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ARTICLE |

SUBLINGUAL ADMINISTRATION OF DRUGS FREE

ROBERT P. WALTON, M.D.
[+] Author Affiliations

CHARLESTON, S. C.

From the Department of Pharmacology, Medical College of the State of South Carolina.


JAMA. 1944;124(3):138-143. doi:10.1001/jama.1944.02850030006002
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In discussions of therapeutic technics there is frequently recurring opinion to the effect that any of the potent nonirritant drugs may be effectively administered by simple application to the oral mucosa.1 Very few drugs, however, are routinely used in this way in regular practice. Recently there were recommendations, both in this country2 and in England,3 that morphine be administered sublingually in those wartime emergencies in which hypodermic injections were not possible. The recommendation was challenged4 and, fortunately, has not been generally accepted. These contradictory opinions demonstrate that there does not exist any clear and general recognition of the scope and limitations of this particular therapeutic technic.

The effectiveness or ineffectiveness of this technic can be determined easily and, in fact, has been determined for many of the common drugs. The methods for establishing such data are simple but do involve more than the mere sublingual administration

REFERENCES

Fantus, Bernard: Technic of Medication , Chicago, American Medical Association Press, 1938;, pp. 233-237.
Barth, K.:  Die Benutzung der Aufsaugfähigskeit der Mundschleimhaut zur Einverleibung von Heilmitteln und ihr Vorzug , Med. Welt 15:241, 1941;.
 Kakowsky [Introduction of Drugs into the Organism by Sublingual Administration] , Sovet. med. 4:24 (No. (12) ) 1940;.
 Conferences on Therapy: Routes of Administration of Drugs , J. A. M. A. 114: 1447 ( (April 13) ) 1940;.
 Sublingual Administration of Morphine, Queries and Minor Notes , J. A. M. A. 120: 1349 ( (Dec. 19) ) 1942;.
 Morphia After Injuries , editorial, Lancet 2:759, 1942;.
Davis, David:  Administration of Morphine , J. A. M. A. 121: 1316 ( (April 17) ) 1943;.
Davis, David, and Ayman, David:  Sublingual Absorption of Drugs: Morphine , Arch. Int. Med. 41:231 ( (Feb.) ) 1928;.
Walton, R. P.:  Absorption of Drugs Through the Oral Mucosa: III. Fat-Water Solubility Coefficient of Alkaloids , Proc. Soc. Exper. Biol. & Med. 32: 1488, 1933;.
Grossmann, M., and Sandor, J.:  Zur klinischen Pharmakologie des Nitroglycerins , Klin. Wchnschr. 2:1833, 1923;.
Evans, W., and Hoyle, C.:  Prevention and Treatment of Individual Attacks of Angina Pectoris , Quart. J. Med. 3: 105, 1934;.
Krantz, J. C.; Carr, C. J.; Forman, S. E., and Ellis, F. W.:  Alkyl Nitrites , J. Pharmacol. & Exper. Therap. 67: 191, 1939;.
Walton, R. P.:  Further Studies Dealing with the Sublingual Absorption of Drugs , J. Pharmacol. & Exper. Therap. 57: 148, 1936;.
