Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.
Compounds that specifically inhibit STEROL 14-DEMETHYLASE. A variety of azole-derived ANTIFUNGAL AGENTS act through this mechanism.
An imidazole antifungal agent that is used topically and by intravenous infusion.
Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.
A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal CELL MEMBRANES. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane.
A basic aluminum complex of sulfated sucrose.
Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
A triazole antifungal agent that inhibits cytochrome P-450-dependent enzymes required for ERGOSTEROL synthesis.
Triazole antifungal agent that is used to treat oropharyngeal CANDIDIASIS and cryptococcal MENINGITIS in AIDS.
Five membered rings containing a NITROGEN atom.
An imidazole derivative that is commonly used as a topical antifungal agent.
An NADPH-dependent P450 enzyme that plays an essential role in the sterol biosynthetic pathway by catalyzing the demethylation of 14-methyl sterols such as lanosterol. The enzyme acts via the repeated hydroxylation of the 14-methyl group, resulting in its stepwise conversion into an alcohol, an aldehyde and then a carboxylate, which is removed as formic acid. Sterol 14-demethylase is an unusual cytochrome P450 enzyme in that it is found in a broad variety of organisms including ANIMALS; PLANTS; FUNGI; and protozoa.
A genus of yeast-like mitosporic Saccharomycetales fungi characterized by producing yeast cells, mycelia, pseudomycelia, and blastophores. It is commonly part of the normal flora of the skin, mouth, intestinal tract, and vagina, but can cause a variety of infections, including CANDIDIASIS; ONYCHOMYCOSIS; vulvovaginal candidiasis (CANDIDIASIS, VULVOVAGINAL), and thrush (see CANDIDIASIS, ORAL). (From Dorland, 28th ed)
A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
A mitosporic fungal genus that causes a variety of skin disorders. Malassezia furfur (Pityrosporum orbiculare) causes TINEA VERSICOLOR.
Oxidoreductases, N-Demethylating are enzymes that catalyze the removal of methyl groups from nitrogen-containing compounds in the body.
A second-generation histamine H1 receptor antagonist used in the treatment of allergic rhinitis and urticaria. Unlike most classical antihistamines (HISTAMINE H1 ANTAGONISTS) it lacks central nervous system depressing effects such as drowsiness.
Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela.
A steroid of interest both because its biosynthesis in FUNGI is a target of ANTIFUNGAL AGENTS, notably AZOLES, and because when it is present in SKIN of animals, ULTRAVIOLET RAYS break a bond to result in ERGOCALCIFEROL.
Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)
Compounds containing phenyl-1-butanone.
Triazoles are a class of synthetic antifungal and antiprotozoal drugs that inhibit the enzyme lanosterol 14α-demethylase, disrupting ergosterol synthesis in fungal cells.
The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
Superficial infections of the skin or its appendages by any of various fungi.
A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries.
A unicellular budding fungus which is the principal pathogenic species causing CANDIDIASIS (moniliasis).
A fluorinated cytosine analog that is used as an antifungal agent.
Infection of the VULVA and VAGINA with a fungus of the genus CANDIDA.
A selective histamine H1-receptor antagonist devoid of central nervous system depressant activity. The drug was used for ALLERGY but withdrawn due to causing LONG QT SYNDROME.
The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
The giving of drugs, chemicals, or other substances by mouth.
A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.
Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).
Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.
A macrolide antibiotic that is similar to ERYTHROMYCIN.
Piperazines are a class of psychoactive drugs that act as anticholinergics, antispasmodics, and central nervous system stimulants, and are sometimes used in the treatment of various medical conditions.

Cytochrome P-450 1A1 expression in human small bowel: interindividual variation and inhibition by ketoconazole. (1/766)

Human cytochrome P-450 1A1 (CYP1A1) is located primarily in extrahepatic tissues. To begin the characterization of this enzyme in the small intestine, we screened a bank of 18 human small intestinal microsomal preparations for CYP1A1 catalytic [(7-ethoxyresorufin O-deethylase (EROD)] activity and protein content. Although EROD activity was below detectable limits in 12 of the preparations, 6 exhibited measurable activity (1.4-123.5 pmol/min/mg), some exceeding that for 2 human liver microsomal preparations (11.0 and 26.4 pmol/min/mg). This variation was not due to variable quality of the preparations because each sample displayed readily detectable CYP3A4 catalytic activity and immunoreactive protein. We inadvertently found that intestinal EROD activity was inhibitable by ketoconazole at a concentration commonly believed to selectively inhibit CYP3A4. The possibility that CYP3A4 metabolizes 7-ethoxyresorufin was excluded because there was no correlation between intestinal CYP3A4 catalytic and EROD activity, and cDNA-expressed human CYP3A4 exhibited no EROD activity. Moreover, CYP1A1 immunoreactive protein was most abundant in the three intestinal preparations with the highest EROD activities, and the mean apparent Ki of ketoconazole observed for these three preparations (40 nM) was essentially identical with that for cDNA-expressed human CYP1A1 (37 nM). In summary, there is large interindividual variation in CYP1A1 expression in human small bowel, and ketoconazole is not a selective CYP3A4 inhibitor in in vitro metabolism studies involving intestinal tissue obtained from some individuals. These observations raise the possibility that in vivo drug interactions involving ketoconazole could result from CYP1A1 inhibition in the intestine in some individuals.  (+info)

Quantitative prediction of metabolic inhibition of midazolam by itraconazole and ketoconazole in rats: implication of concentrative uptake of inhibitors into liver. (2/766)

