Abstract
Tissue damage at the injection site has been described after intramuscular injection of antibiotics, chemotherapeutics, vitamins, lidocaine, diazepam and digoxin in dogs, swine, cows, sheep and hens.
The damage caused by substances commonly used in drug vehicles has also been examined and compared with the effects of saline and distilled, sterile water. After intramuscular injection of saline or sterile water little or no tissue reaction has been observed, while vehicles containing glycerol formal or propylene glycol caused damage to muscle tissue.
The investigations show that both the drug itself and the vehicles may cause tissue damage. In the development of drug preparations for intramuscular administration, which cause minimal tissue damage, it is therefore important to consider all the components of the preparation.
From the point of view of international collaboration it will be of great importance that standard methods are generally accepted for the evaluation of new drugs and for the estimation and prediction of tissue damage after their intramuscular injection.
Kurzfassung
Gewebeschäden an der Injektionsstelle liessen sich nach der intramuskulären Verabreichung von u. a. Antibiotika, chemotherapeutischen Erzeugnissen, Vitaminpräparaten, Lidokain, Diazepam und Digoxin bei Hunden, Schweinen, Kühen, Schafen oder Hühnern feststellen.
Dabei wurde die irritierende Wirkung der üblicherweise in den Bindemitteln enthaltenen Substanzen untersucht und mit der Wirkung von salinem und destilliertem, sterilem Wasser verglichen. Bindemittel, die Formalglyzerin oder Propylenglykol enthalten, verursachten eine Schädigung des Muskelgewebes.
Die erwähnten Untersuchungen ergaben, dass sowohl das Medikament selbst, als auch das Bindemittel Gewebeschäden hervorrufen können. Daher ist bei der Entwicklung von Arzneimitteln, deren gewebeschädigende Wirkung bei intramuskulärer Verabreichung minimal sein soll, darauf zu achten, dass alle Bestandteile des Präparates geprüft werden.
Für eine internationale Zusammenarbeit dürfte es von grosser Bedeutung sein, dass die unterschiedlichen Bewertungsmethoden für neue Medikamente allgemeingültig festgelegt werden; dies gilt auch für die Einschätzung oder vorherige Bestimmung der lokalen Schädigung durch die intramuskuläre Injektion.
Resume
L'effet de lésion tissulaire au point d'injection a été décrit après l'injection intramusculaire d'antibiotiques, de chimiothérapeutiques, de vitamines, lidocaine, diazepam et digoxine chez des chiens, porcs, moutons ou poules. L'effet d'irritation des substances communément utilisées dans les excipients a été examiné et comparé à l'effet de l'eau salée et distillée ou de l'eau sterile. Les excipients contenant du glycérol formaldéhyde ou du propylène glycol ont provoqué des lésions du tissu musculaire.
Les études citées révèlent que le médicament lui-même comme les excipients peuvent provoquer des lésions tissulaires. Aussi fautil tenir compte, pour la mise au point de préparations pharmaceutiques pour l'administration par voie intramusculaire ne causant qu'une lésion minimale des tissus, de tous les composants entrant dans la préparation.
Du point de vue de la collaboration internationale, il sera très important que les différentes méthodes d'évaluation des nouveaux médicaments soient unanimement acceptées ainsi que les méthodes utilisées pour l'estimation ou la prédiction de lésions locales après injection intramusculaire.
Riassunto
Viene descritta l'azione lesiva osservata nei tessuti nel punto di inoculazione per via intramuscolare dei farmaci per uso veterinario, quali antibiotici, chemioterapici, vitamine, lidocaina, diazepam e digoxin. Le osservazioni sono state eseguite su cani, suini, bovini, ovini, o polli.
L'effetto irritante di sostanze d'uso comune in eccipienti farmaceutici è stato confrontato con l'effetto dell'acqua distillata sterile e della soluzione fisiologica, pure sterile.
