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160 Cards in this Set
- Front
- Back
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Rx's Effective against
-Erythrocytic Malaria -Gametocytic Malaria Exoerythrocytic Malaria |
Erythrocytic: Chloroquine, Quinine, Mefloquine, Pyrimethamine, Atovaquone + proguanil (Malarone), Chloroguanide, Malrone, Artemisinins: Artemisinin, Artesunate, Artemether
Targeting Erythrocytic Stage ↓ Sx's: produces Clinical Cure Gametocytic & Exoerythrocytic forms form: Primaquine Targeting Hepatic Forms prevents relapses, but does not ↓ Sx Targeting Gametocytes only slows spread of dz to others |
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Most effective means of controlling malaria
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don't get bitten
-eradicate moquitoes -insect repellent -treat nets, tents, clothes etc w/ permethrin |
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DOC's: Malaria Prophylaxis
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Chloroquine Sensitive:
1. Chlorquine Chloroquine Reistant 1. Mefloquine 2. Doxycycline, Atovaquone w/ proguanil (Malarone) MultiRx Resistant Doxycycline |
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DOC's: Malaria
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Chloroquine sensitive: Chloroquine; Else hydorchloroquine
Chloroquine Reistant Falciparum: Atovaquone w/ proguanile (Malarone) Else: Artemether-lumefantrine (Coartem), Quinin + Doxy,, Femloquine Chloroquine Resistant Vivax: Quinine + Doxy Else: Malarone, Mefloquine; Prevent relapse w/ primaquine Severe malaria: Quinidine plus doxy, clindamycine or tetracycline Else artesunate + atovaquone/proguanil, doxy, clind or mefloquine |
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HIV protease inhibitors
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Top 3:
Saquinavir (Invirase) Ritonavir (norvir) Atazanavir (reyataz) Also: Indinavir (Crixivean) Nelfinavir (Viracept) Amprenavir (Agenerase)/Fosamprenavir (Lexia) Lopinavir/ritonavir (Kelatra) Tipranavir (Aptivus) Darunavir (Prezista) |
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Reverse Transcriptase inhibitors
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lactic acidosis & hepatotixicity: rare but serious
monitor pH & AST/ALT discontinue |
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Amphotericin B
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Special notes: polyene molecule, effective for most systemic fungals (not DOC for for Aspergillus, combined w/ Flucystosine for Crypto); not removed by hemodialysis
Mech: interxn w/ ergosterol → transmembrane ion channels; Rt, Dist: IV; intrathecal (does not x BBB), topical for Candida (∅ Oral) PhK: 24h halflife, 1°ily non-renal excretn; Spct: Effectiveness ≈ amt of ergosterol in membrane: Histo, Crypto, Coccy, Candida, Torulopsis (Candida) glabrata, Blasto, some Aspergillus; Also active vs protozoa (Leishmania, T cruzi, Trich vag, Entamoeba, Naegleria) SE: potent dose dpt nephrotoxin (XXX combine w/ others); increases AST, ALT (more exist) Intrxn: |
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Flucytosine
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Mech: converted to 5-fluorouracil interferes w/ thymidylate synthase, thus blocks fungal DNA synth
Rt, Dist: Oral, x's BBB PhK: Spct: Crypto, Candida, Aspergillus fumigatus, Sporotrix shenckii SE: hair loss, decreases hematapoieses, GI, increases AST, ALT Intrxn: |
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Ketoconazole
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2* choice to Amphotericin B for Systemic Fungal Infxs
Mech: inhibits Lanosine 14 alpha demethylase (fungal CYP3A4) Rt, Dist: Oral, Plasma Bound, 10:1 Serum: Brain ratio PhK: 8h halflife not affected by renal dysfnx, extensively metabolized before excretn Spct: Paracoccidiodomycosis, Blasto, Histo, Coccy, Dermatophytes, Chronic Mucocutaneous Candidia SE: inhibits adrenal & testicular fnx --> gynecomastia Intrxn: increases all CYP3A4 metabolized Rx halflifes -----Contrast to: Fluconazole: better oral absorption, decreased bound, 10:9, un delta urinary excretn, increased halflife w/ renal dysfnx, no delta endocrine fnx |
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Fluconazole
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Mech: inhibits Lanosine 14 alpha demethylase (fungal CYP3A4)
Rt, Dist: Oral, plasma bound, readily x's BBB PhK: Peak Rx in 2h; excreted unchanged in urine, increased increased halflife w/ decreased renal fnx Spct: Aspergillus, Blasto, Crypto, Coccy, Histo, Candida, Aspergillus SE: Intrxn: less CYP3A4 inhibition than Ketoconazole, still ↑ [phenytoin], [cyclosporine], [oral hypoglycemics], fnx of warfarin Contra: progressive hepatic dysfnx, -----Contrast to: Ketoconazole: ~ decreased oral absorptn, increased bound, 10:1 Serum: CSF, extensively metabolized, no deta halflife w/ decreased renal fnx, inhibits adrenal & testicular fnx -----Contrast to: Itraconazole: days to peak [Rx] |
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Itraconazole
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Better v. Aspergillus > Keto/Fluconazole;
Mech: inhibits Lanosine 14 alpha demethylase (fungal CYP3A4) Rt, Dist: Oral; capsules 50% on empty --> 100% on food/cola; oral solution 70% on empty --> 50% on fed; Do not delta between oral solution & capsules; >99% protein bound; PhK: DAYS to reach peak [Rx]. Hepatic Metabolism --> 30+ metabolites. hydroxy itraconazole is active metabolite; Spct: Aspergiullus, Blasto, Histo, Oropharyngal/Esophageal Candida, onychomycosis, refractory dermatophytes SE: GI, Rash, Itchyness Intrxn: inhibits CYP3A4 --Contrast to Fluconazole |
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Voriconazole
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Fnx against molds (Aspergillus)
Mech: inhibits Lanosine 14 alpha demethylase (fungal CYP3A4) Rt, Dist: Oral or IV PhK: similar to fluconazole [Peak Rx in 2h; excreted unchanged in urine, increased increased halflife w/ decreased renal fnx] Spct: DOC for Invasive Aspergillus; also for Scedosporium, Fusarium, esophageal candidiasis SE: reversible visual impairment Intrxn: more than Fluconazole: 2C19, 2C9, 3A4 |
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Caspofungin
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An Echinocandin: not nephrotoxic
DOC: refractory invasive aspergillosis Mech: inhibit beta 1,3-D-glucan cell wall component Rt, Dist: slow IV infusion PhK: 3 day halflife, hepatic elimination Spct: aspergillosis, esophageal candidiasis SE: increased AST, ALT; histamine release, GI, etc Intrxn: |
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Micafungin
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An Echinocandin: not nephrotoxic
Mech: inhibit beta 1,3-D-glucan cell wall component Rt, Dist: IV PhK: Spct: esophageal candidiasis, Candida prophylaxis SE: Intrxn: |
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Anidulafungin
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An Echinocandin: not nephrotoxic
NB: fungicidal Mech: inhibit beta 1,3-D-glucan cell wall component Rt, Dist: IV; PhK: Spct: esophageal candidiasis & other serous yeast & fungal infx SE: Intrxn: |
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Griseofulvin
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Use: ringworm of skin, hair, nails
Mech: binds MT's & destroys mitotic spindle strx; specifically binds to keratin: sequestered in epidermis, makes resistant to infx Rt, Dist: Oral, poor absorption, best in microcystalline form w/ fatty food PhK: peak 4h, majority excreted GI un delta Spct: Dermatophytes (Epidermophyton, Microsporum, Trichophyton) SE: Disulfram like effect, GI, CNS, Hematological, Skin, Photosensitivity, Angioedema, albuminuria, hepatotoxicity, leukopenia etc. Estrogen-like effects in some children. Contra: porphyria, hepatocellular failure Intrxn: decreases fnx of warfarin-like anti-coagulants; barbituates decrease GI absoprtion of griseofulvin |
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Nystatin
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Primarily Used for Candida
Mech: binds membrane sterol --> small molecule channel Rt, Dist: No epidermal/mucosal absorption: Topical or Swish in Mouth, Oral for GI overgrowths, tablets for vaginal PhK: Spct: Candida, Crypto, Histo, Blasto, Dermatophytes (Epidermophyton, Microsporum, Trichophyton) SE: mild GI after oral use Intrxn: |