To evaluate the extent of drug-drug interaction concerning metabolic inhibition in the liver quantitatively, we tried to predict the plasma concentration increasing ratio of midazolam (MDZ) by itraconazole (ITZ) or ketoconazole (KTZ) in rats. MDZ was administered at a dose of 10 mg/kg through the portal vein at 60 min after bolus administration of 20 mg/kg ITZ or during 0.33 mg/h/body of KTZ infusion. The ratio values in the area under the plasma concentration curve of MDZ in the presence of ITZ and KTZ was 2.14 and 1.67, respectively. The liver-unbound concentration to plasma-unbound concentration ratios of ITZ and KTZ were 11 approximately 14 and 1.3, respectively, suggesting a concentrative uptake of both drugs into the liver. ITZ and KTZ competitively inhibited the oxidative metabolism of MDZ in rat liver microsomes, and Ki values of ITZ and KTZ were 0.23 microM and 0.16 microM, respectively. We predicted the ratio values of MDZ in the presence of ITZ and KTZ, using Ki values and unbound concentrations of both drugs in the plasma or liver. The predicted ratio values in the presence of ITZ or KTZ calculated by using unbound concentration in the plasma were 1.03 approximately 1.05 and 1.39, whereas those calculated using unbound concentration in the liver were 1.73 approximately 1.97 and 1.51, respectively, which were very close to the observed ratio values. These findings indicated the necessity to consider the concentrative uptake of inhibitors into the liver for the quantitative prediction of the drug-drug interactions concerning metabolic inhibition in the liver.  (+info)

In vitro metabolism of quinidine: the (3S)-3-hydroxylation of quinidine is a specific marker reaction for cytochrome P-4503A4 activity in human liver microsomes. (3/766)

The aim of this study was to evaluate the (3S)-3-hydroxylation and the N-oxidation of quinidine as biomarkers for cytochrome P-450 (CYP)3A4 activity in human liver microsome preparations. An HPLC method was developed to assay the metabolites (3S)-3-hydroxyquinidine (3-OH-Q) and quinidine N-oxide (Q-N-OX) formed during incubation with microsomes from human liver and from Saccharomyces cerevisiae strains expressing 10 human CYPs. 3-OH-Q formation complied with Michaelis-Menten kinetics (mean values of Vmax and Km: 74.4 nmol/mg/h and 74.2 microM, respectively). Q-N-OX formation followed two-site kinetics with mean values of Vmax, Km and Vmax/Km for the low affinity isozyme of 15.9 nmol/mg/h, 76.1 microM and 0.03 ml/mg/h, respectively. 3-OH-Q and Q-N-OX formations were potently inhibited by ketoconazole, itraconazole, and triacetyloleandomycin. Isozyme specific inhibitors of CYP1A2, -2C9, -2C19, -2D6, and -2E1 did not inhibit 3-OH-Q or Q-N-OX formation, with Ki values comparable with previously reported values. Statistically significant correlations were observed between CYP3A4 content and formations of 3-OH-Q and Q-N-OX in 12 human liver microsome preparations. Studies with yeast-expressed isozymes revealed that only CYP3A4 actively catalyzed the (3S)-3-hydroxylation. CYP3A4 was the most active enzyme in Q-N-OX formation, but CYP2C9 and 2E1 also catalyzed minor proportions of the N-oxidation. In conclusion, our studies demonstrate that only CYP3A4 is actively involved in the formation of 3-OH-Q. Hence, the (3S)-3-hydroxylation of quinidine is a specific probe for CYP3A4 activity in human liver microsome preparations, whereas the N-oxidation of quinidine is a somewhat less specific marker reaction for CYP3A4 activity, because the presence of a low affinity enzyme is demonstrated by different approaches.  (+info)

Metabolism of the antimalarial endoperoxide Ro 42-1611 (arteflene) in the rat: evidence for endoperoxide bioactivation. (4/766)

Ro 42-1611 (arteflene) is a synthetic endoperoxide antimalarial. The antimalarial activity of endoperoxides is attributed to iron(II)-mediated generation of carbon-centered radicals. An alpha, beta-unsaturated ketone (enone; 4-[2',4' bis(trifluoromethyl)phenyl]-3-buten-2-one), obtained from arteflene by reaction with iron(II), was identified previously as the stable product of a reaction that, by inference, also yields a cyclohexyl radical. The activation of arteflene in vivo has been characterized with particular reference to enone formation. [14C]Arteflene (35 micromol/kg) was given i.v. to anesthetized and cannulated male rats: 42.2 +/- 7.0% (mean +/- S.D., n = 7) of the radiolabel was recovered in bile over 5 h. In the majority of rats, the principal biliary metabolites were 8-hydroxyarteflene glucuronide (14.2 +/- 3. 9% dose, 0-3 h) and the cis and trans isomers of the enone (13.5 +/- 4.6% dose, 0-3 h). In conscious rats, 15.3 +/- 1.6% (mean +/- S.D., n = 8) of the radiolabel was recovered in urine over 24 h. The principal urinary metabolite appeared to be a glycine conjugate of a derivative of the enone. Biliary excretion of the glucuronide, but not of the enones, was inhibited by ketoconazole. 8-Hydroxyarteflene was formed extensively by rat and human liver microsomes but no enone was found. Bioactivation is a major pathway of arteflene's metabolism in the rat. Although the mechanism of in vivo bioactivation is unclear, the reaction is not catalyzed by microsomal cytochrome P-450 enzymes.  (+info)

