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Active Ingredient: Fluconazole

This is an antifungal medication used in treating different types of fungal infection. To get a clear picture of how fluconazole works, we must first understand what fungi infections are and why they need to be treated.

What are Fungi?

Fungi are plural of the word fungus which refers to groups of microorganisms that include yeast, molds, rusts, and mushroom. There are over 140,000 different species of fungi living freely in the soil or water or in a dependent relationship between plants and animals. Like most other micro organisms, fungi can be pro-life or a disease-causing agent. Fungi differ from plants in that it lacks chlorophyll which is what plants used in processing their food. A distinct differentiation of other organisms from the plant is the lack of chlorophyll. Fungi are classified into five primary divisions based on their mode of reproduction; the divisions include Chtridiomycota, Zygomycota, Ascomycota, Basidiomycota, and Glomercomycota. There are different medications targeted at each division whereas, there are some serving multiple functions against different fungi classes.

Fungi infections are commoner in settings of chronic illness or an immunity lowering disease. They are fondly called opportunity infection because they occur more secondarily after a primary infection must have weighed the host down significantly. Mycosis can be an AIDs or tuberculosis defining illness; their presence is a pointer to the fact that the body has been overwhelmed already and it had given way to normal commensals whose present ab initio were not unwelcomed.

AntiFungal

I am sure you have heard of words like antibacterial use to represent medications that work against the growth of bacteria or antiviral that attacks the virus at the level of cellular division. Similarly, antifungal is used to refer to medications working against the spread of fungi in the body. You might see the word antifungal being used interchangeably with antimycotic; they are pretty the same thing as mycosis refers to fungal infections. Antifungal agents are drugs used to treat or prevent fungal infections. There are several classes of antifungal, some of which will be explained in details as I progress.

Classes of Antifungals

Azole: This is by far the commonest class of antimycotic agent and is further divided into the subdivisions which are imidazole, triazole, and thiazole. They work by inhibiting one of the enzymes called lanosterol demethylase which is needed in maintaining the integrity and functions of the fungal membrane, which in turn leads to fungal growth inhibition. Examples of medication in this class are clotrimazole, ketoconazole, isoconazole, fluconazole, and itraconazole. Abafungin is also a type of azole but does not work by inhibition of the same enzyme with the other azole.

Polyene antifungals: They binds with the fungal cell membrane and alters in a new cascade of events which eventually leads to the death of the fungi. Their common examples include amphotericin B, candicidin and nystatin. Other common classifications of antifungal include Allylamines and Echinocandins.

Understanding Fluconazole

Now that we have established a clear understanding of what fungi are, the anti fungi and their classes. Let us come down to the subject matter which is fluconazole. Fluconazole is antimycotic agent belonging to azole class of antifungal agents; it is specifically belonging to the subclass triazole which also consists of agents like albaconazole and itraconazole. Fluconazole is a triazole antifungal agent which works by inhibiting fungi cell membrane. Fluconazole was the first antifungal developed to be available in both oral and injection form. The antifungal medications available before fluconazole were strictly for either oral use (like flucytosine), or intravenous use (like amphotericin B) which was a great headache to the pharmaceutical companies. The orally active flucytosine had a very limited action and was very susceptible to resistance whereas amphotericin B had severe side effects. Series of research by the Pfizer Central Research in the mid 70’s and early early 80’s lede development of fluconazole which was patented in the 80’s. fluconazole was the drug that revoltionariserevolutionisefungi diseases.

Dosage and indications

Fluconazole is used in both adult and pediatric age majorly for treating different forms of candidiasis (a type of yeast infection which typically affects the mouth, throat, and vagina; its primary habitat). It comes in oral, suspensions and intravenous forms. Available tablets include 50mg, 100mg, 150mg, and 200mg; whereas oral suspension comes in 10mg/ml or 40mg/ml while intravenous formulations are usually in 2mg/ml. Dosage differs slightly depending on usage.

  • Oropharyngeal Candidiasis: Adult doses is usually a tablet of 200mg on the first day of use, then 100mg every 6 hours for at least 2 weeks after the last symptom. Children with Oropharyngeal candidiasis use pediatrics appropriated dose which is 6mg/kg tablet on the first day of use, then subsequently 3mg/kg every 6 hours up to 2 weeks.
  • Esophageal Candidiasis: The adult dose is similar to the dose in oropharyngeal candidiasis but for a minimum of 3 weeks or at least 2 weeks after the last symptom has abated. Pediatric dosage is also similar to the oropharyngeal candidiasis dosage but can be increased up to 12mg/kg depending on patient response. Children should also be treated for a minimum of 2 weeks and at least 2-3 weeks after the last symptom has stopped. Children with a very low immunity could also have a systemic form of candidiasis whereby the candidiasis would have overwhelmed their blood system; in this case, they can be given 6-12mg/kg daily of either oral or intravenous fluconazole but should not exceed a total of 600mg daily.
  • Vaginal Candidiasis: Adult can also have a Candida infestation of the vagina; treatment is a single dose of oral 150mg fluconazole in uncomplicated cases whereas, in complicated vaginal candidiasis, the 150mg fluconazole tablet should be given daily for the next 3 days.
  • Cryptococcal meningitis: In adults, the dosage is a 400mg tablet on day 1 and then 200mg tablet 4 times in a day for the next 10-12 weeks after a culture negative cerebrospinal fluid. Children with cryptococcal meningitis are usually placed on IV fluconazole of 6-12mg/kg/day or oral of the same dose for the next 10-12 weeks after achieving a culture negative cerebrospinal fluid.