Hinselmann:  Die perorale und perlingual Verabreichung von Testosterone , München. med. Wchnschr. 89: 720, 1942;.
Miescher, K., and Gasche, P.:  Zur lingual Applikation von männlichen Sexualhormon , Schweiz. med. Wchnschr. 72:279, 1942;.
Hurxthal, Lewis M.:  Sublingual Use of Testosterone , J. Clin. Endocrinol. 3:551, 1943;.
Spence, A. W.:  Sublingual Administration of Methyl Testosterone , Brit. M. J. 1: 668, 1942;.
Lisser, Hans; Escamilla, R. F., and Curtis, L. E.:  Testosterone Therapy of Male Eunuchoids: III. Sublingual Administration of Testosterone Compounds , J. Clin. Endocrinol. 2:351, 1942;.
Lisser, Hans, and Curtis, L. E.:  Testosterone Therapy of Male Eunuchoids: IV. Result from Methyl Testosterone Linguets , J. Clin. Endocrinol. 3: 389, 1943;.
Salmon, U. J.; Geist, S. H.; Gaines, J. A., and Walter, R. I.:  The Treatment of Abnormal Uterine Bleeding with Androgens , Am. J. Obst. & Gynec. 41: 991, 1941;.
Joel, C. A.:  Clinical Results Obtained with Sublingual Administration of Methyl Testosterone , J. Clin. Endocrinol. 2: 116, 1942;.
Miescher, K., and Gasche, P.:  Zur lingual Applikation von weiblichem Sexualhormon: Beitrag zur Therapie mit "Ovocyclin-Linguetten," Schweiz. med. Wchnschr. 72:490, 1942;.
Kaufmann, C.:  Kritische Bewertung der Hormontherapie: Häufige Fehler in der Anwendung der weiblichen Keimdrüsenhormone , Deutsche med. Wchnschr. 67: 1171, 1941;.
Reifferscheid, W., and Schmidt: Klin. Wchnschr. 20:440, 1942;.
Hall, G. J.:  Clinical Experiences with Sublingual Administration of Alpha-Estradiol , J. Clin. Endocrinol. 2:26, 1942;.
Salmon, U. J., and Geist, S. H.:  Buccal Absorption of Alpha-Estradiol in Propylene Glycol , Proc. Soc. Exper. Biol. & Med. 45: 766, 1940;.
Herrnberger, K.:  Zur Frage der peroralen Wirksamkeit des Follikelhormons (Oestradiol) und des Corpus-Luteum-Hormones (Progesterone) , Zentralbl. f. Gynäk. 65:13, 1941;.
Giesen, W.:  Beitrag zur Frage der peroralen Wirksamkeit des Follikelhormons , Deutsche med. Wchnschr. 67:547, 1941;.
Joel, C. A.:  Dosage of Female Sex Hormones, Estradiol and Anhydrohydroxyprogesterone by Sublingual Application , J. Clin. Endocrinol. 2: 639, 1942;.
Castrodale, D.; Loeffel, E., and MacBryde, C. M.:  Sublingual Administration of Diethylstilbestrol: Comparison of Routes in Therapy , J. Clin. Endocrinol. 2:569, 1942;.
Anderson, Evelyn; Haymaker, Webb, and Henderson, Edward:  Successful Sublinguinal Therapy in Addison's Disease , J. A. M. A. 115: 2167 ( (Dec. 21) ) 1940;.
Turnoff, David, and Rowntree, L. G.:  Successful Sublingual Therapy in Addison's Disease , J. A. M. A. 116: 2016 ( (May 3) ) 1941;.
Heni, F.:  The Sublingual Administration of Desoxycorticosterone in the Treatment of Addison's Disease , Deutsche med. Wchnschr. 68: 162, 1942;.
Dunlop, D. M.:  Desoxycorticosterone Acetate in Addison's Disease , Brit. M. J. 1:557 ( (May 8) ) 1943;.
