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36 Cards in this Set
- Front
- Back
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Define fungi.
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Fungi are eukaryotes that can survive in extreme conditions where nutrients are sparse. All fungi contain sterols in their cell membrane and not peptidoglycan. Saprophytes are fungi that live of dead organic matter in soil and water and are vital for the carbon cycle
Yeasts: unicellular, spherical organisms that reproduce by budding. In some yeasts, the buds elongate to form filaments ( pseudohyphae) eg candida. Moulds: they are composed of numerous branching, filamentous hyphae known collectively as mycelia. The mycelia produce spores by asexual and sexual reproduction from mating strains. Spores spread out in the atmosphere allowing fungi to colonise new environments. Higher fungi: mushrooms and toadstools. |
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What are dimorphic fungi?
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Dimorphic pathogenic fungi are part of the yeast group of reproduction when invading tissues but become a mould form when living in the environment. The exception is candida which forms pseudohyphae when in the body but they are not classical dimorphic fungi. Classical pathogenic dimorphic fungi are not endemic to UK.
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Define mycology and the classification of mycoses.
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Mycology is the study of fungi and the diseases they cause are called mycoses. Mycoses are classified depending on the mode of entry into host and the degree of tissue involved.
Superficial – mycoses localised to the skin, hair and nails but can extend deeper into keratinised tissue. Examples include dermatophyte infections- filamentous infections such as tinea ( ring worm) and yeast infections such as candida albicans causing oral thrush, vaginitis, cutaneous candidiasis. Subcutaneous – infection confined to dermis, subcutaneous tissue or adjacent structures. The mycoses arise from injury to skin and contamination with organic matter. It is rare in UK Systemic – deep infections of the internal organs with organism gaining entry by lungs, GI tract or through IV lines, Opportunistic – cause infection only in immunocompromised |
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List fungi that can cause superficial mycoses
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- Dermatophytes: filamentous organisms: epidermophyton, microsporium, trichophyton
- Candida albicans: yeast with pseudohyphae |
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Describe dermatophytes
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Dermatophytes are filamentous (moulds)organisms caused superifical infections.
3 main genera: - Epidermophyton - Microsporium - Trichophyton Dermatophytes invade the keratin of skin, nails and hair. Examples of dermatophytes include tinea ( ringworm – name is due to appearance of central clearance and circular growth away from centre). - Tinea capitis - scalp - Tinea barbae - beard - Tinea pedis – athletes foot - Tinis cruris- groin Dermatophytes spread by human to human contact, animals or environment. |
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Describe candida albicans. where is it normally found? what problems does it cause? how is it detected?
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Yeast infections include candida albicans causing oral thrush, vaginitis, cutaneous candidiasis.
Candida albicans is a commensal yeast fungus in the skin, vagina and GI tract and therefore infection is endogenous. It does not normally cause infection but in times of immunodeficiency or ill health the organism multiplies to cause disease. Increased multiplication can be caused by broad spectrum antibiotic treatment and long standing corticosteroids which can remove other flora allowing candida albicans to flourish. also diabetes with high glucose can support candida growth. It can cause oral thrush (ulceration), vaginitis and cutaneous candidadias. Candida albicans can act as an opportunistic fungus by spreading through the blood stream causing systemic infections as seen in neutropenic patients, long standing corticosteroid use and IV line associated infection. It can also cause pharyngitis and oesophagitis leading to dysphagia and weight loss. Candida albicans can be detected in urine via microscopy and cultures and in blood by culures and then microscopy. On microscopic examination, the germtube (pseudophyphae might be seen). |
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Describe the clinical importance of Cryptococcus neoformans.
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Cryptococccus (crap-tococcus) neoformans is a yeast fungi which enters the body via inhalation and causes pneumonia and may cause meningitis in immunocompromised patients, it is thus an opportunistic pathogen. It is a commensal organism in pigeons and multiples by binary fission in pigeon faeces in environment. Susceptible individuals include those with lymphomas, on steroid therapy or cytotoxic therapy or T cell deficiencies (associated with AIDS).
