Micro - Antimicrobials (Antifungals & Parasite Treatment) Flashcards
Pg. 189-191 in First Aid 2014 Sections include: -Antifungal therapy -Amphotericin B -Nystatin -Azoles -Flucytosine -Echinocandins -Terbinafine -Griseofulvin -Antiprotozoan therapy -Chloroquine -Antihelminthic therapy
Which antifungal drug inhibits lanosterol synthesis?
Terbinafine
Which type of antifungal drug inhibits ergosterol synthesis? Give 6 examples of this type of drug.
Azoles; (1) Fluconazole (2) Ketoconazole (3) Clotrimazole (4) Miconazole (5) Itraconazole (6) Voriconazole
Which type of antifungal drug inhibits cell wall synthesis? Give 3 examples of this type of drug.
Echinocandins; (1) Caspofungin (2) Micafungin (3) Anidulafungin
Which type of antifungal drug forms membrane pores? Give 2 examples of this type of drug.
Polyenes; (1) Amphotericin B (2) Nystatin
Which antifungal drug inhibits nucleic acid synthesis?
5-Flucytosine
Draw a visual depicting the methods of antifungal therapy, which include: (1) Lanosterol synthesis (2) Ergosterol synthesis (3) Cell wall synthesis (4) Forms membrane pores (5) Nucleic acid synthesis. Match of these methods to their specific drugs.
See p. 189 in First Aid 2014 for visual
What is the mechanism of Amphotericin B?
Binds ergosterol (unique to fungi); Forms membrane pores that allow leakage of electrolytes; Think: “ amphoTERicin “TEARs” holes in the fungal membrane by forming pores”
In general, what is the clinical use of Amphotericin B? What are specific examples of conditions in which Amphotericin B is used? Include details of use, where applicable/necessary.
Serious, systemic mycoses. Crypotococcus (amphotericin B with/without flucytosine for cryptococcal meningitis), Blastomyces, Coccidioides, Histoplasma, Candida, Mucor. Intrathecally for fungal meningitis.
What is used in supplement to Amphotericin B, and why?
Supplement K+ and Mg2+ because of altered renal tubule permeability
What are 6 toxicities associated with Amphotericin B?
(1) Fever/chills (“shake and bake”) (2) Hypotension (3) Nephrotoxicity (4) Arrhythmias (5) Anemia (6) IV phlebitis (“AMPHOTERRIble”).
What can decrease the nephrotoxicity associated with Amphotericin B?
Hydration lowers nephrotoxicity.
What kind of preparation of Amphotericin B lowers its toxicity?
Liposomal amphotericin B lowers toxicity.
With which other antifungal does Nystatin share its mechanism? What is that mechanism?
Same as amphotericin B; Binds ergosterol (unique to fungi) & Forms membrane pores that allow leakage of electrolytes;
What is the form of nystatin, and why?
Topical form because too toxic for systemic use.
What are 2 clinical uses of nystatin?
“Swish and swallow” for oral candidiasis (thrus); Topical for diaper rash or vaginal candiasis
What are 6 examples of Azoles?
(1) Fluconazole (2) Ketoconazole (3) Clotrimazole (4) Miconazole (5) Itraconazole (6) Voriconazole
What is the mechanism of Azoles?
Inhibit fungal steroid (ergosterol) synthesis, by inhibiting the cytochrome P-450 enzyme that converts lanosterol to ergosterol
In general, what is the clinical use of Azoles?
Local and less serious systemic mycoses
What are 2 clinical uses of Fluconazole?
Fluconazole for chronic suppression of cryptococcal meningitis in AIDS patients and candidal infection of all types
What are 3 clinical uses of Itraconazole?
Itraconazole for Blastomyces, Coccidioides, Histoplasma
What is the clinical use of Clotrimazole? Which other Azole shares this clinical use?
Clotrimazole and Miconazole for topical fungal infections
What are 2 toxicities associated with Azoles?