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Terbinafine
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Concentrates in nail: Highly effective vs onychomycosis
Mech: inhibits fungal squalene monoxygenase, fungicidal vs dermatophytes Rt, Dist: Oral or topical, good GI absorptn, oddly concentrates in nail PhK: peak [Rx] in 2h, no delta dose for hepatic/renal impairment Spct: SE: rare haptotoxicity Intrxn: |
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Miconazole
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Esp for Tinea pedis; Superior to DOC for vulvovaaginal candidiasis (superior to nystatin)
Mech: Rt, Dist: PhK: Spct: Candida, Crypto, Aspergillus SE: Intrxn: |
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[Naftifine]
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Mech: interferes with steorl biosynth
Rt, Dist: Topical PhK: Spct: Dermatophytes, esp tineae pedis, cruris, corporis SE: Contras: ophthalmic use Intrxn: None |
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Clotrimazole
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topical azole, used in candidiasis, may cause burning, local anestheisa
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Ciclopirox
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topical antifungal similar to azoles; esp for tinea pedis, cruris, corporis, versicolor
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Tolnaftate (Tinactin)
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Topical, similar to azoles, Tinea pedis, tinea versicolor. not effecitve vs. onychomycosis
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Undecylenic Acid
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Topical vs Dermatophytes
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Chloroquine (Aralen)
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4 aminoquinolines
Mech: concentrates in parasite's acidic food vacuoles: prevents hemoglobin digestion; Resistance from transport pump ejecting Rx from parasite (same as quinine) Rt, Dist: Oral 1/wk w/ food for prophylaxis PhK: accumulates in melanin rick ts (skin, retina), concentrates in parasitized RBC's; 2mo halflife; Spct: Clinical (sx) cure for all forms; Radical cure for P falciparum & P malariae SE: Less toxic than quinine; Administered too fast: cardiac arrest;; Retinal/Corenal/Ototoxicity (monitor); CNS, GI Contras: Psoriasis & porphyria Intrxn: Anti-inflam at high [Rx] ---hydroxychloroquine used v RA & SLE ( increased toxicity) |
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Quinine/Quinidine
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8 aminioquinolines
combined with doxycycline: DOC for unconscious pt w/ chlorquine resistant falciparum or vivax Mech: concentrates in parasite's acidic food vacuoles: prevents hemoglobin digestion; Resistance from transport pump ejecting Rx from parasite (same as chloroquine) Rt, Dist: oral PhK: ~10 halflife Spct: All erythrocytic forms; gametocidal vs vivax & malariae; SE: Cinchonism (quinine from bark of cinchona tree): tinnitus, HA, dizziness, flushing, delta vision; increases insulin, QT elongation & decreased BP; GI Sx; Hemolysis in G6PD deficients; increases uterine contraxns; SkM relaxn (Legatrim for nocturnal cramps); Blackwater fever ~= hypersensitivity? Intrxn: aspirin-like analgesia, antipyresis Safe for pregnants |
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Doxycycline & Malaria
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Tetracycline
combined with quinidine as DOC for complicated chloroquine-resistant malaria prophylaxis vs multiRx resistant malaria |
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Mefloquine (Lariam)
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First line Rx vs chloroquine resistant malaria
increased Resistance Mech: prevents digestion of hemoglobin Rt, Dist: Oral ONLY PhK: Spct: Erythrocytic forms SE: GI, decreased HR; Sleep/Behavioral disturbances, may cause seizures and psychosis Contra: mental illness, epilepsy, heart problems, Teratogenic in 1st trimester! Intrxn: |
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Pyrimethamine
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same a proguanil, Combined with sulfa
Mech: inhibition of folate metabolism Sulfadoxine inhibits incoproation of PABA into folic acid Pyrimethine & proquanil inhibit DHF reductase blocking DHF --> THF Plasmodial enzyme more sensitive than human, can't use exogenous folate Rt, Dist: PhK: Spct: erythrocytic forms; Pyrimethamine + Sulfadoxine used for presumptive tx; Proguanil + Chlorquine used for prophylaxis; SE: Sulfa rxns Intrxn: |
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Atovaquone (Malarone)
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used with proguanil (blocks DHF reductase: DHF --> THF); synergistic combo
DOC: uncomplicate cloroquine resistant malaria, or pneumocystis jiroveci Prophylaxis vs chloroquin resistant P falciparum Mech: interferes with plasmodial mito fnx Rt, Dist: PhK: Spct: SE: Rare; GI, Rash, Fever, Vomiting/Diarrhea may decrease absorption Intrxn: |
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Halofaintrine
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Mech:
Rt, Dist: Take on empty stomach PhK: Spct: 2nd line Rx for P falciparum & vivax SE: Toxicity: GI, liver, Heart ,Teratogen Intrxn: |
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Artemisinin
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There is stuff in the notes, not in the slides, not really worrying about it
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Primaquine
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Radical cure of vivax and ovale
in combo w/ PCP, used v. PCP Mech: Rt, Dist: PhK: Spct: Ts forms, gametocidal; no effect on RBC stages (no Sx relief) SE: Hemolytic anemia in G6PD, Teratogenic; else mild Intrxn: |
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Acyclovir (Zorivax)
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synthetic guanosine derivative
Spct: Herpes Simplex; some vs VZV; often prophylactic in organ transplants, imno decreased , hairy leukoplakia Mech: phosphorylated by viral thymidine kinase to monophosphate; trapping increases [Rx] ~100x in herpetic cells. host enzymes --> triphosphate: competition w/ dGTP --> inhibits viral polymerase --> chain termination --> no DNA prelication Rt, Dist: Oral, Topical or IV ~5x/d PhK: Renal excretion; 3h halflife --> 20h w/ renal dysnfx SE: non-toxic to normal cells; lethargy if in combo w/ zidovudine; high IV dose = renal obstrxn esp in combo w/ cyclopsorine; hydrate & infuse slowly. Intrxn: Resistance: decreased thymidine kinase, altered viral DNA polymerase, delta receptor specificity NB: valacyclovir is a pro-Rx --> increased serum levels & increased effectiveness Safe for pregnants |
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valacyclovir
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NB: valacyclovir is a pro-Rx --> increased serum levels & increased effectiveness
Safe for pregnants synthetic guanosine derivative Spct: Herpes Simplex; some vs VZV; often prophylactic in organ transplants, imno decreased , hairy leukoplakia Mech: phosphorylated by viral thymidine kinase to monophosphate; trapping increases [Rx] ~100x in herpetic cells. host enzymes --> triphosphate: competition w/ dGTP --> inhibits viral polymerase --> chain termination --> no DNA prelication Rt, Dist: Oral, Topical or IV ~5x/d PhK: Renal excretion; 3h halflife --> 20h w/ renal dysnfx SE: non-toxic to normal cells; lethargy if in combo w/ zidovudine; high IV dose = renal obstrxn esp in combo w/ cyclopsorine; hydrate & infuse slowly. Intrxn: Resistance: decreased thymidine kinase, altered viral DNA polymerase, delta receptor specificity |
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Famcyclovir
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guanosine analogue
Spct: HSV-1, HSV-2, VZV, EBV, HBV; DOC for acute VZV, recurrent gential HSV Mech: phosphorylated by viral thymidine kinase, converted in vivo to penciclovir --> competitive inhibition of viral DNA polymerase Rt, Dist: PhK: halflife >1d, renal excretion SE: testicular toxicity in animal models, not inhumans Intrxn: |