Cryptococcus neoformans has many virulence factors including and antiphagocyic capsule, melanin production and lytic enzymes. Infection initialy presents with subacute meningitis, pneumonia or fungaemic shock. Treatment is amohotericin |
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Describe Pneumocystis jirovecii.
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Pneumocystis jirovecii (old name carinii) is a yeast fungus which grows intracellularly producing serious pneumonia but only in patients with T cell immunodeficiency through HIV, malnutrition, prematurity, primary immune deficiency diseases and those on immune-suppressive drugs. The route of infection is uncertain but endogenous and exogenous routes likely. Transmitted via respiratory route P jirovecci adheres strongly to pneumocytes. Patients present with dyspnoea which develops over days or weeks with an unproductive dry cough. Initially chest x-ray may be normal or may show some consolidation. Bronchoalveolar lavage ( bronchoscope through nose or mouth which squirts fluid into the lungs and then recollects it for examination) specimens are taken.
It used to be considered a protozoan as it has a tropozoite and cyst stage. |
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List common opportunistic mycoses.
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Those suffering from opportunistic fungi infections usually have some serious immune or metabolic defects or have undergone surgery.
- Aspergillosis eg aspergillus fumigatus: filamentous - Candida albicans: yeast - Crytopcoccus neoformans: yeast - Pnemocystis jiroveci: yeast ( once thought to be a protozoa as has tropozoite and cyst forms) All of the above also cause superficial and systemic mycoses. |
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Describe the clinical importance of aspergillosis.
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Aspergillus fumigatus is a ubiquitous filamentous fungus whose spores are present in the air we breathe. They do not normally cause disease except in immunocompromised individuals.
- Farmers lung: spores trigger a type III hypersensitivity (immune complex) reaction in the lungs causing fever, dyspnoea and fibrosis of the lungs. Test for antibodies - Aspergiloma: aspergillus colonises old cavities in the lungs present due to TB or bronchiectasis. - Bronchopulmonary Allergic aspergilosis: Aflotoxins – carcinogenic toxins which can trigger a type 1 hypersensitivity reaction resulting in intermittent airway obstruction. Bronchodilators and steroids are given to treat airways obstruction In neutropenic patients, aspergillosis infections usually start in the lungs but can enter the blood and spread causing systemic infections. Common sites of infection include paranasal sinuses, skin, CNS, inner ear and the eye which have poor prognoses. Neutropenic patients should be managed in rooms with filtered air and infection aggressively treated. Diagnois is by culture ( bronchoalveolar lavage), antibody detection ( farmers lung or allergic aspergilosis) or NAAT. Treatment is with amphotericin B, itraconazole and casofungin. |
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Describe primary pathogenic fungi.
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Pathogenic fungi are not seen in Uk. They have the ability to produce disease in healthy individuals. They cause chronic infections similar to TB with some grotesque pathology. Examples include Histoplasmosis, Blastomycosis, Coccidioidomycosis.
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List antifungal agents.
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Treatment for fungal infections is harder as more similar to human cells.
- Polyenes - Disrupts cell wall integrity amphotericin B – used to treat systemic fungal infections. Nyastin – used topically and GI infections to treat candida and dermatophytes ( superficial mycoses) - Flucytosine 5 - Disrupts RNA synthesis, never use alone as resistance is generated. - Azoles (fluconazole and itraconazole) – disrupt cell wall biosynthesis – BROAD SPECTRUM - Allyamines ( terbinafine) – disrupts cell wall synthesis - DERMATOPHYTES - CASPOFUNGIN – specifically used to treat systemic aspergillosis |
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Outline the characteristics of protozoa.
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Protozoa are single celled eukaryotes that differ from fungi in the cell walls and their life cycles. Simple cycles: active from of protozoa called trophozoite undergoes mitosis to make a cyst form which is inert and involved in transmission, the infectious form.
Complex cycles: the trophozoite undergoes sexual and asexual reproduction producing eggs as well as cysts. |
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Describe the clinical importance of entamoeba histolytica.
