Anesthetics intravenous

The onset of action is fast (within 60 seconds) for the intravenous anesthetic agents and somewhat slower for inhalation and local anesthetics. The induction time for inhalation agents is a function of the equiUbrium estabUshed between the alveolar concentration relative to the inspired concentration of the gas. Onset of anesthesia can be enhanced by increasing the inspired concentration to approximately twice the desired alveolar concentration, then reducing the concentration once induction is achieved (3). The onset of local anesthetic action is influenced by the site, route, dosage (volume and concentration), and pH at the injection site. 

Propofol. 2,6-Diisopropylphenol [2078-54-8] propofol, is a newer intravenous anesthetic used for both induction and maintenance... 

Phencyclidine (l-[l-phenylcyclohexyl] piperidine, PCP) was originally developed as an intravenous anesthetic in the 1950s. Used for this indication, it causes a trance-like state without loss of consciousness and was hence classified as a dissociative anesthetic. However, it was soon withdrawn from human use because it produced unpleasant hallucinations, agitation, and delirium. The product was later used in veterinary medicine. Ketamine, a chemically closely related substance, was developed to replace PCP and is stiU in use as a dissociative anesthetic in children. Ketamine is less potent than PCP, and its effects are of shorter duration. However, it may also cause hallucinations (see the section on ketamine in Chapter 7, Club Drugs ). Much of the ketamine sold on the street (special K, cat Valium) has been diverted from veterinarians offices. 

Fentanyl was introduced to the United States in 1968 by the Janssen Pharmaceutical Company and marketed under the trade name Sublimaze. Its primary purpose was for use as an intravenous anesthetic and analgesic. It is 100 times more potent than morphine in reducing pain, and its duration of action is only 30 minutes (compared to morphine, which lasts several hours). Over the years, fentanyl has proved to be an extremely useful drug, and to date, it is still widely used for surgeries, childbirth, pain associated with cancer and other diseases, and the treatment of trauma-related injuries. Although fentanyl solutions are often given intravenously, pill forms of the drug are also available. 

A hypotensive patient suspected of having internal bleeding is given a dose lower than the usual amount of an intravenous anesthetic. An acceptable level of anesthesia occurs. How is it possible to achieve anesthesia in this patient with a dose of anesthetic that may be inadequate in a normoten-sive patient with adequate blood volume ... 

B. Perfusion of the brain is preserved when hemorrhage occurs. Thus, a greater proportion of the initial dose of anesthetic should appear in the brain, and a dose smaller than what is needed for a normovolemic patient is all that is required. Also, since flow to tissues associated with redistribution of the drug and termination of anesthesia is compromised, anesthesia should be deep and extended. Titrate this patient to a safe level of effect. While poor perfusion of the liver may reduce the exposure of drugs to metabolic enzymes, most intravenous anesthetics rely very little on hepatic clearance to terminate the anesthetic effect when a single bolus is administered. Furthermore, the question implies a direct influence of blood pressure on the efficiency of hepatic enzymes, and there is no evidence to support such a contention. Option C is not true. The opposite of option D is true. No evidence exists that binding of anesthetics is altered by these conditions. 

Reves JG, Glass PSA, and Lubarsky DA. Non-barbiturate Intravenous Anesthetics. In Miller RD (ed.). Anesthesia (5 th ed.). Philadelphia Churchill Livingstone, 2000. 

Hughes MA, Glass PS, Jacobs JR. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology 1992 76 334—41. 

The more active enantiomer at one type of receptor site may not be more active at another receptor type, eg, a type that may be responsible for some other effect. For example, carvedilol, a drug that interacts with adrenoceptors, has a single chiral center and thus two enantiomers (Figure 1-2, Table 1-1). One of these enantiomers, the (S) -) isomer, is a potent B-receptor blocker. The (R)(+) isomer is 100-fold weaker at the receptor. However, the isomers are approximately equipotent as -receptor blockers. Ketamine is an intravenous anesthetic. The (+) enantiomer is a more potent anesthetic and is less toxic than the (-) enantiomer. Unfortunately, the drug is still used as the racemic mixture. 

Ensuring an adequate depth of anesthesia depends on achieving a therapeutic concentration of the anesthetic in the CNS. The rate at which an effective brain concentration is achieved (ie, time to induction of general anesthesia) depends on multiple pharmacokinetic factors that influence the brain uptake and tissue distribution of the anesthetic agent. The pharmacokinetic properties of the intravenous anesthetics (Table 25-1) and the physicochemical properties of the inhaled agents (Table 25-2) directly influence the pharmacodynamic effects of these drugs. These factors also influence the rate of recovery when the administration of anesthetic is discontinued. 

