Mechanism Flashcards
replaces clotting factors, fibrinogen, protein S, protein C, and antithrombin
Fresh frozen plasma
disrupt DNA and RNA synthesis, converted to 5-fluorouracil, by fungi
Flucytosine
chlorinated to form nitrenium ion; toxic to bone marrow precursors
clozapine
These drugs form a ternary complex with topoisomerase II and DNA
Doxorubicin, daunorubicin - anthracyclines
inhibits dihydroorotate dehydrogenase, leading to inhibition of pyrimidine synthesis
Leflunomide
Direct Factor Xa inhibitor not requiring antithrombin
Rivaroxaban
inhibits the re-ligation of the broken DNA strands, leading to apoptosis
Doxorubicin, daunorubicin - anthracyclines
concentrates in parasite food vacuoles; increases free heme and toxicity to parasite
Chloroquine
monoclonal to T cells
Alemtuzumab
monoclonal to B cells
rituximab
competitive inhibitors of dihydrofolate reductase
Trimethoprim and pyrimethamine
binds to both the active site and a second site on the thrombin molecule
Lepirudin
Incorporates into the growing viral DNA chain results in premature chain termination due to inhibition of binding with the incoming nucleotide, cytosine
Lamivudine (nucleoside analog of cytosine), Emtricitabine (fluorinated analog of lamivudine)
complex of ferric oxyhydroxide with polymerized dextran; The complex must be phagocytized by (1) cells before iron becomes available
Iron dextran 1. reticuloendothelial
inhibit incorporation of PABA into dihydropteroic acid interfering with folate metabolism
Sulfonamides: sulfamethoxazole and sulfadiazine
binds DNA and chelates iron, leading to formation of free radicals that cause single- and double-strand DNA breaks
Bleomycin
bind to antithrombin and accelerate the rate at which it inhibits various coagulation proteases, but less effective in inhibiting thrombin
Enoxaparin: low molecular weight heparin
Delivered to transferrin more readily
Sodium Ferric gluconate and iron sucrose
active triphosphate derivative inhibits DNA polymerase, DNA primase, DNA ligase, and ribonucleotide reductase, and is incorporated into DNA and RNA
Fludarabine (antimetabolite, purine analog)
drugs bind β-tubulin blocking its ability to polymerize with α-tubulin into microtubules
Antimitotic drugs - Vincristine and vinblastine (vinca alkaloids)
concentrates in parasite food vacuoles; increases free heme and toxicity to parasite
Amodiaquine
Active drug = Cycloguanil, a triazine metabolite
Proguanil
inhibits vitamin K epoxide reductase which is the enzyme that regenerates reduced vitamin K; action occurs in liver
warfarin
inhibits synthesis of phosphoribosylamine by inhibiting phosphoribosylpyrophosphate synthetase and phosphoribosylpyrophosphate aminotransferase
Mercaptopurine (antimetabolite, purine analog)
bind only to the active site of thrombin
Argatroban and dabigatran
bind competitively to plasminogen blocking the binding of plasminogen to fibrin and subsequent conversion fo plasmin
Aminocaproic acid; Tranexamic acid
The false nucleotide also causes DNA damage upon intercalation
Mercaptopurine (antimetabolite, purine analog)
“Erythrocytic forms of all four human malarial species Folate synthesis blockade ‐ selective ↓ of plasmodial dihydrofolate reductase activity”
Pyrimethamine Proguanil
displaces the repressor, activating the differentiation program, and promoting degradation of the PML-RAR- fusion gene
Tretinoin
“Active against hepatic-stage schizonts Gametocidal “
Primaquine
Blocks IL-1-induced metalloproteinase release from synovial fluid; used for RA patients
Anakinra
block the enzyme lanosterol 14-α-demethylase inhibiting the conversion of lanosterol to ergosterol
azoles
incorporation into RNA inhibits RNA function, RNA processing, and mRNA translation
Fludarabine (antimetabolite, purine analog)
Alkaloid from bark of cinchona tree Rapid-acting, highly effective schizonticide against all four human malaria parasites Gametocidal against P. vivax and P. ovale but not P. falciparum
Quinine and Quinidine
blocks calcineurin and inhibits IL-2, IL-3; IL-4, IFN-γ synthesis
Tacrolimus (FK506)
Incorporates into the growing viral DNA chain results in premature chain termination due to inhibition of binding with the incoming nucleotide, adenosine
Tenofovir (nucleotide analog of adenosine)
increases drug exposure, thereby prolonging the drug’s half-life and allowing reduction in frequency; in addition, thegenetic barrier to resistance is raised
Ritonavir
reduced to tetrahydrofolic acid which acts as an acceptor of one-carbon units
folate
causes release of factor VIII and vWF from endogenous endothelial storage site
DDAVP (desmopressin)
inhibits fungal mitosis by interacting with polymerized microtubules
Griseofulvin
potent inhibitor of DNA polymerase, both in replication and repair; the triphosphate form competes with the physiological substrate deoxycytidine 5’-triphosphate (dCTP) for incorporation into DNA by DNA polymerases.