Gli eccipienti contenenti glicerina o glicole propilenico hanno provocato lesioni nel tessuto muscolare. Dalle indagini descritte appare evidente che sia il farmaco che gli eccipienti possono provecare danni ai tessuti. Pertanto, al fine di migliorare i preparati farmaceutici per somministrazione intramuscolare che possono provocare lesioni anche minime nei tessuti, è importante prendere in considerazione tutti i componenti dei preparati stessi.
Dal punto di vista di una collaborazione internazionale, è di grande importanza che i vari metodi di esame dei nuovi farmaci siano unanimente accettati, compresi i metodi untilizzati per l'esame e la prevenzione dei danni locali conseguenti alla inoculazione per via intramuscolare.
Similar content being viewed by others
References
Batsakis, J.G., Preston, J.A., Briere, R.O. and Giesen, P.C., 1968. Iatrogenic aberrations of serum enzyme activity. Clin. Biochem., 2: 125–133.
Behrens, H., Matschullat, G. and Tuch, K., 1975. Uber die Verträglichkeit öliger Vitaminløsungen beim Schaf nach intramuskulärer Applikation. Dtsch. Tierärztl. Wschr., 82: 27–31.
Benitz, K.-F. and Dambach, G., 1966. Morphologic quantification of muscular lesions after injections of aqueous solutions. Arzneim.-Forsch., 16: 658–661.
Bille, N., 1970. Hypervitaminosis D og calciphylaxis hos husdyr. Hypervitaminosis D and calciphylaxis in domestic animals. Nord. Vet.-Med., 22: 218–233.
Blom, L. and Rasmussen, F., 1976. Tissue damage at the injection site after intramuscular injection of drugs in hens. Br. Poult. Sci., 17: 1–4.
Bree, M.M., Cohen, B.J. and Abrams, G.D., 1971. Injection lesions following intramuscular administration of chloropromazine in rabbits. J. Amer. Vet. Med. Ass., 159: 1598–1602.
Cacace, L., 1972 Elevated serum CPK after drug injections. New Engl. J. Med., 287: 309–310.
Likmeier, H., 1973. “Aseptische Nekrosen” nach i.m. Injektionen beim neugeborenen Welpen. Berl. Münch. Tierärztl. Wschr., 86: 413–414.
Fakawa, K., Ito, Y., Misaki, N. and Bando, K., 1975. A new method for the local irritation test. I. Tissue regeneration test for intramuscular acetic acid injection. J. Pharm. Soc. Japan, 95: 1307–1316.
Gloor, H.O., Vorburger, C. and Schädelin, J., 1977. Intramuskuläre Injektionen und Serumkreatinphophokinase-Aktivität. Schweiz. med. Wschr., 107: 948–952.
Glückert, H. and Benoit, W., 1952. Zur Klinik und Pathologie der Sulfonamidschädigungen am peripheren Nervensystem. Nervenarzt, 23: 17–21.
Gray, J.E., Weaver, R.N., Moran, J. and Feenstra, E.S., 1974. The parenteral toxicity of clindamycin 2-phosphate in laboratory animals. Toxicol. Appl. Pharmacol., 27: 308–321.
Greenblatt, D.J. and Koch-Weser, J., 1976. Intramuscular injection of durgs. New Engl. J. Med., 295: 542–546.
Hagen, R., 1968. Contracture of the quadriceps muscle in children. Acta Orthop. Scandinav., 39: 565–578.
Hansson, D.J., 1961. Local toxic effects of broad-spectrum antibiotics following injection. Antibiot. Chemotherapy, 11: 390–404.
Herigstad, R.R. and Whitehair, C.K., 1974. Local and systemic effects of parenteral injections of sodium selentite in cattle and swine. Vet. Med. Small Animal Clinician, 69: 1035–1038.
Kienel, G., 1973. Eine rationelle Methode zur tierexperimentellen Prüfung der Lokalen Verträglichkeit von itramuskulären Injektionen. Arzneim.-Forsch., 23: 263–266.