Effects of azole antifungal drugs on the transition from yeast cells to hyphae in susceptible and resistant isolates of the pathogenic yeast Candida albicans. (5/766)

Oral infections caused by the yeast Candida albicans are some of the most frequent and earliest opportunistic infections in human immunodeficiency virus-infected patients. The widespread use of azole antifungal drugs has led to the development of drug resistance, creating a major problem in the treatment of yeast infections in AIDS patients and other immunocompromised individuals. Several molecular mechanisms that contribute to drug resistance have been identified. In C. albicans, the ability to morphologically switch from yeast cells (blastospores) to filamentous forms (hyphae) is an important virulence factor which contributes to the dissemination of Candida in host tissues and which promotes infection and invasion. A positive correlation between the level of antifungal drug resistance and the ability to form hyphae in the presence of azole drugs has been identified. Under hypha-inducing conditions in the presence of an azole drug, resistant clinical isolates form hyphae, while susceptible yeast isolates do not. This correlation is observed in a random sample from a population of susceptible and resistant isolates and is independent of the mechanisms of resistance. 35S-methionine incorporation suggests that growth inhibition is not sufficient to explain the inhibition of hyphal formation, but it may contribute to this inhibition.  (+info)

YM116, 2-(1H-imidazol-4-ylmethyl)-9H-carbazole, decreases adrenal androgen synthesis by inhibiting C17-20 lyase activity in NCI-H295 human adrenocortical carcinoma cells. (6/766)

The concentrations of androstenedione and dehydroepiandrosterone, products of C17-20 lyase, in the medium after a 6-hr incubation of NCI-H295 cells were decreased by YM116 (2-(1H-imidazol-4-ylmethyl)-9H-carbazole) (IC50: 3.6 and 2.1 nM) and ketoconazole (IC50: 54.9 and 54.2 nM). 17Alpha-hydroxyprogesterone, a product of 17alpha-hydroxylase, was increased by YM116 (1-30 nM) and by ketoconazole (10-300 nM) and then was decreased at higher concentrations of both agents (IC50: 180 nM for YM116, 906 nM for ketoconazole), indicating that YM116 and ketoconazole were 50- and 16.5-fold more specific inhibitors of C17-20 lyase, respectively, than 17alpha-hydroxylase. Compatible with these findings, progesterone, a substrate of 17alpha-hydroxylase, was increased by these agents. Cortisol production was inhibited by YM116 and ketoconazole (IC50: 50.4 and 80.9 nM, respectively). YM116 was a 14-fold more potent inhibitor of androstenedione production than cortisol production, whereas ketoconazole was a nonselective inhibitor of the production of both steroids. YM116 and ketoconazole inhibited the C17-20 lyase activity in human testicular microsomes (IC50: 4.2 and 17 nM, respectively). These results demonstrate that YM116 reduces the synthesis of adrenal androgens by preferentially inhibiting C17-20 lyase activity.  (+info)

Metabolic interactions between mibefradil and HMG-CoA reductase inhibitors: an in vitro investigation with human liver preparations. (7/766)

AIMS: To determine the effects of mibefradil on the nletabolism in human liver microsomal preparations of the HMG-CoA reductase inhibitors simvastatin, lovastatin, atorvastatin, cerivastatin and fluvastatin. METHODS: Metabolism of the above five statins (0.5, 5 or 10 microM), as well as of specific CYP3A4/5 and CYP2C8/9 marker substrates, was examined in human liver microsomal preparations in the presence and absence of mibefradil (0.1-50 microM). RESULTS: Mibefradil inhibited, in a concentration-dependent fashion, the metabolism of the four statins (simvastatin, lovastatin, atorvastatin and cerivastatin) known to be substrates for CYP3A. The potency of inhibition was such that the IC50 values (<1 microM) for inhibition of all of the CYP3A substrates fell within the therapeutic plasma concentrations of mibefradil, and was comparable with that of ketoconazole. However, the inhibition by mibefradil, unlike that of ketoconazole, was at least in part mechanism-based. Based on the kinetics of its inhibition of hepatic testosterone 6beta-hydroxylase activity, mibefradil was judged to be a powerful mechanism-based inhibitor of CYP3A4/5, with values for Kinactivation, Ki and partition ratio (moles of mibefradil metabolized per moles of enzyme inactivated) of 0.4 min(-1), 2.3 microM and 1.7, respectively. In contrast to the results with substrates of CYP3A, metabolism of fluvastatin, a substrate of CYP2C8/9, and the hydroxylation of tolbutamide, a functional probe for CYP2C8/9, were not inhibited by mibefradil. CONCLUSION: Mibefradil, at therapeutically relevant concentrations, strongly suppressed the metabolism in human liver microsomes of simvastatin, lovastatin, atorvastatin and cerivastatin through its inhibitory effects on CYP3A4/5, while the effects of mibefradil on fluvastatin, a substrate for CYP2C8/9, were minimal in this system. Since mibefradil is a potent mechanism-based inhibitor of CYP3A4/5, it is anticipated that clinically significant drug-drug interactions will likely ensue when mibefradil is coadministered with agents which are cleared primarily by CYP3A-mediated pathways.  (+info)

Effect of selected antimalarial drugs and inhibitors of cytochrome P-450 3A4 on halofantrine metabolism by human liver microsomes. (8/766)