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Entamoeba histolytica is an amoebae, thus a simple protozoa that is characterised by a tropozoite stage that forms pseudopodia for locomotion. The cysts are ingested by contaminated food and water (make sure food is cooked appropriately and water is boiled). It forms a resistant cyst that is only able to reproduce in the large intestines where they lyse enterocytes by proteases and amoebapore, an epithelial cytotoxin and result in ulcerations and dysentery( pain, frequent small volume bloody &mucus stools with an offensive odour).
Asymptomatic carriers are the reservoir of infection, ocasionaly the paraite enters the portal circulation and produces abscesses in the liver, brain, peritoneum. Treatment is with metronidazole which treats amoebic dysentery and amoebic abscesses but does not eradicate the cyst stage that requires diloxanide furoate or paromomycin. Diagnosis - sigmoidoscopy reveals rectal ulceration and trophozoites can be isolated in ulcer biopsies, 3 stool samples are sent for cyst identification. Antigen detection and NAAT. |
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Define dysentery.
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Dysentery is inflammation of the large intestines by bacteria, viral or protozoal ( enamoeba histolytica) infection causing fever, pain, severe diarrhoea and blood and mucus in stools.
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Describe diseases caused by Trichomonas.
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Trichomonas vaginalis is a flagellate protozoa with a simple life cycle, that in the trophozoite form has a flagella for locomotion and food gathering. It is anaerobic and does not have a cyst stage so it can’t survive outside the body.
It is a sexually transmitted disease where females are symptomatic with vaginitis and urethritis and an offensive discharge but males are just carriers. It is treated with metronidazole and treatment of sexual contacts may be necessary to prevent recurrent infection. |
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Describe diseases caused by Giardia.
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Giardia lamblia has a simple life cycle with a flagellate and cyst stage. It is transmitted by ingestion of cysts in contaminated water or food from human or animal faeces. It infects the jejunum where giardia trophozoites binds to wall via sucker discs and multiplies by binary fission. The cause non-inflammatroy, watery diarrhoea that may last for weeks or days.
Persistent giardiasis causes a chronic inflammatory response resulting in loss of intestinal villi, malabsorption syndrome, steatorrhea and weight loss. Anyone with steatorrhoea due to unknown cause should be considered for giardia infection. The cysts are present in the stools - 3 stools should be taken for cysts, ELISA should be done for giardial antigens.. Giardia does not enter the blood. Patients with IgA immunodeficiency, the most common form of primary immunodeficiency, may experience recurrent infections from giardia lamblia as mucosa is not protected against attack. Metronidazole is used for treatment – antibiotic |
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Describe diseases caused by Plasmodium and give a detailed life cycle.
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Malaria is caused by the protozoal parasites plasmodium falciparum, vivax, ovale and malariae.
The sporozoa are injected into the circulation along with an anticoagulant by female anopheles mosquito bit. The parasites multiply within hepatocytes and are released back into the blood where they invade red blood cells and multiply. The parasites provoke the release of cytokines triggering the fever and flu-like symptoms. Infected RBCs develop projections making them adhere to the capillary wall. This may occur in the brain causing cerebral malaria. Some parasites develop into the sexual states, gametocytes, which are taken up by the biting female mosquitos where they develop in the mosquito gut into sporozoites which migrate to the insect salivary glands ready for another bite. Infection by p falciform can rapidly result in death as it affects every organ and can cause cerebral malaria, circulatory shock, acute haemolysis and renal failure, hepatitis and pulmonary oedema. Plasmodium vivax and plasmodium ovale develop dormant stages (hyponozoites) which cause relapses. Those at risk should sleep under mosquito nets, cover exposed skin dusk to dawn and use mosquito repellants. Prophylaxis should be taken |
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Describes african trypanosomiasis.
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Trypanosomes are zoonoses with complex life cycle. They contain a specific DNA containing organelle called a kinetoplast ( same as leishmania). They are transmitted by an insect vector in which part of the organism’s life cycle is completed. African trypanosomiasis is caused by trypanosome brucei, transmitted by the tsetse fly ( a biting fly) that causes sleeping sickness. It evades the host immune ystem by antigenic variation.
