Parenterals, compounding

No data on musculoskeletal involvement in cases of barium exposure by other than oral or inhalation modes have been reported for humans. In animals receiving acute doses of barium compounds parenterally, both muscle twitching and paralysis have been reported. Muscle twitching usually occurred within minutes of injection with flaccid paralysis following (Roza and Berman 1971 Schott and McArdle 1974). Parenteral administration is a very rare route of barium exposure, but once barium has entered the bloodstream and has been systemically distributed, it will have the same effects on the same organ. Similar symptoms are expected to occur in humans acutely exposed to barium via inhalation and oral routes. 

DIRECT CALCIUM COMPOUNDS Parenteral calcium administration may 1 the positive inotropic effects of epinephrine and dobutamine Uncertain postulated that calcium modulates the signal transmission from the receptor Monitor BP closely watch for poor response to these inotropes... 

The pharmacopoeias deal with ingredient water of two types. Purified Water and Water for Injection. The principal difference in biological quality between the two types of water is that Water for Injection is specified to be pyrogen-free (less than 0.25 Eu of bacterial endotoxin per mL). Only water of Water for Injection quality may be used to dissolve, dilute, or compound parenteral products, because endotoxins may pass through 0.22 pm sterilizing filters. Control of bacterial endotoxins is achieved in the first instance through control of microbiological contamination. 

Tellurium excretion patterns depend on the chemical forms and mode of administration of the compounds. Parenterally administered tellurium is excreted mainly in the urine rather than the feces, whereas orally ingested tellurium salts are excreted mainly in the feces (Durbin 1960). After oral dosing to rats, 60 -80% of ingested tellurite is rapidly excreted in the feces. The absorbed tellurium is secreted in the bile and enters the intestine. Small amounts of absorbed elemental tellurium and tellurite are exhaled ( 0.1%) presumably as dime-thyltelluride, and produce a characteristic garlic-like breath odor (De Meio 1946). 

Biomedical Uses. The molybdate ion is added to total parenteral nutrition protocols and appears to alleviate toxicity of some of the amino acid components in these preparations (see Mineral NUTRIENTS) (97). Molybdenum supplements have been shown to reduce iiitrosarnine-induced mammary carcinomas in rats (50). A number of studies have shown that certain heteropolymolybdates (98) and organometaUic molybdenum compounds (99) have antiviral, including anti-AIDS, and antitumor activity (see Antiviral agents Chemotherapeutics, anticancer). 

Toxicology. Inorganic tin and its compounds are generally of a low order of toxicity, largely because of the poor absorption and rapid excretion from the tissues of the metal (42—49). The acidity and alkalinity of their solutions make assessment of their parenteral toxicity difficult. The oral LD q values for selected inorganic tin compounds are Hsted in Table 2. It is estimated that the average U.S. daily intake of tin, which is mostly from processed foods, is 4 mg (see Food processing). 

A number of highly potent DHP-I stable iP-methylcarbapenems having a variety of C-2 substituents have now been described (60,66—69) including SM 7338 [96036-03-2] (42), C yH25N20 S. An acylamiao compound (66) and a iP-methoxy analogue (70) provide other variations. The pyrroHdine substituted iP-methyl-carbapenem SM 7338 (42) is being developed as a broad-spectmm parenteral antibiotic under the name meropenem the synthesis of (42) is by way of the lactone (43) derived by a novel Diels-Alder approach to dihydropyran precursors of (43) (71). 

Although both estrone and estradiol are available for replacement therapy, they suffer the disadvantage of poor activity on oral administration and short duration of action even when administered parenterally, because of ready metabolic disposition. In order to overcome these deficiencies, there was developed a series of esters of estradiol with long-chain fatty acids. These esters are oil-soluble and correspondingly water-insoluble compounds. 

The water-soluble and fat-soluble vitamins in the parenteral multivitamin mix are essential cofactors for numerous biochemical reactions and metabolic processes. Parenteral multivitamins are added daily to the PN. Patients with chronic renal failure are at risk for vitamin A accumulation and potential toxicity. Serum vitamin A concentrations should be measured in patients with renal failure when vitamin A accumulation is a concern. Previously, vitamin K was administered either daily or once weekly because intravenous multivitamin formulations did not contain vitamin K. However, manufacturers have reformulated their parenteral multivitamin products to provide 150 meg of vitamin K in accordance with FDA recommendations. There is a parenteral multivitamin formulation available without vitamin K (e.g., for patients who require warfarin therapy), but standard compounding of PN formulations should include a parenteral multivitamin that contains vitamin K unless otherwise clinically indicated. 

Iron-deficiency anemia in chronic PN patients may be due to underlying clinical conditions and the lack of iron supplementation in PN. Parenteral iron therapy becomes necessary in iron-deficient patients who cannot absorb or tolerate oral iron. Parenteral iron should be used with caution owing to infusion-related adverse effects. A test dose of 25 mg of iron dextran should be administered first, and the patient should be monitored for adverse effects for at least 60 minutes. Intravenous iron dextran then may be added to lipid-free PN at a daily dose of 100 mg until the total iron dose is given. Iron dextran is not compatible with intravenous lipid emulsions at therapeutic doses and can cause oiling out of the emulsion. Other parenteral iron formulations (e.g., iron sucrose and ferric gluconate) have not been evaluated for compounding in PN and should not be added to PN formulations. 

Substances that have been used as preservatives for disperse systems include chlorocresol, chlorobutanol, benzoates, phenylmercuric nitrate, parabens, and others [76,77]. The use of cationic antimicrobial agents such as quaternary ammonium compounds (e.g., benzalkonium chloride) is contraindicated in many cases because they may be inactivated by other formulation components and/or they may alter the charge of the dispersed phase. Clay suspensions and gels should be adequately preserved with nonionic antimicrobial preservatives. The use of preservatives is generally limited to products that are not intended for parenteral use. Intravenous injectable... 

To support the institutional pharmacist in preparing IV admixtures (which typically involves adding one or more drugs to large-volume parenteral fluids), equipment manufacturers have designed laminar flow units, electromechanical compounding units, transfer devices, and filters specifically adaptable to a variety of hospital programs. 

The preparation of salts of organic compounds is one of the most important tools available to the for-mulator. Compounds for both IM and IV solutions may require high solubility in order for the drug to be incorporated into acceptable volumes for bolus administration (see Table 1). Sodium and potassium salts of weak acids and hydrochloride and sulfate salts of weak bases are widely used in parenterals requiring highly soluble compounds, based on their overall safety and history of clinical acceptance. 

When oils are used as vehicles in ophthalmic fluids, they must be of the highest purity. Vegetable oils such as olive oil, castor oil, and sesame oil have been used for extemporaneous compounding. These oils are subject to rancidity and, therefore, must be used carefully. Some commercial oils, such as peanut oil, contain stabilizers that could be irritating. The purest grade of oil, such as that used for parenteral products, would be advisable for ophthalmics. 

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