Antifungal Agents

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Antifungal Agents
2014-10-25 05:10:01
Fungus HIV AIDS parasitic antivirals protozoal infections

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  1. What is a systemic mycoses? how are they characterized in groups?
    • Systemic mycoses: it is a systemic fungal fungal infection. They are difficult to treat, often resist treatment, treatment may required prolonged therapy with drugs that frequently prove toxic. 
    • 2 main groups: Systemic and superficial mycoses infection. 
    • Systemic mycoses infection: opportunistic Immunocompromised host (candidiasis, aspergillosis, cryptococcosis, mucormycosis) and Nonopportunistic (can occur in any host - sporotrichosis, blastomycosis, histoplasmosis(cars eating birds)). 
    • Superficial mycoses infections: Candidiasis and dermatophytes. 
    • * bacterial can become and fungal infection.
  2. What are the 4 classes of anti fungal drugs?
    • 1) Polyene antibiotics. 
    • 2) Azoles
    • 3) Echinocandins
    • 4) Pyrimidine analogs. 
    • * focus on 1 and 2 (Polyene antibiotics and Azoles)
  3. What is the most common polyene antibiotics? MOA? TU? PK? AE? toxicity?
    • The most common polyene antibiotic is Amphotericin B (fungizone). 
    • MOA: It binds to ergosterol in the cell membrane, increasing the permeability of the membrane leaking cations (specially potassium).
    • It could be fungistatic or fungicidal depending on the concentration. 
    • Bacteria lacks sterols in their membrane, thus no rxn. 
    • Toxicity: It could bind to cholesterol as it binds to ergosterol. However, the affinity is greater for ergosterol. 
    • TU: It is the most common drug used for systemic mycoses. 
    • PK: It not absorbed well in the GI tract. Usually administered IV. It doesn't pass the BBB. 
    • AE: Infusion rxns such as fever, chills, rigors, nausea, and headaches. Caused by the pro inflammatory cytokines. Symptoms starts 1-3 hrs after starting infusion. can pretreat with diphenhydramine + acetaminophen (aspirin can help too, but may increase renal damage). IV meperidine or dantrolene can be given if rigors ocrrus. Hydrocortisone can be given with caution )since it makes ppl immunodepressed).
    • Nephrotoxicity:toxic to the kidney cells.  Damage minimized by infusing of 1L of saline on days of treatment. Avoid other nephrotoxins, NSAIDS, and monitor creatinine 3-4 days. 
    • Hypokalemia: low potassium bc of the kidney damage.
  4. What are azoles? what is the main benefit? main disadvantage? what are the most common drugs?
    • Azoles: Broad-spectrum anti fungal drugs. A good alternative for amphotericin B (fungizone). 
    • Benefit: Lower toxicity than amphotericin B (fungizone). and can be given orally. 
    • Disadvantage: Inhibits P450 drug-metabolizing enzymes and can increase the levels of many other drugs.
    • Drugs: -ZOLE suffix -- Intraconazole (sporanox), Fluconazole (diflucan), and ketoconazole (formerly Nizoral)
  5. Itraconazole (sporanox)? MOA? TU? AE?
    • -ZOLE suffix=Azoles antifungal agents. 
    • MOA: it inhibits ergosterol in the cell membrane, increasing the membrane permeability and leakage of cellular components. 
    • TU: Broad spectrum of fungal pathogens. Systemic mycoses (alternative for amphotericin B (gungizone). 
    • AE: it is well tolerated in usual doses. But it could cause GI rxns (nausea, vomiting, diarrhea). The most severe rxn could be cardiac suppression and liver injury.
  6. Fluconazole (diflucan)? MOA? AE? PK?
    • FLuconazole (diflucan): Azole group of antifungal agents. 
    • MOA: same as itraconzole, inhabition of cytochrome P450-dependent synthesis of ergosterol. (fungistatic) 
    • AE: Well tolarated, but common AE are, nausea, headache vomiting, etc. 
    • PK: IV and oral dosage the same.
  7. Ketoconazole (Nizoral)? MOA? TU? PK? AE?
    • Ketoconazole (nizoral): Azole group of antifungal agents. 
    • MOA: Inhibits ergosterol. 
    • TU: alternative to ampho b (fungizone) for systemic mycoses (use in yeast infection). 
    • AE: less toxic and only somewhat less effective. Slow effects. Works better for chronic infections than acute. Adverse effects are well tolerated.
  8. What antibiotic could be confused with azoles bc of the suffix?
    Metronidazole (flagyl)
  9. What drugs can be use for superficial Mycoses? What are the 2 group of organisms that cause these infections?
    • Azoles, Griseofulvin (grifulvin) and Nystatin (Mycostatin-polyene antibiotic, usually used for candidiasis).  