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Penciclovir
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Topical Agent for Herpes Labialis
Mech: competitive inhibition of viral DNA polymerase (Famcyclovir converted to panciciclovir intracellularly by viral thymidine kinase) |
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Trifluridine (Viroptic)
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fluorinated thymidine analogue, used for acyclovir resistant HSV eye infx
Mech: inhibits viral DNA synth Rt, Dist: topical PhK: Spct: HSV 1 & 2 SE: visual haze Intrxn: |
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Docosanol (Abreva)
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OTC topical for HSV cold sores
Mech: Inhibits fusn of plasma membrane & HSV envelope Rt, Dist: Topical PhK: Spct: HSV SE: Intrxn: |
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(Val)Ganciclovir
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synthetic analogue of guanosine
Spct: greater activity vs. CMV than acyclovir Mech: phosphorylated by thymidine kinase in herpetic cellls & by viral protein kinase phosphotransferase in CMV infected cells Rt, Dist: IV for acute CMV, +- combined w/ fscarnet for chronic suppression; valganciclovir oral prophyalxis, used in transplant pts; 5 mo Ocular implant for transplant pts available PhK: SE: more toxic: neurtropenia, throbocytopenia esp w/ IV combo w/ zidovudine; Teratogenic; Also GI, HA, etc; Intrxn: |
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Cidofovir
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cytosine analogue
Spct: CMV retinitis in HIV; resistant Herpes infx Mech: inhibits viral DNA polymerase; no need for intracellular activation = good vs acyclovir/ganciclovir resistant strains Rt, Dist: PhK: SE: Renal tubular necrosis (prevent w/ hydration & probenicid), ocular hypotonia, uveiitis, probenecid-related hypersensitivty Intrxn: |
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Foscarnet
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phosphonoformic acid, organic analogue of pyrophosphate
Spct: acyclovir resistant HSV and CMV retinitis; often combined with ganciclovir) Mech: directly inhibits viral DNA, RNA polymerases & reverse transcriptase Rt, Dist: IV ONLY PhK: Renal excretion SE: nephrotoxicity: adjust dose to Cr clearance; saline pre-load & hydrate; genital ulcers from high [Rx]urinary; teratogenic Intrxn: w/ pentamidine --> hypocalcemia |
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Formivirsen (Vitravene)
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antisense mRNA to CMV
Spct: refractory CMV retinitis Mech: inhibits CMV protein synth (& replication) Rt, Dist: intravitreal injection 1/wk for 3 weeks, 2x every 2 weeks, then 1/mo; PhK: SE: Intrxn: used in combo w/ foscarnet or ganciclovir |
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Oseltamivir (Tamiflu);
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neuraminidase inhibitor
begin w/in 2 days of Sx, tx for 5d Spct: selective for influenza A and B, bird flu; Some A's esp seasonal H1N1 resistant Mech: prevents release of virus from infected cells Rt, Dist: Orally PhK: activated by gut & liver, renal excretn SE: Nausea/Vomiting if on empty Intrxn: contrast to Zanamivir (Relenza): intranasal/oral inhaler (no oral absorptn); No N/V, but may decrease respiratory fnx in COPD or cause brochospasm in asthmatics |
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Zanamivir (Relenza)
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neuraminidase inhibitor
begin w/in 2 days of Sx, tx for 5d Spct: Influenza A and B Mech: prevents release of virus from infected cells Rt, Dist: intranasal/oral inhaler (no oral absorptn) PhK: SE: but may decrease respiratory fnx in COPD or cause brochospasm in asthmatics Intrxn: contrast to Oseltamivir (Tamiflu): oral admin, no respiratory effects, causes N/V if on empty |
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Amantadine (Symmetrel)
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NB: 2nd line to Oseltamvir
Spct: Influenza A2 (Asian) in high risk pts; prophylaxis Mech: blocks uncoating of virus, inhibits release of viral DNA into cytoplasm Rt, Dist: Oral PhK: 20h halflife, 90% renal excretion undelta, 10% metblz'd SE: DA agonism: hallucinations; teratogenic in animals Intrxn: --contrast to rimantidine, does not x BBB --> no CNS effects |
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Rimantadine (Flumadine)
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NB: 2nd line to Oseltamvir
Spct: Influenza A2 (Asian) in high risk pts; prophylaxis Mech: blocks uncoating of virus, inhibits release of viral DNA into cytoplasm Rt, Dist: Oral PhK: 20h halflife, 90% renal excretion undelta, 10% metblz'd SE: teratogenic in animals Intrxn: --contrast to Amantadine, x's BBB --> DA agonist --> hallucinations |
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Ribavirin (Virazole)
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hospitalized children w/ RSV LRT infx
purine nucleoside analogue similar to guanosine Spct: RSV, HSV, Influenza, Combo w/ interferon for HepC, Lassa Mech: conversion to ribavirin-5'-triphosphate, inhibits viral mRNA synth Rt, Dist: aerosol >1/2 day for 3+ days; high dose IV for Lassa Fever; oral in combo w/ IFNa2b or 2 for hepC synergistic PhK: SE: Terotogenic, dyspnea, chest soreness, Cardiac arrest, hypotension, HA; dose dependent anemia & depression +- suicide NB: do not allow pregnant women around aerosol tx! |
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Palivizumab (synagis)
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mab vs RSV
Spct: Mech: Rt, Dist: 1/mo in high risk peds |
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Lamivudine (Epivir)
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Spct: HBV, HIV; used for chronic HepB
Mech: inhibits HBV DNApol & reverse transcriptaze Rt, Dist: PhK: SE: well tolerated Intrxn: Resistance may dvlp; cross resistance w/ entecavir but not adefovir |
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Adefovir (Hepsera)
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Spct: HepB
Mech: inhibits HBV DNA pol Rt, Dist: PhK: SE: renal toxicity, lactic acidosis (etc) Intrxn: |
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Etnecavir (Baraclude)
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Spct: HepB
Mech: competitive inhibition of DNA pol Rt, Dist: PhK: SE: well tolerated Intrxn: NB: better efficacy than lamivudine (Epivir) |
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Telbivudine (Tyzeka)
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Spct: HepB
Mech: competitive inhibition of DNA pol |
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Interferons
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alpha-2b (Intron A, Pegintron), Interferon alpha-2a (Roferon, Pegasys)
Spct: Pegylated alpha-2b: Hepatitis C (in combo w/ oral ribavirin), Chronic HepB alpha-2a + ribavirin + protease inhibitors used in refractory pts Mech: inhibits virla protein synth & replication at numerous levels; induces host to produce enzymes that inhibit penetration, uncoating, translation & transcirption, processing and release, Rt, Dist: Subcu; long acting depot injxns slows absorption, decreases SE's increases efficacy PhK: duration of therapy depends on viral genomm; 2&3 ~6 mo, 1: ~yr SE: flu-like sro, myalgia, arthralgia, GI, DEPRESSION, neutropenia, anemia, trhobocytopenia, Edema & hypotension; Intrxn: |
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Boceprevir (Victrelis)
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may eliminate virus
Spct: HepC genome 1 (in combo w/ IFNs & Ribavirin) Mech: block HCV NS3/4A serine protease req'd to produce viral proteins Rt, Dist: 3x/d oral w/ fatty food, must be refridgerated PhK: SE: Strong inhibitor of CYP3A4; Anemia, Fatigue, Leukopenia, Rash Intrxn: -identical to telaprevir (Incivek) |
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telaprevir (Incivek)
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may eliminate virus
Spct: HepC genome 1 (in combo w/ IFNs & Ribavirin) Mech: block HCV NS3/4A serine protease req'd to produce viral proteins Rt, Dist: 3x/d oral w/ fatty food, must be refridgerated PhK: SE: Strong inhibitor of CYP3A4; Anemia, Fatigue, Leukopenia, Rash Intrxn: Boceprevir (Victrelis) |
