Irritancy after subcutaneous injection

The pharmacological effect of local anesthetics after subcutaneous injection is determined with the method of Bulbring and Wajda (1945) in guinea pigs and modifications thereof (Ther 1953b). 

Irritancy of local anesthetics after subcutaneous injections can be determined by subcutaneous injection into the ears of rabbits (Ulfendahl 1957). This method can be used not only as a screening selection criterion for finding an optimal local anesthetic but also as test method for evaluation of production batches (Hergott 1965). 

Rabbits of either sex weighing 2.5 to 3.5 kg are used. A volume of 0.1 ml of the test solution is injected in the outer part of the rabbit s ear avoiding hitting any blood vessels. The same volume of saline is injected into the contralateral ear. A pale discoloration of the skin appears immediately, which disappears within 1 h in the control. 

The injection site is inspected after 2 and 24 hours. Reactions are scored as absent, slight, moderate or marked (necrosis). 

The method has been used for evaluation of several local anesthetics (Ther 1953a Muschaweck and Rippel 1986). 

---

Occupational exposure may cause local irritation of eyes, nose, throat, and respiratory tract, although lauric acid is considered safe and nonirritating for use in cosmetics.No toxicological effects were observed when lauric acid was administered to rats at 35% of the diet for 2 years.Acute exposure tests in rabbits indicate mild irritation. After subcutaneous injection into mice, lauric acid was shown to be noncarcinogenic. ... 

Subcutaneous irritation is evaluated as follows Rabbits are euthanized by a lethal dose of barbiturate approximately 24 and 72 h after dosing. The subcutaneous injection sites are exposed by dissection, and the reaction is scored for irritation on a scale of 0 to 5 as follows (Shintani et al., 1967 USP, 1995a) ... 

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... 

More research has been devoted to the study of increased vascular permeability than to any other aspect of inflammation, and several excellent reviews on the subject have recently appeared . Increased vascular permeability here refers to the increased tendency for fluid and plasma proteins to pass through the vessel wall into the extravascular space. Various methods of studying the process have been described, usually involving either the assay of extravasated protein or protein-bound dyes such as trypan blue, or the measurement of the degree of swelling produced in a rat s paw after the subcutaneous injection of an irritant (see page 67). 

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]. 

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. 

The first scientists to assess the toxic properties of silicones were from Dow Corning, a leading manufacturer. In studies with laboratory animals, liquid methyl and methyl phenol polysiloxane derivatives were found toxic after oral application, even in small quantities. At the same it was observed that low molecular weight linear PDMS, termed hexamethyl-disiloxane (HMDS) with a viscosity of 0.65 cSt (Tables 16.1 and 16.2), caused mild stupefaction and CNS disturbances, which indicated its absorption from the alimentary tract. Moreover, HMDS induced inflammatory conditions and necrosis in the sites of subcutaneous injections, whereas after intraperitoneal (IP) use it was lethal for some animals [24]. In the 1940s, both Both Rowe and Kernand, and Barondes in 1950, who were leading simultaneous investigations, observed temporary conjunctival irritation (conjunctivitis)... 

IM, Subcutaneous (10%) Nausea (may occur 30 min after injection, usually diminishes with continued therapy), inflammation at injection site Nasal (12%-i0%) Rhinitis, nasal irritation, redness, sores Occasional... 

---