Propofol barbiturates

The other method used is infusion of intravenous anaesthetics such as propofol, etomidate (for induction) and the barbiturates such as thiopental and pentobarbital. Investigations into the mechanism of anaesthesia have made use of all these compounds in order to identify a common mode of action linked to likely mechanisms within the CNS. 

Hypnotics. Common hypnotics are thiopental, propofol, midazolam, etomidate, ketamine and inhaled anesthetics. The incidence of hypersensitivity reactions with thiopental is rare. Recently, thiopental was involved in less than 1% of allergic reactions in France [9]. Ever since Cremophor EL, used as a solvent for some non-barbiturate hypnotics, has been avoided, many previously reported hypersensitivity reactions have disappeared. In the last French surveys, reactions to propofol accounted for less than 2.5% of allergic reactions, and reactions to midazolam, etomidate or ketamine appear to be really rare [9]. Finally, no immune-mediated immediate hypersensitivity reaction involving isoflurane, desflurane or sevoflurane has been reported despite their wide use. 

The GABA-gated chloride ion channel is modulated by several classes of drugs that bind to allosteric sites on the receptor complex the benzodiazepines, barbiturates and related intravenous general anesthetics such as etomidate and propofol, as well as anesthetic steroids and endogenous neurosteroids. It appears that some types of GABAa receptor are directly enhanced by ethanol and volatile general anesthetics (Fig. 16-2) [7,8,20]. 

Refractory status epilepticus that has failed to respond to one of these treatments, and has continued for more than 20-30 min, requires urgent action. The accepted strategy is to paralyze and ventilate the patient and administer an antiepileptic drug in sufficient dosage to suppress EEG evidence of seizure activity. The barbiturate anaesthetic thiopental (thiopentone), the benzodiazepine midazolam, and the anaesthetic propofol have all been used. What little comparative evidence there is remains inconclusive. Such treatment can only be carried out with facilities for artificial ventilation and intensive care, and effects can only be monitored by EEG recording. 

Barbiturates may precipitate episodes of acute intermittent porphyria (AIP) and their use is contraindicated in patients who are predisposed to this condition. Some animal models indicate that ketamine, etomidate, and the benzodiazepines may be porphyrinogenic and propofol is considered to be the intravenous anaesthetic of choice in AlP-prone patients. 

In healthy patients, propofol produces a greater reduction in systemic blood pressure than equivalent doses of barbiturates. This hypotension is a consequence of both direct and indirect effects, namely, direct myocardial depression. 

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. 

Several drugs are used intravenously, alone or in combination with other drugs, to achieve an anesthetic state (as components of balanced anesthesia) or to sedate patients in intensive care units who must be mechanically ventilated. These drugs include the following (1) barbiturates (thiopental, methohexital) (2) benzodiazepines (midazolam, diazepam) (3) opioid analgesics (morphine, fentanyl, sufentanil, alfentanil, remifentanil) (4) propofol (5) ketamine and (6) miscellaneous drugs (droperidol, etomidate, dexmedetomidine). Figure 25-2 shows the structures of... 

Propofol (2,6-diisopropylphenol) is an extremely popular intravenous anesthetic. Its rate of onset of action is similar to that of the intravenous barbiturates recovery is more rapid and patients are able to ambulate sooner after propofol. Furthermore, patients subjectively "feel better" in the immediate postoperative period after propofol as compared with other intravenous anesthetics. Postoperative nausea and vomiting is less common because propofol has antiemetic actions. Propofol is used for both induction and maintenance of anesthesia however, cumulative effects can delay arousal following prolonged infusion. These favorable properties are responsible for the extensive use of propofol as a component of balanced anesthesia and for its great popularity as an anesthetic for use... 

The two principal parenteral anesthetic drugs used clinically are thiopental (an old prototype) and propofol (a relatively new drug). Thiopental is a derivative of barbituric acid, while propofol is a substituted propylphenol. Onset and duration of anesthetic effect for the two drugs are similar. However, recovery is more rapid following infusion with propofol (a desirable feature). The relatively rapid clearance of propofol explains its less severe hangover in patients compared to thiopental and may allow for a more accelerated discharge from the recovery room. 

Central nervous system. Propofol causes dose-dependent cortical depression and is an anticonvulsant. It depresses laryngeal reflexes more than barbiturates, which is an advantage when inserting a laryngeal mask airway. 

Methohexitone is a barbiturate similar to thiopental but its terminal t) is considerably shorter. Since the introduction of propofol, its use is almost entirely confined to inducing anaesthesia for electrocontro-vulsive therapy (ECT). Propofol shortens seizure duration and may reduce the efficacy of ECT. 

Propofol is a non-barbiturate, i.v. anesthetic that provides rapid-onset, short-duration anesthesia. It is widely used in human and small animal anesthesia. Propofol has not yet reached widespread use in equine anesthesia but a number of investigations into its clinical use have now been reported. 

Intravenous anesthetics are also relatively lipid-soluble, which helps account for their rapid onset. This high degree of lipid solubility allows them to rapidly cross the blood-brain barrier and partition into the brain. Barbiturates such as thiopental and methohexitol and the nonbarbiturates etomidate and propofol are often used to induce anesthesia, but only propofol is commonly used today as a general anesthetic by continuous infusion, thus only propofol will be discussed. 

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