Halofantrine (HF) is used in the treatment of uncomplicated multidrug-resistant Plasmodium falciparum malaria. Severe cardiotoxicity has been reported to be correlated with high plasma concentrations of HF but not with that of its metabolite N-debutylhalofantrine. The aim of this study was to investigate the effects of other antimalarial drugs and of ketoconazole, a typical cytochrome P-450 3A4 inhibitor, on HF metabolism by human liver microsomes. Antimalarial drug inhibitory effects were ranked as follows: primaquine > proguanil > mefloquine > quinine > quinidine > artemether > amodiaquine. Artemisine, doxycycline, sulfadoxine, and pyrimethamine showed little or no inhibition of HF metabolism. Mefloquine, quinine, quinidine, and ketoconazole used at maximal plasma concentrations inhibited N-debutylhalofantrine formation noncompetitively with Ki values of 70 microM, 49 microM, 62 microM, and 0.05 microM resulting in 7%, 49%, 26%, and 99% inhibition, respectively, in HF metabolism. In conclusion, we showed that quinine and quinidine coadministered with HF might inhibit its metabolism resulting in the potentiation of HF-induced cardiotoxicity in patients. This requires a close monitoring of ECG. For the same reasons, the concomitant administration of HF and ketoconazole must be avoided. By contrast, none of the other antimalarials studied inhibited HF metabolism and, by extrapolation, cytochrome P-450 3A4 activity.  (+info)

Ketoconazole is an antifungal medication that is used to treat a variety of fungal infections, including dermatophytosis (ringworm), candidiasis (yeast infection), and aspergillosis (lung infection). It works by inhibiting the growth of fungi and preventing them from multiplying. Ketoconazole is available in various forms, including tablets, creams, ointments, and shampoos. It is usually taken orally or applied topically to the affected area, depending on the type of infection being treated. In addition to its antifungal properties, ketoconazole has also been used to treat certain types of skin conditions, such as acne and seborrheic dermatitis. However, it is important to note that ketoconazole can have side effects, including nausea, vomiting, diarrhea, and liver damage, and should only be used under the guidance of a healthcare professional.

Miconazole is an antifungal medication that is used to treat a variety of fungal infections, including athlete's foot, jock itch, ringworm, and vaginal yeast infections. It works by inhibiting the growth of fungi in the body. Miconazole is available in various forms, including creams, ointments, tablets, and suppositories. It is generally well-tolerated, but side effects may include itching, burning, redness, and irritation at the site of application. Miconazole is not recommended for use during pregnancy or breastfeeding without consulting a healthcare provider.

Cytochrome P-450 CYP3A is a group of enzymes that are involved in the metabolism of a wide range of drugs and other substances in the body. These enzymes are found in the liver, lungs, and other organs, and they play a critical role in the elimination of drugs from the body. CYP3A enzymes are responsible for the metabolism of many commonly prescribed medications, including antibiotics, anti-inflammatory drugs, and cholesterol-lowering drugs. They also play a role in the metabolism of some recreational drugs, such as marijuana and cocaine. The activity of CYP3A enzymes can be affected by a variety of factors, including genetics, age, sex, and the presence of other medications. In some cases, interactions between different medications can lead to changes in the metabolism of one or both drugs, which can affect their effectiveness and increase the risk of side effects. In the medical field, understanding the role of CYP3A enzymes in drug metabolism is important for optimizing drug therapy and minimizing the risk of adverse effects. This information is often used to guide the selection and dosing of medications, as well as to develop strategies for managing drug interactions.

The cytochrome P-450 enzyme system is a group of enzymes that are responsible for the metabolism of a wide variety of drugs, toxins, and other substances in the body. These enzymes are found in the liver, lungs, and other organs, and they play a critical role in the detoxification of harmful substances and the elimination of drugs from the body. The cytochrome P-450 enzymes are classified into several families, each of which is responsible for the metabolism of specific types of compounds. For example, the CYP3A family is responsible for the metabolism of a wide variety of drugs, including many commonly prescribed medications. The CYP2D6 family is responsible for the metabolism of some antidepressants, antipsychotics, and other drugs. The activity of the cytochrome P-450 enzyme system can be affected by a variety of factors, including genetic variations, age, sex, and the presence of other medications. In some cases, these factors can lead to differences in the metabolism of drugs, which can affect their effectiveness and the risk of side effects. Overall, the cytochrome P-450 enzyme system plays a critical role in the metabolism of drugs and other substances in the body, and understanding its function is important for the safe and effective use of medications.

Clotrimazole is an antifungal medication that is commonly used to treat fungal infections of the skin, nails, and mucous membranes. It is available in various forms, including creams, ointments, tablets, and suppositories. Clotrimazole works by inhibiting the growth of fungi and is effective against a wide range of fungal species, including Candida, Trichophyton, and Epidermophyton. It is often used to treat conditions such as athlete's foot, jock itch, ringworm, vaginal yeast infections, and thrush. Clotrimazole is generally well-tolerated, but like all medications, it can cause side effects in some people. These may include itching, burning, redness, and swelling at the site of application.

Sucralfate is a medication that is used to treat stomach ulcers, including those caused by the bacteria Helicobacter pylori. It works by forming a protective layer over the ulcer, which helps to reduce stomach acid and protect the ulcer from further damage. Sucralfate is usually taken as a suspension or tablet, and it is usually taken with food or milk to help with absorption. It is not recommended for use in people with kidney disease or who are allergic to any of the ingredients in the medication.

