Anesthetics fentanyl

Morphine has certain undesirable side effects. Among these are respiratory depression, nausea, and vomiting, depression of the cough reflex, cardiovascular depression and hypotension, smooth muscle contraction (constipation), and histamine release (93). Morphine s onset of action, duration, and low therapeutic indices have prompted a search for a more effective opiate iv anesthetic. Extreme simplification of the complex morphine molecule has resulted in anilido —piperidines, the fentanyl class of extremely potent opiate iv anesthetics (118,119). 

Neuroleptic analgesia is so called because the combination of a major tranquilizer, a neuroleptic dmg, and a potent opiate produces an anesthetic state characterized by sedation, apathy, and mental detachment (see Psychopharmacological agents) (152). Iimovar [8067-59-2] a combination of droperidol [648-72-2], C22H22FN2O2, (19) and fentanyl (9) citrate, is used for procedures that do not require muscle relaxation. However, the onset of action is slow. 

Sufentanil, fentanyl, remifentanil, alfentanil, and morphine sulfate should be administered only by those specifically trained in the use of IV and epidural anesthetics Oxygen, resusdtative, and intubation equipment should be readily available. 

Epidural analgesia is frequently used for lower extremity procedures and pain (e.g., knee surgery, labor pain, and some abdominal procedures). Intermittent bolus or continuous infusion of preservative-free opioids (morphine, hydromorphone, or fentanyl) and local anesthetics (bupivacaine) may be used for epidural analgesia. Opiates given by this route may cause pruritus that is relieved by naloxone. Adverse effects including respiratory depression, hypotension, and urinary retention may occur. When epidural routes are used in narcotic-dependent patients, systemic analgesics must also be used to prevent withdrawal since the opioid is not absorbed and remains in the epidural space. Doses of opioids used in epidural analgesia are 10 times less than intravenous doses, and intrathecal doses are 10 times less than epidural doses (i.e., 10 mg of IV morphine is equivalent to 1 mg epidural morphine and 0.1 mg of intrathecally administered morphine).45... 

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. 

Figure 7.3 The chemical structure of fentanyl and its illegal analogues alpha-methyl-fentanyl and 3-methyl-fentanyl are shown here. Fentanyl was originally designed and marketed as an anesthetic, as it is 100 times stronger than morphine.

Concomitant anesthesia - Certain forms of conduction anesthesia, such as spinal anesthesia and some peridural anesthetics, can alter respiration by blocking intercostal nerves. Fentanyl can also alter respiration through other mechanisms. 

Opioids play an important role in anesthetic practice. Opioid analgesics potentiate the efficacy of anesthetics. They can be given as part of the premedication as well as during the operation. Examples of short acting agents with high potency are fentanyl, sufentanyl, alfentanil and remifentanil. Because of their hemodynamic stability these agents can be used for patients with compromised myocardial function. Respiration must be maintained artificially and may be depressed into the postoperative period. They are usually supplemented with inhalation anesthetic, benzodiazepines or propofol. 

Answer This feature of bradycardia is typical of patients who take (3-blockers, which should be continued so they result ultimately in better anesthetic management. The drugs given could have been modified (i.e., etomidate instead of propofol, which does not raise or may cause a slower heart rate). The potent opioids in the fentanyl family all cause vagal transmitted bradycardia. The muscle relaxant vecuronium (norcuron) has no effect on heart rate and could have been replaced by pancuronium, which has a vagolytic effect and will counter bradycardia in the usual induction bolus doses. 

Fentanyl is a semi-synthetic opioid, ft is a much more powerful version of morphine. Fentanyl is used during surgery as an anesthetic and is extremely dangerous when taken in a nonmedical context. First created in Belgium in the 1950s, fentanyl is 80 times more powerful than morphine. Due to its strength, fentanyl is listed as a Schedule I narcotic in the United States. 

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. 

Analgesic efficacy and clinical use Alfentanil is a shortacting potent opioid with analgesic and anesthetic properties (Larijani and Goldberg, 1987). It is less potent than fentanyl but administration can be better controlled. It is mostly used as a supplement to general anesthesia or as a primary anesthetic e.g. in cardiac surgery. Intra-... 

Analgesic efficacy and clinical use Fentanyl (Clotz and Nahata, 1991) is a potent analgesic and anesthetic compound. It is used for the treatment of severe acute and chronic pain, as a pre-medication or adjunct to anesthesia and as a primary anesthetic for the induction or maintenance of anesthesia. In combinations with neuroleptics e.g. droperidole, it induces a pain free and calm state known as neuroleptanalgesia (Foldes, 1973). In this condition, surgery can be performed in an awake patient, who is able to cooperate with the surgeon. 

Analgesic efficacy and clinical use Sufentanil (Rosow, 1984 Monk et al., 1988) is a very potent fentanyl analog with analgesic and anesthetic properties and a more rapid onset and a shorter duration of action. It is used for perioperative analgesia, short duration anesthesia and as an adjunct to various anesthetic procedures including neuroleptanalgesia (Isaacson, 1992). 

A 61-year-old woman undergoing mitral valve surgery received fentanyl, midazolam, nitrous oxide, and propofol infusion 3 mg/kg/hour during a 5-hour anesthetic. She developed lactic acidosis soon after the completion of surgery and required reintubation and ventilation. The peak lactate concentration, which occurred 1 day later, was 14.3 mmol/1. There was also mild disturbance of liver function. She eventually recovered. 

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... 

Adjunctive use of potent opioids (eg, fentanyl and related compounds) contributes cardiovascular stability, enhanced sedation, and profound analgesia. Other intravenous agents such as the benzodiazepines (eg, midazolam, diazepam) have slower onset and recovery features and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines can be used to provide a basal level of sedation and amnesia when used in conjunction with other anesthetic agents. 

Furthermore, high intravenous doses of opioids can cause chest wall rigidity, thereby acutely impairing ventilation, as well as postoperative respiratory depression requiring prolonged assisted ventilation and the administration of opioid antagonists (eg, naloxone). Low doses of fentanyl have been used as premedication and as an adjunct to both intravenous and inhaled anesthetics. 

The combination of droperidol and fentanyl is a fixed ratio preparation called innovar. Since droperidol is a neuroleptic substance, innovar is said to produce neurolept analgesia if combined with a more potent anesthetic, innovar produces neuroleptic anesthesia. A neuroleptic has adrenergic blocking as well as sedative, antiemetic, and anticonvulsant properties. Since innovar can cause extrapyramidal muscle movements, it is contraindicated in Parkinson s patients. 

Murphy and Hug (1982), Hall et al. (1987) used the reduction of enflurane MAC values in dogs as parameter for the anesthetic potency of fentanyl or sufentanyl, respectively. 

Murphy MR, Hug CC (1982) The anesthetic potency of fentanyl in terms of its reduction of enflurane MAC. Anesthesiol 57 485-488... 

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