Anesthetic drugs intravenous anesthetics

The anesthesiologist selects the anesthetic drug that will produce safe anesthesia, analgesia (absence of pain), and in some surgeries, effective skeletal muscle relaxation. General anesthesia is most commonly achieved when the anesthetic vapors are inhaled or administered intravenously (IV). Volatile liquid anesthetics produce anesthesia when their vapors are inhaled. Volatile liquids are liquids that evaporate on exposure to air. Examples of volatile liquids include halothane, desflurane, and enflurane. Gas anesthetics are combined with oxygen and administered by inhalation. Examples of gas anesthetics are nitrous oxide and cyclopropane. 

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 However, it was soon withdrawn from human use because it produced unpleasant hallucinations, agitation, and delirium.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. 

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. 

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. 

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. 

Since local anesthetics have membrane-stabilizing effects, both parenteral (eg, intravenous lidocaine) and oral (eg, mexiletine, tocainide) formulations of local anesthetics have been used to treat patients with neuropathic pain syndromes because these syndromes are thought to involve uncontrolled, rapid, sensory fiber firing. Systemic local anesthetic drugs are commonly used as adjuvants to the combination of a tricyclic antidepressant (eg, amitriptyline) and an anticonvulsant (eg, carbamazepine) in chronic pain patients who fail to respond to the combination of antidepressant and anticonvulsant. 

Seizures induced by local anesthetics are usually treated with intravenous anesthetic drugs (eg, thiopental 1-2 mg/kg, propofol 0.5-1 mg/kg, midazolam 0.03-0.06 mg/kg). The muscular manifestations of a seizure can be blocked using a short-acting neuromuscular relaxant drug (eg, succinylcholine, 0.25-0.5 mg/kg IV). It should be emphasized that succinylcholine does not alter the CNS manifestations of local anesthetic-induced seizure activity. Rapid tracheal intubation can prevent pulmonary aspiration of gastric contents and facilitate hyperventilation. 

Finally, newer intravenous anesthetics such as etomidate (Amidate) and propofol (Diprivan) are available. Etomidate is a hypnoticlike drug that causes a rapid onset of general anesthesia with a minimum of cardiopulmonary side effects. Flence, this drug may be useful in patients with compromised cardiovascular or respiratory function. Propofol is a short-acting hypnotic that is useful as a general anesthetic in some... 

Recovery is sufficiently rapid with many intravenous drugs to permit their extensive use for short ambulatory (outpatient) surgical procedures. In the case of propofol, recovery times are similar to those seen with the shortest-acting inhaled anesthetics. The anesthetic potency of intravenous anesthetics, including thiopental, ketamine, and propofol, is adequate to permit their use as the sole anesthetic in short surgical procedures when combined with nitrous oxide and opioid analgesics. 

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