Itraconazole is an antifungal medication that is used to treat a variety of fungal infections, including aspergillosis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, and onychomycosis. It is available in both oral and intravenous forms and works by inhibiting the growth of fungi. Itraconazole is also used to treat certain types of invasive fungal infections in patients with weakened immune systems, such as those with HIV/AIDS or cancer. It is important to note that Itraconazole can interact with other medications and may cause side effects, so it should only be taken under the guidance of a healthcare professional.

Fluconazole is an antifungal medication that is used to treat a variety of fungal infections, including candidiasis (a yeast infection), cryptococcal meningitis, and aspergillosis (a lung infection caused by a fungus). It is available in both oral and intravenous forms and is often used to treat fungal infections that are resistant to other antifungal medications. Fluconazole works by inhibiting the growth of fungi and preventing them from multiplying in the body. It is generally well-tolerated, but like all medications, it can cause side effects in some people. These may include nausea, vomiting, diarrhea, and abdominal pain.

Azoles are a class of synthetic organic compounds that contain a five-membered heterocyclic ring with one or two nitrogen atoms. In the medical field, azoles are commonly used as antifungal agents to treat a variety of fungal infections, including dermatophytosis, candidiasis, and aspergillosis. There are several different types of azoles, including fluconazole, itraconazole, voriconazole, and posaconazole, each with its own specific mechanism of action and indications for use. Azoles work by inhibiting the synthesis of ergosterol, a vital component of fungal cell membranes, which leads to cell death and the resolution of the infection. Azoles are generally well-tolerated and have a low risk of side effects, although some patients may experience gastrointestinal symptoms, such as nausea, vomiting, or diarrhea. In addition, azoles can interact with other medications, including some antibiotics and immunosuppressants, so it is important to inform your healthcare provider of all medications you are taking before starting treatment with an azole.

Econazole is an antifungal medication that is used to treat various fungal infections of the skin, such as athlete's foot, jock itch, and ringworm. It works by inhibiting the growth and spread of fungi in the body. Econazole is available in various forms, including creams, ointments, and tablets, and is typically applied to the affected area of the skin once or twice a day. It is important to follow the instructions provided by your healthcare provider and to complete the full course of treatment, even if your symptoms improve before the medication is finished.

Sterol 14-demethylase is an enzyme that plays a crucial role in the biosynthesis of cholesterol in the human body. It is responsible for converting lanosterol, a precursor of cholesterol, into 4,4-dimethylzymosterol, which is then converted into cholesterol by other enzymes. In the medical field, the activity of sterol 14-demethylase is often measured as a way to assess the efficiency of cholesterol biosynthesis in the body. Abnormal levels of this enzyme activity can be associated with various medical conditions, including hypercholesterolemia (high cholesterol levels), which is a risk factor for cardiovascular disease. In addition, drugs that inhibit the activity of sterol 14-demethylase, such as statins, are commonly used to lower cholesterol levels in patients with high cholesterol or other cardiovascular risk factors. These drugs work by blocking the enzyme's ability to convert lanosterol into cholesterol, thereby reducing the amount of cholesterol produced by the body.

Imidazoles are a class of organic compounds that contain a five-membered heterocyclic ring with two nitrogen atoms and three carbon atoms. In the medical field, imidazoles are commonly used as antifungal agents, particularly for the treatment of dermatophytic infections such as athlete's foot, ringworm, and jock itch. They work by inhibiting the growth of fungi by interfering with their metabolism. One of the most well-known imidazole antifungal agents is clotrimazole, which is used topically to treat skin and nail infections caused by fungi. Other imidazole antifungal agents include miconazole, ketoconazole, and itraconazole, which are used to treat a variety of fungal infections, including systemic infections such as cryptococcal meningitis and aspergillosis. Imidazoles are also used in other medical applications, such as in the treatment of parasitic infections, as well as in the development of new drugs for the treatment of cancer and other diseases.

Oxidoreductases, N-demethylating are a group of enzymes that catalyze the removal of a methyl group from a nitrogen atom in a molecule. These enzymes are important in the metabolism of many drugs and other compounds, as the removal of a methyl group can alter the chemical properties of the molecule and affect its activity. In the medical field, these enzymes are often studied in the context of drug metabolism and the development of new drugs. They may also be targeted for therapeutic purposes, for example in the treatment of certain types of cancer.

Loratadine is a medication used to treat allergy symptoms such as runny nose, sneezing, itching, and watery eyes. It belongs to a class of drugs called antihistamines, which work by blocking the action of histamine, a chemical produced by the body in response to an allergen. Loratadine is available over-the-counter (OTC) and is also used to treat seasonal allergies and chronic idiopathic urticaria (hives). It is generally well-tolerated and has fewer side effects than older antihistamines.

Amphotericin B is an antifungal medication that is used to treat a variety of fungal infections, including systemic candidiasis, aspergillosis, cryptococcosis, and histoplasmosis. It is a polyene antifungal agent that works by disrupting the fungal cell membrane, leading to cell death. Amphotericin B is available in both intravenous and oral forms. The intravenous form is typically used for severe or life-threatening infections, while the oral form is used for less severe infections or as a maintenance therapy. Amphotericin B can cause serious side effects, including kidney damage, fever, chills, nausea, vomiting, and allergic reactions. It is therefore typically administered under close medical supervision, and the dosage and duration of treatment are carefully adjusted based on the patient's response and the severity of the infection.

