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28 Cards in this Set

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  • Back
expression of P450 enz's is controlled by
AHR - aryl hydrocarbon receptor
CAR - constitutive androstane receptor
SXR/PXR - xenobiotic receptor (protection against exogenously derived aromatic compounds and toxins)
xenobiotic response is regulated by what transcription factor?
SXR --> induces P450 enz's; P-glycoprotein (MDR gene); other catabolic enz's
pharmacological interaction is a response at the level of
receptor
ie. MAOI and SSRI
metabolic interaction involves
metabolic enz's or MDRs
1. allopurinol enhances mercaptopurine (inhib XO)
2. barbituates increase metabolism of doxirubicin
3. rifampin acts on SXR to inc P450 expression and P-glycoprotein
therapeutic window ED50/LD50, a high value, close to 1?
high value = safe drug at effective doses

~1 = narrow window, toxic
immediate drug allergy (Type I) - drug attaches to?
RBC or protein
type I sensitivity drug allergy is mediated by
IgE and mast cell degranulation
vascular sm muscle relaxation, inc vascular permeab, hypotention, bronchioconstriction,
type II sensitivity drug allergy is characterized by
immune-mediated destruction of blood cells elicited by bound drug
type II sensitivity drug allergy may involve
IgM and IgG and cellular components,
ie. lupus from hydralazine
hemolytic anemia from metyldopa
TPP from quinidine
type III sensitivity drug allergy involves
serum sickness, vasculitis
symptoms of type III drug sensitivity
erythematous skin eruptions, arthralgia, arthritis, and fever
type III drug sensitivity - mediated by
Ab-mediated, IgM and IgG, complement fixation, lymphocyte infiltration
ie. sulfonamides, thiouracil, anticonvulsants
alkylating agents function by
covalently attach to DNA, proteins and disrupt replication
alkylating agents - ie.
cyclophosphamide, chlorambucil, busulfan, cisplatin, carmustine (nitrosourea)
anti tumor antibiotics
ie.
intercalate DNA
doxorubicin, daunorubicin, dactinomycin
plant alkaloids fxn by
disrupt mitotic appartus, including microtubule assembly and fxn
ie. plant alkaloids
vincristine (ITP, lupus),
vinblastine (ITP, lupus)
etoposide
paclitaxel
antimetabolites fxn by
inhibiting enzymatic steps related to syn and processing of nucleotides and folates
ie. antimetabolites
thioguanine, mercaptopurine, fluorouracil, cytosine arabinoside (ara-C), methotrexate (RA, primary biliary cirrhosis, myasthenia gravis, etc)
major side effects of chemotherapeutic drugs
Bone Marrow suppression (myelosuppression)
Increased risk of infections
Leutropenia
Thrombocytopenia
noteworthy rxns:
cisplatin
anaphalytic rxns
noteworthy rxns:
etoposide
acute allergic drug rxns
busulfan
uses:
side effects:
uses: CML, PV, essential thrombocytopenia
SE: BILT, pulm fibrosis, adrenal insufficiency, skin toxicity
clorambucil
uses:
side effects:
uses: CLL, macroglobuliemia, PV
SE: BILT, leukemogenic, hepatotoxicity
cyclophosphamide
uses:
side effects:
uses: ALL, CLL, non-Hodgekin's lymphoma, MM, PV
SE: BILT, alopecia, N/V, hepatotoxicity, hemorrhagic cystitis
hematopoietic GF's
EPO
uses:
SE:
uses: anemia (1' or 2' to treatments), myelodysplastic disorders, bone marrow malignancies, chronic renal failure
SE: rapid rise in hematocrit, HTN, thrombotic complications
C-GSF or CM-GSF
uses:
SE:
uses: neutropenia, increase neutrophils following myelosuppressive therapies, chemo
SE: induration at site of injection, cytokine syndrome, skin rash, bone pain, vasculitis
IL-11
uses:
SE:
megakaryocyte GF
uses: increase platelets, neutrophils, thrombocytopenia
SE: cytokine syndrome, dizziness, cardiovascular effects (fluid retention), anemia, dyspnea, atrial arrythmias