The first 22 pairs of chromosomes (called autosomes) are numbered from 1 to 22, from largest to smallest. The 23rd pair of chromosomes are the sex chromosomes. Normal females have two X chromosomes, while normal males have one X chromosome and one Y chromosome. The characteristics of the chromosomes in a cell as they are seen under a light microscope are called the karyotype. During meiosis, when germ cells divide to create sperm and egg (gametes), each half should have the same number of chromosomes. But sometimes, the whole pair of chromosomes will end up in one gamete, and the other gamete will not get that chromosome at all. Most embryos cannot survive with a missing or extra autosome (numbered chromosome) and are spontaneously aborted. The most frequent aneuploidy in humans is trisomy 16 and fetuses affected with the full version of this chromosome abnormality do not survive to term, although it is possible for surviving individuals to have the mosaic form, where trisomy 16 exists in some cells but not all. The most common aneuploidy that infants can survive with is trisomy 21, which is found in Down syndrome, affecting 1 in 800 births. Trisomy 18 (Edwards syndrome) affects 1 in 6,000 births, and trisomy 13 (Patau syndrome) affects 1 in 10,000 births. 10% of infants with trisomy 18 or 13 reach 1 year of age.Changes in chromosome number may not necessarily be present in all cells in an individual.
Another resistance mechanism employed by both C. albicans and C. glabrata is increasing the rate of efflux of the azole drug from the cell, by both ATP-binding cassette and major facilitator superfamily transporters. Other gene mutations are also known to contribute to development of resistance. C. glabrata develops resistance by up regulating CDR genes, and resistance in C. krusei is mediated by reduced sensitivity of the target enzyme to inhibition by the agent.The full spectrum of fungal susceptibility and resistance to fluconazole can be found in the TOKU-Es product data sheet. According to the United States Centers for Disease Control, fluconazole resistance among Candida strains in the U.S. is about 7%. Contraindications
Fluconazole is contraindicated in patients who:
Drink alcohol
have known hypersensitivity to other azole medicines such as ketoconazole;
are taking terfenadine, if 400 mg per day multidose of fluconazole is administered;
concomitant administration of fluconazole and quinidine, especially when fluconazole is administered in high dosages;
take SSRIs such as fluoxetine or sertraline. Side effects
Adverse drug reactions associated with fluconazole therapy include:
Common (≥1% of patients): rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhea, and/or elevated liver enzymes
Infrequent (0.1–1% of patients): anorexia, fatigue, constipation
Rare (<0.1% of patients): oliguria, hypokalaemia, paraesthesia, seizures, alopecia, Stevens–Johnson syndrome, thrombocytopenia, other blood dyscrasias, serious hepatotoxicity including liver failure, anaphylactic/anaphylactoid reactions
Very rare: prolonged QT interval, torsades de pointes
FDA is now saying treatment with chronic, high doses of fluconazole during the first trimester of pregnancy may be associated with a rare and distinct set of birth defects in infants.If taken during pregnancy it may result in harm.