Antifungal Agents
Polyenes:
Amphotericin B -- broad spectrum; used systemically;
can cause nephrotoxicity, hepatotoxicity, and anemia;
the nephrotoxicity may be irreversible
Nystatin -- more toxic than Amphotericin B
* bind to ergosterol in fungal membranes, making
them unstable
Antimetabolites:
Flucytosine -- will get to CNS; resistance develops quickly, so often given w/ amphotericin B
Antifungal azoles:
Clotrimazole -- used topically
Miconazole -- used topically...can also be given IV;
Ketoconazole -- given IV
Fluconazole -- given IV; readily enters CNS;
* Azoles act by inhibiting the fungal P-450 enzyme
necessary for synthesis of ergosterol
* About 1:10,000 patients on ketoconazole may develop
a progressive and potentially fatal hepato-toxicity
Others:
Griseofulvin -- only given orally; unique in that it is
concentrated in tissues containing keratin; headaches
and GI disturbances are common adverse effects
Antiparasitic Agents
Antimalarial agents:
Chloroquine -- extensive tissue binding; is a blood
schizonticide; large cumulative doses may result
in irreversible retinopathy, myopathy, and ototoxicity
Mefloquine -- only given orally; indicated in chloroquine
resistant P. falciparum
Primaquine -- only known tissue schizonticide; can
cause hemolytic anemia in patients w/ Glucose-6-
phosphate dehydrogenase(G6PdH) deficiency
Pyrimethamine -- is a dihydrofolate reductase inhibitor
for the protozoa; useful for prophylaxis
Fansidar -- combination of pyrimethamine + sulfadoxine
Antiprotozoals:
Metronidazole -- gets into CNS well; oral or IV; has a
disulfiram-like effect
Pentamidine -- only IM or aerosol; does not cross BBB, but
will cross the placenta; is the primary drug for P.
carinii in AIDS patients; toxic to -cells of the pancreas;
hepatotoxicity and nephrotoxicity are also seen
Antihelminthic drugs:
Mebendazole -- given orally, not well absorbed; inhibits
the synthesis of microtubules in nematodes; effective
against pinworms, hookworms, and ascariasis
Thiabendazole -- absorbed by GI; blocks microtubule
synth.
Praziquantel -- rapidly hydroxylated in liver; increases
the permeability of the worm to Ca2+; used for
schistosomiasis and other helminthic infections
Pyrantel pamoate -- poorly absorbed from GI; triggers
thre release of Ach in worms, causing a neuro-
muscular blockade & paralysis; primarily used for
Ascaris and pinworm infections
Antiviral Chemotherapy
Uptake inhibitors:
Amantadine -- useful only in Influenza A and rubella
Rimantadine -- lower incidence of effects than
amantadine
* Adverse effects represent CNS actions: insomnia,
nervousness, decreased concentration, depression...
Nucleoside analogues:
Ribavirin -- effective as an aerosol; no serious side-effects
Vidarabine -- used for herpes simplex or varicella zoster;
given topically or IV; is the least toxic of this class
Acyclovir -- anti-herpes; HSV-1 is more sensitive than
HSV-2; resistance due to thymidine kinase-deficient
strains
Ganciclovir -- only use for severe, life-threatening CMV
infections
Azidothymidine (AZT) -- 75% excreted as glucuronide in
the urine
Dideoxyinosine (ddI) -- also used for HIV infections
Protease inhibitors:
Saquinavir …and...others...
* These drugs block aspartyl protease
Endogenous factors:
interferon-
Cancer Chemotherapy
Normal cells sensitive to anticancer drugs:
Bone marrow
Oral mucosa
GI mucosa
Skin follicles
Hair follicles
Gonadal cells
Alkylating agents: -- CCNS drugs
Chloroethyl amines:
Cyclophosphamide -- can be give orally; can cause
hemorrhagic cystitis
Mechlorethamine
Chlorambucil -- can be give orally
Melphalan -- can be give orally
Nitrosoureas: -- can cross the BBB
Carmustine (BCNU)
Lomustine (CCNU) -- can be give orally
Azirdines:
Thiotepa
Triethylenemelamine
Alkylsulfonates:
Busulfan -- can be give orally; can cause adrenal
insufficiency, and pulmonary fibrosis
Platinum compounds:
Cis-platin -- highly nephrotoxic
Carboplatin
Hydrazines:
Procarbazine -- is also highly carcinogenic!
* General toxicities of alkylating agents include: alopecia,
bone marrow suppression, loss of GI mucosa, decreased
gonadal function
Antimetabolites:
Methotrexate -- inhibits dihydrofolate reductase
Mercaptopurine -- nucleoside analogue
Thioguanine -- nucleoside analogue
Fluorouracil -- nucleoside analogue
Cytarabine -- inhibits DNA polymerase in the S phase
Plant alkaloids: -- all are given IV
Vincristine -- block the assembly of microtubules; used in
leukemias, HD and NHLs (...think hodgkin’s)
Vinblastine -- block the assembly of microtubules; used in
testicular and breast cancers, and lymphomas
Etoposide (VP-16) -- increases the degradation of DNA;
useful in small cell lung cancers...as well as others...
Paclitaxel (Taxol) -- stabilizes microtubules, so they
cannot move
Antibiotics:
Anthracyclines: -- intercalate between base pairs in DNA,
thereby blocking DNA and RNA synthesis
Doxorubicin -- broad spectrum
Daunorubicin -- only used for acute leukemias
Mitoxantrone -- useful vs. AML, NHLs, and breast ca.
Dactinomycin
Bleomycin -- only one of these that is CCS; creates oxygen
radicals that fragment DNA
Plicamycin -- unusually, it can also be used to reverse
hypocalcemia...due to its effects on osteoclasts
Mitomycin C -- X-links DNA
* Bleomycin can induce irreversible pulmonary fibrosis
* The anthracyclines can cause a potentially fatal
cumulative cardiotoxicity
Hormone & hormone antagonists:
Prednisone -- sometimes used in combination therapy
Estrogens -- can induce remission of prostatic ca.
Tamoxifen -- estrogen receptor antagonist; used for
estrogen-dependent breast ca.
Flutamide -- anti-androgen used in prostate ca.
Leuprolide -- analogue of GnRH...removes the growth
stimulus for prostate ca.
Aminoglutethimide -- an aromatase inhibitor; useful in the
treatment of metastatic breast ca.