconds, with maximal effects occurring in about 1 minute and the duration of anesthesia persisting 5–8 minutes. The duration of action of thiopental is variable. The duration of action of single doses of thiopental sodium usually is determined by the redistribution of the drug from the CNS rather than by the rate of elimination. However, the duration of the anesthetic effect is prolonged following repeated injections of thiopental sodium or by administration of a continuous infusion, because of the drug‘s accumulation in the adipose tissue. Decline of thiopental serum concentrations begins within approximately 1 minute after administration of single doses of thiopental sodium and emergence from anesthesia is initiated. Following IV administration of thiopental sodium, time to recovery from anesthesia is variable. Recovery may be rapid following administration of a small single dose. However, since thiopental is highly lipid soluble, prolonged anesthesia may occur after repeated doses because of accumulation of the drug in fat tissue. Thiopental concentrations may be 6–12 times higher in adipose tissue than in plasma, and elimination of the drug may be slow from tissue storage sites. Peak adipose tissue concentrations are attained within 1.5–10 hours following administration of 150–1500 mg of thiopental sodium, administered by a rapid IV bolus injection. Time to recovery from anesthesia appears to be slower in patients receiving thiopental sodium than in those receiving propofol. In a double-blind, comparative, crossover study in healthy adults receiving propofol (2.5 mg/kg initially, followed by 1 mg/kg 3 minutes later) or thiopental sodium (5 mg/kg initially, followed by 2 mg/kg 3 minutes later), improvement of psychomotor performance (as measured by patient response to verbal command) was faster in patients receiving propofol (mean time: 33 minutes) than in those receiving thiopental sodium (mean time: 62 minutes). In addition, psychomotor performance was impaired for up to 5 hours after administration of thiopental sodium and for 1 hour after propofol. Following usual induction doses of thiopental sodium, venous concentrations of thiopental reportedly were 50 and 39 mcg/mL in men and women, respectively, when measured 20 seconds after loss of consciousness (assessed by loss of lid reflex). In patients with status epilepticus, there is considerable interpatient variation in the relationship of thiopental concentrations and therapeutic effect, but limited data indicate that seizure control is observed at plasma concentrations of 15–50 mcg/mL. To induce profound coma for the management of cerebral ischemia, 5–10 mg/kg per hour IV infusions of thiopental sodium, administered for 2–3 days, were associated with serum thiopental concentrations of 60–100 mcg/mL. Evidence of cerebral activity (movement in response to noxious stimuli) occurred when plasma thiopental concentrations decreased to 13–30 mcg/mL. Recovery of motor responses was proportional to plasma concentrations at the end of the IV infusions and occurred 6–24 and 30–60 hours after thiopental concentrations of 17.5–32 and 36–64 mcg/mL, respectively. Following rectal administration of single 4-mg/kg doses of thiopental sodium in adults, the onset of sedative and/or hypnotic action usually occurs within 10 minutes, with maximum effects being achieved within 30 minutes and the approximate duration of hypnosis or basal anesthesia persisting for up to 1 hour. In children following rectal administration of thiopental, onset of action is rapid, occurring within 8–10 minutes, and the duration of action ranges from 40 minutes to about 5 hours. Following rectal administration of thiopental doses of 20, 30, and 40 mg/kg in children (2–8 years of age) average peak plasma concentrations of 10.2, 12.7, and 18.3 mcg/mL were achieved within 20–30 minutes. Rectal absorption of thiopental may be unpredictable when using a suspension rather than a solution of the drug. •Distribution Following IV administration, thiopental is rapidly distributed to all tissues and fluids with high concentrations in brain and liver. Lipid solubility of thiopental, and to a lesser extent its protein binding, are the dominant factors in the drug’s distribution in the body. Following IV administration of thiopental sodium in rats, the drug distributes into brain, heart, intestines, spleen, pancreas; peak tissue concentrations are achieved in about 1 minute. Thiopental equilibrates rapidly in highly perfused organs and tissues (e.g., CNS, viscera), while the uptake is delayed in less perfused organs and tissues (e.g., muscle, adipose tissue). In rats, peak tissue concentrations occur in about 6, 30, and 