Parenterally administered

Parenterally administered cephalosporins that are metabolically stable and that are resistant to many types of jS-lactamases include eefuroxime, cefamandole, cefotaxime and cefoxitin, which has a 7a-methoxy group at R. Injectable cephalosporins with anti-pseudomonal activity include cefsulodin and cefoperazone. 

Parenterally administered penicillin is recommended for all stages of syphilis. Alternative agents may be used in allergic individuals and include doxycycline, minocycline, tetracycline, or erythromycin base or stearate. Some patients may not respond favorably to alternative modalities. Therefore, in patients who must be administered penicillin (i.e., patients who are pregnant or have central nervous system [CNS] involvement) or are allergic, desensitization must be performed before the drug is initiated. 

Parenteral administration of drugs by intravenous (IV), intramuscular (IM), or subcutaneous (SC) routes is now an established and essential part of medical practice. Advantages for parenterally administered drugs include the following rapid onset, predictable effect, predictable and nearly complete bioavailability, and avoidance of the gastrointestinal (GI) tract and, hence, the problems of variable absorption, drug inactivation, and GI distress. In addition, the parenteral route provides reliable drug administration in very ill or comatose patients. 

Table 5. Parenterally administered antimicrobial agents which can be used alone or combined to provide effective coverage of the mixed aerobic-anaerobic infections arising from human colonic bacteria for patients requiring preventive therapy...

All opiate derivatives are associated with constipation, but the degree of intestinal inhibitory effects seems to differ between agents. Orally administered opiates appear to have greater inhibitory effect than parenterally administered agents oral codeine is well known as a potent antimotility agent. 

Oral or parenteral Several days (up to 3) Up to 2 weeks I, II, III, NDA I II III, NDA 2 species 2 weeks 2 species 4 weeks 2 species up to 4 weeks 2 species up to 3 months For parenterally administered drugs compatibility with blood and local tolerance at injection site where applicable. 

Both irritation and local tolerance studies assess the short-term hazard of pharmaceutical agents in the immediate region of their application or installation. In particular, these studies are done (expected) to assess topically or parenterally administered drugs. 

There are a number of special concerns about the safety of materials that are routinely injected (parenterally administered) into the body. By definition, these concerns are all associated with materials that are the products of the pharmaceutical and (in some minor cases) medical device industries. Such parenteral routes include three major ones IV (intravenous), IM (intramuscular), and SC (subcutaneous) and a number of minor routes (such as intra-arterial) that are not considered here. 

Sterility. Sterility is largely a concern to be answered in the process of preparing a final clinical formulation, and it is not addressed in detail in this chapter. However, it should be clear that it is essential that no viable microorganisms are present in any material to be parenterally administered (except for vaccines). 

Classen, W., Altmann, B., Gretener, P., Souppart, C., Skelton-Stroud, P. and Krinke, G. (1999) Differential effects of orally versus parenterally administered qinghaosu derivative artemether in dogs. Experimental and Toxicologic Pathology, 51, 507-516. 

Depending on their size and surface charge, parenterally administered liposomes interact with the reticuloendothelial system (RES) and provoke an immune response. 

Parenteral Administer IV, IM, or subcutaneously. Avoid too rapid IV injection. Absorption and utilization are somewhat more efficient with the IM route, which is usually preferred. 

Maintenance treatment Once the patient has been started on naltrexone, 50 mg every 24 hours will produce adequate clinical blockade of the actions of parenterally administered opioids. A flexible dosing regimen may be employed. Thus, patients may receive 50 mg every weekday with a 100 mg dose on Saturday, 100 mg every other day, or 150 mg every third day. 

Optimal therapy for such patients frequently requires parenterally administered additional medication and close monitoring, preferably in an intensive care setting. 

Epidural/Intrathecal- Presence of infection at the injection microinfusion site concomitant anticoagulant therapy uncontrolled bleeding diathesis parenterally administered corticosteroids within a 2-week period, other concomitant drug therapy or medical condition that would contraindicate the technique of epidural or intrathecal analgesia acute bronchial asthma upper airway obstruction. 

