Antimicrobial Drugs manual flashcards

Chemotherapy

• not just cancer treatment

• drugs specific in : cancerous cells, cancerous tissues, infectious microorganisms

Paul Ehrlich

• discovery of compound 606

• antimicrobial agent that proved to be an effective syphilis treatment

Alexander fleming

• discovered a naturally produced antimicrobial

• Penicillin

• 1928

Howard Florey and Ernst Chain

• discovered how to scale up penicillin production

• purified it and showed its efficiency as an antimicrobial

• did human trials in 1940s

Bacteriostatic

• reversible inhibition of bacterial growth

• bacterial growth can restart after elimination of drug

Bactericidal

• kill the target bacterial

-static vs -cidal is selected based on?

• type of infection

• immune status of pt

Broad spectrum antimicrobial use can lead to ….

superinfection

How does superinfection occur?

• normal microbiota keeps opportunistic pathogens in check

• broad-spectrum antibiotics kill non resistant cells

• drug resistant pathogens proliferate and cause superinfection

drug administered IV

• the plasma concentration peaks quickly then gradually decreses

drugs administered orally or intramuscularly

• it takes longer for the concentration to reach peak then decreases

B-lactams, penicillin’s, cephalosporins, monobactams, carbapenems

• target: Penicillin-binding proteins

• action: inhibit cell wall biosynthesis

Glycopeptides

• target: peptidoglycan subunits

• action: inhibit cell wall biosynthesis

Bacitracin

• target: peptidoglycan subunit transport

• action: inhibit cell wall biosynthesis

Aminoglycosides, tetracyclines

• target: 30s ribosomal subunit

• action: inhibit biosynthesis of proteins

Macrolides, lincosamides, chloramphenicol, oxazolidinones

• target: 50s ribosomal subunits

• action: inhibit biosynthesis of proteins

Polymyxins B, colistin, daptomycin

• target: lipopolysaccharide, inner and outer membranes

• action: disrupt membranes

Rifamycin

• target: RNA

• action: inhibit nucleic acid synthesis

Fluoroquinolones

• target: DNA

• action: inhibit nucleic acid synthesis

Sulfonamides, trimethoprim

• target: folic acid synthesis enzyme

• action: inhibit metabolic pathways (antimetabolites)

Isonicotinic acid hydrazide

• target: mycolic acid synthesis

• action: inhibit cell wall synthesis

Diarylquinoline

• target: Mycobacterial ATP synthase

• action: Mycobacterial ATP synthase inhibitor

penicillin given orally

• amoxicillin

• penicillin V

• sometimes amipicillin

Penicillin given parenterally

• penicillin G

• methicillin

• sometimes ampicillin

Penicillin G and V

• natural

• narrow spectrum

• against gram-positive and a few gram-negative bacteria

Amoxicillin and Ampicillin

• semisynthetic

• narrow spectrum

• against gram-positive but with increased gram-negative spectrum

Methicillin

• narrow spectrum

• against gram-positive bacterial only (including strains producing penicillinase)

Cephalosporin

• natural

• narrow spectrum

• similar to penicillin but increased gram-negative spectrum

First generation cephalosporins

• semisynthetic

• narrow spectrum

• similar to cephalosporin C

second generation cephalosporins

• semisynthetic

• narrow spectrum

• increased gram-negative spectrum compared w first gen

Third and fourth generation cephalosporins

• semisynthetic

• broad-spectrum

• against gram-positive and gram-negative bacteria

• including some b-lactamase producers

Fifth generation cephalosporins

• semisynthetic

• broad spectrum

• against gram-pos and gram-neg bacteria

• including MRSA

Drugs that inhibit bacterial cell wall synthesis

• penicillin

• cephalosporins

• Monobactams

• Carbapenems

• Glycopeptides

• Bacitracin

Monobactams

• semisynthetic

• ex: aztreonam

• narrow spectrum: against gram-neg (some b-lactamase producers)

Carbapenems

• semisynthetic

• ex: imipenem, meropenems, doripenem

• broadest spectrum of b-lactams: against gram-pos and gram-neg and many b-lactamase producers

Glycopeptides

• inhibit cell wall synthesis

• natrual

• narrow spectrum: against gram-positive bacteria, including MRSA,

• ex vancomycin

Bacitracin

• inhibits cell wall synthesis

• natural antibiotic

• broad spectrum: against gram-positive and negative bacteria

Chloramphenicol, macrolides, lincosamides

• classes of antibiotics that inhibit protein synthesis.

