U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Class (Stereo):
CHEMICAL (ACHIRAL)



Acetohydroxamic acid (also known as AHA or by the trade name Lithostat) is a synthetic drug derived from hydroxylamine and ethyl acetate, is similar in structure to urea. In the urine, it acts as an antagonist of the bacterial enzyme urease. Acetohydroxamic acid is used to lower the level of ammonia in the urine, which may help with some types of urinary infections. Acetohydroxamic Acid has no direct antimicrobial action and does not acidify urine directly. It is used, in addition to antibiotics or medical procedures, to treat chronic urea-splitting urinary infections. In 1983 the US Food and Drug Administration approved acetohydroxamic acid (AHA) as an orphan drug for "prevention of so-called struvite stones" under the newly enacted Orphan Drug Act of 1983.
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.
Ranitidine, a histamine H2-receptor antagonist, is now well established as a potent inhibitor of gastric acid secretion effective in the treatment and prophylaxis of gastrointestinal lesions aggravated by gastric acid secretion.
Status:
First approved in 1983

Class (Stereo):
CHEMICAL (ABSOLUTE)



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.
Bumetanide is indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome. It blocks the reabsorption of sodium and fluid from the kidney's tubules. The most frequent clinical adverse reactions considered probably or possibly related to bumetanide are muscle cramps (seen in 1.1% of treated patients), dizziness (1.1%), hypotension (0.8%), headache (0.6%), nausea (0.6%) and encephalopathy (in patients with preexisting liver disease) (0.6%). One or more of these adverse reactions have been reported in approximately 4.1% of patients treated with Bumex (bumetanide). Lithium should generally not be given with diuretics (such as Bumex (bumetanide)) because they reduce its renal clearance and add a high risk of lithium toxicity. Bumex (bumetanide) may potentiate the effect of various antihypertensive drugs, necessitating a reduction in the dosage of these drugs.
Indapamide is an antihypertensive and a diuretic. It contains both a polar sulfamoyl chlorobenzamide moiety and a lipid- soluble methylindoline moiety. Indapamide blocks the slow component of delayed rectifier potassium current (IKs) without altering the rapid component (IKr) or the inward rectifier current. Specifically it blocks or antagonizes the action the proteins KCNQ1 and KCNE1. Indapamide is also thought to stimulate the synthesis of the vasodilatory hypotensive prostaglandin PGE2. Indapamide is used for the treatment of hypertension, alone or in combination with other antihypertensive drugs, as well as for the treatment of salt and fluid retention associated with congestive heart failure or edema from pregnancy (appropriate only in the management of edema of pathologic origin during pregnancy when clearly needed). Also used for the management of edema as a result of various causes.
Status:

Class (Stereo):
CHEMICAL (RACEMIC)



Tioconazole is an antifungal medication of the imidazole class used to treat infections caused by a fungus or yeast. Tioconazole is a broad-spectrum imidazole antifungal agent that inhibits the growth of human pathogenic yeasts. Tioconazole exhibits fungicidal activity in vitro against Candida albicans, other species of the genus Candida, and against Torulopsis glabrata. Tioconazole prevents the growth and function of some fungal organisms by interfering with the production of substances needed to preserve the cell membrane. This drug is effective only for infections caused by fungal organisms. Tioconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol, an essential component of the yeast membrane. In this way, tioconazole inhibits ergosterol synthesis, resulting in increased cellular permeability. Tioconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms and the uptake of purine, impair triglyceride and/or phospholipid biosynthesis, and inhibit the movement of calcium and potassium ions across the cell membrane by blocking the ion transport pathway known as the Gardos channel. Side effects (for the women's formulas) may include temporary burning/irritation of the vaginal area, moderate drowsiness, headache similar to a sinus headache, hives, and upper respiratory infection.
Status:
First approved in 1983

Class (Stereo):
CHEMICAL (ABSOLUTE)

Hemin (trade name Panhematin) is a protoporphyrin IX containing a ferric iron ion (heme B) with a chloride ligand, which is is indicated for the amelioration of recurrent attacks of acute intermittent porphyria temporally related to the menstrual cycle in susceptible women. Manifestations such as pain, hypertension, tachycardia, abnormal mental status and mild to progressive neurologic signs may be controlled in selected patients with this disorder. the therapy for the acute porphyrias is not curative. Heme acts to limit the hepatic and/or marrow synthesis of porphyrin. This action is likely due to the inhibition of δ-aminolevulinic acid synthetase, the enzyme which limits the rate of the porphyrin/heme biosynthetic pathway. The exact mechanism by which hematin produces symptomatic improvement in patients with acute episodes of the hepatic porphyrias has not been elucidated.
Status:
First approved in 1983

Class (Stereo):
CHEMICAL (ABSOLUTE)



Cefuroxime is a semisynthetic, broad-spectrum, cephalosporin antibiotic. Cefuroxime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefuroxime has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria. Cefuroxime has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infection: Enterobacter spp., Escherichia coli, Klebsiella spp., Haemophilus influenzae, Neisseria meningitidis, Neisseria gonorrhoeae, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes. Cefuroxime is indicated for the treatment of patients with septicemia, meningitis, gonorrhea, lower respiratory tract, urinary tract, skin and skin-structure, bone and joint infections caused by susceptible strains of the designated organisms.