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Zidovudine (Retrovir)
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2nd Line HIV Tx (to Tenofovir/Emtricitabine)
deoxythimidine analogue, Reverse transcriptase inhibitor Spct: HIV, Psoriasis & Adult T cell leukemia (also retroviruses) Indic: Early in AIDs, Pregnancy, high doses in AIDS dementia Mech: converted intracellularly to active triphosphate --> incorporated into DNA Rt, Dist: Oral 5x/d; Good CNS penetration; IV during labor + baby's 1st 6 weeks PhK: first pass: 2/3 bioavailability; majority Hepatic metblzm, rest renal excretn SE: Anemia, neutropenia, CNS, GI Intrxn: increased toxicity in combo w/ neuro, nephro, or hematopoietically toxic rx's: Dapson, pentamidine, amphotericin B, vincristine, vinblastine, doxorubicin, IFN); + acetaminophen or ganciclovir --> increases neutropenia + acyclovir --> somnolence/lethargy + cimetidine or benzos --> inhibits liver metblzm + probenecid impairs elimination Virus may gain resistance via mutation Reverse Transcirptase Inhibitors: monitor for rare but serious lactic acidosis & hepatotoxicty; discontinue |
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Lamivudine (Epivir, 3TC)
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2nd Line HIV Tx (to Tenofovir/Emtricitabine)
cytosine analogue, NB: monoRx --> guarenteed mutation which increases sensitivity to zidovudine (Retrovir) Spct: combo w/ zidovudine (Retrovir) or other RTI's for HIV; inhibits HepB DnA pol, good for chonic HepB Mech: competitive inhibitor of reverse transcriptase Rt, Dist: oral PhK: renal SE: very well tolerated Intrxn: cross resistance with emtricitabine (also a cytosine analogue) Reverse Transcirptase Inhibitors: monitor for rare but serious lactic acidosis & hepatotoxicty; discontinue |
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Tenofovir (Viread)
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Adenosine analogue
HIV DOC in combo w/ emtricitabine Spct: refractory HIV-1 Mech: Rt, Dist: oral c food PhK: SE: Intense GI Intrxn: Reverse Transcirptase Inhibitors: monitor for rare but serious lactic acidosis & hepatotoxicty; discontinue |
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Emtricitabine (Emtriva)
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cytosine analogue
in combo w/ Tenofovir DOC for HIV Spct: HIV, lamivudine resistant HepB Mech: competitive inhibitor of reverse transcriptase Rt, Dist: oral 1/d PhK: SE: well tolerated; diarrhea, nausea rash Intrxn: cross resistance with lamivudine (also a cytosine analogue) Reverse Transcirptase Inhibitors: monitor for rare but serious lactic acidosis & hepatotoxicty; discontinue |
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Didanosine; ddI (Videx)
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Spct: HIV
Mech: inhibits mito DNA synth Rt, Dist: inactivated by acid; given on epty stomach in buffer PhK: active renal secretion SE: peripheral neuropathy; pancreatities eps in prior alcoholism increased risk in combo c pentamidine; anemia, granulocytopenia, hyperurivemia; discontinue for lactic acidosis or hepatotoxicity; Intrxn: AIDS likely to mutate between Didanozine resistance and zidovudine resistance Tetracyclines, Fluoroquinolones will be chelated by buffer; Ketoconazole et al need acid for absorption will not work; do not combine with other neuropathic drugs (Didanosine, Stavudine, Isoniazid, Zalcitabine) Reverse Transcirptase Inhibitors: monitor for rare but serious lactic acidosis & hepatotoxicty; discontinue |
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Stavudine (Zerit)
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dideoxythymidine
Spct: advanced HI in adults who do not tolerate other therapy Mech: phosphorylated and incorported into DNA; inhibits reverse transcripatze Rt, Dist: oral; PhK: renal excretn SE: peripheral neuropathy Intrxn: do not combine with zidovudine which inhibits phosphorylation do not combine with other neuropathic drugs (Didanosine, Stavudine, Isoniazid, Zalcitabine) Reverse Transcirptase Inhibitors: monitor for rare but serious lactic acidosis & hepatotoxicty; discontinue |
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Zalcitabine (ddC; Hivid)
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dideoxycytidine)
Spct: Mech: inhibits reverse transcriptase and terminates DNA chain; Rt, Dist: oral, food decreases absoprtion PhK: renal excretn SE: inhibits mammallian DNA polymerases and mitochondiral DNA synth --> peripheral neuropathy; Intrxn: do not combine with other neuropathic drugs (Didanosine, Stavudine, Isoniazid, Zalcitabine) Reverse Transcirptase Inhibitors: monitor for rare but serious lactic acidosis & hepatotoxicty; discontinue |
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Abacvir (Ziagen)
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guanosine analogue
Spct: Mech: reverse transcriptase inhibitor Rt, Dist: oral PhK: SE: serious hypersnsitivity, uncommon but fatal; most commonly N/V/D Intrxn: resistance dvlps slowly Reverse Transcirptase Inhibitors: monitor for rare but serious lactic acidosis & hepatotoxicty; discontinue |
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Efavirenz (Sustiva)
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DOC non-nucleotide RTI, combo c NRTI's (Zidovuldine et al)
Spct: HIV Mech: binds directly to reverse transcriptase Rt, Dist: oral w/ fat PhK: long halflife, CYP3A4 metabolizm SE: TERATOGENIC, CNS Intrxn: incudes CYP3A4 |
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Nevirapine (Viramune)
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DOC non-nucleotide RTI in pregnant pts, combo c NRTI's (Zidovuldine et al)
Spct: HIV Mech: binds directly to reverse transcriptase Rt, Dist: PhK: CYP3A4 metabolizm SE: Stevens-Jonson Sro, exacerbated by corticosteroids; Heptatitis Intrxn: induces CYP3A4; |
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Delavirdine mesylate (Rescriptor)
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Spct: HIV
Mech: binds directly to reverse transcriptase Rt, Dist: absoprtion decreased by antacids; poor CNS penetration PhK: CYP3A4 metabolizm SE: teratogenic; etc Intrxn: inhibits CYP3A |
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Etravirine (Intelence)
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Spct: HIV resistant to other NNRTI's
Mech: binds directly to reverse transcriptase Rt, Dist: PhK: metabolized by CYP3A4 SE: Intrxn: Induces CYP3A$ |
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Atazenavir (Reyataz)
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no cross resistance w/ other PI's, less effect on lipoproteins than other PI's
Spct: HIV DOC (convient dosing) Mech: protease inhibitor Rt, Dist: 1/d oral w/ light meal; PhK: CYP3A4 metablzm SE: inhibits UGT1A1 --> increased bilirubin; rash, nausea; (All PI's: altered body fat redistribution, insulin resistance, increased cholesterol, spontaneous bleeding in hemophelias;) Intrxn: Inhibits CYP3A$ (All PI's: anything which induces CYP3A4 decreases halflifes, do no combine with St Johns' Wort, statins) |
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Darunavir (Prezista)
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Spct: HIV, DO2ndC to Atazenavir: safer & more effective than other PI's
Mech: protease inhibitor Rt, Dist: PhK: (All PI's: CYP3A4 metablzm) SE: HA, nightmares; (All PI's: altered body fat redistribution, insulin resistance, increased cholesterol, spontaneous bleeding in hemophelias) Intrxn: (All PI's: anything which induces CYP3A4 decreases halflifes, do no combine with St Johns' Wort, statins) |
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Ritonavir (Norvir)
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Spct: HIV, combined c other protase inhibitor to increase their bioavilability
Mech: protease inhibitor Rt, Dist: PhK: (All PI's: CYP3A4 metablzm) SE: GI, acro-parethesias (All PI's:altered body fat redistribution, insulin resistance, increased cholesterol, spontaneous bleeding in hemophelias) Intrxn: Inhibits CYP3A4 (All PI's:anything which induces CYP3A4 decreases halflifes, do no combine with St Johns' Wort, statins) contains EtOH- cautn w/ Rx's like metronidazole specifically contraindicated with (long list) |
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Saquinavir (Invirase)
