ID Final: Harrold Cumulative Material-MOAs

Isoniazid

inhibits mycobacterium cell wall synthesis by interfering with the synthesis of mycolic acid

Ethambutol

inhibits arabinosyl transferase

Rifampin

binds to the β-subunit of DNA-dependent RNA polymerase (DDRP), thus blocks DNA

Pyrazinamide

decreases pH within the M. tuberculosis organism, preventing its growth

Bedaquiniline

inhibits the mycobacterial ATP synthase

Pretomanid

generates ROS (including nitric oxide) to inhibit cell wall synthesis and cause respiratory poisoning in non-replication bacteria

Polyene Antibiotics (amphotericin B and nystatin)

bind to ergosterol and form pores/channels

Imidazoles/Triazoles/Azoles

inhibits the synthesis of ergosterol, specifically, they inhibit the demethylation of lanosterol

Griseofulvin

binds to tubulin, disrupts the mitotic spindle, and inhibits mitosis

Flucytosine

inhibits thymidylate synthetase, therefore decreasing the formation of dTMP and stopping fungal cell DNA replication

Allyamines (Naftidine, Terbinafine, Butenafine)

inhibits squalene epoxidase

Sterol 14α-demethylase, squalene epoxidase

both azoles and allyamines inhibit the biosynthesis of ergosterol

azoles → inhibit ___ ___-___

allyamines → inhibit ___ ___

Tolnaftate

allyamines (inhibits squalene epoxidase)

Ciclopirox

production of reactive oxygen species (ROS) due to its ability to chelate iron (Fe3+)

Tavaborale

inhibiting leucine tRNA synthetase

Echinocandins (Caspofungin, Micafungin, Anidulafungin)

inhibiting the enzyme Glucan Synthase, therefore inhibiting the fungal synthesis of 𝛽(1,3) D-glucan

Ibrexafungerp

same MOA as echinocandins, to inhibit glucan synthase

Nueraminidase Inhibitors (Oseltamivir, Zanamivir, Peramivir)

mimic the sialic acid transition state to inhibit the enzyme nueraminidase

Baloxavir Marboxil

inhibits the endonuclease activity of polymerase acidic (PA) protein, preventing viral gene transcription and replication

Nirmatrelvir

inhibits SARS-CoV-2 main protease (Mpro), preventing viral replication

metabolism, duration

Why is ritonavir used in combination with nirmatrelvir?

-Ritonavir inhibits CYP3A4, which prevents the ___ of nirmatrelvir, increases its plasma levels, and increases its ____ of action.

Molnupiravir

N4-hydroxycytidine (NHC) triphosphate is phosphorylated to its active triphosphate, incorporated into SARS-CoV-2 RNA, results in accumulation of errors

Remdesivir

inhibits SARS-CoV-2 RNA dependent RNA polymerase (RDRP)

Casirivimab, Imdevimab

block attachment of the human ACE 2 receptor to SARS-CoV-2

JAK Inhibitors (baricitinib, tofacitanib)

prevents the phosphorylation of key proteins, therefore inhibiting signal transduction, cause immune activation and inflammation?

IL-6 Inhibitors (tocilizumab, sarilumab)

preventing systemic inflammation and hypoxemic respiratory failure

Dexamethasone

decreases inflammation by suppression of neutrophil migration

Acyclovir, Valacyclovir

immediate chain termination via inhibition of viral DNA polymerase due to a lack of a 3'-OH group

Famciclovir, Penciclovir

incorporated into the DNA chain and due to the conformational flexibility making the 3'-OH groups much less available to form bonds, inhibit DNA synthesis

Trifluridine

2 metabolites--the monophosphate inhibits thymidylate synthetase; the triphosphate incorporated into DNA and alters normal hydrogen bonding and base pairing

Docosanol

prevents viral entry into target cell by preventing the fusion between the viral particle and the human cell

Ribavirin

potent competitive inhibitor of IMP dehydrogenase to ↓[GTP], inhibits viral-specific RNA polymerase by mimicking GTP or ATP, inhibits viral-specific mRNA capping enzyme?

Palivizumab

neutralizing and fusion-inhibitory activity against RSV

Tinidazole

nitro group that undergoes oxidation/reduction reactions to generate ROS

Nitazoxanide

block the parasitic enzyme pyruvate:ferredoxin oxidoreductase

Paromomycin

binds to the 30S ribosome and freezes the initiation complex, lead to the “nonsense” proteins

Albendazole, Mebendazole

inhibit fumarate reductase, bind to tubulin and cap the association end

Triclabendazole

absorbed by the tegument (outer covering of the parasite) resulting in decreased resting membrane potential and inhibition of tubulin function as well as protein/enzyme synthesis?

Ivermectin

decreases motility of microflaria, increases Cl- influx or acts as GABA agonist, causes the degeneration of microfilariae in utero resulting in a reduction of microfilariae produced/released

Praziquantel

What drug's MOA depends on the parasite:

in helminths: muscle contractions and paralysis because of an influx of calcium

in intravascular worms: damages the worm tegument and exposes antigens

Permethrin

inhibits sodium influx through nerve cell membrane channels in parasites

Abametapir

metalloproteinase inhibitor, decreases egg development and survival of lice

Quinolones

forms π-π stacking bonds, therefore exposing the toxic heme to the Plasmodium

Atovaquine

selectively inhibits plasmodium mitochondrial respiratory chain at Complex III due to its structural similarity to coenzyme Q

Proguanil

inhibits dihydrofolate reductase

Artesunate

peroxide group that reacts with the Fe2+ on heme; lethal carbon radicals