Parenteral Administer each dose over at least 60 minutes. Intermittent infusion is the preferred administration method. 

The emetines include emetine and dehydroemetine. These drugs act only against trophozoites. Their mechanism of action is based on eukaryote protein synthesis. They are parenterally administered because oral preparations are absorbed erratically and may induce severe vomiting. They are widely distributed and accumulate in liver, lungs and other tissues. The emetines are slowly elimination via the kidneys. Local side-effects in the area of the intramuscular injection are pain, tenderness and muscle weakness. Serious toxicity is common if the drugs are given for more than 10 days. Side effects include nausea, vomiting, diarrhoea but also cardiotoxicity. 

The reflex nature of the bradycardia induced by parenterally administered norepinephrine can readily be demonstrated by administration of atropine, a choli-noreceptor antagonist. Atropine abolishes the compensatory vagal reflexes. Under conditions of vagal blockade, the direct cardiac stimulatory effects of norepinephrine are unmasked. There is marked tachycardia, an increase in stroke volume, and as a consequence, a marked increase in cardiac output (Fig. 10.4). 

Sodium nitroprusside is a powerful parenterally administered vasodilator that is used in treating hypertensive emergencies as well as severe heart failure. Nitroprusside dilates both arterial and venous vessels, resulting in reduced peripheral vascular resistance and venous return. The action occurs as a result of activation of guanylyl cyclase, either via release of nitric oxide or by direct stimulation of the enzyme. The result is increased intracellular cGMP, which relaxes vascular smooth muscle (Figure 12-2). 

Diazoxide is an effective and relatively long-acting parenterally administered arteriolar dilator that is occasionally used to treat hypertensive emergencies. Injection of diazoxide results in a rapid fall in systemic vascular resistance and mean arterial blood pressure associated with substantial tachycardia and increase in cardiac output. Studies of its mechanism suggest that it prevents vascular smooth muscle contraction by opening potassium channels and stabilizing the membrane potential at the resting level. 

When used in patients with diminished renal function, parenterally administered mannitol is retained intravenously and causes osmotic extraction of water from cells, leading to hyponatremia. 

Well-tolerated parenteral forms of the high-potency older drugs haloperidol and fluphenazine are available for rapid initiation of treatment as well as for maintenance treatment in noncompliant patients. Since the parenterally administered drugs may have much greater bioavailability than the oral forms, doses should be only a fraction of what might be given orally, and the manufacturer s literature should be consulted. Fluphenazine decanoate and haloperidol decanoate are suitable for long-term parenteral maintenance therapy in patients who cannot or will not take oral medication. 

Rajewski R, et al. Preliminary safety evaluation of parenterally administered sulfoalkylether (3-cyclodextrin derivatives. J Phann Sci 1995 84(8) 927. 

Absorption of orally administered cefquinome is poor, but absorption following intramuscular or subcutaneous administration proceeds relatively quickly. A small fraction of the intramammarily administered cefquinome is absorbed systemically. Distribution of cefquinome is not extensive following parenteral administration of radiolabeled cefquinome the highest activities were found in injection-site tissues, kidney, and liver. Excretion of parenterally administered cefquinome is predominantly renal, while intramammarily administered cefquinome is excreted mainly in milk. Cefquinome is metabolically quite stable. 

Organic arsenicals are poorly absorbed from the gastrointestinal tract and are excreted mainly in feces (1). After their absorption, organic arsenicals are distributed throughout the body and rapidly excreted in the urine without being metabolized to a great extent. Elimination of the parenterally administered compounds is nearly complete within 24-48 h, while several days are required for elimination of the compounds from the gut. 

Insulin preparations that are commercially available differ in their relative onset of action, maximal activity, and duration of action. Conjugation of the insulin molecule with either zinc or protamine, or both, will convert the normally rapidly absorbed parenterally administered insulin to a preparation with a more prolonged duration of action. The various formulations of insulin are usually classified as short acting (0.5 to 14 h), intermediate acting (1 to 28 h), and long acting (4 to 36 h). The duration of action can vary, however, depending on injection volume, injection site, and blood flow at the site of administration. 

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