Muscle fibrosis associated with intramuscular chlorpromazine administration. A preliminary report

Blom

Aaes‐Jørgensen

et al. 1985

Findings made by computerized tomography scanning of pelvis of patients suggested that the majority of injections intended to be intramuscular in fact are delivered in the fat tissue. This finding has raised the question what difference it makes when drugs are injected intramuscularly or intralipomatously. We have studied local toxicity after intramuscular or intralipomatous injection of different drugs in pigs, which have a subcutaneous layer of fat comparable to that of man. The pigs were killed 1, 3, 7 or 14 days after injection of antibiotics, vitamins, neuroleptics, diazepam, digoxin, pentazocine, sulphadimidine and vehicles. The tissues at the injection site were examined macro- and microscopically. In another series of experiments an aqueous or two different oily preparations of the neuroleptic drug cis(Z)-clopenthixol were given intramuscularly or intralipomatously to pigs and a series of blood samples were taken for drug level determination. The tissue examinations showed that all drugs causing local muscle damage after intramuscular injection caused considerably less extensive damage with a faster regeneration after intralipomatous injection. The pharmacokinetic study showed that there was virtually no difference between plasma-concentration-time curves after intramuscular or intralipomatous injection. Our findings indicate that intralipomatous injection of irritating drugs is better tolerated than intramuscular injection since intralipomatous injection causes less local toxicity. Our findings also suggest that the pharmacokinetics are not different. However, further studies are required to substantiate whether the findings are of general relevance.

Section: Discussionsupporting

confidence: 92%

Local Toxicity of Different Drugs after Intramuscular or Intralipomatous Injection in Pigs: Serum Concentrations after Three Different Formulations of cis(Z)–Clopenthixol

Blom

Aaes‐Jørgensen

et al. 1985

“…Microscopic examination of the muscle tissue from the rabbits given cis(Z)-clopenthixol was not included in the present study. The drug caused massive muscle necrosis and the histological changes of similar muscle lesions in experimental animals have been described previously (Paget & Scott 1957;Hanson 1961;Benitz& Dambach 1966;Steiness et al 1974Steiness et al & 1978Rasmussen & Svendsen 1976;Brumback et al 1982). cis(Z)-clopenthixol is a neuroleptic drug which is known from previous experiments to cause substantial local muscle damage consisting of a well-defined area of muscle necrosis (Svendsen 1983).…”

Section: Discussionsupporting

confidence: 61%

Intramuscular Injections and Local Muscle Damage: An Experimental Study of the Effect of Injection Speed

1983

Physiological saline (0.9%) was administered intramuscularly into the longissimus dorsi muscle of rabbits (four animals per group) at different injection speeds (1 ml/sec. or 1 m1/10 sec.) and at different dose volumes (2 or 6 ml). The injection sites were examined post mortem 30 minutes after the injection. The same procedure was used for the administration of a solution of 1 % cis(Z)-clopenthixol, a neuroleptic drug, in 0.9% NaCl at speeds of 2 m1/2 sec., 2 m1/6 sec., 2 m1/20 sec., or 2 m1/60 sec. The injection sites of these rabbits were examined post martem 3 days after the injection. The muscle tissue at the injection sites was examined for macroscopic changes by serial sectioning. If a demarcated area of necrotic tissue was found, the necrotic area was dissected from the surrounding muscle tissue and weighed. Muscle tissue from rabbits receiving an injection of 0.9% NaCl was prepared for microscopic examination. In almost all rabbits given 0.9% NaCl the needle track was indicated by slight bleeding. In some of the rabbits which received 2 o r 6 ml of 0.9% NaCl over 2 or 6 sec., slight bleeding was also seen in the muscle tissue adjacent to the needle track. Since no further changes were seen, it is concluded that very fast injection of 0.9% NaCl only causes slight bleedingprobably fromdisruption of the local tissue. The needle track was identified microscopically by haemorrhages and disruption of muscle fibres. Muscle bundles were separated and muscles fibres were eosinophilic or vacuolated. In the rabbits given 1 % cis(Z)-clopenthixol, a well-demarcated area of necrotic muscle tissue was found at the injection sites. There was no difference between the mean weights of necrotic tissues from the groups given 2 ml over 2.20 or 60 sec. (mean weightsfS.E.M., 5.15f0.41, 4.6750.03, or 4.59f0.15 g, respectively). However, the mean weight of necrotic tissue from animals given 2 ml over 6 sec. (5.69f0.24 g) was significantly higher than that of the mean weights after injections given over 20 or 6Osec. From these findings it is concluded that injection speed is not an important factor for local damaging effect of intramuscular drug preparations. However, very slow injection may reduce the local damage but only slightly.

“…Previous studies have shown that chlorpromazine causes local muscle damage in animals (Benitz & Dambach 1966;Warnock & Ellman 1969;Meltzer et al 1970;Bree et al 1971;Klein er al. 1973;Kiister 1973) and man (Meltzer et al 1970;O'Connor 1980;Brumback et al 1982). All aqueous formulations included in the present study caused local muscle damage at the injection site as indicated by the presence of a substantial amount of necrotic muscle tissue.…”

Section: )mentioning

confidence: 83%

“…A number of neuroleptic drugs are marketed as aqueous formulations for intramuscular administration. It is known from the literature (Bree et al 1971;O'Connor 1980;Brumback et al 1982) and investigations in this laboratory that several neuroleptic drugs cause local muscle injury at the injection site. Neuroleptic drugs therefore seem to be useful as a tool for studies on local damaging effect of different formulations.…”

mentioning

confidence: 95%

Local Muscle Damage and Oily Vehicles: A Study on Local Reactions in Rabbits after Intramuscular Injection of Neuroleptic Drugs in Aqueous or Oily Vehicles

1983

The local muscle damaging effect of a series of neuroleptics formulated in water or in oily vehicles (Viscoleo, sesame oil, methyl oleate or squalane) has been investigated after intramuscular injection in rabbits. Each drug preparation (2 ml) was administered intramuscularly in the central part of the longissimus dorsi muscle of four rabbits. The rabbits were killed three days after the injection, and the injection site was examined macroscopically. Areas of necrotic muscle tissue were isolated by dissection and weighed. All preparations in aqueous solution caused local muscle damage (large necrotic area) at the injection site. This effect was almost completely neutralized by the Viscoleo vehicle. The sesame oil, methyl oleate and squalane vehicles also neutralized the local damaging effect, but not to the same extent as that of the Viscoleo vehicle.