Ceftriaxone is a broad-spectrum cephalosporin antibiotic with a very long half-life. Ceftriaxone is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Ceftriaxone has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria. It is approved for the treatment of lower respiratory tract infections, acute bacterial otitis media, skin infections, urinary tract infections, pelvic inflammatory disease, bacterial septicemia, bone and joint infections, intraabdominal infection, meningitis, and surgical prophylaxis. Common adverse reactions include erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, pseudomembranous enterocolitis, hemolytic anemia, hypersensitivity reaction, kernicterus, renal failure, and lung injury. Vancomycin, amsacrine, aminoglycosides, and fluconazole are incompatible with Ceftriaxone in admixtures. Precipitation of Ceftriaxone-calcium can occur when Ceftriaxone for Injection is mixed with calcium-containing solutions in the same intravenous administration line.

Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a β-lactam structurally related to the penicillins and possesses the ability to inactivate a wide variety of β-lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active against the clinically important plasmid-mediated β-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins. Clavulanic acid is used in conjunction with amoxicillin for the treatment of bronchitis and urinary tract, skin, and soft tissue infections caused by beta-lactamase producing organisms. Clavulanic acid competitively and irreversibly inhibits a wide variety of beta-lactamases, commonly found in microorganisms resistant to penicillins and cephalosporins. Binding and irreversibly inhibiting the beta-lactamase results in a restauration of the antimicrobial activity of beta-lactam antibiotics against lactamase-secreting-resistant bacteria. By inactivating beta-lactamase (the bacterial resistance protein), the accompanying penicillin/cephalosporin drugs may be made more potent as well.

Cyclosporins are cyclic polypeptide macrolides that were originally derived from the soil fungus Tolypocladium inflatum. Cyclosporine (also known as cyclosporine A) was discovered by Sandoz and developed for the tretment of immune disorders. The drug was approved by FDA for such diseases as Rheumatoid Arthritis, Psoriasis (Neoral), Keratoconjunctivitis sicca (Restasis) and prevention of transplant rejections (Neoral and Sandimmune). Cyclosporine’s primary immunosuppressive mechanism of action is inhibition of T-lymphocyte function. Upon administration cyclosporine binds to cyclophilin A and thus inhibits calcineurin, leading to immune system suppression.

Etoposide (trade name Etopophos) is a semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. It has been in clinical use for more than two decades and remains one of the most highly prescribed anticancer drugs in the world. The primary cytotoxic target for etoposide is topoisomerase II. This ubiquitous enzyme regulates DNA under- and over winding, and removes knots and tangles from the genome by generating transient double-stranded breaks in the double helix. Etoposide kills cells by stabilizing a covalent enzyme-cleaved DNA complex (known as the cleavage complex) that is a transient intermediate in the catalytic cycle of topoisomerase II. The accumulation of cleavage complexes in treated cells leads to the generation of permanent DNA strand breaks, which trigger recombination/repair pathways, mutagenesis, and chromosomal translocations. If these breaks overwhelm the cell, they can initiate death pathways. Thus, etoposide converts topoisomerase II from an essential enzyme to a potent cellular toxin that fragments the genome. Although the topoisomerase II-DNA cleavage complex is an important target for cancer chemotherapy, there also is evidence that topoisomerase II-mediated DNA strand breaks induced by etoposide and other agents can trigger chromosomal translocations that lead to specific types of leukemia. Etopophos (etoposide phosphate) is indicated in the management of the following neoplasms: Refractory Testicular Tumors-and for Small Cell Lung Cancer. The in vitro cytotoxicity observed for etoposide phosphate is significantly less than that seen with etoposide, which is believed due to the necessity for conversion in vivo to the active moiety, etoposide, by dephosphorylation. The mechanism of action is believed to be the same as that of etoposide.

