Antivirals and antifungals

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2nd Year Medicine (GI) Karteikarten am Antivirals and antifungals, erstellt von lpgalbraith am 06/05/2016.
lpgalbraith
Karteikarten von lpgalbraith, aktualisiert more than 1 year ago
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What are the stages of viral replication? 1. Fusion 2. Uncoating 3. Nucleic acid replication 4. Protein synthesis 5. Assembly and release of new virus
Which viruses are RNA based? Influenza A, B, C Measles, mumps Rabies Polio, rhinovirus HIV Rubella, hepatitis Rotavirus
Which viruses are DNA based? HSV, varicella, adenovirus, papilloma virus, smallpox
Which drug targets the fusion of viruses? Enfurvitide - used as salvage therapy in HIV
Mechanism of enfurvitide? Binds to gp41 in HIV surface, inhibiting CD4/HIV interaction
Side effects of enfurvitide? Injection site pain, depression, infections (especially bacterial pneumonia)
Which drug targets uncoating of viruses? Amantadine (influenza)
Mechanism of amantadine Inhibits viral ion channel (prone to mutations). Ion channel required to get H+ ions into bleb
Side effects of amantadine CNS (dopaminergic effects) - nervousness, anxiety, insomnia
Drugs that target nucleic acid replication? Zidovudine (HIV), nevirapine (HIV), acyclovir (herpes)
Mechanism of zidovudine? Inhibits reverse transcriptase in HIV, incorporates into viral DNA (nucleoside reverse transcriptase (viral enzyme) inhibitor), slows replication
Mechanism of nevirapine? Non-nucleoside inhibits reverse transcriptase by binding at a non active site in HIV
Side effects of zidovidine and nevirapine? Anaemia, bone marrow suppression, liver toxicity
Mechanism of acyclovir? Inhibits DNA polymerase in herpes, incorporates in viral DNA - leads to chain termination. Requires activation by viral enzymes (thymidine kinase) - increases specificity
Side effects of acyclovir Nausea, vomiting, headache
Anti-virals that inhibit protein synthesis Indinavir (HIV),
Mechanism of indinavir Binds to active site of HIV protease (protease inhibitor). Prevents cleavage of new proteins required for formation and assembly of virus coat
Side effects of indinavir Kidney stones, hyperlipidaemia, restriction on what food can be taken and requires precise dosing
What antivirals inhibits release of viruses? Oseltavir (tamiflu) for influenza
Mechanism of oseltavir Blocks viral release by inhibiting influenza neuraminidase activity
Side effects of oseltavir Nausea, vomiting, diarrhoea, headache, possible neurological (self harm)
How does HIV resist RT nucleoside inhibitors? Mutation of the drug binding site on RT enzyme
How does HIV resist RT non-nucleoside inhibitors? Single point gene mutations
How does HIV resist protease inhibitors Mutation in HIV target protein, multiple mutations required for high level resistance
What are the types of fungi? True yeast - single celled eukaryotic organisms e.g. Cryptococcus Yeast-like fungi - non branching filaments e.g. Candida albicans Filamentous fungi - branching filaments e.g. aspergillus
What are the targets of antifungal drugs? Cell wall synthesis, nucleic acid and mitotic spindle
What groups of antifungals are cell wall synthesis inhibitors? Polyenes Imidazoles Triazole Terbinafine
Which group of antifungal is a nucleic acid synthesis inhibitor? Flucytosine
Which group of antifungals is a mitotic spindle inhibitor? Griseofulvin
What is the mechanism of polyenes? Generates a pore in the cell wall by binding to ergosterol
Side effects of polyenes Few, used topically, some GI upset internally, nephrotoxicity
Examples of polyenes Amphotericin - IV used for systemic fungal infection (C. albicans) Nystatin - C. albicans infection of skin and mucous membranes, oesophageal and intestinal candidiasis
Mechanism of imidazoles Lead to growth arrest by inhibiting lanosterol demethylase - fluidity of cell wall increases, cell permeability increases. (lanosterol demethylase required for conversion of lansosterol to ergosterol)
Types of imidazoles and uses Clotrimazole - vaginal candidiasis, ringworm Miconazole - locally for oral infections, intestinal infections Ketoconazole - best oral absorption, fatal hepatotoxicity, systemic mycoses, vulval candiasis
What is the mechanism of triazoles? Also inhibits lanosterol demethylase
What are the types of triazoles and what are their uses? Fluconazole - CSF penetration, candida, cryptococcus Itraconazole - mucocutaneous candidiasis (used with caution in HF as contraindicated with Ca channel blockers) Voriconazole - wide spectrum, life threatening aspergillosis
What is the mechanism of terbinafine? Inhibits squalene epoxidase (converts squalene to lansosterol). Toxic levels of squalene build up, active against dermatophyte (ringworm of nail)
What is terbinafine contraindicated against? Sub-acute cutaneous lupus
What is the mechanism of griseofulvin? Interferes with microtubules of mitotic spindle, inhibits division of fungal cells - active against dermatophytes
Drugs used in aspergillosis Amphotericin*, voriconazole
Drugs used in candidiasis Amphotericin*, nystatin, fluconazole, flucytosine + iv amphotericin
Drugs used in cryptococcus? Amphotericin iv, fluconazole po, flucytosine
Drugs used in histoplasmosis Itraconazole*, amphotericin iv if severe
Drugs used in skin and nail *Itraconazole, griseofulvin
Drugs used in immunocompromised Fluconazole, amphotericin iv
What is the mechanism of flucytosine? Inhibit conversion of uracil to DNA, only used in combination with amphotericin or fluconazole
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