Anti-infective Agents Flashcards
Germicidal agent
Kills the microorganism
Germistatic agent
Prevents the microorganism’s growth
Disinfectant
Destroys “bugs” on inanimate objects
Antibacterial properties of alcohols
Primary alcohols: antibacterial properties increase with molecular weight (through octanol)
Branching decreases antibacterial properties
Phenols
One of the first classes of compounds to be used as a surgical antiseptic
Today, fairly obsolete (skin irritants)
Alkyl, aryl, and halogen substitution increase potency
Oxidizing agents
Exert activity through generation of oxygen or oxygen radicals in tissues
Especially effective against anaerobic bacteria
Topical treatments (ex-benzoyl peroxide)
Iodine
Inhibits proteins: iodinates aromatic amino acid residues and oxidizes sulfhydryl groups (cysteine)
Hypochlorous acid (HClO)
Usually exist as hypochlorite salts
Chlorinates nitrogen atoms in amides and oxidizes sulfhydryl groups in proteins
Cationic surfactants
Detergents, which can be used as anti-infectives
Common structural features: quaternary nitrogen atom and long aliphatic tail
Preservatives
Compounds added to foods, drugs, and cosmetics that prevent microbial contamination
Typically effective at low concentrations and non-toxic to host
2 types of fungal infections
Superficial (ringworm, skin, and nail infections)
Deep-seated (systemic infections)
Source of selectivity for targeting fungal infections
Fungi use ergosterol in their lipid bilayers, whereas humans use cholesterol
Topical antifungal agents
Fatty acids (resemble natural antifungal on skin) Phenols and derivatives: interfere with cell membrane integrity and function in fungi
Antimetabolites
Drugs that prevent the production or degradation of a normal cellular metabolite
Flucytosine
Nucleoside antifungal that is used to treat systemic infections
Converted into 5-fluorouracil in the body, preventing synthesis of thymine (and thus, DNA)
2 classes of antifungal antibiotics
Polyenes
Griseofulvin
Natural products: hard to synthesize
Allylamine antifungals
Act by interfering with ergosterol biosynthesis: inhibit squalene epoxidase while leaving mammalian enzymes unaffected
Azole antifungals
Broadly effective against many topical and systemic infections
At low concentrations, inhibit fungal cell growth (inhibit membrane-bound enzymes)
At high concentrations, kill fungal cells (cause damage to cell membranes)
Quinolones
Synthetic antibacterial agents derived from nalidixic acid
Inhibit bacterial DNA synthesis via inhibition of DNA gyrase
Quinolone SAR
Must have alkyl group bound to nitrogen
Adding substituents to carbon atom to the right of the nitrogen removes activity
Adding a fluorine at C6 (4 carbons to the left of the nitrogen) increases activity
First developed effective systemic agents for bacterial infections
Sulfonamides (sulfa drugs; original drug: prontosil)
How sulfonamides work
Inhibition of tetrahydrofolate (THF) coenzyme synthesis from pteridine diphosphate and p-aminobenzoic acid (PABA)
Limitations of sulfonamides
Can cause crystalluria (crystallizing in kidney, damaging it)
Have been overprescribed: some bacterial strains are resistant to it (can increase synthesis of PABA, competing with the drug, or can pump the drug out faster than it can enter)
Sulfonamide SAR
Aniline ring is necessary for activity (cannot be alkylated)
Sulfonamide portion of molecule (SO2 and amine) is most likely the active structure
Trimethoprim
Antibacterial agent: inhibits dihydrofolate reductase (enzyme required for synthesis of tetrahydrofolate coenzyme)
Sulfones
Less effective than sulfonamides, but effective in treating leprosy
Dapsone is the only one with appreciable clinical utility
