Analgesics with narcotic activity

A procedure for isolating narcotic analgesics from biological material has been worked out by MuLii [106]. 

Other investigators have extracted narcotics from urine in a similar way [33]. Since most morphine derivatives and synthetic narcotics are eliminated as glucuronides by the human body, hydrolysis has been carried out by heating the urine with one-tenth of its volume of concentrated hydrochloric acid for 1 h at 100° C [33]. Acid hydrolysis is also described elsewhere [50]. 

Eberhardt and Norden [45] have extracted narcotics from urine by making alkaline with ammonium hydroxide and shaking with ethyl acetate. Interfering phenothiazines and their metabohtes could be 

TLC of analgesics with narcotic action has usually been carried out on silica gel G layers (cf. Table 109a). Alumina 6 [33] and cellulose 

Silica gel G. Coarser particles sieved out with fine sieve of Swiss Pharmacopoeia. Layer prepared by standard method, p. 85 

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Table 109 a. Experimental condition for TLC of analgesics with narcotic activity... 

Scopolamine (42), an optically active, viscous Hquid, also isolated from Solanaceae, eg. Datura metell. decomposes on standing and is thus usually both used and stored as its hydrobromide salt. The salt is employed as a sedative or, less commonly, as a prophylactic for motion sickness. It also has some history of use ia conjunction with narcotics as it appears to enhance their analgesic effects. BiogeneticaHy, scopolamine is clearly an oxidation product of atropiae, or, more precisely, because it is optically active, of (—)-hyoscyamiae. 

Lai, H. Gianutsos, G. and Puri, S.K. A comparison of narcotic analgesics with neuroleptics on behavioral measures of dopaminergic activity. Life Sci 17 29-32, 1975. 

Darvon , d-propoxyphene hydrochloride, is a synthetic, nonantipyritic, orally effective analgesic, with similar pharmacological activity and effects to codeine. Darvon is not a narcotic but can be substituted for codeine, and is useful in any condition associated with pain. Chemically, this analgesic is not analogous to codeine or to morphine. 

Propoxyphene is a widely prescribed narcotic analgesic with a potency approximately one-half that of codeine when each is orally administered. Typical oral doses of propoxyphene have about the same analgesic effect as 600 mg aspirin. Only the (+)-isomer (Darvon, others) binds to p. receptors to produce analgesia the (-)-isomer (Novrad appropriately the mirror image spelling of Darvon) is devoid of analgesic activity but is effective as an antitussive agent. Propoxyphene is prescribed most often as a combination with acetaminophen or aspirin. 

The 93-propyl levo Isomer (3c) was considerably more potent subcutaneously than morphine, while the 9oi-propyl levo Isomer (3d) was equipotent with morphine as an analgesic. None of the optical isomers suppressed withdrawal signs in monkeys the 9f5-propyl levo isomer exacerbated the withdrawal syndrome, indicating that it possesses some narcotic antagonist activity.The most active compound (4) of six homobenzomorphans was as potent subcutaneously as morphine (measured by pressure stimuli on mouse tail).115,116 Simplified procedures for the synthesis of the 6,7-benzomor-phan series have been described.117,118 Several 11-hydroxy and 11-alkoxy-2,6-methano-3-benzazocines display as potent analgesic and narcotic antagonist activity as cyclazocine.H ... 

Monoamine oxidase inhibitors (MAOIs) must be administered with utmost caution in conjunction with narcotic analgesics by virtue of their extremely intensified activity, for instance patients treated with MAOIs when treated with meperidine give rise to such a severe reaction that may sometimes even prove to be fatal. 

It is a narcotic analgesic with utilities similar to those of morphine, but its analgesic activity is relatively much less. It exhibits only mild sedative effects. 

A not uncommon side effect observed with morphine and some of the other narcotic analgesics is constipation due to decreased motility of the gastrointestinal tract. It proved possible to so modify pethidine as to retain the side effect at the expense of analgesic activity. Relief of diarrhea, it will be realized, is a far from trivial indication. Alkylation of the anion from diphenylacetonitrile (95) with ethylene dibromide gives the intermediate, 96. Alkylation of normeperidine (81) with that halide... 

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). 

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