Ergosterol is a type of sterol that is found in the cell membranes of fungi and some protists. It is an essential component of the fungal cell membrane, playing a role in maintaining the membrane's structure and fluidity. In the medical field, ergosterol is often used as a diagnostic marker for fungal infections, as it is not present in human cells. It is also used as a target for antifungal drugs, as many antifungal agents work by inhibiting ergosterol biosynthesis in fungal cells. In addition to its role in fungal cell membranes, ergosterol has been studied for its potential therapeutic applications in other areas of medicine. For example, it has been shown to have anti-inflammatory and anti-cancer properties, and it is being investigated as a potential treatment for a variety of diseases, including cancer, Alzheimer's disease, and multiple sclerosis.

Butyrophenones are a class of psychoactive drugs that are used as antipsychotic medications. They are similar in structure to the neurotransmitter dopamine and work by blocking the action of dopamine in the brain, which helps to reduce symptoms of psychosis such as hallucinations and delusions. Some examples of butyrophenones include haloperidol, loxapine, and trifluoperazine. These drugs are typically used to treat conditions such as schizophrenia and bipolar disorder, and may also be used to manage symptoms of Huntington's disease and Tourette's syndrome. Butyrophenones can have a number of side effects, including drowsiness, dizziness, and movement disorders such as tardive dyskinesia.

Triazoles are a class of synthetic organic compounds that contain a three-membered ring of nitrogen atoms. They are widely used in the medical field as antifungal agents, particularly for the treatment of invasive fungal infections such as candidiasis, aspergillosis, and cryptococcosis. The most commonly used triazole antifungal agents are fluconazole, itraconazole, voriconazole, and posaconazole. These drugs work by inhibiting the synthesis of ergosterol, a vital component of fungal cell membranes, which leads to the disruption of the membrane's integrity and ultimately the death of the fungal cell. Triazoles are also used in other medical applications, such as in the treatment of certain types of cancer, as well as in the development of new drugs for the treatment of other diseases.

Dermatomycoses are a group of fungal infections that affect the skin and nails. These infections are caused by dermatophytes, which are a type of fungus that thrives in warm, moist environments, such as the skin, nails, and hair. Dermatomycoses can be classified into three main types: superficial, subcutaneous, and systemic. Superficial dermatomycoses affect only the outer layers of the skin and nails, and are usually mild and self-limiting. Examples of superficial dermatomycoses include athlete's foot, ringworm, and jock itch. Subcutaneous dermatomycoses involve deeper layers of the skin and can cause more serious symptoms, such as swelling, redness, and pain. Examples of subcutaneous dermatomycoses include sporotrichosis and chromoblastomycosis. Systemic dermatomycoses are rare and can affect multiple organs, including the lungs, brain, and heart. These infections are more difficult to treat and can be life-threatening if left untreated. Examples of systemic dermatomycoses include histoplasmosis and coccidioidomycosis. Treatment for dermatomycoses typically involves the use of antifungal medications, such as creams, ointments, or oral tablets. In severe cases, hospitalization may be necessary for intravenous antifungal therapy. Prevention of dermatomycoses involves maintaining good hygiene, avoiding contact with infected individuals or animals, and wearing protective clothing in high-risk environments.

Triazolam is a benzodiazepine medication that is used to treat anxiety disorders, insomnia, and other conditions that cause difficulty sleeping. It works by enhancing the effects of a neurotransmitter called gamma-aminobutyric acid (GABA), which helps to calm the brain and reduce anxiety and tension. Triazolam is available in tablet form and is typically taken orally, usually at bedtime. It is a short-acting benzodiazepine, meaning that its effects wear off relatively quickly, typically within a few hours. This makes it useful for treating insomnia, as it can help to induce sleep and reduce the time it takes to fall asleep. Triazolam can be habit-forming and can cause dependence if used for extended periods of time or in high doses. It can also cause side effects, including drowsiness, dizziness, headache, nausea, and impaired coordination. It is important to follow the instructions of a healthcare provider when taking triazolam and to avoid using it for longer than recommended.

Flucytosine is an antifungal medication that is used to treat fungal infections, particularly those caused by the yeast Candida. It works by inhibiting the growth and reproduction of the fungus. Flucytosine is usually given in combination with other antifungal medications, such as amphotericin B or azoles, to increase its effectiveness. It is typically administered orally in the form of a tablet or capsule, although it can also be given intravenously in severe cases. Flucytosine is generally well-tolerated, but it can cause side effects such as nausea, vomiting, and diarrhea. It is important to take this medication exactly as prescribed by a healthcare provider to ensure that it is effective and to minimize the risk of side effects.

Candidiasis, vulvovaginal, is a fungal infection that affects the vulva and vagina. It is caused by the overgrowth of the yeast Candida albicans, which is normally present in small amounts in the vagina. The infection is more common in women who are pregnant, have a weakened immune system, or are taking antibiotics or corticosteroids. Symptoms of vulvovaginal candidiasis include itching, burning, redness, and a thick, white discharge. Treatment typically involves the use of antifungal medications, such as creams or suppositories, applied to the affected area. In severe cases, oral antifungal medication may be prescribed.

Terfenadine is a second-generation antihistamine medication that is used to treat symptoms of allergies such as runny nose, sneezing, itching, and watery eyes. It works by blocking the action of histamine, a chemical that is released by the body in response to an allergic reaction. Terfenadine is available in tablet form and is typically taken once or twice a day, depending on the severity of symptoms. It is generally well-tolerated, but like all medications, it can cause side effects. Common side effects of terfenadine include dizziness, drowsiness, headache, and stomach upset. In rare cases, it can cause more serious side effects such as heart rhythm problems, which can be life-threatening. Terfenadine is contraindicated in patients with a history of QT prolongation, heart block, or certain other heart conditions, as well as in patients who are taking certain other medications that can prolong the QT interval. It is also not recommended for use in children under the age of 12, as there is limited data on its safety and effectiveness in this population.

