Raloxifene (marketed as Evista by Eli Lilly and Company) is an oral selective estrogen receptor modulator (SERM) that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast. Raloxifene binds to estrogen receptors, resulting in differential expression of multiple estrogen-regulated genes in different tissues. Raloxifene produces estrogen-like effects on bone, reducing resorption of bone and increasing bone mineral density in postmenopausal women, thus slowing the rate of bone loss. The maintenance of bone mass by raloxifene and estrogens is, in part, through the regulation of the gene-encoding transforming growth factor-β3 (TGF-β3), which is a bone matrix protein with antiosteoclastic properties. Raloxifene activates TGF-β3 through pathways that are estrogen receptor-mediated but involve DNA sequences distinct from the estrogen response element. The drug also binds to the estrogen receptor and acts as an estrogen agonist in preosteoclastic cells, which results in the inhibition of their proliferative capacity. This inhibition is thought to contribute to the drug's effect on bone resorption. Other mechanisms include the suppression of the activity of the bone-resorbing cytokine interleukin-6 promoter activity. Raloxifene also antagonizes the effects of estrogen on mammary tissue and blocks uterotrophic responses to estrogen. By competing with estrogens for the estrogen receptors in reproductive tissue, raloxifene prevents the transcriptional activation of genes containing the estrogen response element. As well, raloxifene inhibits the estradiol-dependent proliferation of MCF-7 human mammary tumor cells in vitro. The mechanism of action of raloxifene has not been fully determined, but evidence suggests that the drug's tissue-specific estrogen agonist or antagonist activity is related to the structural differences between the raloxifene-estrogen receptor complex (specifically the surface topography of AF-2) and the estrogen-estrogen receptor complex. Also, the existence of at least 2 estrogen receptors (ERα, ERβ) may contribute to the tissue specificity of raloxifene. Raloxifene is indicated for the treatment and prevention of osteoporosis in postmenopausal women. It is also used for reduction of risk and treatment of invasive breast cancer, and it also reduces breast density. For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate. Common adverse events considered to be drug-related were hot flashes and leg cramps.

Fomepizole (4-methylpyrazole) is a competitive ADH inhibitor. Fomepizole has been shown in vitro to block alcohol dehydrogenase enzyme activity in dog, monkey and human liver. Fomepizole is indicated as an antidote for ethylene glycol (such as antifreeze) or methanol poisoning, or for use in suspected ethylene glycol or methanol ingestion, either alone or in combination with hemodialysis. It should be given when a known or suspected toxic ethylene glycol or methanol ingestion has occurred and the patient has metabolic acidosis and elevated osmolar gap. The most frequent adverse events reported as drug-related or unknown relationship were headache (14%), nausea (11%), and dizziness, increased drowsiness, and bad taste/metallic taste. Reciprocal interactions may occur with concomitant use of fomepizole and drugs that increase or inhibit the cytochrome P450 system (e.g. phenytoin, carbamazepine, cimetidine, ketoconazole). Fomepizole has been shown to induce the expression of CYP2E1 and to inhibit its activity. These effects were enhanced in rats that had been exposed to ethanol. Fomepizole may also inhibit other CYP enzymes and therefore may alter the exposure to other drugs that are metabolised by CYP enzymes.

Brimonidine reduces the amount of fluid in the eye, which decreases pressure inside the eye. Brimonidine ophthalmic (for the eyes) is used to treat open-angle glaucoma or ocular hypertension (high pressure inside the eye). Brimonidine is an alpha adrenergic receptor agonist (primarily alpha-2). Fluorophotometric studies in animals and humans suggest that Brimonidine has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow. Adverse reactions occurring in approximately 10­20% of the subjects receiving brimonidine ophthalmic solution (0.1-0.2%) included: allergic conjunctivitis, conjunctival hyperemia, and eye pruritus. Because Brimonidine may reduce blood pressure, caution in using drugs such as antihypertensives and/or cardiac glycosides with Brimonidine is advised.

There is no information in the literature about pharmacological and biological application of definite isomer of valsatran, R – form (also known as VALSARTAN, D- or CGP-49309). However there were found, that in the tablets of valsartan, which are used to treat high blood pressure and to heart failure, the R-enantiomer was an impurity.

Ritonavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Ritonavir binds to the protease active site and inhibits the activity of the enzyme. It is FDA approved for the treatment of HIV-1 infection. In patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving Ritonavir, may increase plasma concentrations of medications metabolized by CYP3A. The most frequently reported adverse drug reactions among patients receiving Ritonavir alone or in combination with other antiretroviral drugs were gastrointestinal (including diarrhea, nausea, vomiting, abdominal pain (upper and lower)), neurological disturbances (including paresthesia and oral paresthesia), rash, and fatigue/asthenia.

Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from the Camptotheca acuminata tree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. DNA topoisomerases are enzymes in the cell nucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug. Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death). Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (−1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, Topotecan acts as an uncompetitive inhibitor. Topotecan is used for the treatment of advanced ovarian cancer in patients with disease that has recurred or progressed following therapy with platinum-based regimens. Also used as a second-line therapy for treatment-sensitive small cell lung cancer, as well as in combination with cisplatin for the treatment of stage IV-B, recurrent, or persistent cervical cancer not amenable to curative treatment with surgery and/or radiation therapy. Topotecan is sold under the trade name Hycamtin.

Sodium phenylbutyrate is a salt of an aromatic fatty acid. The compound is used to treat urea cycle disorders, because its metabolites offer an alternative pathway to the urea cycle to allow excretion of excess nitrogen. Sodium phenylbutyrate is also a histone deacetylase inhibitor and chemical chaperone, leading respectively to research into its use as an anti-cancer agent and in protein misfolding diseases such as cystic fibrosis. It is used as adjunctive therapy for the management of chronic urea cycle disorders due to deficiencies in carbamylphosphate (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase. It is indicated in all neonatal- onset efficiency presenting within the first 28 days of life. Also indicated in patients with late-onset, presenting after the first month of life with a history of hyperammonemic encephalopathy. Sodium phenylbutyrate is a pro-drug and is rapidly metabolized to phenylacetate. Phenylacetate is a metabolically active compound that conjugates with glutamine via acetylation to form phenylacetylglutamine. The kidneys then excrete Phenylacetylglutamine. PBA (phenylbutyric acid) is absorbed from the intestine and converted by way of β-oxidation to the active moiety, phenylacetic acid (PAA). PAA is conjugated with glutamine in the liver and kidney by way of N-acyl coenzyme A-l-glutamine N-acyltransferase to form phenylacetylglutamine (PAGN). Like urea, PAGN incorporates two waste nitrogens and is excreted in the urine. On a molar basis, it is comparable to urea (each containing two moles of nitrogen). Therefore, phenylacetylglutamine provides an alternate vehicle for waste nitrogen excretion.

Fosfomycin (marketed under the trade names Monurol and Monuril) is a broad-spectrum antibiotic. Monurol (fosfomycin tromethamine) sachet contains fosfomycin tromethamine, a synthetic, broad spectrum, bactericidal antibiotic for oral administration. Monurol is indicated only for the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis. Fosfomycin is a phosphoenolpyruvate analogue produced by Streptomyces that irreversibly inhibits enolpyruvate transferase (MurA), which prevents the formation of N-acetylmuramic acid, an essential element of the peptidoglycan cell wall.

Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. Irinotecan is sold under the brand name Camptosar among others. CAMPTOSAR is a topoisomerase inhibitor indicated for: • First-line therapy in combination with 5-fluorouracil and leucovorin for patients with metastatic carcinoma of the colon or rectum. • Patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy. Irinotecan is a derivative of camptothecin. Camptothecins interact specifically with the enzyme topoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strand breaks. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks.

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (nNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). HIV-2 RT and eukaryotic DNA polymerases (such as human DNA polymerases alpha, beta, or sigma) are not inhibited by nevirapine. Nevirapine is, in general, only prescribed after the immune system has declined and infections have become evident. It is always taken with at least one other HIV medication such as Retrovir or Videx. The virus can develop resistance to nevirapine if the drug is taken alone, although even if used properly, nevirapine is effective for only a limited time. Nevirapine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. The activity of nevirapine does not compete with template or nucleoside triphosphates. Nevirapine is used for use in combination with other antiretroviral drugs in the ongoing treatment of HIV-1 infection.