2940 Fentanyl A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078) 437-38-7 3345 C22H28N2O 336.220160 White powder. 87.5°C 200 mg/L (at 25°C) Epidural; parental (transdermal, intramuscular). Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Fentanyl's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hypopolarization and reduced neuronal excitability. Fentanyl is metabolized primarily via human cytochrome P450 3A4 isoenzyme system. Route of Elimination: Fentanyl is metabolized primarily via human cytochrome P450 3A4 isoenzyme system and mostly eliminated in urine. Within 72 hours of IV fentanyl administration, approximately 75% of the dose is excreted in urine, mostly as metabolites with less than 10% representing unchanged drug. Half Life: 7 hours (range 3-12) LD50: 3.1 mg/kg (rat) LD50: 0.03 mg/kg (monkeys) No indication of carcinogenicity to humans (not listed by IARC). For the treatment of cancer patients with severe pain that breaks through their regular narcotic therapy. Used as an inhalation anesthetic. (L1484) Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose. More common symptoms are dizziness, light-headedness, or feeling faint; drowsiness; nausea or vomiting; unusual tiredness or weakness. Less common or rare ones are blurred or double vision or other vision problems; confusion; constipation; convulsions (seizures); difficult or painful urination; mental depression; shortness of breath, trouble in breathing, tightness in the chest, or wheezing; skin rash, hives, or itching; unusual excitement (L1484) For the management of hypoventilation, immediate countermeasures include removing the Fentanyl and physically or verbally stimulating the patient. These actions can be followed by administration of a specific narcotic antagonist such as naloxone. The duration of hypoventilation following an overdose may be longer than the effects of the narcotic antagonist's action (the half-life of naloxone ranges from 30 to 81 minutes). The interval between IV antagonist doses should be carefully chosen because of the possibility of re-narcotization after system removal; repeated administration of naloxone may be necessary. Reversal of the narcotic effect may result in acute onset of pain and the release of catecholamines. Always ensure a patent airway is established and maintained, administer oxygen and assist or control respiration as indicated and use an oropharyngeal airway or endotracheal tube if necessary. Adequate body temperature and fluid intake should be maintained. (L1712) 2009-07-21T20:27:42Z 2014-12-24T20:25:53Z Fentanyl 119915 Fentanyl DB00813 true CCC(=O)N(C1CCN(CCC2=CC=CC=C2)CC1)C1=CC=CC=C1 C22H28N2O InChI=1S/C22H28N2O/c1-2-22(25)24(20-11-7-4-8-12-20)21-14-17-23(18-15-21)16-13-19-9-5-3-6-10-19/h3-12,21H,2,13-18H2,1H3 InChIKey=PJMPHNIQZUBGLI-UHFFFAOYSA-N 336.4705 336.220163528 Exogenous Solid 4.05 HMDB14951 CHEMBL596 3228 <p>Mark Rubino, &#8220;Process of making fentanyl intermediates.&#8221; U.S. Patent US20060100438, issued May 11, 2006.</p>