Generalised lymphadenopathy may occur and the skin may be oedematous. The patient will have hypergammaglobulinaemia and is susceptible to secondary bacterial infection. When parasites invade the brain, they cause a chronic progressive encephalitis. The patient lapses into coma and death is often the result of secondary bacterial pneumonia. Parasites are found in blood, CSF or lymph node aspirate. Serological tests are available. lumbar puncture should only be performed after circulating parasites have been eliminated to avoid risk of innoculation. The cerebral complications must be treated with melB - melarsoprol. |
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Describe leishmaniasis
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Leishmaniasis is transmitted by sandflies L tropica and L braziliensis cause cutaneous leishmaniasis and L donovani causes visceral leishmania. Leishmania are protozoa with complex life cycles and contain a specific DNA containing organelle called a kinetoplast. Sandflies inject the infective promastigotes which survive ingestion by macrophages where they become amastigotes, multiplying within cells of reticuloendothelial system. In visceral leishmaniasis, cytokine release by macrophages gives rise to fever and general wasting. Bone marrow is replaced by parasites so the patient becomes anaemic, leukopenic and thrombocytopenic. Reactive hypergammaglobulinaemia makes patients susceptible to secondary bacterial infections- untreated patients will die in 2 years. Cutaneous leishmaniasis is characterized by chronic granulomatous lesions at the site of the bite with seatellite lesions. It might lead to destruction of structures around the mouth and nose ( espundia). Diagnosis by culture and microscopy of skin biopsy, bone marrow sample, or splenic aspirate. NAAT is used for primary diagnosis and speciation. Treated by amphotericin B. |
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Describe south american trypanosomiasis
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Trypanosomes are zoonoses with complex life cycle. They contain a specific DNA containing organelle called a kinetoplast ( same as leishmania). They are transmitted by an insect vector in which part of the organism’s life cycle is completed. South American trypanosomiasis is caused by trypanosome cruzi, transmited by the bite of reduviid bugs. They cause chagas’s disease of which there are 3 phases: acute infection with cutaneous oedema, intermittent fever, shock and significant mortality in children, latent infection and late manifetations such as achalasia, megacolon, cardiac dysrhymias, cardiomyopathy and neuropathy.
Diagnosis is by microscopy or culture or serological tests. Benznidazole is given. |
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Describe diseases caused by Cryptosporidium
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Crytospordium parvum is an apicomplexa protozoa with a complex life cycle. It is a zoonoses and so humans usually become infected from contact with farm animals and contaminated water and milk. The organism gains entry into the small intestines where they affect the glucose-Na co transporter, increasing fluid release. Therefore watery diarrhoea is experienced along with abdominal cramps. In immunocompromised individuals the prolonged diarrhoea can be life threatening due to fluid and electrolyte imbalance. Billary tree, gallbladder and respiratory tract involvement may occur. They form highly resistant oocytes in the small intestine which are released into the environment in stools
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Name the 3 intestinal protozoa.
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- Entamoeba histolytica
- Giardia lamblia - Cryptospordium parvum |
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Describe disease caused by Toxoplasma gondii.
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Toxoplasma gondii infects all warm blooded animals including humans but can only complete life cycle in cats which ingest cysts by eating cysts in intermediate host tissue ( mice) and egest oocysts in faeces. Humans can therefore ingest cysts by eating intermediate hosts such as pigs, cows etc or from direct ingestion of oocysts from cat faeces. Also the infection can pass to the foetus during pregnancy acroos the placenta. Symptoms are usually flu like in healthy individuals - swollen glands, fever. But in immunocompromised individuals toxoplasmosis is life threatening and can cause myocarditis ( heart infection), retinochoroiditis ( retina and choroid of the eye infection), meningoencephaltits ( brain and meninges) and MASS LESIONS IN BRAIN(HIV) AND death.
In neonates, the fetus may be stillborn, die soon after birth or have cerebral calcification, cerebral palsy or epilepsy. Diagnosis is confired by specific IgM antibodies. |
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List causes of congenital infections.
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Congenital infections include rubella, CMV, HIV, toxoplasma, treponema pallidum, parvovirus, and varicella zoster virus ( mum gets chickenpox a week before birth).
This will cause growth retardation, congenital malformation, fetal loss. |
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List causes of perinatal infection.