Wilson, A.:  Sublingual Therapy in Addison's Disease . Lancet 1: 762. 1942;.
Anderson, Evelyn, and Haymaker, Webb:  Technic of Sublingual Administration of Desoxycorticosterone Acetate in the Treatment of Addison's Disease , Clinics 1:476, 1942;.
Thorn, G. W.; Greif, R. L.; Coutinho, S. O., and Eisenberg, H.:  Relative Effectiveness of Several Methods of Administering Desoxycorticosterone Acetate: Addison's Disease , J. Clin. Endocrinol. 1:967, 1941;.
Mandelbaum, Joseph, and Schlessinger, Leo:  Absorptionof Vitamin A Through Human Skin , Arch. Dermat. & Syph. 46:431 ( (Sept.) ) 1942;.
Eller, J. J., and Wolff, Shirley:  Hormones and Vitamins in Cosmetics , J. A. M. A. 114:1865 ( (May 11) ); 2002 (May 18) 1940;.
Vollmer, Hermann; Abler, Charles, and Altman, H. S.:  Percutaneous Administration of Vitamin K , Am. J. Dis. Child. 64:462 ( (Sept.) ) 1942;.
Macht, D. I.:  Absorption of Drugs and Poisons Through the Skin and Mucous Membranes , J. A. M. A. 110:409 ( (Feb. 5) ) 1938;.
Walton, R. P., and Lacey, C. F.:  Absorption of Drugs Through the Oral Mucosa , J. Pharmacol. & Exper. Therap. 54:61, 1935;.
Franke, F. E., and Thomas, J. E.:  Minimum Fatal Dose of Nicotine for Unanesthetized Dogs , Proc. Soc. Exper. Biol. & Med. 29: 1177, 1932;.
Walton, R. P., and Lacey, C.F.:  A Comparison of the Motor Effects of Morphine, Codeine and Dihydromorphinone Hydrochloride (Dilaudid) on Thierry Fistulae , J. Pharmacol. & Exper. Therap. 54: 53, 1935;.
Walton, R. P.:  Absorption of Drugs Through the Oral Mucosa , Proc. Soc. Exper. Biol. & Med. 32: 1486 and 1488, 1935;.
Walton, R. P.; Smith, J. B., and Cook, F. M.:  Absorption of Ergot Alkaloids , J. Pharmacol. & Exper. Therap. 66:39, 1939;.
Lennox, W. G.:  Ergonovine versus Ergotamine as Terminator of Migraine Headaches , Am. J. M. Sc. 195:458, 1938;.
Adair, F. L.; Davis, M. E.; Kharasch, M. S., and Legault, R. R.:  Study of New and Potent Ergot Derivative, Ergotocin , Am. J. Obst. & Gynec. 30: 466, 1935;.
Kelly, T. W. G.:  Ergotamine Tartrate in Migraine , Lancet 1: 777, 1937;.
Von Storch, T. J. C.:  Complications Following the Use of Ergotamine Tartrate , J. A. M. A. 111:293 ( (July 23) ) 1938;.
Wallgren, A.:  Lingual Application of Eumydrin in Treatment of Congenital Pyloric Stenosis , Arch. Dis. Childhood 15: 103, 1940;.
Walton.9 Walton and Lacey.35
Beckman, H.: Treatment in General Practice , Philadelphia, W. B. Saunders Company, 1942;, p. 360.
Kuschel, H.:  Ueber die Wirkung von Cardiazol bei enteraler und perlingualer Zufuhr , Arch. f. exper. Path. u. Pharmakol. 193:330, 1939;.
Eggleston, Cary, and White, T. J.:  Absorption of Strophanthin Following Sublingual and Perlingual Administration , J. A. M. A. 89: 583 ( (Aug. 20) ) 1927;.
McCullagh, E. P., and Lewis, L. A.:  Comparison of Effectiveness of Various Methods of Administration of Insulin , J. Clin. Endocrinol. 2: 435, 1942;.
Fantus.1 McCullagh and Lewis.49

