Drug metabolism thiopental

The inactive metabolites are excreted in the urine. The administration of bicarbonate enhances the urinary excretion of barbiturates that have a pK of 7.4 (phenobarbital and thiopental). This generalization is not true of other barbiturates. The long-term administration of barbiturates activates the cytochrome P-450 drug-metabolizing system. 

The barbiturates were formerly the mainstay of treatment used to sedate the patient or to induce and maintain sleep. Today, they have been largely replaced by the benzodiazepines, mainly because barbiturates induce tolerance, drug-metabolizing enzymes, physical dependence, and very severe withdrawal symptoms. Foremost is their ability to cause coma in toxic doses. Certain barbiturates, such as the very short-acting thiopental, are still used to induce anesthesia (see p. 115). 

An alternative process that can lead to the termination or alteration of biologic activity is metabolism. In general, lipophilic xenobiotics are transformed to more polar and hence more readily excreted products. The role that metabolism plays in the inactivation of lipid-soluble drugs can be quite dramatic. For example, lipophilic barbiturates such as thiopental and pentobarbital would have extremely long half-lives if it were not for their metabolic conversion to more water-soluble compounds. 

In addition, the sleep-producing action of barbiturates is used to relax and partially anesthetize patients before some surgical procedures. Before some major brain surgeries, barbiturates (usually pentobarbital or thiopental) are used to temporarily induce coma in an effort to protect the brain these drugs can reduce the metabolic rate of brain tissue and control cerebral blood flow. 

Cerebral metabolism and oxygen utilization are decreased after thiopental administration in proportion to the degree of cerebral depression. Cerebral blood flow is also decreased, but much less so than oxygen consumption. This makes thiopental a desirable drug for use in patients with cerebral swelling (eg, head trauma, brain tumors), since intracranial pressure and blood volume are not increased (in contrast to the volatile anesthetics). 

All three barbiturates are primarily eliminated by hepatic metabolism and renal excretion of inactive metabolites a small fraction of thiopental undergoes desulfuration to the longer-acting hypnotic pentobarbital. Each drug is highly protein bound (Table 13-2). Hepatic disease or other conditions that reduce serum protein concentration will decrease the volume of distribution and thereby increase the initial free concentration and hypnotic effect of an induction dose. 

The pharmacokinetics of propofol are summarized in Table 13-2. Propofol s duration q/ier infusion (shorter than that of thiopental) can be explained by its very high clearance, coupled with the slow diffusion of drug from the peripheral to the central compartment. The rapid clearance of propofol explains its less severe hangover compared with barbiturates and may allow for a more rapid discharge from the recovery room. Propofol is metabolized in the liver to less active metabolites that are renally excreted Propofol is highly protein bound, and its pharmacokinetics, like those of the barbiturates, may be affected by conditions that alter serum protein levels. 

As soon as a drug finds its way into the blood stream, it tries to approach the site of biological action. Hence, the distribution of a drug is markedly influenced by such vital factors as tissue distribution and membrane penetration, which largely depends on the physico-chemical characteristics of the drug. For instance, the effect of the ultra-short acting barbiturate thiopental may be explained on its dissociation constant and lipid solubility. It is worthwhile to observe here that the dmation of thiopental is not influenced by its rate of excretion or metabolism, but by its rate of distribution. 

Thiopental sodium. A single induction dose of 3 to 5 mg kg may cause unconsciousness within a short span of 30 to 40 seconds. Its action is, however, terminated by the immediate redistribution of drug away from the brain. It has been observed that there exists a transient decrease in blood pressure (20%), and a simultaneous compensatory enhancement in the heart rate on injection. Thiopental is largely metabolized in the liver, although the kidney and muscle tissue may participate concurrently. 

Uitra-short Acting Thiopental Thiamylal Methohexital Hexobarbital Duration <3 hours. These drugs are deposited in fat, then secondarily metabolized by the liver. ... 

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