Irritancy after intramuscular injection

Local anesthetics can cause irritation and necrosis in muscular tissue. Most studies are performed in rabbits (Luduena et al. 1960 Baeder et al. 1974). 

Groups of three rabbits of either sex weighing 2 to 3.5 kg are injected intramuscularly in the glutaeal muscle with one ml solution of the local anesthetic with and without vasoconstrictor in various concentrations. Each muscle injection site is used only once. The animals are sacrificed at 1-, 2-, or 7-days intervals. The injection sites are examined macroscopically, fixed in Zenker-formalin and embedded in paraffin. Histologic preparations are made in the usual way for microscopic examination. 

The slides are checked for inflammatory signs, such as edema, leukocytic infiltration or foci of coagulative necrosis. 

Several studies were performed on myotoxicity of local anesthetics. 

Basson (1978), Basson Carlson (1980) described myotoxicity after single and repeated injections of mepivacaine in the rat. Young rats received single or repeated injections of 2% mepivacaine into the tibialis anterior or extensor digitorum longus muscles. Repeated injections consisted of 6 injections of the anesthetic (100 il per injection into the tibialis anterior) on different schedules, at intervals of 21/2 hours, 24 hours, or 4 days. The muscles were examined histologically for evidence of myotoxicity at 0 to 7 and 20 days after the last injection. Single injections showed that mepivacaine is a myotoxic 

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Shintani, S., Yamazaki, M., Nakamura, M. and Nakayama, I. (1967). A new method to determine the irritation of drugs after intramuscular injection in rabbits. Tox. Appl. Pharm. 11 293-301. 

Local irritation can produce severe pain after intramuscular injection and thrombophlebitis after intravenous injection. Renal toxicity, including interstitial nephritis and even tubular necrosis, has been demonstrated and has caused the withdrawal of cephaloridine from clinical use. 

Rasmussen, F. Hogh, P. (1971) Irritating effect and concentration at the injection site after intramuscular injection of antibiotic preparations in cows and pigs. Nordisk Veterinaer-Medicin, 23, 593-605. 

Heparin is prescribed on a unit (lU) rather than milligram basis. Tlie dose must be determined on an individual basis. Heparin is not absorbed after oral administration and therefore must be given parenterally. Intravenous administration results in an almost immediate anticoagulant effect. There is an approximate 2-hour delay in onset of drug action after subcutaneous administration. Intramuscular injection of heparin is to be avoided because of unpredictable absorption rates, local bleeding, and irritation. Heparin is not bound to plasma proteins or secreted into breast mUk, and it does not cross the placenta. 

Deferoxamine is only used parenterally. It is more toxic when used in patients with a low iron burden. After subcutaneous infusion many patients have some local irritation and swelling. Rapid intravenous injection can be followed by flushing, wheals, tachycardia, hypotension, acute adult respiratory distress, and renal insufficiency shock or convulsions can also occur. Headache, blurred vision, dysuria, diarrhea, and leg or hand cramps have been reported. Intramuscular injection can be painful. Hypersensitivity reactions occasionally occur, with rash, fever, and edema anaphylactic shock has been encountered (SEDA-7, 262) (7,8). As a test dose in patients with aluminium storage... 

The toxicity of palytoxin via several other routes of administration has been investigated (Table 32.7). This substance is highly toxic after intramuscular or subcutaneous injection, or following intratracheal instillation [90,96]. No toxicity was recorded after intrarectal administration of palytoxin at 10 [tg/kg [90]. Renal necrosis and pulmonary damage were recorded in animals given palytoxin intradermally [96], and local irritation and swelling, associated with edema and necrosis, were observed after both intradermal injection and percutaneous application. Severe irritation, involving ulceration and conjunctivitis, was induced by application of palytoxin to the eye [96]. 

Lewisite (15-chlorovinyldichloroarsine) was synthesized in 1918 for use as a weapon, and its clinical effects are similar to those of mustard in many respects, although the cellular mechanisms are believed to differ. However, unlike mustard. Lewisite liquid or vapor produces irritation and pain seconds to minutes after contact. Immediate decontamination may limit damage to skin or eyes, and intramuscular injections of a specific antidote, dimercaprol, or British antiLewisite (BAL) will reduce the severity of systemic effects. BAL has toxic effects of its own, however, and must be used with care. 

Ohata reported that the simultaneous intramuscular administration of aminopyrine and barbital resulted in a high plasma level by the formation of a molecular ccxnpound conpared with single administration of the conponents (2,3). Further, Pitha et al. reported that the toxic effect increased and set in rapidly without symptoms of hypervitami-nosis A when dimethyl- 3 CD was administered simultaneously with retinoic acid, and the survival rate was improved when dimethyl-3-CD was administered alone after the hypervitaminosis A had been established (4). It has also been reported that CDs have such advantages as removal of local irritation induced by intramuscular injection (5), protection of a drug-induced haemolysis (6), and so on. 

Intramuscular irritation is evaluated as follows Rabbits are sacrificed by lethal dose of barbiturate approximately 24 and 72 h after dosing. The left and right lateral vastus muscles of each rabbit are excised. The reaction resulting from injection is scored for muscle irritation using the scale shown here. 

In 20 women (mean age 67 years) who received intramuscular triptorelin 3.75 mg 6-weekly for endometriosis, nine developed mood disturbance after the second injection and appeared to be cumulative, since the symptoms only started after the second injection and worsened with successive injections (32). One woman withdrew after the third injection because of severe irritability. 

Parenteral products with osmotic values differing from the physiological value may cause phlebitis and irritation. This is especially applicable when the injection remains relatively long at the site of injection such as after subcutaneous, intramuscular, epidural and intrathecal administration. There is a higher chance of phlebitis in small vessels after intravenous administration. However, it is not known which limits should be considered to prevent phlebitis and irritation. According to some sources [22] the osmolarity of an intravenous injection should not be higher than 500 mOsm/kg. For subcutaneous and intramuscular administration the range is smaller. 

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