    • Candida species (yeast infection) and dermatophytic infections (ringworm)
  10. How is HSV and VZV infections usually treated? PK and AE? MOA?
    • Acyclovir (zovirax) 
    • PK and AE: IV- could cause phlebitis and reversible nephrotoxicity. Oral therapy- GI and vertigo. Topical- stinging sensation. 
    • MOA: Inhibition of viral replication by suppressing synthesis of viral DNA.
  11. How is Cytomegalovirus infection (CMV) treated? MOA? AE?
    • Ganciclovir (cytovene, vitrasert).
    • MOA: synthetic antiviral agent that block the virus.
    • AE: because can cause severe AE, granulocytopenia (low granulocytes count), and thombocutopenia (deficiency of platelets in the blood, it should only be used to treat CMV.
  12. How is HCV treated? HBV? AE of each treatment?
    • HCV: a combination b/t interferon alfa (usually subQ) + Ribavirin (usually oral) combination with subQ pefinterferon alfa. 
    • AE: interferon alfa --> flu-like-syndrome and neuropsychiatric effects (depression). Ribavirin combination --> Hemolytic anemia and fetal injury (category x). 
    • HBV: Treated with interferon alfa or lamivudine. 
    • AE:
  13. What are the drugs used to treat influenza?
    • Neuraminidase inhibitors: -AMIVIR suffix. Oseltamivir (tamiflu) and zanamirvir (relenza) 
    • Adamantanes: -MANTADINE suffix. Amantadine (symmetrel) and Rimantadine (flumadine).
  14. What are the types of antiretroviral drugs that inhibit enzymes required for HIV?
    • Reverse transcriptase inhibitors
    • Integrase inhibitors 
    • Protease inihbitors
  15. What are the antiretroviral drugs that block viral entry into cells?
    • Fusion inhibitors 
    • CCR5 antagonists.
  16. What is the drug used for HIV that contains 4 meds in one pill? what about the one containing 3 in one pill?
    • Stribild (the quad) 
    • Atripia (3 in 1)
  17. What are the laboratories to monitor HIV infection and drug therapy?
    • Viral load (plasma HIV RNA): best measurement for predicting clinical outcome. high HIV RNA low poor prognosis. 
    • CD4 T-cell count: It helps to know in what type of the infection is the patient. 
    • CBC with differential:
  18. What does  HAART stand for? ART? When is ART recommended?
    • HAART:High active antiretroviral therapy. 
    • ART: Antiretroviral Therapy. Recommended for positive HIV pregnant women.
  19. What is the most common opportunistic infection in HIV? and how is it treated?
    • PCP: Pneumocystis carinii pneumonia. 
    • Treatment: Trimetrophim plus sulfamethoxazole (sometimes used for UTIs).
  20. HIV is a _____ 
    and Gonorrhea is an _____
    • Disease. 
    • Infection.
  21. What are the 2 types of malaria? and what are the major objective of care?
    • Vivax malaria and falciparum malaria. 
    • Treatment of acute attack, prevention of relapse, and prophylaxis.
  22. What are some common drugs used for Malaria?  what is it important to know about them? AE?
    • Chloroquine (aralen): drug of choice for different types of malaria. High activity against erythrocytic forms, but not active for exoerythrocytic forms. Doses for prophylaxis are low. High doses for treatment are taken only briefly.
    • AE: GI effects, Visual disturbances, hepatotoxicity (be careful with liver disease pts), pruritus, and headaches. 
    • Quinine: Active against erythrocytic forms of malaria. IV route combined with doxycycline, tetracycline, or clindamycin for severe malaria. 
    • AE: hemolytic anemia, and pregnancy category X.
  23. What is the drug usually used for protozoal infections? AE?
    • Metronidazole (flagyl, protostat). 
    • It is active against several species. 
    • Drug of choice for symptomatic intestinal amebiasis and systemic amebiasis. 
    • AE: Nausea, headache, dry mouth, unpleasant metallic taste, and harmless darkening of urine. 
    • If combined with alcohol, may have disulfiram-like actions.
  24. What are the 3 principal agents used to treat ectoparasiticides? whats the oral treatment?
    • Permetrin (nix, elimite, acticin), malathion (ovide), and crotamiton (Eurax).
    • oral treatment: Ivermectin (stromectol)
  25. Permethrin TU? what are the trade names?
    • TU: Toxic to mites, lice, and their ova (also fleas and ticks) 
    • Names: Nix, elimite, acticin.
  26. Malathion TU? trade name?
    • TU: kills lice and their ova, approved for treatment of head lice. 
    • Names: Ovide.
  27. Crotamiton TU? trade names?
    • TU: Used to treat scabies. 
    • Names: Eurax.

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