Machnik, G., Löw, O., Schicketanz, H. and Simon, G., 1971. Versuche zur quantitativen Erfassung der lokalen Gewebsschädigung nach intramuskulärer Injektion wässriger Lösungen. Zbl. Pharm., 110: 913–941.
McCloskey, J.R. and Chung, S.M.K., 1977. Quadriceps contracture as a result of multiple intramuscular injection. Am. J. Dis. Child., 131: 416–417.
Meltzer, H., 1969. Intramuscular chloropromazine and creatine kinase: Acute psychosis or local muscle trauma. Science, 164: 726–727.
Meltzer, H.Y., Mrozak, S. and Boyer, M., 1970. Effect of intramuscular injections on serum creatine phosphokinase activity. Amer. J. Med. Sci., 259: 42–48.
Paget, G.E. and Scott, H.McG., 1957. A comparison of the local effects of various intramuscular injections in the rat. Brit. J. Pharmacol., 12: 427–433.
Rasmussen, F. and Høgh, P., 1971. Lokalirritation og koncentrationer pa injektionsstedet efter intramusckulaer injektion af antibiotikaholdige praeparater pa køer og grise. Irritating effect and concentrations at the injection site after intramuscular injection of antibiotic preparations in cows and pigs. Nord. Vet.-Med., 23: 593–605.
Rasmussen, F., Nielsen, P. and Svendsen, O., 1973. Vaevsbeskadigelser og koncentrationer pa injektionsstedet samt restkoncentrationer i muskulatur, lever og nyrer efter intramusculaer injektion af injectabile sulfadimidini 0,2 g/ml pa grise. Tissue injuries, concentrations at the injection site and the concentrations in muscles, liver and kidney after intramuscular injection of injectable sulphadimidine 0.2 g/ml in pigs. Nord. Vet.-Med., 25: 256–261.
Rasmussen, F. and Ladefoged, O., 1974. Tissue damage at the injection site after intramuscular injection of drug preparations formulated by addition of polyvinylpyrrolidone. Acta. vet. scand., 15: 636–638.
Rasmussen, F. and Svendsen, O., 1976. Tissue damage and concentrations at the injection site after intramuscular injection of chemotherapeutics and vehicles in swine. Res. Vet. Sci., 20: 55–60.
Shintani, S., Yamazaki, M., Nakamura, M. and Nakayama, I., 1967. A new method to determine the irritation of drugs after intramuscular injection in rabbits. Toxicol. Appl. Pharmacol., 11: 293–301.
Sidell, F.R., Culver, D.L. and Kaminskis, A., 1974. Serum creatine phosphokinase activity after intramuscular injection. J. Amer. Med. Ass., 229: 1894–1897.
Steiness, E., Svendsen, O. and Rasmussen, F., 1974. Plasma digoxin after parenteral administration. Local reaction after intramuscular injection. Clin. Pharmacol. Ther., 16: 430–434.
Steiness, E., Svendsen, O., Rasmussen, F. and Nielsen, P., 1977. Prediction of local damage after intramuscular injection. In: Hans Bundgaard, Per Juul and Helmer Kofod (Editors), Drug design and adverse reactions. Munksgaard, Copenhagen; Academic Press, New York; Nancodo, Tokyo.
Steiness, E., Rasmussen, F., Svendsen, O. and Nielsen, P., 1978. A comparative study of serum creatine phosphokinase (CPK) activity in rabbits, pigs and humans after intramuscular injection of local damaging drugs. Acta Pharmacol. et Toxicol., 1978.
Svendsen, O., 1972. Histologiske forandringer efter intramuskulaere injektioner med antibiotikaholdige praeparater. Histologic changes after intramuscular injection with antibiotic preparations. Nord. Vet.-Med., 24: 181–185.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rasmussen, F. Tissue damage at the injection site after intramuscular injection of drugs. Vet Res Commun 2, 173–182 (1978). https://doi.org/10.1007/BF02291447
Issue Date:
DOI: https://doi.org/10.1007/BF02291447