Cytarabine (antimetabolite, a cytidine analog)
bind directly to reverse transcriptase resulting in allosteric inhibition of RNA- and DNA-dependent DNA polymerase
Nonnucleoside: Efavirenz
vitamin K1 - found in green leafy vegetables
Phytonadione
causes a permanent conformational change in antithrombin
fondaparinux
block HIV-1 integrase activity, preventing viral DNA from integrating with cellular DNA
Integrase inhibitor: raltegravir
Binds specifically and selectively to CCR5
Penetration blocker: Maraviroc
competitively binds to the ATP binding site on the bcr-abl which inhibits phosphorylation of proteins involved in CML clone proliferation
Tyrosine kinase inhibitor - Imatinib
prodrug that is converted in the liver to MTIC which interrupts DNA replication by causing methylation of guanine
Dacarbazine
S-FKBP complex leads to inhibition of mTOR
sirolimus
inhibits dihydrofolate reductase
Methotrexate
have lympholytic effects and are able to suppress mitosis in lymphocytes
Glucocorticoids - Prednisone, Dexamethasone
inhibits reverse transcriptase by competing with endogenous deoxynucleotides (adenosine) for the catalytic site of the enzyme
Tenofovir (nucleotide analog of adenosine)
inosine monophosphate dehydrogenase (IMPDH) inhibitors, leading to inhibition of purine synthesis
MPA or MMF; (Mycophenolic Acid and Mycophenolate Mofetil)
oxidized to form reactive hydroxylamine; toxic to bone marrow precursors
dapsone
Also required for the active forms of proteins C and S
Phytonadione
“Disrupts plasmodia mitochondria electron transport Acts against Tissue/Erythrocytic schizonts”
“Atovaquone-proguanil aka Malarone”
Xa and IIa inhibitors
heparin and LMWH
production of free radicals following iron catalyzed cleavage of artemisinin endoperoxide bridge in the parasite’s food vacuole inhibition of parasite’s calcium ATPase
Artemisinin
Produced using recombinant DNA technology using cultured cells transfected with the human factor VIII/IX gene
Recombinant factor VIII/IX
catalyzes the hydrolysis of circulating asparagine to aspartic acid and ammonia depriving malignant cells of the asparagine necessary for protein synthesis, leading to cell death
Asparaginase
contain vitamin K-dependent factors II, VII, IX, and X, activated factor VII and IX
Prothrombin complex concentrate (PCC) and activated PCC (aPCC)
These drugs do not compete with nucleoside triphosphates nor require phosphorylation to be active
Nonnucleoside: Efavirenz
bind to antithrombin and accelerate the rate at which it inhibits various coagulation proteases
Unfractionated heparin and fondaparinux
biotransformed into false purine nucleotides which inhibit phosphoribosylpyrophosphate synthetase and phosphoribosylpyrophosphate aminotransferase
Mercaptopurine (antimetabolite, purine analog)
prevent post-translational cleavage of the Gag-Pol polyprotein by protease resulting in the production of immature, noninfectious viral particle
Protease inhibitors: Atazanavir, Darunavir, Ritonavir
potent CYP3A4 inhibitory properties used to “boost” the levels of other protease inhibitors when given in combination, thus acting as a pharmacokinetic enhancer rather than an antiretroviral agent
Ritonavir
Inhibits clot lysis for treatment of oral bleeding because of the high concentration of fibrinolytic enzymes found in saliva
Aminocaproic acid; Tranexamic acid
has a high affinity for ferric iron. Once bound with iron, it is excreted in the urine
Deferoxamine has a high affinity for ferric iron. Once bound with iron, feroxamine is excreted in the urine
Binds to the CD20 antigen on the surface of pre-B cells and mature B cells, resulting in the depletion of B cells from peripheral blood, lymph nodes, and bone marrow
Rituximab
highly reactive alkyl groups that forms covalent bonds between guanines resulting in cross-linking between two DNA strands. DNA cannot be replicated resulting in cell death
Cyclophosphamide
36 amino acid peptide which binds to gp41 inhibiting fusion of HIV with the target cell
Fusion inhibitor: Enfuvirtide
Antibodies against CD25 – the high affinity IL-2 receptor (CD25 – expressed only on activated T-cells)
Daclizumab and Basiliximab
selectively toxic because human cells do not contain β-(1,3)-D-glucan
echinocandins (capsofungin)
Antifibrinolytic
Aminocaproic acid; Tranexamic acid
Effective for patients with adequate endogenous stores of vWF
DDAVP (desmopressin)
selectively toxic because in human cells the major sterol is cholesterol rather than ergosterol
The polyenes, the azoles, and terbinafine
Directly interact with the thrombin molecule; Able to inhibit circulating and clotbound thrombin
Direct thrombin inhibitors: Lepirudin; Argatroban and dabigatran
Down-regulates expression of cytokines IL-1, IL-4 and TNF-α
Glucocorticoids
Binds to ergosterol in fungal cell membranes forming pores or channels
Polyenes: Amphotericin B
non-specific (binds TNF-α and TNF-β) and inhibits both – approved for rheumatoid arthritis
Etanercept
cell-cycle-specific agents blocking cells in mitosis (M phase). Cell division is arrested in metaphase.
Antimitotic drugs - Vincristine and vinblastine (vinca alkaloids)
↓Bacterial protein synthesis (also ↓Protein synthesis in plasmodial species)
Doxycycline
can form radical intermediates, which in turn can react with oxygen to produce superoxide anion radicals which attack DNA and oxidize DNA bases
Doxorubicin, daunorubicin - anthracyclines
integrase strand transfer inhibitor (INSTI)
Integrase inhibitor: raltegravir
blocks calcineurin and inhibits IL-2 synthesis
cyclosporine
inhibits reverse transcriptase by competing with endogenous deoxynucleotides (cytosine) for the catalytic site of the enzyme
Lamivudine (nucleoside analog of cytosine), Emtricitabine (fluorinated analog of lamivudine),
TNF-α-specific inhibitors - approved for rheumatoid arthritis, Crohn’s disease, ulcerative colitis
Infliximab and Adalimumab
Strong blood schizonticidal activity against P. falciparum and P. vivax
Mefloquine
Cofactor in the activation of factors II, VII, IX, and X
Phytonadione
