Fentanyl

The transdermal system provides continuous systemic delivery of fentanyl for 72 h. The amount of drug released from the system per hour is proportional to the surface area. Following application of the patch to the skin, a depot of fentanyl concentrates in the upper skin layers. This is then available to the systemic circulation. There is an initial rise in blood fentanyl concentration after application followed by a leveling off that occurs 12 to 24 h later. Peak blood concentrations occur between 24 and 72 h after application. The skin does not appear to metabolize fentanyl when delivered transdermally. 

Fentanyl is highly lipophilic. It is rapidly distributed to tissues such as the brain, heart, kidneys, and lungs, followed by slower movement into muscle and fat. 

Trade Name Manufacturer Cou ntry Year Introduced  

A solution of 192 g of 1 -phenethyl-4-hydroxy-4-aminomethyl piperidine in BOO cc of diethyi-carbonate is heated for 1 /i hours to refiux at about B0°C in the presence of sodium methylate (prepared for immediate use from 2 g of sodium). After this time, the ethyl alcohol formed during the reaction is slowly distilled while the maximum temperature is reached. The excess ethyl carbonate is distilled under reduced pressure. A crystallized residue Is then obtained, which is stirred with 400 cc of water and 400 cc of ether. The solution is filtered and 125 g (77.6%) of practically pure product melting at 232°C to 233°C, are obtained. 

The starting material was prepared in a yield of 5B% by reduction of the corresponding cyanohydrin. It in turn was prepared from 1-(2-phenylethyl)-4-plperidone and potassium cyanide to give the cyanohydrin which was reduced by lithium aluminum hydride. 

Merck Index 3924 Kleeman Engel p. 397 OCDS Vol. 2 p. 291 (19B0) 

Regnier, G., Canevari, R. and Le Douarec, J.-C. U.S. Parent 3,399,192 August 27, 196B assigned to Science Union et Cie, Societe Francaise de Recherche Medicale, France 

T rade Name Manufacturer Country Year Introduced  

Chemical Name N-phenvl-N-[1-(2-phenvlethvl)-4-piperidinylpropanamide Common Name — 

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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). 

Sufentanil [56030-54-7] (Sufenta), is five to ten times as potent as fentanyl. Sufentanil also has a short... 

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. 

Despite the limitations imposed by the physiology of the skin, several marketed controUed release transdermal dmg dehvery systems are available in the United States for example, scopolamine [51-34-3] for the treatment of motion sickness, nitroglycerin [55-63-0] for angina, estradiol [50-28-2] for the rehef of postmenopausal symptoms and osteoporosis, clonidine [4205-90-7] for the treatment of hypertension, fentanyl [437-38-7] as an analgesic, and nicotine [54-11-5] as an aid to smoking cessation. These systems are designed to dehver dmg for periods of one to seven days. 

Methenolone acetate A ndro tardy 1-0 estradiol Estradiol valerate Aniline Fentanyl Salicylanilide Anisoyl chloride Benzobromarone... 

Phenyl toloxamine o-Benzylphenoxy-/3-chloropropane Benproperine 4-Benzylplperldine Ifenprodil tartrate 1 -Benzyl-4-piperidone Fentanyl Pipamperone Tinoridine... 

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