Antimicrobials Flashcards
Penicillin
Binds to transpeptidases involved in the synthesis of cell-wall peptidoglycans in gram-positive bacteria.
Can be degraded by β-lactamases secreted by bacteria
Penicillin-like drugs include amoxicillin and ampicillin.
Cephalosporins are another class of β-lactams.
Tetracycline
Used against gram-negative bacteria.
Binds 70S bacterial ribosomes - able to bind RNA and protein sites on the 30S subunit.
Other compounds targeting bacterial ribosomes include aminoglycosides (streptomycin), chloramphenicol, and macrolides (erythromycin).
Quinolones: levofloxacin, ciprofloxacin
Used against gram-negative bacteria.
DNA gyrase (topoisomerase II) and topoisomerase IV inhibitors - prevent DNA transcription, replication and repair.
Quorum-sensing pathways
Quorum sensing is involved in bacterial communication for biofilm and colony formation.
Potential target to combat antibiotic resistance.
Pore forming peptides
Form a membrane attack complex and cause cell lysis.
As bacterial membranes differ from human ones, these can be specifically targeted.
Bacteriophages
Potential treatment of bacterial infections.
HIV treatment: enfuvirtide, fostemsavir
CD4 attachment inhibitors - prevent entry into host cells
HIV treatment: Maraviroc
CCR5 inhibitor - prevents entry into host cells
Reverse transcriptase inhibitors
Used against retroviruses, prevent conversion of viral RNA into DNA.
Can be nucleosides, nucleotides or non-nucleotides.
HIV protease inhibitors
Ritonavir and Saquinavir
Ritonavir can also be used for SARS-CoV-2
HIV integrase inhibitors
Raltegravir, Dolutegravir, Elvitegravir
SARS-CoV-2 treatment: Sotrovimab
ACE2 receptor inhibitor
Blocks viral entry into host cells
SARS-CoV-2 treatment: molnupiravir, remdesevir
RNA replication inhibitors
SARS-CoV-2 protease inhibitors
Paxlovid and the HIV inhibitor Ritonavir
Quinine
Malaria treatment
Interferes with Plasmodium’s ability to use haemoglobin
Inhibits purine nucleoside phosphorylase, resulting in deficient RNA, DNA and protein biosynthesis
Chloroquine
Malaria treatment
Heme can produce ROSs that damage DNA and proteins - needs to crystallise following haemoglobin digestion to become safe.
Chloroquine prevents heme crystallisation →cell lysis and damage to the Plasmodium inside.
Resistance can develop as the transporter PfCRP can pump the drug out of the cell.
Artemisinin
Malaria treatment
Prodrug of dihydroartemisinin
Acts at the same stage of parasitic development as chloroquine
Produces free radicals when interacting with heme and acts on many targets at different stages
Clotrimazole (imidazole)
Candida (yeast) infections
Inhibits the fungal enzyme 14α-demethylase, conversion of lanosterol to ergosterol, and synthesis of membrane lipids
Affects cell wall permeability
Fluconazole (triazole)
Candida (yeast) infections
Inhibits the fungal enzyme 14α-demethylase and ergosterol formation
Better specificity
Terbinafine (Lamisil)
Athlete’s foot
Inhibits ergosterol synthesis by inhibiting squalene epoxidase, which catalyses the conversion of squalene to lanosterol
Parasitic worm treatments: mebendazole, albendazole
Disrupt tubulin in microtubules, preventing replication
Parasitic worm treatments: pyrantel, morantel, levamisole
Act on nAChRs to paralyse the worm
Parasitic worm treatments: ivermectin, doramectin
Act on Glutamate-gated chloride channels (GluCls) to paralyse the worm.
Parasitic worm treatments: Praziquantel
Induces calcium influx, paralysing the worm.
Parasitic insects
Can be killed with antihistamines specific to insect histamine
