Antiparasitic +fungal

• Anti-protozoan
• inhibits enzymes involved in energy metabolism

• USE- blood-borne African Sleeping Sickness (Trypanosoma brucei)
• - NO CNS involvement

• Ant-protozoan
• - Inhibits sulfhydryl groups in parasite enzymes

USE- CNS-involved African Sleeping Sickness ( Trypanosoma brucei)

• Anti-protozoan
• -Forms intracellular free radicals, toxic to parasites

USE- Chaga's disease (Trypanosoma cruzi)

• Anti-protozoan
• -Inhibits glycolysis at PFK reaction

USE-Leishmaniasis (cutaneous, mucosal, visceral)

• Anti-malarial (anti-protozoan)
• -MECH- Block plasmodium heme polymerase-> accum toxic Hb breakdown products that kill it.
• block TNF-a
• -USE- Malaria- BLOOD schizonticide. (PO)
• good for P. malaria. But P. vivax, and P.ovale will replapse b/c liver hypnozoite.
• -most P.falciparam are resistant!
• -SE- hemolysis in severe G6PD deficiency
• vertigo, pruritis, urticaria, toxic psychosis, ocular toxicity (at high doses)
• BUT STILL SAFE IN PREGNANCY AT LOW DOSE

• Anti-malarial (anti-protozoan)
• unknowm mech
• USE- multdrug-resistant Plasmodium falciparum

• Anti-malarial, Anti-protozoan
• -USE- emergency RX for SEVERE or Drug-resistant P. falciparum (use in combo with pyrimethamine/sulfonamide)
• - treat Babesiosis (Babesia) (Quinidine + clindamycin)

• Quinine sulfate- oral
• Quinine gluconate- IV

SE- cardiotoxicity!!

• Anti-malarial (anti-protozoan)
• -USE-(PO) tissue schizonticide for P. vivax, P.ovale. to prevent replase from dormant liver hypnozoite.
• -Kill gametocide.
• -Use in combo with blood schizonticide (chloroquine).

• MECH- inhibit heme polym.
• SE- GI upset, pruritis, headaches
• G6PD-deficiency patients can get hemolysis, methemoglobinemia.
• DO NOT GIVE IV! GET HYPOTENSION!
• DO NOT GIVE TO PREGNANT WOMEN OR G6PD PATIENTS!!!

• chinese wormwood, Artemisia annua- ancient herbal remedy for malaria!
• MECH- bind malarial pigment--> free radicals
• great potency

• Antihelminthic
• USE-Kill tapeworms (cestodes), flukes (trematodes)
• increase membrane permeability of calcium->contraciton, paralysis of tapeworms and flukes

• Antiprotozoan
• -inhibit dihydrofolate reductase in parasite--> inhibit THF syn.

• USE-chloroquine-resistant P. falciparum malaria
• - Toxoplasmosis !
• Fansidar=Pyrimethamine+ sulfadizine (cheap, so used in 3rd worlds)

(resistance by mutation in DHFR enzyme)

Antibacterial +Antiprotozoal.

-MECH- free radical toxic metabolites

• -USE- anaerobes BELOW diaphram!
• Giardia, Entamoeba, Trichomonas, Gardnerella baginalis, Anaerobes (Bacteroides, Clostridium)
• -NOT actinomycetes!

-SE- metallic taste, Antabuse rxn, peripheral neuropathy, inhibit warfarin breakdown (increase PT)

• Pyrimethamine
• Fansidar
• Sulfonamides
• Proguanil

• Antimicrobial, Antiprotozoal
• Atovaquone + Proguanil

• USE- acute, uncomplicated P. falciparum malaria.
• -combo is synergistic! (Atovaquone cause rapid resistance)

• MECH- Atovaquone- inhibit ETC of Plasmodium (Cyt bc1). Proganil- inhibit DHFR (via metabolite cycloguanil)
• -resistance to Atovaquone via mutation in cyt-b

Antimicrobial

USE- alone-Pneumocystis carinii pneumonia (PCP)

• most intestine nematodes
• -Mebendazole (decr glu uptake)
• -Pyrantel pamoate (NM agonist-->spastic paralysis)

• Most tapeworms (cestodes) and flukes (trematodes)
• -Praziquantel (incr Ca influx, vacuolization)

• Antihelminthic
• -broad spectrum antiparasitic, kills nematodes and arthropod parasites.

USE-kill Stronglyloides stercoralis, kill Onchocerca volvulus (river blindness)

• MECH- macrocyclic lactones made by Streptomyces avermitillis.
• - GABA-agonist--> paralyze the parasite. Safe for humans b/c GABA in CNS only, and this doesn't cross BBB

• Antihelminth
• - inhibit glucose uptake, microtubule synthesis

• USE- kill nematodes!
• also tapeworm Echinococcus granulosus

• Antihelminth
• - Nm agonist at NMJ--> depol blockade--> paralysis.
• -No effect on tapeworms or flukes!