• bind to 50s ribosomal subunits

• bacteriostatic

• prevent peptide bond formation

• stop protein synthesis

Aminoglycosides

• class of antibiotics that inhibit protein synthesis.

• bind to 30s ribosomal subunits

• bactericidal

• broad spectrum

• cause misreading of mRNA

• impair proofreading→ production of faulty proteins

Tetracyclines

• class of antibiotics that inhibit protein synthesis.

• bind to 30s ribosomal subunits

• bacteriostatic

• prevent tRNA attachment

• inhibit protein synthesis

Polymyxins

• kill cells through disruption of outer cell membrane and cytoplasmic membrane

• gram-negative bacteria

• B: topical to prevent wound infections

• E: oral or IV

Lipopeptide

• inserts into cytoplasmic membrane, disrupting and killing cell

• gram-positive bacteria

• complicated skin and skin structure infections

Rifamycin

• inhibits bacterial RNA polymerase activity

• blocks transcription- kills cell

• ex: rifampin

• used for therapy for tuberculosis tx

Fluoroquinolones

• inhibits activity of DNA gyrase and blocks DNA replication -killing cell

• ex: ciprofloxacin, ofloxacin, moxifloxacin

• broad-spectrum antibiotics used for various infections

• effective against both gram-positive and gram-negative bacteria

• used for skin and systemic infections

Sulfonamides and trimethoprim

• antimetabolites

• interfere in bacterial synthesis of folic acid by blocking purine and pyrimidine biosynthesis

• inhibiting bacterial growth

Antimetabolite drugs

• sulfonamides

• sulfones

• folic acid synthesis target

Sterols function in antifungal drug development

• sterol in humans: cholesterol

• sterol in fungi: ergosterol

• ergosterol good target for antifungal drug development

Imidazole’s, triazoles, Allylamines

• antifungal drugs

• inhibit ergosterol synthesis

• im: skin

• tri: systemic yeast

• ally: skin infections-athletes foot, fingernails, toe

Polyenes

• antifungal

• ex: nystatin-yeast infections, topically: amphotericin B: skin fungal

• bind ergosterol in cell membrane and create spores that disrupt the membrane

Echinocandins

• antifungal

• ex: caspofungin

• inhibit cell wall synthesis

Naphthoquinone

• antiprotozoal

• inhibit electron transport in mitochondria

• used for Malaria, babesiosis, and toxoplasmosis

Sulfonamide

• antiprotozoal

• inhibit folic acid synthesis

• malaria and toxoplasmosis

Nitroimidazoles

• antiprotozoal

• disrupt DNA synthesis

• used for amoebiasis and giardiasis

Quinolines

• antimalarial

• interfere with heme detoxification

• used for malaria treatment

Anthelminthic drugs

• benzimidazoles: inhibit microtubule formation- reduce glucose uptake

• avermectins: block neural transmitting - paralysis and starvation

• Thioxanthones: inhibit RNA synthesis

Antiviral drugs- HIV

• Etravirine: non-nucleoside non competitive inhibition

• Ritonavir: inhibition of protease

• Raltegravir: inhibition of integrase

• Enfuvirtide: inhibition of membrane fusion

Antiviral drugs- influenza

Amantadine, rimantadine: inhibit escape of virus from endosomes

oseltamivir, zanamivir, peramivir: inhibit neuraminidase

Antiviral- herpes sv

acyclovir and vidarabine : nucleoside analog inhibition of nucleic acid synthesis

Antiviral- hepat c

sofosbuvir: nucleoside analog inhibition of nucleic acid synthesis

simeprevir: inhibition of protease

Antiviral: serous enterovirus infection

• pleconaril

• inhibit viral uncoating

Block penetration

• b-lactams

• tetracylines

• fluoroquinolones

Target modification

• fluoroquinolones

• ritamycins

• vancomycin

• b-lactams

• macrolides

• aminoglycosides

inactivation of enzymes

• b-lactams

• aminoglycosides

• macrolides

• rifamycins

Efflux pump

• fluroquinolones

• aminoglycosides

• tetracyclines

• b-lactams

• macrolides