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160 Cards in this Set

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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
Most effective means of controlling malaria
don't get bitten

-eradicate moquitoes
-insect repellent
-treat nets, tents, clothes etc w/ permethrin
DOC's: Malaria Prophylaxis
Chloroquine Sensitive:
1. Chlorquine

Chloroquine Reistant
1. Mefloquine
2. Doxycycline, Atovaquone w/ proguanil (Malarone)

MultiRx Resistant
Doxycycline
DOC's: Malaria
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
HIV protease inhibitors
Top 3:
Saquinavir (Invirase)
Ritonavir (norvir)
Atazanavir (reyataz)

Also:
Indinavir (Crixivean)
Nelfinavir (Viracept)
Amprenavir (Agenerase)/Fosamprenavir (Lexia)
Lopinavir/ritonavir (Kelatra)
Tipranavir (Aptivus)
Darunavir (Prezista)
Reverse Transcriptase inhibitors
lactic acidosis & hepatotixicity: rare but serious

monitor pH & AST/ALT
discontinue
Amphotericin B
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:
Flucytosine
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:
Ketoconazole
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
Fluconazole
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]
Itraconazole
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
Voriconazole
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
Caspofungin
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:
Micafungin
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:
Anidulafungin
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:
Griseofulvin
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
Nystatin
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:
Terbinafine
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:
Miconazole
Esp for Tinea pedis; Superior to DOC for vulvovaaginal candidiasis (superior to nystatin)
Mech:
Rt, Dist:
PhK:
Spct: Candida, Crypto, Aspergillus
SE:
Intrxn:
[Naftifine]
Mech: interferes with steorl biosynth
Rt, Dist: Topical
PhK:
Spct: Dermatophytes, esp tineae pedis, cruris, corporis
SE:
Contras: ophthalmic use
Intrxn: None
Clotrimazole
topical azole, used in candidiasis, may cause burning, local anestheisa
Ciclopirox
topical antifungal similar to azoles; esp for tinea pedis, cruris, corporis, versicolor
Tolnaftate (Tinactin)
Topical, similar to azoles, Tinea pedis, tinea versicolor. not effecitve vs. onychomycosis
Undecylenic Acid
Topical vs Dermatophytes
Chloroquine (Aralen)
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)
Quinine/Quinidine
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
Doxycycline & Malaria
Tetracycline
combined with quinidine as DOC for complicated chloroquine-resistant malaria
prophylaxis vs multiRx resistant malaria
Mefloquine (Lariam)
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:
Pyrimethamine
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:
Atovaquone (Malarone)
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:
Halofaintrine
Mech:
Rt, Dist: Take on empty stomach
PhK:
Spct: 2nd line Rx for P falciparum & vivax
SE: Toxicity: GI, liver, Heart ,Teratogen
Intrxn:
Artemisinin
There is stuff in the notes, not in the slides, not really worrying about it
Primaquine
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:
Acyclovir (Zorivax)
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
valacyclovir
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
Famcyclovir
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:
Penciclovir
Topical Agent for Herpes Labialis
Mech: competitive inhibition of viral DNA polymerase