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Spct: HIV
Mech: protease inhibitor Rt, Dist: low bioavailability, soft gell better, better if taken with grapefuidt juice, ritonavir PhK: CYP3A4 metablzm SE: GI; altered body fat redistribution, insulin resistance, increased cholesterol, spontaneous bleeding in hemophelias Intrxn: anything which induces CYP3A4 decreases halflifes, do no combine with St Johns' Wort, statins |
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Indinavir (Crixavan)
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Spct: HIV
Mech: protease inhibitor Rt, Dist: good for empty stomach, enters CNS PhK: CYP3A4 metablzm SE: neprholithiasis (hydrate), aSx hyperbilirubinemia (All PI's: altered body fat redistribution, insulin resistance, increased cholesterol, spontaneous bleeding in hemophelias) Intrxn: (All PI's: anything which induces CYP3A4 decreases halflifes, do no combine with St Johns' Wort, statins;) |
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Nelfinivar (Viracept)
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little corss resistance w/ other PI's
Spct: Mech: protease inhibitor Rt, Dist: best absorbed w/ food PhK: both induces and inhibits CYP3A4; (CYP3A4 metablzm) SE: mostly GI (All PI's: altered body fat redistribution, insulin resistance, increased cholesterol, spontaneous bleeding in hemophelias) Intrxn: (All PI's: anything which induces CYP3A4 decreases halflifes, do no combine with St Johns' Wort, statins) |
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(Fos)amprenavir (Agenerase, Lexia)
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Spct: HIV
Mech: protease inhibitor Rt, Dist: oral, do not take w/ high fat PhK: (All PI's: CYP3A4 metablzm) SE: Stevens-Johnson Sro; NVD, Paresthesias(All PI's: altered body fat redistribution, insulin resistance, increased cholesterol, spontaneous bleeding in hemophelias) Intrxn: oral solution contains proylene glycol, do not give with dilusfiram or metronidazole! Inhibits CYP3A4; (All PI's: anything which induces CYP3A4 decreases halflifes, do no combine with St Johns' Wort, statins) |
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Lopinavir/Ritonavir (Kaletra)
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Spct: HIV
Mech: Protease inhibitor Rt, Dist: PhK: SE: GI, increased AST,ALT if pre-existing hepatic dz(All PI's: altered body fat redistribution, insulin resistance, increased cholesterol, spontaneous bleeding in hemophelias) Intrxn: lopinavir is added to increase availability of lopinaviir; (All PI's: anything which induces CYP3A4 decreases halflifes, do no combine with St Johns' Wort, statins) |
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Tipranavir (Aptivus)
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First in class of non-peptidic protease inhibitors, may work on PI resistant HIV
Spct: HIV Mech: protease inhibitors Rt, Dist: Give in conjnx w/ ritonavir to inhibit metbolsm and increase bioavailability; give w/ food to increase absorption; PhK: mostly excreted unchagned in feces SE: (All PI's: altered body fat redistribution, insulin resistance, increased cholesterol, spontaneous bleeding in hemophelias) Intrxn: should not be combined with drugs metabolied by CYP3A4 that have narrow theraputic ranges (benzos, statins, amiodarone); ; (All PI's: anything which induces CYP3A4 decreases halflifes, do no combine with St Johns' Wort, statins) |
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Raltegravir (Isentress)
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Spct: HIV; treatment resistant pts
Mech: integrase inhibitor Rt, Dist: PhK: SE: NVD, HA |
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Maraviroc (Selzentry)
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Spct: CCR5 tropic HIV infx HIV in who m other tx not effective
Mech: inhibits fusion by binding CCR5 Rt, Dist: PhK: SE: Rash; well tolerated |
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Enfuvirtide (Fuzeon)
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Spct: HIV, no cross ressitance; use din advanced dz in combo w/ other anti-retrovirals;;
Mech: fusion inhibitor; binds gp41 prevents conformational change re'd for membrane fusion Rt, Dist: subcu injx (peptide) PhK: SE: pneumonia more likely. Intrxn: |
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DOC: Entamoeba histolytica
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Metronidazole (Flagyl)
plus luminal amebicide |
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DOC: Giardia
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Metronidazole (Flagyl)
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Trichomonas vaginalis
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Metronidazole (Flagyl)
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Toxoplasma gondii
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Pyrimethamine (Daraprim)
plus Sulfadiazine plus folinic acid |
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Pneumocystis jiroveci
(Pneumocystis carinii) |
Trimethoprim plus Sulfamethoxazole (Bactrim)
plus folinic acid |
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Ascaris lumbricoides
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Mebendazole (Vermox) or Pyrantel pamoate (Antiminth)
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Enterobius vermicularis
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Mebendazole (Vermox) or Pyrantel pamoate (Antiminth)
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Necator americanus
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Mebendazole (Vermox) or Pyrantel pamoate (Antiminth)
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Trichinella spiralis
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Mebendazole (Vermox)
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Tapeworms (cestodes)
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Niclosamide (Niclocide)
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Cysticercosis
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Praziquantel (Biltricide)
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Schistosoma mansoni
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Praziquantel (Biltricide)
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Schistosoma haematobium
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Praziquantel (Biltricide)
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Schistosoma japonicum
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Praziquantel (Biltricide)
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Flukes
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the only fluke not treatable by Praziquantel is the
sheep liver fluke Fasciola hepatica – triclabendazole or bithionol are recommended |
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Metronidazole
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alone and in combination with Diloxanide Furoate (Furamide), Iodoquinol
(Yodoxin; Moebiquin), or Paromomycin (Humatin); drug of choice for E. histolytica, G. lamblia, & T. vaginalis; also for treatment of some anaerobic bacteria - Bacteroides fragilis and Clostridum difficile; mechanism: inhibition of DNA function; kinetics: oral or parenteral administration, metabolized by liver (drug interactions), distributes widely incl. CSF; toxicity (Common: GI irritation, metallic taste, disulfiram effect – all allow continued therapy. Rare: headache, ataxia, seizures, |
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Tinidazole (Tindimax)
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similar to metronidazole, treatment of E. histolytica, G. lamblia, & T. vaginalis
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Diloxanide Furoate (Furamide)
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treatment of asymptomatic E. histolytica, combined with metronidazole for more
serious infections (FYI – not recommended for use during pregnancy; currently no commercial production) |
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Iodoquinol (Yodoxin, Moebiquin)
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treatment of asymptomatic E. histolytica, combined with metronidazole for
more serious infections; toxicity - (rare): skin reactions, thyroid enlargement, headache, diarrhea |