It must be said that the organism candida is a normal commensal of human but becomes harmful in settings of low-level immunity. In fact, most individuals with oral or oropharyngeal candidiasis are usually positive to HIV infection. When seen in children, a quick serological workup must be done for the child and the mother to know their status.

Candidiasis is a group of fungal infections caused by yeast. The most common type is oropharyngeal candidiasis which usually presents with thick whitish patches on the tongue called oral thrush, sore and painful mouth and difficulty in swallowing. Esophageal candidiasis can present in addition to difficulty in swallowing, pain while trying to swallow, chest pain, nausea, and vomiting. Candidiasis of the genitourinary tract can affect the vagina, labia major and minora, the penis and the bladder.

Cryptococcal meningitis, on the other hand, is an infection of the covering of the brain meninges (the dura, pia and arachnoid matter) caused by fungi. It can also be caused by non-fungus like viruses and bacteria. It is also very rare in healthy people; basically seen in people with low immunity as pointed out for candidiasis earlier. It can be caused by Cryptococcus neoformans or cryptococcus gatti as seen in a patient suffering from the progression of HIV to AIDS. It is diagnosed by taken cerebrospinal fluid for fluid analysis which is why the same procedure must be repeated before declaring a patient cryptococcal meningitis cleared. It is primarily treated by oral flucytosine and intravenous amphotericin B as primary medications. Fluconazole is usually a secondary option or sometimes given to be used for 8 weeks after the first negative result cerebrospinal fluid analysis.

How to use fluconazole

Fluconazole tablets can be used with or without food, while you should shake the oral suspension well before using. You must also make sure you do not use more than the prescribed amount. For intravenous use, your attending physician will secure an intravenous line first (it is just a little prick pain you will feel), through which the medication will be given. Intravenous used is usually reserved for very serious infections. Fluconazole should be kept away from children at room temperature. Do not allow your children to use this medication themselves and make sure you dispose of any exposed tablet appropriately.

Drug Interaction

Most medications have some form of interactions with other medications and you should never commence a new set of medications without informing your caregiver of the medications you are presently using. The use of fluconazole is contraindicated with erythromycin and quinidine. These medications are not supposed to be used together in any form, you should inform your caregiver so that you can be given a close substitute. If you are on amiodarone or clopidogrel, you should also not used together with fluconazole; fluconazole increases the level of amiodarone and reduces clopidogrel level in the system. If you are using statins (e.g atorvastatin to lower blood cholesterol level) or losartan with fluconazole, you should watch closely.

Adverse effects

Fluconazole usually does not have very serious adverse effects; the common side effects include a headache seen in greater than 10% of patient and any of Nausea, abdominal pain, diarrhea and rash affecting between 1-10% of patients on fluconazole. There has however been the incidence of Steven-Johnson Syndrome, Pallor, Jaundice, and seizures in very rare cases with a patient on fluconazole. You must, however, remain careful, if you have some form of sensitivity to other azoles like itraconazole and ketoconazole.

Steven-Johnson syndrome is a type of hypersensitivity reaction that typically affects the skin andmucousbrane. It is a potentially lethal condition that can present with joint and muscle pain with skin dryness. A more severe form of skin and mucous membrane reaction is called toxic epidermal necrosis and has not been reported with fluconazole use. However, if you notice any form of adverse reaction while on fluconazole, you must stop the medication and present to the hospital immediately.

A bit of Pharmacology

Fluconazole is said to work by selective inhiinhibitinggal cytochrome P-450 dependent enzyme lanosterol 14 alpha-methmethylethylase. With oral medications, about 90% of the drug is said to be bio-available in the plasma in 1-2 hour after drug ingestion. It is said to cross the blood-brain barrier which is the reason why it is useful in Cryptococcal meningitis. It is partially metabolized in the liver and has an elimination half-life of 30 hours. Over 80% of the medication is excreted in the urine in unchanged form while 11% is excreted as metabolites. Fluconazole tablet is best to store at a temperature below 86 degree Fahrenheit (30 degree Celsius). Injections can be stored in the fridge but it must be prevented from freezing. Temperature between 86 degree Fahrenheit (30 degree Celsius) and 41 degrees fahrenheit (5 degree Celsius) is considered adequate.

Use of fluconazole in pregnancy

There have been reports suggesting increased risk of miscarriage in women who are pregnant.. So, it is advisable for women who are either pregnant or intending to get pregnant to consult their doctor for alternate medication. A Danish study suggest increased incidence of spontaneous abortion between 7 and 22 weeks of gestation in women who are on fluconazole as compared to those who are not.

Fluconazole is a triazole used for the treatment of a wide range mycotic disease. It is efficient for oral and intravenous use in both adult and children; they must however be used with care as it can sometimes be reacted to.

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