(Famcyclovir converted to panciciclovir intracellularly by viral thymidine kinase)
Trifluridine (Viroptic)
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:
Docosanol (Abreva)
OTC topical for HSV cold sores
Mech: Inhibits fusn of plasma membrane & HSV envelope
Rt, Dist: Topical
PhK:
Spct: HSV
SE:
Intrxn:
(Val)Ganciclovir
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:
Cidofovir
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:
Foscarnet
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
Formivirsen (Vitravene)
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
Oseltamivir (Tamiflu);
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
Zanamivir (Relenza)
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
Amantadine (Symmetrel)
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
Rimantadine (Flumadine)
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
Ribavirin (Virazole)
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!
Palivizumab (synagis)
mab vs RSV
Spct:
Mech:
Rt, Dist: 1/mo in high risk peds
Lamivudine (Epivir)
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
Adefovir (Hepsera)
Spct: HepB
Mech: inhibits HBV DNA pol
Rt, Dist:
PhK:
SE: renal toxicity, lactic acidosis (etc)
Intrxn:
Etnecavir (Baraclude)
Spct: HepB
Mech: competitive inhibition of DNA pol
Rt, Dist:
PhK:
SE: well tolerated
Intrxn:
NB: better efficacy than lamivudine (Epivir)
Telbivudine (Tyzeka)
Spct: HepB
Mech: competitive inhibition of DNA pol
Interferons
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:
Boceprevir (Victrelis)
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)
telaprevir (Incivek)
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)
Zidovudine (Retrovir)
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
Lamivudine (Epivir, 3TC)
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
Tenofovir (Viread)
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
Emtricitabine (Emtriva)
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
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, 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
Stavudine (Zerit)
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
Zalcitabine (ddC; Hivid)
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
Abacvir (Ziagen)
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
Efavirenz (Sustiva)
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
Nevirapine (Viramune)
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;
Delavirdine mesylate (Rescriptor)
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
Etravirine (Intelence)
Spct: HIV resistant to other NNRTI's
Mech: binds directly to reverse transcriptase
Rt, Dist:
PhK: metabolized by CYP3A4
SE:
Intrxn: Induces CYP3A$
Atazenavir (Reyataz)
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)
Darunavir (Prezista)
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)
Ritonavir (Norvir)
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)
Saquinavir (Invirase)
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
Indinavir (Crixavan)
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;)
Nelfinivar (Viracept)
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)
(Fos)amprenavir (Agenerase, Lexia)
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)
Lopinavir/Ritonavir (Kaletra)
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)
Tipranavir (Aptivus)
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)
Raltegravir (Isentress)
Spct: HIV; treatment resistant pts
Mech: integrase inhibitor
Rt, Dist:
PhK:
SE: NVD, HA
Maraviroc (Selzentry)
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
Enfuvirtide (Fuzeon)
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:
DOC: Entamoeba histolytica
Metronidazole (Flagyl)
plus luminal amebicide
DOC: Giardia
Metronidazole (Flagyl)
Trichomonas vaginalis
Metronidazole (Flagyl)
Toxoplasma gondii
Pyrimethamine (Daraprim)
plus Sulfadiazine plus folinic acid
Pneumocystis jiroveci
(Pneumocystis carinii)
Trimethoprim plus Sulfamethoxazole (Bactrim)
plus folinic acid
Ascaris lumbricoides
Mebendazole (Vermox) or Pyrantel pamoate (Antiminth)
Enterobius vermicularis
Mebendazole (Vermox) or Pyrantel pamoate (Antiminth)
Necator americanus
Mebendazole (Vermox) or Pyrantel pamoate (Antiminth)
Trichinella spiralis
Mebendazole (Vermox)
Tapeworms (cestodes)
Niclosamide (Niclocide)
Cysticercosis
Praziquantel (Biltricide)
Schistosoma mansoni
Praziquantel (Biltricide)
Schistosoma haematobium
Praziquantel (Biltricide)
Schistosoma japonicum
Praziquantel (Biltricide)
Flukes
the only fluke not treatable by Praziquantel is the
sheep liver fluke Fasciola hepatica – triclabendazole or
bithionol are recommended
Metronidazole
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,
Tinidazole (Tindimax)
similar to metronidazole, treatment of E. histolytica, G. lamblia, & T. vaginalis
Diloxanide Furoate (Furamide)
treatment of asymptomatic E. histolytica, combined with metronidazole for more
serious infections (FYI – not recommended for use during pregnancy; currently no commercial production)
Iodoquinol (Yodoxin, Moebiquin)
treatment of asymptomatic E. histolytica, combined with metronidazole for
more serious infections; toxicity - (rare): skin reactions, thyroid enlargement, headache, diarrhea
Paromomycin (Humatin)
treatment of asymptomatic E. histolytica, combined with metronidazole for more
serious infections; effective for T. vaginalis; aminoglycoside antibiotic; toxicity – GI upset