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Paromomycin (Humatin)
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treatment of asymptomatic E. histolytica, combined with metronidazole for more
serious infections; effective for T. vaginalis; aminoglycoside antibiotic; toxicity – GI upset |
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Quinacrine (Atabrine)
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for giardiasis (alternative to metronidazole), cheap, oral, more toxic than metronidazole,
more toxic in children |
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Furazolidone (Furoxone)
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used for giardiasis, liquid preparation
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Trimethoprim plus Sulfamethoxazole (Bactrim)
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Drugs of choice for pneumocystosis,
alternative for toxoplasmosis (replaced by Pyrimethamine plus Sulfadiazine plus folinic acid), P. carinii prophylaxis in AIDS patients, mechanism: inhibition of folate metabolism, Toxicity: (common) rash, pruritis, cytopenias and transaminase elevation |
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Pentamidine (Pentam)
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alternative treatment of P. carinii – both active infection and prophylaxis, administered
IM or by nebulizer, Toxicity: hypotension, arrhythmias, hypoglycemia, (FYI occasional: hyperglycemia, tachycardia, headache, vomiting, bronchospasm, renal dysfunction, hepatic failure), for patients intolerant to trimethoprim plus sulfamethoxazole |
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Atovaquone (Mepron)
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alternative for pneumocystosis
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Pyrimethamine (Daraprim) plus Sulfadiazine plus folinic acid
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Treatment of choice for toxoplasmosis
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Mebendazole (Vermox)
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Drug of choice for: roundworm, whipworm, hookworm, and pinworm, trichinosis (with
corticosteroids), effective against some tapeworms, useful against mixed infections, Mechanism: binds tubulin and disrupts protein function, low absorption low toxicity – but GI discomfort and teratogenicity may occur |
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Pyrantel pamoate (Antiminth)
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2nd drug of choice for these nematodes (roundworm, pinworm, and hookworm);
mechanism: cholinesterase inhibitor; low absorption low toxicity (dizziness, headache, and drowsiness); available OTC |
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Niclosamide (Niclocide)
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Drug of choice for most tapeworms (FYI, niclosamide is not available in the US and
praziquantel is considered choice by some authorities); oral administration, not absorbed; low toxicity, some GI upset + reactions to dead worm material |
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Praziquantel (Biltricide)
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Broad spectrum; drug of choice for all species of shistosomes (flukes), effective for
tapeworms as well; mechanism: increases Ca+2 permeability, paralyzing the parasite; well absorbed, useful for systemic infections; some GI upset + reactions to dead worm material |
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Alkylating Agents (General)
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Class: Alkylating Agent (Antineoplastic)
Spct: damage occurs mostly late G1 and S, though activity throughout Mech: transfers reactive alkyl group to DNA molecule to form a covalent bond --> miscoding & breakage, or extensive crosslinking Rt, Dist: PhK: SE: vesicant, (ts dmg @ injx); acutely: vomiting (CTZ), delayed: bone marrow depression; Sterility, teratogenesis Anti-neoplastic: rapidly dividing cells Intrxn: Resistance via DNA repair enzymes, decreased permeability to Rx and increased glutathione |
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Mechlorethamine (Mustargen)
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Class: Alkylating Agent (Antineoplastic)
Spct: Hodgkin's Sz: MOPP regiment; M and G1 most sensitive Mech: transfers reactive alkyl group to DNA molecule to form a covalent bond --> miscoding & breakage, or extensive crosslinking Rt, Dist: parenteral, topical PhK: 10 min halflife SE: hyperuricemia c ARF & nephrolithiasis (alkalinize urine + allopurinol); normal alkylating agent SE's: vesicant, (ts dmg @ injx); acutely: vomiting (CTZ), delayed: bone marrow depression; Sterility, teratogenesis; Anti-neoplastic: rapidly dividing cells Intrxn: |
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Cyclophosphamide (Cytoxan)
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Class: Alkylating Agent (Antineoplastic)
Spct: non-Hodgkin's & Burkitt's lymphoma; Breast, Lung ovarian, endometrial and cervical carcinoma; Immunosuppression (wegen'ers, RA, organ transplants, lupus nephritis)\ Mech: transfers reactive alkyl group to DNA molecule to form a covalent bond --> miscoding & breakage, or extensive crosslinking Rt, Dist: Oral PhK: req's metabolic activation by p450 SE: not a vesicant, hematologic, alopecia, hemorrhagic cystitis (prevent w/ hyydration,voiding MESNA--offers sulfhydryl groups as binding sites for acrolein to reduce toxicity) SIADH 2/ water intoxication; [n/v/anorexia, sterility hyperuricemia] Intrxn: |
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Busulfan (Myleran)
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Class: Alkyl Sulfonate
Mech: bifunctional alkylator Spct: CML Rt, Dist: oral PhK: 3m halflife SE: few side effects beyond myelosuppression, hyperuricemia --use hydration & allopurinol Intrxn: |
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Carmustine (BCNU)
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Class: Nitrosurea
Spct: brain tumors, kills at all phases Mech: Rt, Dist: oral, IV PhK: highly lipid soluble, req's in vivo activation SE: profound myelosuppression [et al] Intrxn: --seems identical to Lomustine (CCNU) --contrast to streptozocin: nitrosurea s myelosuppression, selective for islet cell carcinomas (Pancreatic/metastatic) |
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Lomustine (CCNU)
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Class: Nitrosurea
Spct: brain tumors, kills at all phases Mech: Rt, Dist: oral, IV PhK: highly lipid soluble, req's in vivo activation SE: profound myelosuppression [et al] Intrxn: --seems identical to Carmustine (BCNU) --contrast to streptozocin: nitrosurea s myelosuppression, non-lipid soluble, selective for islet cell carcinomas (Pancreatic/metastatic) |
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Streptozocin (Zanosar)
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Class: Nitrosurea
Spct: selective for islet cell carcinomas (Pancreatic/metastatic), all phases Mech: Rt, Dist: oral, IV PhK: req's in vivo activation SE: does not cause profound myelosuppression [et al] Intrxn: --contrast to Carmustine (BCNU) & Lomustine profound myelosuppression, highly lipid soluble used for brain tumors |
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Dacarbazine
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Class: Triazene
Spct: hodgkin's dz- all phases Mech: DNA cross linking Rt, Dist: IV 1/mo PhK: 20 minutes, p450 activation SE: Intrxn: |
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Cisplatin (Platinol)
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Class: Platinum Complexes
Spct: used in testicular CA cocktails, most effect in S phase, all phases Mech: inter-intrastrand DNA crosslinking Rt, Dist: IV 5 days 1/mo PhK: <1h SE: renal, acoustic nerve damage [n/v, anaphylaxis]; carboplatin is less toxic than cisplatin, less effective Intrxn: |
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Methotrexate
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Class: Folic acid analogue
Mech: inhibits DHF Reductase --> THF; cannot produce thymidine; Spct: ALL in children, choriocarcinoma, immunosuppression esp organ transplants, RA Rt, Dist: PhK: PPB XxBBB SE: [Rx]hi can precipitate in renal tubules; hepatotoxic, pulmonary infiltrates; Normal anti-neo: bone marrow, alopecia, teratogenic, sterility Intrxn: leucovoricin (folinic acid) "leucovorin rescue" reduces toxicity resistance via increased folic acid uptake + increased [DHF reductase] [PPB displaced by salicylates, phenytoin] |
