Anesthetics pharmacological effects

Zipeprol [34758-83-3] (58) is another European antitussive with a wide range of pharmacological effects, including antispasmodic, antihistaminic, and local anesthetic activities (85,86). It has been reported that zipeprol has been abused in Italy because high doses cause hallucinations (87). Spontaneous withdrawal symptoms similar to those of opiates have been observed withdrawal symptoms can also be precipitated by naloxone. Zipeprol can be... 

Local anesthetics interact with peripheral nerve cell membranes and exert a pharmacological effect [34]. Potential oscillation was measured in the presence of 20 mM hydrochlorides of procaine, lidocaine, tetracaine, and dibucaine (structures shown in Fig. 16) [19]. Amplitude and the oscillatory and induction periods changed, the extent depending on the... 

Although PCP was developed as an anesthetic, its profile as an anesthetic is very different from typical general anesthetics of the CNS-depressant class (Domino 1964). Nonetheless, PCP has a number of behavioral and pharmacological effects similar to those of depressants such as the barbiturates (Balster and Wessinger 1983). PCP has profound motor effects, as evidenced by effects on rotorod performance and similar measures (Kalir et al. 1969 ... 

Domino EF, Chodoff P, Corssen G (1965) Pharmacologic effects of Cl-581, a new dissociative anesthetic, in man. Clin Pharmacol Ther 6 279-291 Doraiswamy PM (2002) Non-cholinergic strategies for treating and preventing Alzheimer s disease. CNS Drugs 16 811-824... 

Estazolam potentiates the CNS depressant effects of phenothiazines, narcotics, antihistamines, MAOIs, barbiturates, alcohol, general anesthetics, and TCAs. Use with cimetidine, disulfiram, oral contraceptives, and isoniazid may diminish hepatic metabolism and result in increased plasma concentrations of estazolam and increased CNS depressant effects. Fleavy smoking (more than 20 cigarettes/day) accelerates estazolam s clearance. Theophylline antagonizes estazolam s pharmacological effects. 

A few substances that are almost completely inert in the chemical sense nevertheless have significant pharmacologic effects. For example, xenon, an "inert" gas, has anesthetic effects at elevated pressures. 

Nitrous oxide appears to have little effect on uterine musculature. However, the halogenated anesthetics are potent uterine muscle relaxants and produce this effect in a concentration-dependent fashion. This pharmacologic effect can be used to advantage when profound uterine relaxation is required for an intrauterine fetal manipulation or manual extraction of a retained placenta during delivery. However, it can also lead to increased uterine bleeding. 

It was at the turn of the twentieth century that the importance of lipid solubility in drug action was also independently described by Meyer and Overton (the significance of the oil/water partition coefficient was discussed in Chapter 2). The importance of lipid solubility in drug action subsequently became manifested in the lipoid theory of cellular depression. In essence, this theory correlated a pharmacological effect (e.g., CNS depression) with a physical property (i.e., lipid solubility) rather than a structure-activity relationship. In the process, the theory was attempting to explain the diverse chemical structures that exist within the hypnotic and general anesthetic classes of drugs (see Chapter 11). Today, we realize the limitations of the lipoid theory and appreciate that the distinction between physical and chemical factors is illusory, since chemical structure is a determinant of physical properties. 

The pharmacological effect of local anesthetics after subcutaneous injection is determined with the method of Bulbring and Wajda (1945) in guinea pigs and modifications thereof (Ther 1953b). 

Ketamine, more commonly known on the street as Special K and to the scientist as ketamine hydrochloride, is a unique drug with a combination of pharmacological effects. Although it is primarily used by veterinarians as an animal tranquilizer, it is available for limited uses in humans. Chemically, it is similar to phencyclidine (PCP or angel dust), a Schedule II drug that was the first of a new class of general anesthetics called dissociative anesthetics. As the name implies, dissociative anesthetics produce in patients a feeling of detachment and disconnection from pain and the environment. 

Cocaine exhibits several pharmacologic effects. After local application it acts as an anesthetic by blocking the initiation and conduction of nerve impulses. In addition, it has been shown to block neuronal reuptake of norepinephrine, thus potentiating adrenergic activity. Moderate doses increase heart rate and cause vasoconstriction. The most striking systemic effect of cocaine is central nervous system stimulation. 

