Narcotics research, rehabilitation, and treatment. Hearings, Ninety ...
Narcotics research, rehabilitation, and treatment. Hearings, Ninety ... Narcotics research, rehabilitation, and treatment. Hearings, Ninety ...
16strong narcotic use is ^Yith drugs other than morphine at the presenttime.Chairman Pepper. Well, we expect to contact and elicit a responsefrom the American Medical Association on this matter.(The correspondence referred to above follows :)[Exhibit No. 1]American Medical Association,Chicago, III., July 9, 1911.Mr. Pattl L. Pekito,Chief Counsel, Select Committee on Crime, House of Representatives,Congress of the United States, Washington, B.C.Dear Mr. Perito: This is in response to your letter requesting our opinionconcerning the substitutability of synthetic drugs for codeine and morphine. Attachedto this letter is a brief review of various available synthetic drugs. As youwill note from the conclusions stated therein, it is our opinion that at the presenttime no drug is fully satisfactory as a substitute for morphine or codeine.We indeed appreciate the concern of the committee in its efforts to find ameans of curtailing the drug abiise problem prevalent today, and I want to assureyou that the medical profession is also desirous of attaining this goal. We donot believe, however, that removing moTphine and codeine from the physicians'drug armamentarium is an appropriate remedy. We strongly recommend thatthese drugs should remain available to physicians so that their patients will notbe deprived of the valuable benefits of these drugs.Thank you for the opportunity of providing our views, and we would appreciatethis letter and memorandum being included in the record of your hearings. If wecan be of further assistance to the committee, we shall be pleased to do so.Sincerely,Richard S. Wilbur, M.D.[Attachment]MORPHINE substitutesThousands of compounds have been synthesized and tested in the search fora substitute for morphine. In addition to analgesic potency, this search hasfocused on lack of addiction liability as a primary objective. To date, these effortshave not been completely successful, although some advances have been made.At the present time, nine strong analgesics, that are prepared synthetically (i.e.,not derived from opium) are available on the market. These are :1. Levorphanol Tartrate (Levo-Dromoran),2. Methadone Hydrochloride (Dolophine).3. Meperidine Hydrochloride (Demerol).4. Pentazocine (Talwin).5. Alphoprodine Hydrochloride (Nisentil).6. Anileridine Phosphate (Leritine).7. PiminO'dine Esylate (Alvodine).8. Fentanyl (Sublimaze).9. Methotrimeprazine (Levoprome).Meperidine was the first of this group to be introduced and although earlierit was thought to be nonaddicting. later it was found to have an addictionliability approaching that of morphine. Nevertheless, it is the most widely usedof the strong analgesics. This may suggest that it is capable of substituting formorphine in many cases ; however, it is recognized that meperidine Is not anadequate sub.stitute in certain ca.ses, e.g., acute myocardial infarction.Several of the available compounds are chemically related to meperidine, drugnumbers 5-8 in the above list. These were prepared in the attempt to improveon the properties of meperidine. The actions of these drugs are generally similarto those of meperidine, and although each has individual characteristics, whichlimits its use in certain conditions, none is superior to meperidine, and like itnone of these would be an adequate substitute for morphine in all cases.Both levorphanol tartrate (Levo-Dromoran) No. 1 and methadone hydrochloride(Dolophine) No. 2, are effective strong analgesics and have otherproperties in common with morphine, including addiction liability ; however, in
:17practice, experience has indicated that neither would meet the requirepients inall cases of an adequate morphine substitute.The newest member of this group is No. 4 pentazocine (Talwin). It is theonly one with a low addiction potential, being less than that of codeine ; thus,it is not subject to the controls of the narcotic laws. Although pentazocine is aneffective strong analgesic, as with all other drugs in this group, in certain cases,morphine would be preferable. Additional compai-ative studies are necessary tofully evaluate the potential use of this new drug, particularly in relation tothe older drugs.Compound 9, methotrimeprazine (Levoprome), differs chemically from allothers of this group, being a phenothiazine derivative and related to the antipsychoticgroup of drugs. Although it does have strong analgesic properties,its side effects of marked sedation and hypotension greatly limit its uses andwould prevent it from being an daequate substitute for morphine.Most controlled studies with these drugs have been conducted to determineequivalent analgesic potencies (i.e., milligram dosage), and have been carriedout in only a few types of pain, e.g., postoperative, cancer. Their broader usefulnessin a variety of painful conditions has been determined by clinicalexperience.On the basis of this evidence it is concluded that, taken as a whole, thegroup of available strong analgesics could be substituted for morphine in somecases ; however, no single agent of this group is capable of substituting alonefor morphine. At present, evidence from experimental studies are not availableto define the preferred drug in each case. Many additional comparative studiesand further experience are necessary, particularly with newer agents likepentazocine, to determine their ultimate efiicacy in various conditions. Furthermore,there are certain situations, e.g., acute myocardial infarction, adjunctto anesthesia in cardiac surgery, pulmonary edema of heart failure, certaincancer patients, in which none of the synthetic analgesics are capable of satisfactorilyreplacing morphine.CODEINE SUBSTITUTESTo act as a satisfactory substitute for codeine, a drug would need to havethe following properties1. Analgesic activity.2. Antitussive activity.3. Oral effectiveness.4. Low addiction potential.Of the presently available drugs none possesses all of these properties; however,it is not necessary for a comiwund to have both analgesic and antitussiveproperties to be useful. Those drugs that have one or more of these propertiesare considered individually below from the standpoint of a potential codeinesubstitute.Propoxyphene (Darvon) is an orally effective analgesic but it is less potentthan codeine and would not provide pain