Both the inhaled and the intravenous anesthetics can depress spontaneous and evoked activity of neurons in many regions of the brain. Older concepts of the mechanism of anesthesia evoked nonspecific interactions of these agents with the lipid matrix of the nerve membrane (the so-called Meyer-Overton principle)—interactions that were thought to lead to secondary changes in ion flux. More recently, evidence has accumulated suggesting that the modification of ion currents by anesthetics results from more direct interactions with specific nerve membrane components. The ionic mechanisms involved for different anesthetics may vary, but at clinically relevant concentrations they appear to involve interactions with members of the ligand-gated ion channel family. 

Inhaled (volatile) anesthetics are delivered to the lungs in gas mixtures in which concentrations and flow rates are easy to measure and control. However, dose-response characteristics of volatile anesthetics are difficult to quantify. Although achievement of an anesthetic state depends on the concentration of the anesthetic in the brain (ie, at the effect site), concentrations in the brain tissue are obviously impossible to measure under clinical conditions. Furthermore, neither the lower nor the upper ends of the graded dose-response curve defining the effect on the central nervous system can be ethically determined because at very low gas concentrations awareness of pain may occur. Moreover, at high concentrations there is a high risk of severe cardiovascular and respiratory depression. Nevertheless, a useful estimate of anesthetic potency can be obtained using quantal dose-response principles for both the inhaled and intravenous anesthetics. 

MAC values of the inhaled anesthetics are additive. For example, nitrous oxide (60-70%) can be used as a carrier gas producing 40% of a MAC, thereby decreasing the anesthetic requirement of both volatile and intravenous anesthetics. The addition of nitrous oxide (60% tension, 40% MAC) to 70% of a volatile agent s MAC would yield a total of 110% of a MAC, a value sufficient for surgical anesthesia in most patients. 

In the last two decades there has been increasing use of intravenous anesthetics in anesthesia, both as adjuncts to inhaled anesthetics and as part of techniques that do not include any inhaled anesthetics (eg, total intravenous anesthesia). The properties of some of the commonly used intravenous anesthetics are summarized in Table 25-1. Unlike inhaled anesthetics, intravenous agents do not require specialized vaporizer equipment for their delivery or facilities for... 

Recovery is sufficiently rapid with most intravenous drugs to permit their use for short ambulatory (outpatient) surgical procedures. In the case of propofol, recovery times are similar to those seen with sevoflurane and desflurane. Although most intravenous anesthetics lack antinociceptive (analgesic) properties, their potency is adequate for short superficial surgical procedures when combined with nitrous oxide or local anesthetics, or both. Adjunctive use of potent opioids (eg, fentanyl, sufentanil or remifentanil see Chapter 31) contributes to improved cardiovascular stability, enhanced sedation, and perioperative analgesia. However, opioid compounds also enhance the ventilatory depressant effects of the intravenous agents and increase postoperative emesis. Benzodiazepines (eg, midazolam, diazepam) have a slower onset and slower recovery than the barbiturates or propofol and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines (eg, midazolam) can be used to provide anxiolysis, sedation, and amnesia when used as part of an inhalational, intravenous, or balanced anesthetic technique. 

A specialized form of conscious sedation is occasionally required in the ICU, when patients are under severe stress and require mechanical ventilation for prolonged periods. In this situation, sedative-hypnotic drugs or low doses of intravenous anesthetics, neuromuscular blocking drugs, and dexmedetomidine may be combined. 

Etomidate is a carboxylated imidazole that can be used for induction of anesthesia in patients with limited cardiovascular reserve. Its major advantage over other intravenous anesthetics is that it causes minimal cardiovascular and respiratory depression. Etomidate produces a rapid loss of consciousness, with minimal hypotension even in elderly patients with poor cardiovascular reserve. The heart rate is usually unchanged, and the incidence of apnea is low. The drug has no analgesic effects, and coadministration of opioid analgesics is required to decrease cardiac responses during tracheal intubation and to lessen spontaneous muscle movements. Following an induction dose, initial recovery from etomidate is less rapid (< 10 minutes) compared with recovery from propofol. 

Ketamine is the only intravenous anesthetic that possesses both anesthetic and analgesic properties, as well as the ability to produce dose-related cardiovascular stimulation. Heart rate, arterial blood pressure, and cardiac output can be significantly increased above baseline values. These variables reach a peak 2-4 minutes after an intravenous bolus... 

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