Quinacrine (Atabrine)
for giardiasis (alternative to metronidazole), cheap, oral, more toxic than metronidazole,
more toxic in children
Furazolidone (Furoxone)
used for giardiasis, liquid preparation
Trimethoprim plus Sulfamethoxazole (Bactrim)
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
Pentamidine (Pentam)
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
Atovaquone (Mepron)
alternative for pneumocystosis
Pyrimethamine (Daraprim) plus Sulfadiazine plus folinic acid
Treatment of choice for toxoplasmosis
Mebendazole (Vermox)
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
Pyrantel pamoate (Antiminth)
2nd drug of choice for these nematodes (roundworm, pinworm, and hookworm);
mechanism: cholinesterase inhibitor; low absorption  low toxicity (dizziness, headache, and drowsiness);
available OTC
Niclosamide (Niclocide)
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
Praziquantel (Biltricide)
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
Alkylating Agents (General)
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
Mechlorethamine (Mustargen)
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:
Cyclophosphamide (Cytoxan)
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:
Busulfan (Myleran)
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:
Carmustine (BCNU)
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)
Lomustine (CCNU)
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)
Streptozocin (Zanosar)
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
Dacarbazine
Class: Triazene
Spct: hodgkin's dz- all phases
Mech: DNA cross linking
Rt, Dist: IV 1/mo
PhK: 20 minutes, p450 activation
SE:
Intrxn:
Cisplatin (Platinol)
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:
Methotrexate
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]
6-Mercaptopurine (Purinethol)
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
Thioguanine (6-thioguanine)
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
Mercaptopurine (Purinethol)
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
[Pentostat (Nipent)]
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)
[cladribine (leustatin)]
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)
[Fludarabine (Fludra)]
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
Fluorouraicil (5-FU, Adrucil)
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
Capecitabine (Xeloda)
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
Cytarabine (ara-C, Cytosar-U)
Class: pyrimidine analogue
Spct: S phase, AML
Mech:
Rt, Dist:
PhK:
SE: myelosuppression w/ severe leukopenia
Intrxn:
Hydroxyurea (Hydrea)
Class: pyridmidine analogue
Spct: S phase, Chornic granulocytic leukemia
Mech:
Rt, Dist:
PhK:
SE: radiation recall w/ hyperpigmentation
Intrxn:
Daunorubicin hydrochloride (Cerubidine)
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
Doxorubicin hydrochloride (Adriamycin)
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
[Idarubicin and Mitoxantrone]
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
Bleomycin sulfate (Blenoxane)
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:
Mitomycin (Mutamycin)
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:
Dactinomycin (Actinomycin D, Cosmegen)
Class:
Mech: binds dsDNA
Spct: rapidly proliferating cells; wil'ms tumor, Rhabdomyosarcoma, choriocarcinoma
Rt, Dist:
PhK:
SE: radiation recall
Intrxn:
Vinblastine sulfate (Velban)
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
Vincristine
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
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
Intrxn:
Docetaxel (Taxotere)
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
Class: topoisomerase inhibors
Etoposide (Vepeside), Topectan, Irinotecan, Asaparginase
Interferon Alpha (Roferon A)
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
IL2 (Proleukin)
Spct: advanced malignant melanoma, renal cell CA
Mech: induces T cell response to tumor cells

nB: supplement with immunomodulatory unit
Granulocyte colony simulating factor
used to prevent neutropenia induced by high dose chemotherapy

nB: supplement with immunomodulatory unit
Imatinib
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:
Cyclosporine (Sandimmune)
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
Tacrolimus
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
Sirolimus (Rapamune)
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
Mycophenolate Mofetil (CellCept)
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
Azathioprine (Imuran)
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
[Leflunomide (Arava)]
Class: cell proliferation inhibitors
Spct: RA
Mech: inhibits de novo pyrimidine synth
Rt, Dist:
PhK:
SE: liver failure, teratogenic
Cyclophosphamide (Cytotoxan)
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
Thalidomide (Thalomid)
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
Muromonab-CD3 (orthoclone OKT3)
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
Daclizumab (Zenapax)
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)
Basiliximab (Simulect Powder)
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)
Lymphocyte Immmune Globuline (Atgam)
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:
Immunomodulators and Immune Suppressants
:-(
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
Drugs with a Disulfram-Like Effect,
Drugs which contain EtOH
DLE: Griseofulvin, Motronidazole

EtOH; amprenavir, ritonavir