relief comparable to codeine in manycases. Propoxyphene has low addictive liability but no antitussive activity.Pentazocine (Talwin) lacks antitussive activity but possesses the other threeproperties necessary to substitute for codeine. However, insuflBcient comparativedata are presently available to fully evaluate its potential as a substitutefor codeine as an oral analgesic.Several agents are marketed as antitussive agents : these are orally effectiveand have no or low addiction potential. The most widely used of this group isdextromethorphan. Although it and the others of this group may be adequatefor relief of the milder types of cough, i.e.. associated with the common upperrespiratory infections, they would be inadequate for severe cough. For usein this situation, a strong analgesic with antitussive activity such as methadonemay be required, but this drug has a greater addiction liability than codeine.In conclusion, no other single drug has all the properties of codeine : thus,none would be a satisfactory substitute. That other drugs have some of theproperties of codeine is recognized, but an adequate substitute for codeine'suse either as an analgesic or antitussive is not available at present.NARCOTIC ANTAGONISTSThe use of the narcotic antagonists in addition to morphine and codeinewould be affected by a ban on opium and opium derivatives. Two of the three
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- Page 17 and 18: urden that such addiction imposes u
- Page 19 and 20: 1 (lata; (->) the sliariiis" oF iii
- Page 21 and 22: 9Chairman Pepper. The committee is
- Page 23 and 24: ::11quota production from unrecogni
- Page 25 and 26: 13in this country. This raises the
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- Page 33 and 34: 21When methadone was first introduc
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- Page 40 and 41: '.28Fiscal years-1967 1968 1969 197
- Page 42 and 43: 30rally in opium. By indirect, the
- Page 44 and 45: 32We can, I think, most helpfully g
- Page 46 and 47: 34so intense that we haven't done v
- Page 48 and 49: Dr. Eddy. Well, physicians, usually
- Page 50 and 51: 38Dr. Eddy. No.Chairman Pepper. Now
- Page 52 and 53: :40get away with it as Dr. Keats su
- Page 54 and 55: :—:42public health hazard was jud
- Page 56 and 57: :44Bibliography(1 Nathan B. Eddy. "
- Page 58 and 59: 46(52) Nathan B. Eddy. "Dilaudid."
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- Page 66 and 67: 54Chairman Pepper. Have you found t
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- Page 70 and 71: 58Chairman Pepper. Without objectio
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16strong narcotic use is ^Yith drugs other than morphine at the presenttime.Chairman Pepper. Well, we expect to contact <strong>and</strong> elicit a responsefrom the American Medical Association on this matter.(The correspondence referred to above follows :)[Exhibit No. 1]American Medical Association,Chicago, III., July 9, 1911.Mr. Pattl L. Pekito,Chief Counsel, Select Committee on Crime, House of Representatives,Congress of the United States, Washington, B.C.Dear Mr. Perito: This is in response to your letter requesting our opinionconcerning the substitutability of synthetic drugs for codeine <strong>and</strong> morphine. Attachedto this letter is a brief review of various available synthetic drugs. As youwill note from the conclusions stated therein, it is our opinion that at the presenttime no drug is fully satisfactory as a substitute for morphine or codeine.We indeed appreciate the concern of the committee in its efforts to find ameans of curtailing the drug abiise problem prevalent today, <strong>and</strong> I want to assureyou that the medical profession is also desirous of attaining this goal. We donot believe, however, that removing moTphine <strong>and</strong> codeine from the physicians'drug armamentarium is an appropriate remedy. We strongly recommend thatthese drugs should remain available to physicians so that their patients will notbe deprived of the valuable benefits of these drugs.Thank you for the opportunity of providing our views, <strong>and</strong> we would appreciatethis letter <strong>and</strong> memor<strong>and</strong>um being included in the record of your hearings. If wecan be of further assistance to the committee, we shall be pleased to do so.Sincerely,Richard S. Wilbur, M.D.[Attachment]MORPHINE substitutesThous<strong>and</strong>s of compounds have been synthesized <strong>and</strong> tested in the search fora substitute for morphine. In addition to analgesic potency, this search hasfocused on lack of addiction liability as a primary objective. To date, these effortshave not been completely successful, although some advances have been made.At the present time, nine strong analgesics, that are prepared synthetically (i.e.,not derived from opium) are available on the market. These are :1. Levorphanol Tartrate (Levo-Dromoran),2. Methadone Hydrochloride (Dolophine).3. Meperidine Hydrochloride (Demerol).4. Pentazocine (Talwin).5. Alphoprodine Hydrochloride (Nisentil).6. Anileridine Phosphate (Leritine).7. PiminO'dine Esylate (Alvodine).8. Fentanyl (Sublimaze).9. Methotrimeprazine (Levoprome).Meperidine was the first of this group to be introduced <strong>and</strong> although earlierit was thought to be nonaddicting. later it was found to have an addictionliability approaching that of morphine. Nevertheless, it is the most widely usedof the strong analgesics. This may suggest that it is capable of substituting formorphine in many cases ; however, it is recognized that meperidine Is not anadequate sub.stitute in certain ca.ses, e.g., acute myocardial infarction.Several of the available compounds are chemically related to meperidine, drugnumbers 5-8 in the above list. These were prepared in the attempt to improveon the properties of meperidine. The actions of these drugs are generally similarto those of meperidine, <strong>and</strong> although each has individual characteristics, whichlimits its use in certain conditions, none is superior to meperidine, <strong>and</strong> like itnone of these would be an adequate substitute for morphine in all cases.Both levorphanol tartrate (Levo-Dromoran) No. 1 <strong>and</strong> methadone hydrochloride(Dolophine) No. 2, are effective strong analgesics <strong>and</strong> have otherproperties in common with morphine, including addiction liability ; however, in
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