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6-Mercaptopurine (Purinethol)
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Class: purine analogues
Mech: converted by HGPRT (hypoxanthine-guanine phosphoribosyl transferase) to nucleotide; interferes w/ both DNA & RNA synth Spct: leukemia; ~ selective for lymphoid cells in S phase Rt, Dist: oral w/ food PhK: metabolized by xanthine oxidase to 6-thiouric acid SE: myelosuppression, cholestatic jaundice, hyperuciemia (SE reduced c allopurinol) Intrxn: breakdown blocked by allopurinol: reduce [6MP} resistance: decreased HGPRT --contrast to thioguanine, not metzd by xanthine oxidase, unaffected by allopurinol |
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Thioguanine (6-thioguanine)
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Class: purine analogues, similar to 6-mercatopurine
Mech: converted by HGPRT (hypoxanthine-guanine phosphoribosyl transferase) to nucleotide; interferes w/ both DNA & RNA synth Spct: leukemia, relatively selective for llymphoid cells Rt, Dist: PhK: SE: myelosuppression Intrxn: resistance: decreased HGPRT --contrast to 6MP: metzd by xanthine oxidase to 6-thiouric acid; excretion reduced w/ allopurinol |
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Mercaptopurine (Purinethol)
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Class: purine analogues
Mech: converted by HGPRT (hypoxanthine-guanine phosphoribosyl transferase) to nucleotide; interferes w/ both DNA & RNA synth Spct: relatively selective for lymphoid cells Rt, Dist: PhK: SE: myelosuppression Intrxn: resistance: decreased HGPRT |
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[Pentostat (Nipent)]
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Class: purine analogues
Mech: converted by HGPRT (hypoxanthine-guanine phosphoribosyl transferase) to nucleotide; interferes w/ both DNA & RNA synth Spct: hairy cell leukemia, relatively selective for lymphoid cells Rt, Dist: PhK: SE: myelosuppression Intrxn: resistance: decreased HGPRT --identical to cladribine (leustatin) |
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[cladribine (leustatin)]
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Class: purine analogues
Mech: converted by HGPRT (hypoxanthine-guanine phosphoribosyl transferase) to nucleotide; interferes w/ both DNA & RNA synth Spct: hairy cell leukemia, relatively selective for lymphoid cells Rt, Dist: PhK: SE: myelosuppression Intrxn: resistance: decreased HGPRT --identical to Pentostat (Nipent) |
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[Fludarabine (Fludra)]
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Class: purine analogues
Mech: converted by HGPRT (hypoxanthine-guanine phosphoribosyl transferase) to nucleotide; interferes w/ both DNA & RNA synth Spct: CLL & low grade lymphomas, relatively selective for llymphoid cells Rt, Dist: PhK: SE: myelosuppression Intrxn: resistance: decreased HGPRT |
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Fluorouraicil (5-FU, Adrucil)
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Class: Pyrimidine analogues
Mech: converted intracellularly to 5-FUMP nuceotide, inhibits thymidylate synthase, RLS in DNA synth Spct: selectively topix to G1 and S; topical cream for premalignant keratoses; combo w/ leuocovirn for colorectal CA Rt, Dist: IV, topical cream PhK: short halflife SE: GI tract ulceration, myelosuppression Intrxn: leucovorin (folinic acid) increases responsiveness to 5fu by providing folate for intraceullar conversion |
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Capecitabine (Xeloda)
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Class: pyrmidine analogue
Spct: metastatic breast CA, colorectal Mech: pro-drug converted to 5FU in tumors Rt, Dist: PhK: SE: does not produce alopecia, myelosuppression uncommon |
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Cytarabine (ara-C, Cytosar-U)
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Class: pyrimidine analogue
Spct: S phase, AML Mech: Rt, Dist: PhK: SE: myelosuppression w/ severe leukopenia Intrxn: |
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Hydroxyurea (Hydrea)
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Class: pyridmidine analogue
Spct: S phase, Chornic granulocytic leukemia Mech: Rt, Dist: PhK: SE: radiation recall w/ hyperpigmentation Intrxn: |
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Daunorubicin hydrochloride (Cerubidine)
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Class: anthracycline antibiotic
Mech: intercalates w/ DNA & destroys DNA Spct: any phase, mostly S; non-lymphoblastic leukemia Rt, Dist: IV PhK: SE: cardiotoxicity, decreased by iron chelators; Red urine Intrxn: resistance: decreased uptake or P glycoprotein pumping out |
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Doxorubicin hydrochloride (Adriamycin)
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Class: anthracycline antibiotic
Mech: intercalates w/ DNA & destroys DNA Spct: any phase, mostly S; lymphoma; solid breast tumors; sarcomas, thyroid cancer Rt, Dist: IV PhK: SE: cardiotoxicity, decreased by iron chelators; Intrxn: resistance: decreased uptake or P glycoprotein pumping out |
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[Idarubicin and Mitoxantrone]
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Incomplete
Class: anthracycline antibiotic Mech: intercalates w/ DNA & destroys DNA Spct: any phase, mostly S; Rt, Dist: PhK: SE: cardiotoxicity; Intrxn: resistance: decreased uptake or P glycoprotein pumping out |
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Bleomycin sulfate (Blenoxane)
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Class: bleomycin antibiotic
Mech: glycoproteins which causes fragmentation of of DNA Spct: max in G2 and early M; advanced testicular CA & ovarian ca Rt, Dist: PhK: SE: pulmonary fibrosis, anaphylactic sx; very little myelosuppression Intrxn: |
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Mitomycin (Mutamycin)
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Class: bleomycin antibiotic
Spct: adenoCA's of GI tract Mech: Rt, Dist: PhK: must be metabolized by hepatic p450 to be active SE: delayed but profound myelosuppression Intrxn: |
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Dactinomycin (Actinomycin D, Cosmegen)
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Class:
Mech: binds dsDNA Spct: rapidly proliferating cells; wil'ms tumor, Rhabdomyosarcoma, choriocarcinoma Rt, Dist: PhK: SE: radiation recall Intrxn: |
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Vinblastine sulfate (Velban)
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Class: plant alkaloids
Spct: specific for M phase; testicular carcionma in combo w/ bleomycin and cisplatin Mech: binds tubulin disrupts mitotic spindle with metaphase arrest Rt, Dist: PhK: SE: myelosuppression (microtuble axonal transport) Intrxn: resistance: P glycoprotein |
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Vincristine
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Class: plant alkaloids
Spct: specific for M phase; Childood leukemia, Hodkin's dz, non-hodgkin's lymphoma Mech: binds tubulin disrupts mitotic spindle with metaphase arrest Rt, Dist: PhK: SE: peripheral neuropathy Intrxn: resistance: P glycoprotein |
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Paclitaxel (Taxol)
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one of the most active and most toxic anti-cancer drgs
Class: plant alkaloids Spct: breast, ovary; G2 and M phase Mech: binds tubulin & microtubluin, arrests mitosis; Rt, Dist: PhK: SE: peripheral neorpathy (microtuble axonal transport), myalgia, myelosuppresison, anaphylaxis Intrxn: |
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Docetaxel (Taxotere)
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Similar to paclitaxel, but more toxic
Paclitaxel (Taxol) one of the most active and most toxic anti-cancer drgs Class: plant alkaloids Spct: breast, ovary; G2 and M phase Mech: binds tubulin & microtubluin, arrests mitosis; Rt, Dist: PhK: SE: peripheral neorpathy (microtuble axonal transport), myalgia, myelosuppresison, anaphylaxis |
