Fentanyl action

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. 

Fentanyl highly potent but with a short duration of action, used for short analgesia in surgical settings. 

Colpaert, F.C. Fal, H. Niemegeers, C.J.E. Lenaerts, F.M. and Janssen, P.A.J. Investigations on drug produced and subjectively experienced discriminative stimuli. I. The fentanyl cue, a tool to investigate subjectively experienced drug actions. Life Sci 16 705-716, 1975. 

The answer is c. (Hardman, pp 543—544. Katzang, p 2533) Fentanyl is a chemical relative of meperidine that is nearly 100 times more potent than morphine. The duration of action, usually between 30 and 60 min after parenteral administration, is shorter than that of meperidine. Fentanyl citrate is only available for parenteral administration intramuscularly and intravenously. Tran sbuc cal ( lollipop ) and transdermal patches avoid first-pass metabolism of fentanyl. 

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. 

Due to the success of fentanyl, Janssen and other pharmaceutical companies started to produce other legal fentanyl analogues with a wider range of potency and duration of action, including ... 

The analgesic action of fentanyl surpasses that of morphine by approximately 100-fold. It has a suppressive action on the respiratory center and slows heart rate. Fentanyl is used in... 

The main difference between alfentanil and fentanyl lies in its short-lasting action. It is used in anesthesiological practice along with barbiturates during short surgical interventions. Synonyms for this drug are alfenta, rapifen, and others. 

The neuroleptic droperidol possesses antipsychotic, sedative, and antishock action. It potentiates the action of drugs for narcosis. In psychiatric practice, droperidol is used for psy-chomotor excitement and hallucinations. The principal use of this drug lies in anesthesiology for neuroleptanalgesia in combination with fentanyl. It is used in premedication as well as in surgical operations and post-operational circumstances. Synonyms of this drug are talam-onal, droleptan, leptofen, innovar, and others. 

Uses HTN, stable or unstable angina Action CCB relaxes coronary vascular smooth muscle Dose 2.5-10 mg/d PO -1- w/ h atic impair Caution [C, ] Disp Tabs SE Peripheral edema, HA, palpitations, flushing Interactions t Effect of hypotension M7 antih5rpCTtensives, fentanyl, nitrates, quinidine, EtOH, grapefruit juice t risk of neurotox W/Li -1- effects W/ NSAIDs EMS Concurrent EtOH and... 

Uses Obesity Action Blocks uptake of norepinephrine, serotonin, dopamine Dose 10 mg/d PO, may to 5 mg after 4 wk Caution [C, -] w/ SSRIs, Li, dextromethorphan, opioids Contra MAOI w/in 14 d, uncontrolled HTN, arrhythmias Disp Caps SE HA, insomnia, xerostomia, constipation, rhinitis, tach, HTN Interactions T Risk of serotonin synd W/ dextromethorphan, ergots, fentanyl, Li, meperidine, MAOIs, naratriptan, pentazocine, rizatriptan, sumatriptan, SSRIs, tryptophan, zolmitriptan, St. John s wort effects W/ cimetidine, erythromycin, ketoconazole T CNS depression W/ EtOH EMS Use fentanyl w/ caution, may T risk of serotonin synd concurrent EtOH use can T CNS depression OD May cause tach, HTN, diaphoresis, HA, fever, agitation, muscle tremors, and Szs symptomatic and supportive... 

WARNING Exacerbation of ischemic heart Dz w/ abrupt D/C Uses HTN MI Action p-Adrenergic receptor blocker, pj, P2 Dose HTN 10-20 mg bid, up to 60 mg/d MI 10 mg bid Caution [C (1st tri D if 2nd or 3rd tri), +] Contra CHF, cardiogenic shock, bradycardia, heart block, COPD, asthma Disp Tabs SE Sexual dysfxn, arrhythmia, dizziness, fatigue, CHF Interactions t Effects W/ antihyper-tensives, ciprofloxacin, fentanyl, nitrates, quinidine, res pine t bradycardia and... 

Fentanyl is 80 to 100 times as potent as morphine. Sufentanil (Sufenta) is 500- to 1,000-fold more potent than morphine, while alfentanil (Alfenta) is approximately 20 times more potent than morphine. Their onset of action is usually less than 20 minutes after administration. Dosage is determined by the lean body mass of the patient, since the drugs are lipophilic and tend to get trapped in body fat, which acts as a reservoir, prolonging their half-life. In addition, redistribution of the drugs from the brain to fat stores leads to a rapid offset of action. Droperidol, a neuroleptic agent, is generally administered in combination with fentanyl for IV anesthesia. 

The butyrophenones are chemically unrelated to the phenothiazines, but show a similar antipsychotic action. They were developed by P. A. Jansen and derived from fentanyl-type analgesics (see chapter 5). More than 4000 derivatives have been synthesized, of which the three most widely used antipsychotics are shown. Pimozide (4.91) is clearly derived from benperidol (4.92), even though it is no longer a butyrophenone. 

Most of the haemodynamic effects of opioids are related to decreased central sympathetic outflow, specific vagal effects or, in the case of morphine and pethidine, histamine release. Fentanyl and its analogues do not cause histamine release. All opioids, with the exception of pethidine, produce bradycardia by actions on the afferent fibres of the vagus and the nucleus tractus solitarius and nucleus commissuralis, which have very high densities of opioid receptors. Pethidine often produces tachycardia, possibly due to its structural similarity to atropine. In isolated heart or heart-muscle preparations, opioids produce a dose-related negative inotropic effect, but only at concentrations 100 to several thousand times those found clinically. 

After epidural injection, an opioid may transfer into the cerebrospinal fluid (CSF), into the blood or bind to epidural fat, the extent depending on their lipophilicity. After epidural administration, morphine passes slowly into the CSF. Sufentanil, which is highly lipid soluble, can be detected in the plasma within 2-5 minutes after epidural injection and part of the analgesic effect of the more lipid soluble opioids may be due to a supraspinal action amplifying the direct spinal action. Epidural fentanyl and sufentanil produce a more consistent and intense analgesia than morphine, with a faster onset. Flowever, the duration is short but this can be overcome by giving them by continuous epidural infusions. 

Phenothiazines with shorter side chains have considerable H -receptor-blocking action and have been used for relief of pruritus or, in the case of promethazine, as preoperative sedatives. The butyrophenone droperidol is used in combination with an opioid, fentanyl, in neuroleptanesthesia. The use of these drugs in anesthesia practice is described in Chapter 25. 

---