MOA's and resistances to ALL categories - bacterial, fungal, viral, and parasitic

V: MOA of entecavir?

guanosine analog that is a competitive inhibitor of HBV DNA polymerase

V: MOA of IFN-a?

Binds to receptors on cell surface + initiates cytokine signaling in target cells to clear virus and boost immune activities

V: MOA of acyclovir?

Reduced to triphosphate form and is competitive with dGTP for viral DNA polymerase and chain termination following incorporation into viral DNA (block viral DNA replication)

V: MOA of tenofivir disoproxil?

Adenosine nucleoside that inhibits reverse transcriptase of HIV/HBV causing premature chain termination

V: MOA of ribavirin?

Guanosine nucleoside causing direct inhibition of HCV enzymes, decrease GTP, and promotes lethal mutagenesis of viral RNA

V: MOA of ledipasvir?

NS5A inhibitor that is a substrate + inhibitor of drug efflux transporter P-Gp/BCRP

V: MOA of sofosbuvir (prodrug)?

NS5B inhibitor - UTP analog is incorporated into viral RNA by RNA polymerase causing chain termination

V: MOA of nevirapine and rilpivirine?

Target viral reverse transcriptase

V: MOA of ritonavir, darunavir, and atazanavir?

Target HIV protease post-translational process preventing new infection

V: MOA of amantadine and rimantadine?

Block viral M2 proton ion channel inhibiting uncaring of viral RNA within infected host cells

V: MOA of baloxavir and marboxil (prodrug)?

Interferes with viral RNA transcription + blocks virus replication

V: MOA of oseltamivir and panamivir?

Competitively/reversibly inhibit neuraminidase

V: MOA of dolutegravir?

Targets HIV integrase and blocks integration of viral DNA into host genome preventing viral replication

V: MOA of maraviroc?

Inhibitor of CCR5 co-receptor which hinders effective attachment of virus to CD4+ T-cells

F: MOA of griseofulvin?

Interrupts fungal microtubule function/inhibits fungal mitosis

F: MOA of caspofungin and micafungin?

Irreversibly inhibits fungal beta 1,3-glucan synthesis which impairs cell wall intergrity, increases permeability and causes cell death

F: MOA of azoles?

Fungal CYP enzyme inhibition which decreases ergosterol synthesis leading to inhibition of fungal membrane assembly

F: MOA of amphotericin B?

Binds to ergosterol forming pores in cell membrane that allows leakage of K+, Cl-, Na+, H+ and water influx causing cell death

F: MOA of flucytosine?

Taken by fungal cells via cytosine permeate and converted intracellularly to 5-FU to FdUMP to FUTP to DNA synthesis and RNA function inhibition

P: MOA of chloroquine?

Concentrated in parasite digestive vacuoles, preventing heme from being converted into hemozoin causing buildup of free heme which is toxic to parasite

P: MOA of mefloquine?

Strong blood schizonticide

P: MOA of doxycycline?

Inhibitor of bacterial protein synthesis effective against erythrocytic schizonts

P: MOA of pyrimethamine?

Inhibits dihydrofolate reductase (DHFR) in malaria parasites

P: MOA of atovaquone?

Targeting parasite's cytochrome bc1 (cytbc1) complex in mitochondria

P: MOA of proguanil?

Selectively inhibits malarial DHFR leading to depletion of folate, therefore halting DNA synthesis - also enhances atovaquones mitochondrial toxicity

B: MOA of fosfomycin?

Inhibits MurA, an enzyme that catalyzes initial step of cell wall synthesis

B: MOA of metronidazole?

Prodrug, activated by organism that disrupts DNA structure and replication

B: MOA of rifampin?

Inhibits RNA synthesis by binding to DNA-dependent RNA polymerase

B: MOA of ciprofloxacin, moxifloxacin and levofloxacin?

Inhibit topoisomerase IV and DNA gyrase

B: MOA of SMX/TMX?

S: Mimics PABA to inhibit dihydropteroate synthetase T: Inhibits DHFR

B: MOA of nitrofurantoin?

reduced primarily by bacterial enzymes --> damages bacterial DNA

B: MOA of gentamicin, tobramycin, amikacin, streptomycin and neomycin?

Passively transported through porins, then actively transported into cytoplasm (oxygen-dependent) where they bind to 30S ribosomal subunit which causes misreading of mRNA + causes premature detachment of amino acid chain

B: MOA of tetracycline, minocycline and doxycycline?

Block "A" binding site on 30S unit, reversible, causes tRNA to be unable to bind to start protein synthesis

B: MOA of erythromycin, clindamycin and azithromycin?

Binds near P site on 50S which prevents tRNA moving from "A" site to "P: site and protein synthesis is stopped

B: MOA of beta lactams?

Bind to transpeptidases + inhibit cross-linking leading to cell wall synthesis inhibition

B: MOA of daptomycin?

Inserts tail into the cytoplasmic membrane which leads to loss of K+ from cells and membrane depolarizes which leads to cell death - works SLOWLY

B: MOA of vancomycin?

Weakens peptidoglycan + cell is susceptible to lysis - works SLOWLY

Resistance of acyclovir due to?

virus mutations in viral kinases and/or viral DNA polymerases

Resistance of caspofungin and micafungin due to?

Candida glabrata in immunocompromised pts

Resistance with amphotericin B due to?

Interruption of binding of AmpB to ergosterol leading less modified ergosterol = reduced binding affinity

Resistance with chloroquine due to?

Mutations in a putative efflux transporter (PfCRT)

Resistance with pyrimethamine due to?

Mutations in the parasite enzyme of dihydrofolate reductase

Resistance with atovaquone due to?

Mutations of the cytochrome bc1 (cytbc1)

Resistance with rifampin due to?

Single-point mutation that alters binding site on RNA polymerase, esp when used as a monotherapy

Resistance with cipra, levo and moxa due to?

Mutations in DNA gyros or topoisomerase IV at binding sites, proteins can bind + protect topoisomerase or active transport of drug out of cell

Resistance with sulfonamides due to?

Overproduction of PABA

Resistance with aminoglycosides due to?

enzymatic inactivation, porin down regulation or deletion and/or alteration in binding site

Resistance with beta lactams due to?

Alterations in PBP, change in porin channels and beta-lactamases

Resistance with daptomycin due to?

Cell wall thickens

Resistance with vancomycin due to?

VRE occurs when D-ala is replaced with D-lac - no binding site