Midazolam is a medication that belongs to a class of drugs called benzodiazepines. It is primarily used as a sedative, anxiolytic (anti-anxiety), and muscle relaxant. It is also used to treat seizures, including those that occur as part of a procedure to control bleeding in the brain. Midazolam is available in both oral and injectable forms, and it can be given as a single dose or as part of a continuous infusion. It works by enhancing the effects of a neurotransmitter called gamma-aminobutyric acid (GABA), which helps to calm the brain and reduce anxiety and muscle tension. Midazolam is commonly used in medical settings for a variety of procedures, including dental procedures, endoscopy, and surgery. It is also used to treat agitation and aggression in people with certain mental health conditions, such as schizophrenia and bipolar disorder. However, midazolam can be habit-forming and can cause side effects, including drowsiness, dizziness, confusion, and memory impairment. It can also cause respiratory depression, which can be life-threatening if not properly monitored. Therefore, it is typically only used under the supervision of a healthcare professional.

Mixed-function oxygenases are a class of enzymes that catalyze the oxidation of a wide range of substrates, including drugs, toxins, and endogenous compounds. These enzymes typically contain a non-heme iron or copper atom in their active site, which is coordinated by a variety of amino acid residues. Mixed-function oxygenases are involved in a variety of biological processes, including drug metabolism, xenobiotic detoxification, and the synthesis of important biological molecules such as cholesterol and bile acids. They are also involved in the metabolism of many environmental pollutants, including polycyclic aromatic hydrocarbons and halogenated hydrocarbons. In the medical field, mixed-function oxygenases are important because they play a key role in the metabolism of many drugs, which can affect their efficacy and toxicity. For example, the cytochrome P450 family of mixed-function oxygenases is responsible for the metabolism of many commonly prescribed drugs, including anti-inflammatory drugs, antidepressants, and anticoagulants. Understanding the role of these enzymes in drug metabolism is important for optimizing drug therapy and minimizing adverse drug reactions.

Troleandomycin is an antibiotic medication that is used to treat a variety of bacterial infections, including pneumonia, bronchitis, and skin infections. It is a macrolide antibiotic, which means that it works by inhibiting the growth of bacteria by interfering with their ability to synthesize proteins. Troleandomycin is typically taken by mouth in the form of tablets or capsules, and it is usually prescribed for a duration of 7 to 14 days. It is important to follow the dosing instructions provided by your healthcare provider and to complete the full course of treatment, even if you start to feel better before the medication is finished. Troleandomycin may cause side effects such as nausea, vomiting, diarrhea, and abdominal pain. It may also interact with other medications, so it is important to tell your healthcare provider about all of the medications you are taking before starting treatment with troleandomycin.

Piperazines are a class of organic compounds that contain a six-membered ring with two nitrogen atoms. They are commonly used in the medical field as drugs and are known for their anticholinergic, antispasmodic, and sedative properties. Some examples of piperazine-based drugs include antihistamines, antipsychotics, and antidiarrheals. Piperazines can also be used as intermediates in the synthesis of other drugs.

