Fentanyl effects

Lichtor JL, Zacny J, felbaum JL, Lane BS, Rupani G, Thisted RA, Dohm C, Korttila K. Alcohol a r sedation with i.v. midazolam-fentanyl effects on psychomotor functioning. Br JAnaesdi (1991) 67, 579-84. 

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). 

Fentanyl transdermal is a transdermal system that is effective in the management of the severe pain associated with cancer. The transdermal system allows for a timed-release patch containing the drug fentanyl to be activated over a 72-hour period. A small number of patients may require systems applied every 48 hours. The nurse monitors for adverse effects in the same manner as for other narcotic analgesics (eg, the nurse notifies the primary health care provider if the respiratory rate is 10/min or less). 

Opioids maybe administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most common, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). Oral opioids have an onset of effect of 45 minutes, so intravenous or subcutaneous administration maybe preferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcutaneous or epidural route. 

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... 

Few studies have explored the efficacy of opioids specifically for OA. The APS recommends against the use of codeine and propoxyphene for OA because of the high incidence of adverse effects and limited analgesic effectiveness. Oxycodone is the most extensively studied of the agents recommended for OA. However, other narcotic analgesics such as morphine, hydromorphone, methadone, and transdermal fentanyl are also effective. 

Severe pain should be treated with an opioid such as morphine, hydromorphone, methadone, or fentanyl. Moderate pain can be treated effectively in most cases with a weak opioid such as codeine or hydrocodone, usually in combination with acetaminophen. Meperidine should be avoided owing to its relatively short analgesic effect and its toxic metabolite, normeperidine. Normeperidine may accumulate with repeated dosing and can lead to central nervous system side effects including seizures. 

Percutaneous patches are used in small animals. Fentanyl is a drug used for pain control and is quite effective. Unfortunately, it is quite toxic to animals and young children if accidentally ingested. 

Users of fentanyl analogues report that these drugs produce a rapid rush or euphoria that is similar to that felt with heroin, followed by a sedated, dream-like state. As analgesics, they also produce a profound loss of pain sensation and have common unwanted side effects such as sleepiness and constipation. However, because they are so potent, fentanyl analogues can... 

Kharasch ED, Whittington D, and Hoffer C (2004) Influence of hepatic and intestinal cytochrome P4503A activity on the acute disposition and effects of oral transmucosal fentanyl. Anesthesiology 101 729-737. 

Russia remains secretive about this operation. Reporters learned that they drilled holes in the floor and used vents high on the wall to pump gas into the theater. Regrettably, however, they were unable to learn the precise nature of the gas, beyond the admission by a Russian scientist that it was a derivative of Fentanyl. Several highly potent drugs fit that definition, including carfentanil, sufentanil, alfentanil, remifentanil and etorphine. Any of these can produce anesthesia, lasting from minutes to hours. A Russian medical authority later added that they used 5x the effective dose in order to guarantee a rapid effect on the terrorists. It is not clear exactly what this means. 

The interior volume of the theater, estimated from illustrations, was probably less than three hundred thousand cubic feet, i.e., about 10,000 cubic meters. Based on doses used for anesthesia, a concentration of as little as 2-3 mg per cubic meter of a super-potent Fentanyl derivative might be sufficient for a building that size, if instantaneous incapacitation is not required. This assumes continuous inhalation for about 30 minutes. Thus, if evenly distributed, the total amount of drug required might be in the range of a few dozen grams - almost certainly less than a pound. If the Russian authority pumped in 5x the effective dose (as it claimed), its uneven distribution in the air would likely have caused many deaths. But only one in six died. 

Some articles, for example, include an identical table of effective and lethal doses of high potency Fentanyl derivatives. The estimated safety margins are as high as 30,000. I could find no source for these data. I sent out several inquiries but thus far have received no definitive answers. I also discussed the questions with Harry Salem, who continues to study the toxicology of opioids at Edgewood. He is hopeful that the concomitant use of drugs tailored to suppress the effect of potent opioids on respiration may produce much safer agents. 

Concomitant narcotic administration - The respiratory depressant effect of fentanyl may persist longer than the analgesic effect. Consider the total dose of all opioid analgesics used before ordering narcotic analgesics during recovery from anesthesia. Use opioids in reduced doses initially, %to 1/3 those usually recommended. 

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... 

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