Intravenous irritation

Acute Intravenous Irritation in the Male Rabbit. The design here is similar to the intramuscular assay, except that injections are made into the veins in specific muscle masses. 

Intravenous irritation is evaluated as follows Rabbits are sacrificed by a lethal dose of barbiturate following the 72-h irritation evaluation. The injection site and surrounding tissue are grossly evaluated at approximately 24 and 72 h after dosing on a scale of 0 to 3 as follows. 

Hexachlorocyclotriphosphazene (cycHc trimer) is a respiratory irritant. Nausea has also been noted on exposure (10). Intravenous and intraperitoneal toxicity measurements were made on mice. The highest nonlethal dose (LDq) was measured as 20 mg/kg (11). Linear chloropolymer is also beUeved to be toxic (10). Upon organic substitution, the high molecular weight linear polymers have been shown to be inert. Rat implants of eight different polyphosphazene homopolymers indicated low levels of tissue toxicity (12). EZ has been found to be reasonably compatible with blood (13), and has lower hpid absorption than fiuorosihcone. 

Other adverse reactions associated with penicillin are hematopoietic changes such as anemia, thrombocytopenia (low platelet count), leukopenia (low white blood cell count), and bone marrow depression. When penicillin is given orally, glossitis (inflammation of the tongue), stomatitis (inflammation of die mouth), dry mouth, gastritis, nausea, vomiting, and abdominal pain occur. When penicillin is given intramuscularly (IM), there may be pain at die injection site Irritation of the vein and phlebitis (inflammation of a vein) may occur witii intravenous (IV) administration. 

Iron salts occasionally cause gastrointestinal irritation, nausea, vomiting, constipation, diarrhea, headache, backache, and allergic reactions. The stools usually appear darker (black). Iron dextran is given by the parenteral route Hypersensitivity reactions, including fatal anaphylactic reactions, have been reported with the use of this form of iron. Additional adverse reactions include soreness, inflammation, and sterile abscesses at the intramuscular (IM) injection site Intravenous (IV) administration may result in phlebitis at the injection site When iron is administered via the IM route, a brownish discoloration of tlie skin may occur. Fhtients with rheumatoid arthritis may experience an acute exacerbation of joint pain, and swelling may occur when iron dextran is administered. 

The pretreatment of MH-susceptible patients with oral or intravenous dantrolene prior to surgery in order to avoid a crisis is controversial. Most physicians do not recommend prophylactic pretreatment except in patients who have had a previously documented episode. However, if pretreatment is desired, it is recommended that therapy be begun with intravenous dantrolene in a dose of 2 mg/Kg just prior to induction of anesthesia. This prevents the uncertainty of predictive blood values associated with the use of the oral route. The adverse effects of intravenous dantrolene prophylaxis include phlebitis and tissue necrosis. Patients who receive prophylactic treatment with oral dantrolene often complain of incapacitation, gastrointestinal irritation, prolonged drowsiness, and clinically significant respiratory muscle weakness. 

Advantages Simplified regimen for patient Increased patient compliance at home Decreased labor Decreased costs Decreased risk of contamination (due to less manipulation) Minimize infusion-related reactions from intravenous lipid emulsions Decreased vein irritation (especially with PPN) Improved stability compared to TNA Increased number of compatible medications Decreased bacterial growth compared to TNA Easier visual inspection Can use 0.22-micron bacterial retention filter Cost savings if unused (i.e. not spiked) intravenous lipid emulsion can be reused... 

Disadvantages Decreased stability compared to 2-in-1 PN Cannot use 0.22-micron bacterial retention filter Increased bacterial growth compared to 2-in-1 PN Visual inspection is difficult Limited compatibility with medications Increased labor and costs (if intravenous lipid emulsion infused separately) Increased vein irritation, especially if PPN is not coinfused with intravenous lipid emulsion... 

Intravenous medication is injected directly into a vein either to obtain an extremely rapid and predictable response or to avoid irritation of other tissues. This route of administration also provides maximum availability and assurance in delivering the drug to the site of action. However, a major danger of this route of administration is that the rapidity of absorption makes effective administration of an antidote very difficult, if not impossible, in most instances. Care must often be... 

The parenteral routes include three major ones IV (intravenous), IM (intramuscular), and SC (subcutaneous) and a number of minor routes (such as intraarterial) that are not considered here. Administration by the parenteral routes raises a number of special safety concerns in addition to the usual systemic safety questions. These include irritation (vascular, muscular, or subcutaneous), pyrogenicity, blood compatibility, and sterility (Avis, 1985 Ballard, 1968). The background of each of these, along with the underlying mechanisms and factors that influence the level of occurrence of such an effect, are discussed in Chapter 11. 

Solubility/miscibility Generally very soluble or miscible in water. Soluble in ethanol, com oil, and olive oil. Insoluble in mineral oil Biological considerations Surfactant. May cause micelle formation, with incumbent effects on bioavailability if included at concentrations of 1% or higher. May be associated with irritation if given intravenously or intramuscularly. Dogs have the peculiarity that Tweens injected parenterally induce the spontaneous systemic release of histamine. This response is particularly striking with IV injection, and therefore Tweens should not be used as components of IV vehicles in dogs... 

Acute toxicity - two species by two routes of administration (one is usually intravenous to ensure systemic exposure and the other is by the proposed chnical route). Usually an evaluation of the maximum repeatable dose (MRD) and possibly local irritancy... 

In rats exposed to 700 ppm, effects included excitement followed by eye irritation and drowsiness. The rat LCso for 4 hours was 233 ppm. Repeated daily exposure of rats to an average of 19 ppm caused moderate respiratory irritation. Intravenous injection into rabbits and cats caused depression of the central nervous system death occurred at doses of 800-1400 mg/]. ... 

Hafnium salts are mild irritants of the eye and the skin and have produced liver damage in animals. In mice, the LDso of hafnyl chloride by intraperitoneal injection was 112 mg/kg. In cats, intravenous administration of hafnyl chloride at lOmg/kg was fatal. Rats fed a diet containing 1% for 12 weeks showed slight changes in the liver, consisting of perinuclear vacuolization of the parenchymal cells and coarse granularity of the cytoplasm. The application of 1 mg of hafnium chloride to the eyes of rabbits produced transient irritation. Topical application of hafiiium chloride crystals to unabraded rabbit skin produced transient edema and erythema application to abraded skin caused ulceration. ... 

---