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Perinatal infection is when infection is caused during birth. Examples include neisseria gonorrhoeae, chlamydia, Herpes simplex virus, varicella zoster virus, group B strep agalactiae(meningitis and septicaemia), E.coli, listeria.
Infection causes meningitis, septicaemia, pneumonia and preterm labour. |
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List causes of postnatal infections.
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Causes include neisseria gonorrhoeae, chlamydia, Breast milk: HIV, CMV, umbilicus: staphylococcus aureus (scaled skin syndrome - superficial blisters), clostridium tetani or person to person contact: group B strep agalactiae, listeria or E coli.
Manifestations include septicaemia, meningitis, conjunctivitis and pneumonitis. |
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Describe azoles
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Azoles are antifungals that include clotrimazole, miconazole, fluconazole and itraconazoles and act by blocking the action of cytocrome P450 and sterol 14 alpha demethylase(allows incorporation of 14 methyl sterol in the fungal membrane instead ergosterol. Resistance can develop during long term treaments.
CLOTRIMAZOLE AND MICONAZOLE - topical preparations for minor fungal infections. fluconazole - yeast infectiosn: candida and cryptococcus Itraconazole - yeast and filamenotus - candida, cryptococcus, dermatophytes, aspergillus Voriconazole - broad spectrum, best treatement for aspergillus. Flucytosine - candida, cryptococcus and some moulds. |
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Describe fluconazole.
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Fluconazole is an azole antifungal and so blocks the cytochrome P450 and sterol 14alpha demethylase.
It is given orally, topically and parenterally. It is widely distributed, crosse the blood brain barrier and is active agains CANDIDA and CRYPTOCOCCUS but NOT filamenotus fungi. It may cause liver enzyme abnormalities. It has significant drug interactions increasing cyclosporin ( T cell specific drug) and oral hypoglycaemic drugs and reducing rate of warfarin metabolism. |
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Describe itraconazole.
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Itraconazole is an antifungal azole, inhibiting cytochrome p450 and sterol 14alpha demethylase and is used to treat yeasts CANDIDA, CRYTOCOCCUS & HISTOPLASMA and filamentous fungi: ASPERGILLUS and DERMATOPHYTES.
resistance is rare and can be given orally. |
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Describe voriconaxole and posoconazole.
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Voriconazole is a broad spectrum triazole that treats many yeasts and filamentous fungal infections and is better that amphotericin for aspergilus infection.
Posoconazole also has a wide spectrum. |
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Describe flucytosine.
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flucytosine is a synthetic fluorinated pyrimidine that inhibits candida and cryptoccus neoformans and some moulds by disrupting protein synthesis. It is well absorbe oraly and be given IV. Can cause bone marrow suppresion, thrombocytopenia and abnormal liver function tests. Resistance develops rapidly with monotherapy.
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Describe echinocandins.
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Caspofungin was the first echinocandins which act by inhibiting 1,3,B glucan, a homopolysaccharide in the cell wall of many pathogenic fungi.
treats CANDIDA AND ASPERGILLUS. |
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Describe terbinafine.
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Terbinafine inhibits squalene epoxidase with resultant accumulation of aberrant and toxic sterols in the cell wall. It is indicated for the oral treatment of superficial DERMATOPHYTE infection which have failed to respond to local therapy. Stevens johnson syndrome and toxic epidermal necrolysis and hepatic toxicity are adverse effects. Treatment should be continued for up to 6 weeks for skin infections and 3 months for nail infections.
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Describe griseofulvin.
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griseofulvin inhibits dermatophytes by inhibiting mitosis. it is now rarely used
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Describe polyenes.
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Polyenes - include 2 cyclic macrolides in use: NYASTIN and AMPHOTERICIN B which are are used against all fungi.
They bind ergosterol in the fungal membrane formaing a pore which causes leakage of intracellular contents and cell death. NYASTON - given orally for prevention of fungal infection in immunocompromised. Does not work for dermatophyte infections!! AMPHOTERICIN - given parenterally used to treat systemic infections. Can cause renal tubular damage. Lipid formaulations are less toxic. |