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Fantus, Bernard: Technic of Medication , Chicago, American Medical Association Press, 1938;, pp. 233-237.
Barth, K.:  Die Benutzung der Aufsaugfähigskeit der Mundschleimhaut zur Einverleibung von Heilmitteln und ihr Vorzug , Med. Welt 15:241, 1941;.
 Kakowsky [Introduction of Drugs into the Organism by Sublingual Administration] , Sovet. med. 4:24 (No. (12) ) 1940;.
 Conferences on Therapy: Routes of Administration of Drugs , J. A. M. A. 114: 1447 ( (April 13) ) 1940;.
 Sublingual Administration of Morphine, Queries and Minor Notes , J. A. M. A. 120: 1349 ( (Dec. 19) ) 1942;.
 Morphia After Injuries , editorial, Lancet 2:759, 1942;.
Davis, David:  Administration of Morphine , J. A. M. A. 121: 1316 ( (April 17) ) 1943;.
Davis, David, and Ayman, David:  Sublingual Absorption of Drugs: Morphine , Arch. Int. Med. 41:231 ( (Feb.) ) 1928;.
Walton, R. P.:  Absorption of Drugs Through the Oral Mucosa: III. Fat-Water Solubility Coefficient of Alkaloids , Proc. Soc. Exper. Biol. & Med. 32: 1488, 1933;.
Grossmann, M., and Sandor, J.:  Zur klinischen Pharmakologie des Nitroglycerins , Klin. Wchnschr. 2:1833, 1923;.
Evans, W., and Hoyle, C.:  Prevention and Treatment of Individual Attacks of Angina Pectoris , Quart. J. Med. 3: 105, 1934;.
Krantz, J. C.; Carr, C. J.; Forman, S. E., and Ellis, F. W.:  Alkyl Nitrites , J. Pharmacol. & Exper. Therap. 67: 191, 1939;.
Walton, R. P.:  Further Studies Dealing with the Sublingual Absorption of Drugs , J. Pharmacol. & Exper. Therap. 57: 148, 1936;.
Hinselmann:  Die perorale und perlingual Verabreichung von Testosterone , München. med. Wchnschr. 89: 720, 1942;.
Miescher, K., and Gasche, P.:  Zur lingual Applikation von männlichen Sexualhormon , Schweiz. med. Wchnschr. 72:279, 1942;.
Hurxthal, Lewis M.:  Sublingual Use of Testosterone , J. Clin. Endocrinol. 3:551, 1943;.
Spence, A. W.:  Sublingual Administration of Methyl Testosterone , Brit. M. J. 1: 668, 1942;.
Lisser, Hans; Escamilla, R. F., and Curtis, L. E.:  Testosterone Therapy of Male Eunuchoids: III. Sublingual Administration of Testosterone Compounds , J. Clin. Endocrinol. 2:351, 1942;.
Lisser, Hans, and Curtis, L. E.:  Testosterone Therapy of Male Eunuchoids: IV. Result from Methyl Testosterone Linguets , J. Clin. Endocrinol. 3: 389, 1943;.
Salmon, U. J.; Geist, S. H.; Gaines, J. A., and Walter, R. I.:  The Treatment of Abnormal Uterine Bleeding with Androgens , Am. J. Obst. & Gynec. 41: 991, 1941;.
Joel, C. A.:  Clinical Results Obtained with Sublingual Administration of Methyl Testosterone , J. Clin. Endocrinol. 2: 116, 1942;.
Miescher, K., and Gasche, P.:  Zur lingual Applikation von weiblichem Sexualhormon: Beitrag zur Therapie mit "Ovocyclin-Linguetten," Schweiz. med. Wchnschr. 72:490, 1942;.
Kaufmann, C.:  Kritische Bewertung der Hormontherapie: Häufige Fehler in der Anwendung der weiblichen Keimdrüsenhormone , Deutsche med. Wchnschr. 67: 1171, 1941;.
Reifferscheid, W., and Schmidt: Klin. Wchnschr. 20:440, 1942;.
Hall, G. J.:  Clinical Experiences with Sublingual Administration of Alpha-Estradiol , J. Clin. Endocrinol. 2:26, 1942;.
Salmon, U. J., and Geist, S. H.:  Buccal Absorption of Alpha-Estradiol in Propylene Glycol , Proc. Soc. Exper. Biol. & Med. 45: 766, 1940;.
Herrnberger, K.:  Zur Frage der peroralen Wirksamkeit des Follikelhormons (Oestradiol) und des Corpus-Luteum-Hormones (Progesterone) , Zentralbl. f. Gynäk. 65:13, 1941;.
Giesen, W.:  Beitrag zur Frage der peroralen Wirksamkeit des Follikelhormons , Deutsche med. Wchnschr. 67:547, 1941;.
Joel, C. A.:  Dosage of Female Sex Hormones, Estradiol and Anhydrohydroxyprogesterone by Sublingual Application , J. Clin. Endocrinol. 2: 639, 1942;.