60–120 minutes in muscle or testes, skin, and adipose tissue, respectively. Thiopental penetrates the blood-brain barrier rapidly, and its rate of entry into the brain is limited only by the rate of cerebral blood flow. CSF concentrations of the drug are slightly lower than those in plasma. The steady-state volume of distribution (VSS) of thiopental following IV administration reportedly is about 0.4–4 L/kg in adults. The VSS may vary according to dosage and mode of administration (single- or multiple-dose); the pharmacokinetic model (e.g., 1-, 2-, 3-, or 4-compartment) used to describe the drug; and gender, age, or weight of the patient. Limited data indicate that the average VSS is greater in women 20–40 years old (1.2 L/kg) than in men of the same age (0.417 L/kg). It has been suggested that the initial volume of distribution (Vd) may change with age; however, these changes may be associated with the pharmacokinetic model used. The VSS is 3–4 times higher in obese patients compared with lean patients possibly because of the highly lipophilic nature of the drug. At concentrations of 10–50 mcg/mL, thiopental is approximately 80% (range: 60–97%) bound to plasma proteins, mainly to albumin. The extent of protein binding of thiopental may be affected by drug or plasma protein concentrations, changes in serum pH, and presence of other drugs or biologics competing for thiopental binding sites. However, the clinical importance of these effects have not been fully elucidated. Protein binding may be reduced in patients with renal or hepatic impairment; the fraction of free thiopental in plasma reportedly has been twofold higher in patients with such impairments than in healthy individuals, possibly because of hypoalbuminemia and qualitative changes in serum albumin. Thiopental readily crosses the human placenta and is distributed into fetal blood and umbilical vein blood at delivery. The drug is detected in fetal blood within seconds after administration and peak fetal blood concentrations occur in about 3 minutes; however, the drug is rapidly redistributed in the fetus, and brain concentrations are lower than those detected in the umbilical vein. In one study in women undergoing cesarean section who received rapid IV injection of thiopental sodium (5 mg/kg) for induction of anesthesia, the ratio of umbilical venous to maternal blood concentrations was about 0.77. Higher ratios (0.96) of umbilical venous to maternal blood concentrations also have been reported. Thiopental is distributed into milk in humans; colostrum-to-plasma ratios 4 and 9 hours after induction anesthesia with the drug reportedly were 0.67 and 0.68, respectively. •Elimination The elimination of thiopental is complex. Following small IV doses of thiopental, the drug appears to decline in a monoexponential (first-order) fashion, with an elimination half-life of about 3–22 hours. Following a rapid IV (‘‘bolus’’) injection, pharmacokinetics of thiopental can be described by a triexponential equation; the drug appears to undergo a rapid and slow distribution phase followed by a terminal elimination phase. In the rapid distribution phase, thiopental equilibrates rapidly in highly perfused organs (CNS, viscera), while in the slow distribution phase the drug equilibrates between the highly perfused organs and adipose tissue. In adults, the mean plasma half-lives in the initial distribution phase and slow distribution phase are about 1.7–13.2 and 39.5–161.4 minutes, respectively. In addition, at high therapeutic concentrations, pharmacokinetics of thiopental can be characterized by Michaelis-Menten kinetics, with a first-order elimination half-life is 9.72–49.4 hours. In pediatric patients (5 months to 13 years of age), the elimination half-life of thiopental was about one-half the elimination half-life in adults (about 6 hours); however, the elimination half-life in neonates was increased by twofold compared with their mothers’ (about 15 hours). Thiopental is metabolized mainly in the liver (by the cytochrome P-450 [CYP] microsomal enzyme system) and to a lesser extent in other organs and tissues (e.g., kidneys, brain). Thiopental undergoes desulfuration to form pentobarbital, an active metabolite. However, both thiopental and pentobarbital undergo oxidation and hydroxylation to form the corresponding carboxylic acid metabolites and alcohols, respectively; all detected metabolites have been found to be pharmacologically inactive. Total body clearance of thiopental reportedly is 1.96–4.3 mg/mL per kg in healthy adults. Thiopental is excreted mainly in urine as inactive metabolites, with small amounts as unchanged drug.
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