(1) Testosterone synthesis inhibition (gynecomastia, esp. with ketoconazole) (2) Liver dysfunction (inhibits cytochrome P-450)
Which Azole is most associated with testosterone synthesis inhibition? Which condition does this cause?
Testosterone synthesis inhibition (gynecomastia, esp. with ketoconazole)
What is the mechanism of Flucytosine?
Inhibits DNA and RNA biosynthesis by conversion of 5-fluorouracil by cytosine deaminase
What is the clinical use for flucytosine? For what fungal infection is it especially used? With what other antifungal drug is it used in combination?
Systemic fungal infections (esp. meningitis caused by Cryptococcus) in combination with amphotericin B
What is the toxicity of Flucytosine?
Bone marrow suppression
What are 3 examples of Echinocandins?
(1) Caspofungin (2) Micafungin (3) Anidulafungin
What is the mechanism of Echinocandins ?
Inhibits cell wall synthesis by inhibiting synthesis of Beta-glucan
What are 2 clinical uses of Echinocandins?
(1) Invasive aspergillosis (2) Candida
What are 2 toxicities associated with Echinocandins?
(1) GI upset (2) Flushing (by histamine release)
Which antifungal causes flushing? What is the mechanism by which this flushing occurs?
Echinocandins - Flushing (by histamine release)
What is the mechanism of Terbinafine?
Inhibits the fungal enzyme squalene epoxidase
What is the clinical use of Terbinafine, and especially in what contexts?
Dermatophytoses (especially onychomycosis - fungal infection of finger or toe nails)
What are 4 toxicities associated with Terbinafine?
(1) GI upset (2) Headaches (3) Hepatotoxicity (4) Taste disturbance
What is the mechanism of Griseofulvin? Where does it deposit?
Interferes with microtubule function; Disrupts mitosis. Deposits in keratin-containing tissues (e.g., nails)
In general, what is the clinical use of Griseofulvin? What kind of fungus does it inhibit?
Oral treatment of superficial infections; Inhibits growth of dermatophytes (tinea, ringworm)
What are 6 toxicities associated with Griseofulvin?
(1) Teratogenic (2) Carcinogenic (3) Confusion (4) Headaches (5-6) Increased P-450 and Warfarin metabolism
Which antiprotozoal therapy is used to treat toxoplasmosis?
Pyrimethamine (toxoplasmosis)
Which antiprotozoal therapy is used to treat Trypanosoma brucei?
Suramin and melarsoprol (Trypanosoma brucei)
Which antiprotozoal therapy is used to treat T. cruzi?
Nifurtimox
Which antiprotozoal therapy is used to treat Leishmaniasis?
Sodium stibogluconate (Leishmaniasis)
What is the mechanism of chloroquine, and what effect does it have?
Blocks detoxification of heme into hemozoin. Heme accumulates and is toxic to plasmodia.
What is the clinical use of Chloroquine? What (of relevance) does it not treat, and why?
Treatment of plasmodial species other than P. falciparum (frequency of resistance in P. falciparum is too high).
In which kind of Plasmodium is high resistance to Chloroquine found? What causes this resistance?
P. falciparum; Resistance due to membrane pump that decreases intracellular concentration of drug.
What is used to treat P. falciparum?
Treat P. falciparum with artemether/lumefantrine or atovaquone/proguanil
What antiprotozoal therapy is used in the case of life-threatening malaria? Differentiate what is used in the US versus elsewhere.
For life-threatening malaria, use quinidine in the U.S. (quinine elsewhere) or artesunate
What are 2 toxicities associated with Chloroquine? What population is especially affected by one of these toxicities?
(1) Retinopathy (2) Pruritus (especially in dark-skinned individuals)
What are 5 examples of antihelminthic therapy? What function do they share?
(1) Mebendazole (2) Pyrantel pamoate (3) Ivermectin (4) Diethylcarbamazine (5) Praziquantel; Immobilize helminths
Which antihelminthic therapy is used against flukes (trematodes)? Give an example of such flukes.
Use praziquantel against flukes (trematodes) such as Schistosoma.