The pharmacological effects of tiletamine plus zolazepam are very similar to the effects produced by ketamine. When used as the sole anesthetic in the horse, tiletamine plus zolazepam can cause excitation and hyperresponsiveness. This combination is only used in the horse after adequate sedation. In general, it produces a dose-related loss of consciousness, characterized as a cataleptic state, and analgesia. Ocular and airway reflexes are well maintained. The combination induces mild cardiovascular stimulation secondary to centrally mediated sympathetic nervous system stimulation. There is minimal respiratory depression. 

The foregoing studies have dealt chiefly with model substrates in vitro. Several of the early papers by Augustinsson, referred to in Section 4.1.1, considered substrate specificity from the viewpoint of species variations. It is also important to recognize that plasma cholinesterase may be associated with the hydrolysis, in vivo, of a large number of drugs (K4, LI, L4) that contain ester bonds susceptible to enzymic hydrolysis. Apart from succinylcholine (Section 3.1), cholinesterase is known to be responsible in man for the hydrolysis of cocaine (S40), procaine (K2), and other esters with local anesthetic properties. Whether enzymatic hydrolysis terminates the pharmacologic effect depends on the whole mechanism of action of the particular drug. 

The first hint that a physical property of a drug could be related to biological activity appeared almost 100 years ago when scientists recognized that chloroform (CHCI3), diethyl ether, cyclopropane, and nitrous oxide (N2O) were all useful general anesthetics. Clearly, the chemical stmctures of these diverse compounds could not account for their similar pharmacological effects. Instead, some physical property must explain the similarity of their biological activities. 

The MAC is defined as the lowest alveolar anesthetic gas to air percentage that will yield pharmacologic effects. An anesthetic with a high MAC thus requires a large amount of anesthetic to induce anesthesia, while a drug with a low MAC requires a lower amount to yield the same effect. 

Thus, it may be possible in the future to selectively target the various modulatory sites on the GABAa receptor to produce preferential pharmacological effects—for example, benzodiazepines that are anxiolytic without sedative effects, antischizophrenic agents that lack sedation and extrapyramidal side effects, and general anesthetics that do not alter respiratory and/or heart rates. 

The MAOIs interfere with the hepatic metabolism of many prescription and nonprescription (over-the-counter) drugs and may potentiate the actions of their pharmacological effects (i.e., cold decongestants, sympathomimetic amines, general anesthetics, barbiturates, and morphine). 

Comparative investigations on the stereoisomerides of ephedrine, made by Fujii (301), Pak and Read (302), Chopra, Dikshit and Pillai (303, 304, 305), Chen, Wu and Henriksen (306) and others, showed that they have similar pharmacological effects to those of ephedrine, but differ in some particular direction and intensity of action. Compared indirectly with adrenaline, in pithed cats, i-ephedrine is about three times stronger than d-ephedrine. f-Ephedrine is five times as potent as d- -ephedrine, which is seven times as potent as f- -ephedrine (307). Pak and Read, by direct comparison in anesthetized dogs, found that f-ephedrine is twice as effective as d- -ephedrine. 

C. Pharmacokinetics. Cocaine Is well absorbed from all routes, and toxicity has been described after mucosal application as a local anesthetic. Smoking and intravenous Injection produce maximum effects within 1-2 minutes, while oral or mucosal absorption may take up to 20-30 minutes. Once absorbed, cocaine is eliminated by metabolism and hydrolysis with a half-life of about 60 minutes. In the presence of ethanol, cocaine Is transesterified to cocaethyl-ene, which has similar pharmacologic effects and a longer half-life than cocaine. (See also Table 11-59.)... 

The anesthetic and anxiolytic effects of androgens, mainly T and 5a-androstane-3a,17(S-diol (3a,5a-Adiol), is another hot topic these steroids are classified now as, not only androgens, but also neuroactive steroids. The determination of the brain and circulating levels of these steroids in animal models is useful for the elucidation of their physiological roles and pharmacological effects. Based on this information, papers that deal with the determination of these steroids in the rat brain and serum/plasma are recently increasing. 

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