Castrodale, D.; Loeffel, E., and MacBryde, C. M.:  Sublingual Administration of Diethylstilbestrol: Comparison of Routes in Therapy , J. Clin. Endocrinol. 2:569, 1942;.
Anderson, Evelyn; Haymaker, Webb, and Henderson, Edward:  Successful Sublinguinal Therapy in Addison's Disease , J. A. M. A. 115: 2167 ( (Dec. 21) ) 1940;.
Turnoff, David, and Rowntree, L. G.:  Successful Sublingual Therapy in Addison's Disease , J. A. M. A. 116: 2016 ( (May 3) ) 1941;.
Heni, F.:  The Sublingual Administration of Desoxycorticosterone in the Treatment of Addison's Disease , Deutsche med. Wchnschr. 68: 162, 1942;.
Dunlop, D. M.:  Desoxycorticosterone Acetate in Addison's Disease , Brit. M. J. 1:557 ( (May 8) ) 1943;.
Wilson, A.:  Sublingual Therapy in Addison's Disease . Lancet 1: 762. 1942;.
Anderson, Evelyn, and Haymaker, Webb:  Technic of Sublingual Administration of Desoxycorticosterone Acetate in the Treatment of Addison's Disease , Clinics 1:476, 1942;.
Thorn, G. W.; Greif, R. L.; Coutinho, S. O., and Eisenberg, H.:  Relative Effectiveness of Several Methods of Administering Desoxycorticosterone Acetate: Addison's Disease , J. Clin. Endocrinol. 1:967, 1941;.
Mandelbaum, Joseph, and Schlessinger, Leo:  Absorptionof Vitamin A Through Human Skin , Arch. Dermat. & Syph. 46:431 ( (Sept.) ) 1942;.
Eller, J. J., and Wolff, Shirley:  Hormones and Vitamins in Cosmetics , J. A. M. A. 114:1865 ( (May 11) ); 2002 (May 18) 1940;.
Vollmer, Hermann; Abler, Charles, and Altman, H. S.:  Percutaneous Administration of Vitamin K , Am. J. Dis. Child. 64:462 ( (Sept.) ) 1942;.
Macht, D. I.:  Absorption of Drugs and Poisons Through the Skin and Mucous Membranes , J. A. M. A. 110:409 ( (Feb. 5) ) 1938;.
Walton, R. P., and Lacey, C. F.:  Absorption of Drugs Through the Oral Mucosa , J. Pharmacol. & Exper. Therap. 54:61, 1935;.
Franke, F. E., and Thomas, J. E.:  Minimum Fatal Dose of Nicotine for Unanesthetized Dogs , Proc. Soc. Exper. Biol. & Med. 29: 1177, 1932;.
Walton, R. P., and Lacey, C.F.:  A Comparison of the Motor Effects of Morphine, Codeine and Dihydromorphinone Hydrochloride (Dilaudid) on Thierry Fistulae , J. Pharmacol. & Exper. Therap. 54: 53, 1935;.
Walton, R. P.:  Absorption of Drugs Through the Oral Mucosa , Proc. Soc. Exper. Biol. & Med. 32: 1486 and 1488, 1935;.
Walton, R. P.; Smith, J. B., and Cook, F. M.:  Absorption of Ergot Alkaloids , J. Pharmacol. & Exper. Therap. 66:39, 1939;.
Lennox, W. G.:  Ergonovine versus Ergotamine as Terminator of Migraine Headaches , Am. J. M. Sc. 195:458, 1938;.
Adair, F. L.; Davis, M. E.; Kharasch, M. S., and Legault, R. R.:  Study of New and Potent Ergot Derivative, Ergotocin , Am. J. Obst. & Gynec. 30: 466, 1935;.
Kelly, T. W. G.:  Ergotamine Tartrate in Migraine , Lancet 1: 777, 1937;.
Von Storch, T. J. C.:  Complications Following the Use of Ergotamine Tartrate , J. A. M. A. 111:293 ( (July 23) ) 1938;.
Wallgren, A.:  Lingual Application of Eumydrin in Treatment of Congenital Pyloric Stenosis , Arch. Dis. Childhood 15: 103, 1940;.
Walton.9 Walton and Lacey.35
Beckman, H.: Treatment in General Practice , Philadelphia, W. B. Saunders Company, 1942;, p. 360.
Kuschel, H.:  Ueber die Wirkung von Cardiazol bei enteraler und perlingualer Zufuhr , Arch. f. exper. Path. u. Pharmakol. 193:330, 1939;.
Eggleston, Cary, and White, T. J.:  Absorption of Strophanthin Following Sublingual and Perlingual Administration , J. A. M. A. 89: 583 ( (Aug. 20) ) 1927;.
McCullagh, E. P., and Lewis, L. A.:  Comparison of Effectiveness of Various Methods of Administration of Insulin , J. Clin. Endocrinol. 2: 435, 1942;.
Fantus.1 McCullagh and Lewis.49
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