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Class: topoisomerase inhibors
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Etoposide (Vepeside), Topectan, Irinotecan, Asaparginase
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Interferon Alpha (Roferon A)
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Class:
Spct: hairly cell leukemia, kaposi's sarcoma Mech: antiproliferative immunomodulation Rt, Dist: PhK: SE: flu like sro, depression Intrxn: contraindicated by hypersensitivity to alpha IFN mouse Ig or any component cauution in pre-existing organic dz nB: supplement with immunomodulatory unit |
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IL2 (Proleukin)
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Spct: advanced malignant melanoma, renal cell CA
Mech: induces T cell response to tumor cells nB: supplement with immunomodulatory unit |
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Granulocyte colony simulating factor
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used to prevent neutropenia induced by high dose chemotherapy
nB: supplement with immunomodulatory unit |
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Imatinib
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Mech: inhibits Bcr-Abl (philadelphia t:9:22) in CML & GIST
Rt, Dist: oral, ppb PhK: SE: immunosuppression; do not immunize while on imatinab, do not give to recently vaccinated vs polio Intrxn: |
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Cyclosporine (Sandimmune)
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Class: T cell suppressant
Spct: used to prevent rejection in organ transplant pts; autoimmune disorders Mech: binds to cyclophilin, inhibits fnx of calcineurin needed for T cell activation; (calcineurin needed for mvmt of NFAT nuclear factor for activating T lymphos into nucleus; Rt, Dist: very low, widely variable bioavailability PhK: metabolized by CYP3A4 w/ LOW THERAPUTIC RANGE; monitor, be cautious about interxns SE: htn, renal toxicity (esp w/ low hydration), CNS, hyperglycemia, gingival hyperlasia Intrxn: tacrolimus now used more commonly, lower toxicity phenobarbital, phenytoin, and rifampin induce CYP3A and decrease concentration o erythromycin, ketoconazole, grapefruit juice, verapamil inhibit CYP3A and increase concentration |
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Tacrolimus
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Class: T cell suppressant
Spct: preventing organ rejection Mech:binds to cyclophilin, inhibits fnx of calcineurin needed for T cell activation; (calcineurin needed for mvmt of NFAT nuclear factor for activating T lymphos into nucleus; Rt, Dist: take on empty stomach PhK: metabolized by CYP3A4 w/ low therapytic range SE: nephrotoxicity, htn, hyperglycemia, neurotixicity w/ insomnia Intrxn: caution with ACEI's or ARBs --> renal damage + aminoglycosides --> increased renal toxicity phenobarbital, phenytoin, and rifampin induce CYP3A and decrease concentration o erythromycin, ketoconazole, grapefruit juice, verapamil inhibit CYP3A and increase concentration |
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Sirolimus (Rapamune)
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Class: cell proliferation inhibitors
Spct: transplants Mech: blocks T cell responsveness to IL2 Rt, Dist: oral on empty PhK: CYP3A5 SE: profound myelosuppression; increased TAG's Intrxn: does not cause renal damage, starting to replace cyclosporin & tacrlimus |
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Mycophenolate Mofetil (CellCept)
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Class: cell proliferation inhibitors
Spct: to prevent rejection Mech: inhibits monophosphate dehydrogenase needed for de novo synth of purine in T and B; other cells can use salvage pathways so fairly selective; sepectively suppressses lymphocyte proliferation and antibody formation by B cells; inhibits recruitment of WBC's to inflam sites Rt, Dist: PhK: SE: increased infections, skin rash; teratogenic |
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Azathioprine (Imuran)
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Class: cell proliferation inhibitors
Spct: prevents rejection, severe RA Mech: converted in vivo to 6mercaptopurine, inhibits de novo purine synth, blocks gene translation and inhibits cell proliferation Rt, Dist: PhK: SE: myelowsuppression, infx, teratogenic Intrxn: metabolized by xnathine oxidase; pt tx'ed w/ allopurinol should have dose of azathioprine reduced significantly |
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[Leflunomide (Arava)]
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Class: cell proliferation inhibitors
Spct: RA Mech: inhibits de novo pyrimidine synth Rt, Dist: PhK: SE: liver failure, teratogenic |
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Cyclophosphamide (Cytotoxan)
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Spct: transplatn rescue, bone marrow transplants, antineoplastic
Mech: direct effect on mature T's and B's, can inhibit established immune response Rt, Dist: PhK: must be activated by p45- SE: hemorrhagic cystitis, myelosuppression, bladder fibrosis & CA, teratogenic |
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Thalidomide (Thalomid)
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Class: cell proliferation inhibitors
Spct: graft vs. host, multiple myeloma, AML Mech: suppresses TNF alpha; shifts T cells towards Th2 w/ increased IL4 and 5; decreases neutrophenis, enhances CMI; Rt, Dist: PhK: SE: category X, absolutely contraindicated; DVT's |
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Muromonab-CD3 (orthoclone OKT3)
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Class: antibody (mouse)
Spct: acute transplant rejection Mech: blocks CD3 receptor prevents activity and generation of new cytotoxic T's w/in minutes after admin; Rt, Dist: parenteral for 2 weeks; PhK: SE: cytokine release sro: flu-like response, shock; pretx w/ corticosteroids; fever, chills & nausea |
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Daclizumab (Zenapax)
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Class: humanized chimeric mab's
Spct: renal transplants Mech: bind IL2R, Rt, Dist: PhK: long halflife, weeks SE: does not cause cytokine release sro, but may cause anaphylaxis Intrxn: --identical to Basiliximab (Simulect Powder) |
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Basiliximab (Simulect Powder)
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Class: humanized chimeric mab's
Spct: renal transplants Mech: bind IL2R, Rt, Dist: PhK: long halflife, weeks SE: does not cause cytokine release sro, but may cause anaphylaxis Intrxn: --identical to Daclizumab (Zenapax) |
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Lymphocyte Immmune Globuline (Atgam)
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Class: IgG fractions to T cells from horses or rabbits
Spct: acute rejection episodes Mech: binds to receptors on T cells, reducing circulatin gnumber, imparis response of remaining T cells Rt, Dist: PhK: IV for days SE: allergic anaphylaxis, hypotension, lymphomas at injx site Intrxn: |
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Immunomodulators and Immune Suppressants
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:-(
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HIV Rx
SE's: Peripheral Neropathy & Pancreatitis |
Didanosine; ddI (Videx)
Spct: HIV Mech: inhibits mito DNA synth Rt, Dist: inactivated by acid; given on epty stomach in buffer PhK: active renal secretion SE: peripheral neuropathy; pancreatities eps in prior alcoholism increased risk in combo c pentamidine; anemia, granulocytopenia, hyperucivemia; Intrxn: AIDS likely to mutate between Didanozine resistance and zidovudine resistance Tetracyclines, Fluoroquinolones will be chelated by buffer; Ketoconazole et al need acid for absorption will not work; do not combine with other neuropathic drugs (Didanosine, Stavudine, Isoniazid, Zalcitabine) Reverse Transcirptase Inhibitors: monitor for rare but serious lactic acidosis & hepatotoxicty; discontinue |
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Drugs with a Disulfram-Like Effect,
Drugs which contain EtOH |
DLE: Griseofulvin, Motronidazole
EtOH; amprenavir, ritonavir |