Streptozotocin (Streptozocin, STZ, Zanosar) is a naturally occurring chemical that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine for treating certain cancers of the Islets of Langerhans and used in medical research to produce an animal model for hyperglycemia in a large dose as well as Type 1 diabetes with multiple low doses. Streptozocin inhibits DNA synthesis in bacterial and mammalian cells. In bacterial cells, a specific interaction with cytosine moieties leads to degradation of DNA. The biochemical mechanism leading to mammalian cell death has not been definitely established; streptozocin inhibits cell proliferation at a considerably lower level than that needed to inhibit precursor incorporation into DNA or to inhibit several of the enzymes involved in DNA synthesis. Although streptozocin inhibits the progression of cells into mitosis, no specific phase of the cell cycle is particularly sensitive to its lethal effects. Streptozocin is active in the L1210 leukemic mouse over a fairly wide range of parenteral dosage schedules. In experiments in many animal species, streptozocin induced a diabetes that resembles human hyperglycemic nonketotic diabetes mellitus. This phenomenon, which has been extensively studied, appears to be mediated through a lowering of beta cell nicotinamide adenine dinucleotide (NAD) and consequent histopathologic alteration of pancreatic islet beta cells. The metabolism and the chemical dissociation of streptozocin that occurs under physiologic conditions has not been extensively studied. When administered intravenously to a variety of experimental animals, streptozocin disappears from the blood very rapidly. In all species tested, it was found to concentrate in the liver and kidney. As much as 20% of the drug (or metabolites containing an N-nitrosourea group) is metabolized and/or excreted by the kidney. Metabolic products have not yet been identified.

Alclometasone is synthetic glucocorticoid steroid for topical use. Alclometasone dipropionate cream USP and alclometasone dipropionate ointment USP are indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. It may be used in pediatric patients 1 year of age or older, although the safety and efficacy of drug use for longer than 3 weeks have not been established. Like other topical corticosteroids, alclometasone dipropionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Alclometasone initially binds the corticosteroid receptor. This complex migrates to the nucleus where it binds to different glucocorticoid response elements on the DNA. This in turn enhances and represses various genes, especially those involved in inflammatory pathways.

Etomidate (AMIDATE®) is an imidazole derivative anesthetic and hypnotic with little effect on blood gases, ventilation, or the cardiovascular system. It is intended for the induction of general anesthesia by intravenous injection. Etomidate (AMIDATE®) is also indicated for the supplementation of subpotent anesthetic agents, such as nitrous oxide in oxygen, during maintenance of anesthesia for short operative procedures such as dilation and curettage or cervical conization. It also produces a unique toxicity among anesthetic drugs - inhibition of adrenal steroid synthesis that far outlasts its hypnotic action and that may reduce survival of critically ill patients. The major molecular targets mediating anesthetic effects of etomidate (AMIDATE®) in the central nervous system are specific gamma-aminobutyric acid (GABA) type A receptor subtypes. The R(+) isomer of etomidate is 10 times more potent than its S(-) isomer at potentiating GABA-A receptor activity.

Valrubicin is a semisynthetic analog of the anthracycline doxorubicin, and is administered by infusion directly into the bladder. Valrubicin is an anthracycline that affects a variety of inter-related biological functions, most of which involve nucleic acid metabolism. It readily penetrates into cells, where after DNA intercalation, it inhibits the incorporation of nucleosides into nucleic acids, causes extensive chromosomal damage, and arrests cell cycle in G2. Although valrubicin does not bind strongly to DNA, a principal mechanism of its action, mediated by valrubicin metabolites, is interference with the normal DNA breaking-resealing action of DNA topoisomerase II. Valrubicin is FDA approved drug, sold under the trade name Valstar.

Sucralfate (trade name CARAFATE) is a medication primarily taken to treat active duodenal ulcers. Sucralfate is also used for the treatment of gastroesophageal reflux disease (GERD) and stress ulcers. Sucralfate is a sucrose sulfate-aluminium complex that binds to the ulcer, creating a physical barrier that protects the gastrointestinal tract from stomach acid and prevents the degradation of mucus. Sucralfate is only minimally absorbed from the gastrointestinal tract. The small amounts of the sulfated disaccharide that are absorbed are excreted primarily in the urine.

Flunisolide is a synthetic corticosteroid. It is administered either as an oral metered-dose inhaler for the treatment of asthma or as a nasal spray for treating allergic rhinitis. Corticosteroids are naturally occurring hormones that prevent or suppress inflammation and immune responses. When given as an intranasal spray, flunisolide reduces watery nasal discharge (rhinorrhea), nasal congestion, postnasal drip, sneezing, and itching oat the back of the throat that are common allergic symptoms. Flunisolide is a glucocorticoid receptor agonist. The antiinflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. The immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding. Flunisolide binds to plasma transcortin, and it becomes active when it is not bound to transcortin. It is used for the maintenance treatment of asthma as a prophylactic therapy. Flunisolide is marketed as AeroBid, Nasalide, Nasarel.