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  • High doses of ketoconazole are sometimes used to treat Cushing syndrome (a condition that occurs when there is too much corticosteroid hormone in the body) and advanced prostate cancer (cancer of a male reproductive gland). (medlineplus.gov)
  • The dominant lethal mutation test in male and female mice revealed that single oral doses of ketoconazole as high as 80 mg/kg produced no mutation in any stage of germ cell development. (nih.gov)
  • They do not apply to topical formulations of ketoconazole in creams, shampoos, foams, and gels. (medscape.com)
  • Drug safety assessment of oral formulations of ketoconazole. (nih.gov)
  • Ketoconazole tablets should be used only when other effective antifungal therapy is not available or tolerated and the potential benefits are considered to outweigh the potential risks. (nih.gov)
  • Ketoconazole, USP is a synthetic broad-spectrum antifungal agent. (nih.gov)
  • Ketoconazole is a well documented cause of clinically apparent acute drug induced liver injury and is no longer recommended as a first line antifungal agent. (nih.gov)
  • Ketoconazole: an orally effective antifungal agent. (nih.gov)
  • After a single topical application to the chest, back and arms of normal volunteers, systemic absorption of ketoconazole was not detected at the 5 ng/mL level in blood over a 72-hour period. (nih.gov)
  • these effects have not been seen with topical ketoconazole. (nih.gov)
  • Topical medications including clotrimazole and ketoconazole are used to treat ringworm of the body as well as tinea versicolor. (healthychildren.org)
  • Ketoconazole should only be used to treat fungal infections when other medications are not available or cannot be tolerated. (medlineplus.gov)
  • Oral ketoconazole is now indicated only for certain life-threatening fungal infections, known as endemic mycoses, in patients who fail to respond to other treatments or who cannot tolerate them. (medscape.com)
  • Ketoconazole is an imidazole fungicidal agent with a very broad spectrum of activity against many fungal species that is used for treatment of superficial and systemic fungal infections. (nih.gov)
  • Because ketoconazole tablets have been associated with serious adverse reactions (see WARNINGS section), ketoconazole tablets are not indicated for treatment of onychomycosis, cutaneous dermatophyte infections, or Candida infections. (nih.gov)
  • In the United States, the FDA is withdrawing the indication of ketoconazole tablets completely for Candida and dermatophyte infections. (medscape.com)
  • Clinicians should no longer prescribe ketoconazole ( Nizoral , Janssen Pharmaceuticals) tablets as a first-line therapy for any fungal infection because of the risk for severe liver injury, adrenal insufficiency, and adverse drug interactions, the US Food and Drug Administration (FDA) announced today. (medscape.com)
  • Prescription ketoconazole shampoo is used to treat tinea versicolor. (nih.gov)
  • Ketoconazole shampoo is also effective, as are several other antifungals that are applied directed onto the affected area. (healthychildren.org)
  • A ketoconazole shampoo should be used twice a week until symptoms are controlled and then once a week thereafter. (msdmanuals.com)
  • In vitro studies have shown that CYP3A4 is the major enzyme involved in the metabolism of ketoconazole. (nih.gov)
  • In vitro studies suggest that ketoconazole impairs the synthesis of ergosterol, which is a vital component of fungal cell membranes. (nih.gov)
  • Ketoconazole is a weak dibasic agent and thus requires acidity for dissolution and absorption. (nih.gov)
  • Absorption of ketoconazole tablets is reduced in subjects with reduced gastric acidity, such as subjects taking medications known as acid neutralizing medicines (e.g. aluminum hydroxide) and gastric acid secretion suppressors (e.g. (nih.gov)
  • Absorption of ketoconazole under fasted conditions in these subjects is increased when ketoconazole tablets are administered with an acidic beverage (such as non-diet cola). (nih.gov)
  • Following absorption from the gastrointestinal tract, ketoconazole tablets are converted into several inactive metabolites. (nih.gov)
  • Ketoconazole has been shown to be teratogenic (syndactylia and oligodactylia) in the rat when given orally in the diet at 80 mg/kg/day, (10 times the maximum recommended human oral dose). (nih.gov)
  • no longer available in the US), methadone (Dolophine, Methadose), and ranolazine (Ranexa) while you are taking ketoconazole. (medlineplus.gov)
  • tell your doctor and pharmacist if you are allergic to ketoconazole or any other medications or any of the ingredients in ketoconazole tablets. (medlineplus.gov)
  • Limited pharmacokinetic data are available on the use of ketoconazole tablets in the pediatric population. (nih.gov)
  • The agency action coincides with today's recommendation by European Union (EU) drug regulators to withdraw ketoconazole tablets from EU national markets. (medscape.com)
  • The FDA instructs clinicians not to prescribe ketoconazole tablets for any patients with underlying liver disease. (medscape.com)
  • Ketoconazole is in a class of antifungals called imidazoles. (medlineplus.gov)
  • Oral antifungals such as ketoconazole, fluconazole, and itraconazole have been shown to be effective in adults. (healthychildren.org)
  • Ketoconazole can cause elevated plasma concentrations of these drugs and may prolong QT intervals, sometimes resulting in life-threatening ventricular dysrhythmias such as torsades de pointes. (nih.gov)
  • Ketoconazole can cause QT prolongation (an irregular heart rhythm that can lead to fainting, loss of consciousness, seizures, or sudden death). (medlineplus.gov)
  • Ketoconazole cream, 2% is contraindicated in persons who have shown hypersensitivity to the active or excipient ingredients of this formulation. (nih.gov)
  • Ketoconazole, USP is a white or almost white powder that is soluble in acids. (nih.gov)
  • Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with ketoconazole and each time you refill your prescription. (medlineplus.gov)
  • Do not drink any alcoholic beverages during your treatment with ketoconazole because drinking alcoholic beverages may increase the risk that you will develop liver damage. (medlineplus.gov)
  • Toxic hepatitis following ketoconazole treatment. (nih.gov)
  • Ketoconazole comes as a tablet to take by mouth. (medlineplus.gov)
  • Measurable ketoconazole plasma concentrations have been observed in pre-term infants (single or daily doses of 3 to 10 mg/kg) and in pediatric patients 5 months of age and older (daily doses of 3 to 13 mg/kg) when the drug was administered as a suspension, tablet or crushed tablet. (nih.gov)
  • Ketoconazole has not been shown to be safe or effective for these uses. (medlineplus.gov)
  • Ketoconazole should not be used to treat fungal meningitis (infection of the membranes surrounding the brain and spinal cord caused by a fungus) or fungal nail infections. (medlineplus.gov)
  • When ketoconazole cream, 2% was applied dermally to intact or abraded skin of beagle dogs for 28 consecutive days at a dose of 80 mg, there were no detectable plasma levels using an assay method having a lower detection limit of 2 ng/mL. (nih.gov)
  • Ketoconazole cream, 2% is not for ophthalmic use. (nih.gov)
  • You may need to take ketoconazole for 6 months or longer to cure your infection completely. (medlineplus.gov)
  • In patients with hepatic or renal impairment, the overall pharmacokinetics of ketoconazole was not significantly different when compared with healthy subjects. (nih.gov)
  • After pretreatment with omeprazole, a proton pump inhibitor, the bioavailability of a single 200 mg dose of ketoconazole under fasted conditions was decreased to 17% of the bioavailability of ketoconazole administered alone. (nih.gov)
  • The study aimed to select a suitable solvent capable to solubilize ketoconazole (KETO) and serve as a permeation enhancer across the skin . (bvsalud.org)