• USE- kill tapeworms!
• Ascaris lumbicoides, Ancyostoma duodenale, Necator americanus (as alternative to bendazoles)

Antihelminth

• USE- kills tissue nematodes!
• Loa loa, Wuchereria bancrofti , Toxocara canis

Antifungal

• USE-Serious, systemic mycosis! Cryptococcus, Blatomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor.
• -Fungal meningitis (intrathecal)

MECH- bind ergosterol (unique to fungi)--> holes in mem.

• UNIQUE- Synergistic with Flucytosine.
• No resistance! only IV, intrathecal!, NOT cleared by dialysis.
• -Antagonistic with -azole antifungals.
• -binds heavily to plasma proteincs
• - does NOT cross BBB

• SE- Nephrotoxicity (80%!), fever/chills, tachypnea, nausea/vomit, hypotension, arrhythmias, anemia, IV-phlebitis, hypokalemia, hypomagnesemia, weight loss.
• -Newer forms (lisosomal amphotericin) less toxic, but expensive!

Antifungal

USE- topical! - oral candidiasis (thrush), diaper rash, vaginal candidiasis.

• MECH- same as Amphotericin B
• -bind ergosterol--> poke holes in mem.

SE- same as Amphotericin B (nephrotoxicity, anemia, fever/chills..) too toxic for systemic, so only topical!

• Antifungal
• -synthetic cytosine-analog

USE- oral, systemic mycosis (Candida, Cryptococcus) in combo w/ Amphotericin B.

MECH- inhibit thymidylate synthetase-->inhibit pyrimidine synthesis.

• UNIQUE- do NOT use alone! rapid resistance!
• - good distribution everywhere
• -cleared unchanged by urine, dyalisis

• SE- bone marrow suppression, nausea/vomit, diarrhea,
• MUST ADJUST DOSE FOR RENAL PATIENTS, DON'T USE ABOVE 120ug/ml!!

Antifungal

USE- Invasive aspergillosis, Candida

MECH-inhibit beta-glucan syn--> inhibit cell wall synthesis

SE- GI upset, flushing

Antifungal

USE- dermatophytoses (esp. onychomycosis- fungus in finger, toenails.)

MECH- inhibit enzyme squalene epoxidase

Antifungal

• USE- oral, superficial fungal infections.
• - dermatophytes (tinea, ringworm)

• MECH- inhibit microtubule fxn--> inhibit mitosis
• - deposit in keratin-containing tissues (nails)

SE- teratogenic, carcinogenic, confusion, headache, induce Cyps! (increase Warfarin breakdown).

• Antifungal
• "-azole"

USE- Candida (all types), Cryptococcal meningitis (can cross BBB), Coccidiodal meningitis.

MECH- inhibit P450-->inhibit syn of ergosterol from lanosterol.

• UNIQUE- well absorbed, cross BBB, excreted unchanged in urine.
• -adjust dose for renal failure patients!

SE- inhibit hormone synthesis (gynecomastia), hepatotoxicity (inhibit Cyps), fever, chills

• Antifungal
• "-azole"

• USE- systemic mycoses in immunocompromised pts.
• -Blasomycosis, Histoplasmosis, Aspergillosis, Onychomycosis (nail fungus).

MECH- inhibit P450-->inhibit syn of ergosterol from lanosterol.

• UNIQUE- IV, oral
• -need acid to be absorbed, so take with food.
• -metabolized exclusively by liver!
• -don't need to adjust dose for renal fxn.

SE- inhibit hormone synthesis (gynecomastia), hepatotoxicity (inhibit Cyps), fever, chills

• Antifungal
• "-azole"

USE- severe Aspergillus infections, Fluconazole-resistant Candidal infections.

MECH- inhibit P450-->inhibit syn of ergosterol from lanosterol.

UNIQUE- well absorbed, but low CSF levels.dose adjust for both renal and liver failure!!

SE- inhibit hormone synthesis (gynecomastia), hepatotoxicity (inhibit Cyps), fever, chills

-antagonistic with Amphotericin B (b/c decrease syn of its sterol target)

• Antifungal
• "-azole"

USE-prophylaxis for Aspergillosis and Candida for immunocompromised.

UNIQUE- broad spectrum

MECH- inhibit P450-->inhibit syn of ergosterol from lanosterol.

SE- inhibit hormone synthesis (gynecomastia), hepatotoxicity (inhibit Cyps), fever, chills

-antagonistic with Amphotericin B (b/c decrease syn of its sterol target)

Antifungal"-azole"

• USE- Blastomyces, Coccidiodes, Histoplasma, Candida albicans.
• - also used for hypercortisolism!

UNIQUE- older, more toxic than others.

MECH- inhibit P450-->inhibit syn of ergosterol from lanosterol.

SE-adrenal suppression, inhibit hormone synthesis (gynecomastia), hypocholesterolemia, hypothyrodism, hepatotoxicity (inhibit Cyps), fever, chills

-antagonistic with Amphotericin B (b/c decrease syn of its sterol target)