Chapter 20: Antimicrobial Drugs Flashcards
(32 cards)
Antimicrobials agents
-Treat infectious disease
-(type of) Chemotherapeutic agent- broad term for chemical agents used to treat disease
-Synthetic drugs- substances made by a chemist in a lab
-Antibiotics- substances made by organisms to inhibit or kill microbes (ex. Penicillin (fungus))
History of chemotherapy
-Paul Ehrlich
-Searching for a “magic bullet” for Syphilis
-Salvarsan was an arsenic containing drug that lacked selective toxicity
History of penicillin
-1928- Penicillin produced by the mold, Penicillium- Alexander Fleming
-1940- Howard Florey and Ernst Chain did first clinical trials and put it on the market
Spectrum of activity of Antimicrobial drugs: narrow spectrum
-Narrow-spectrum drugs affect only a select group of microbes
-Ex. Penicillin: Gram-(+) bacteria
-Advantages: no going to destroy normal microbiome, less likely to promote drug resistance
-Disadvantages: have to identify pathogen
Spectrum of activity of Antimicrobial drugs: broad spectrum
-Broad-spectrum drugs affect a large # of microbes
-Ex. Tetracycline- Mycobacteria, gram-(+), gram-(-) bacteria, chlamydia, Rickettsia
-Advantages: do not need to identify pathogen
-Disadvantage: may disrupt normal flora, may promote drug resistance if used for a long period of time
Modes of Action of Antimicrobial Drugs
1) inhibition of cell wall (peptidoglycan) synthesis: penicillins, cephalosporins, bacitracin, vancomycin
2) inhibition of protein synthesis: erythromycin, streptomycin, tetracycline
3) Inhibition of nucleic acid replication and transcription: quinolones, rifampin
4) Injury to plasma membrane: polymyxin B
5) Inhibition of essential metabolite synthesis: sulfonamides, trimethoprim
Inhibitors of wall synthesis
-Contain beta-lactam ring
-Penicillin G (requires inj)
-Penicillin V (orally)
-Semisynthetic penicillins:
-Oxacillin: narrow spectrum, only gram-(+), but resistant to penicillanse
-Ampicillin: extended spectrum, many gram-(-)
-cephalosporins
Antibacterial antibiotics inhibitors of cell wall syntheisis
-Penicillin-resistant penicillins
-MRSA appears
-Extended-spectrum penicllins
-Ampicillim, amoxicillin
-Penicillin + beta lactamase inhibitors
-Amoxicllin + clavulanic acid = Augmentin
-Carbapenems (imipenem)
-Very broad spectrum
Nuclear structure of Cephalosporin and Penicillin compared
-Cephalosporins
-1st-generation: act against Gram-(+) bacteria
-2nd generation: extended spectrum includes gram-(-) bacteria
-3rd generation: includes pseudomonas
Cell wall synthesis inhibitors
-Polypeptide antibiotics
-Bacitracin (neosporin)
-Against Gram-(+)
-Vancomycin
-Narrow spectrum
-Important “last line” against antibiotic resistant S. aureus (MRSA)
-Antimycobacterial antibiotics
-Isoniazid (INH) inhibits mycolic acid synthesis
-Ethambutol inhibits incorporation of mycolic acid
Antibacterial antibiotics inhibitors of protein synthesis
-Chloramphenicol
-Broad spectrum
-Bone marrow suppression
-Aminoglycosides
-Streptomycin- broad spectrum; including mycobacteria
-Gentamicin- broad spectrum; including Pseudomonas
-Erythromycin
-Gram-(+)
-Legionellosis
-Mycoplasmal
-No cell wall
-Pneumonia
-No cell wall
-Azithromycin
-Dosage- 5 days
-Better penetration
-Tetracycline
-Broad spectrum
-Including Chlamydia and Rickettsia
-Animal Crossing feed additives
-Doxycycline
-Glycyclines
-Structurally similar to Tetracycline
-Broad spectrum
-MRSA and Acintobacter baumanii
-Tigecycline (Tygacil)
Antibacterial antibiotics injury to plasma membrane
-Polymyxin B
-Combines w/ phospholipids to disrupt bacterial membrane
-Topical
-Pseudomonas aeruginosa
-Daptomycin
-To treat MRSA
Anitmicrobial antibiotic inhiitobors of nucleic acid synthesis
-Rifamycin (Rifampin)
-Inhibit RNA synthesis
-Antituberculosis
-Quinolones and fluroquinolones (ex. Ciprofloxacin)
-Inhibit DNA replication (gyrase)
-UTI’s
Competitive inhibitors of essential metabolite
-Sulfanamides (sulfa drugs)
-Competitivelty ihinit folic acid syntheis
-Broad spectrum
-Trimethropim and Sulfamethoxazole
-Synergism
-Broader spectrum
-Reduces emergence of resistant strains
Antifungual drugs of inhibition of Erosterol synthesis
-Polyenes
-Amphotericin B
-Used for systemic mycoses
-Azoles
-Miconazole, Triazole, Ketoconazole for dermatomycoses
Antiviral drugs: enzyme inhibitors
-Neuraminidase inhiitors
-influenza : Ostelamivir (Tamiflu), Zanamivir (Relenza)
-Alpha INF: Hep B, C
-Nucleoside or nucleotide analogs, protease inhibitors, integrase inhibitors, fusion inhibitrs
-HIV
Antiprotozoal drugs
-Chloroquine
-Inhibit DNA synthesis
-Metronidazole
-Interfere w/ metabolism
-Trichomonas
-Giardia
-Mebendazole
-Inhibit nutrient absorption
-Intestinal roundworms
-Pyrantel pamoate
-Neuromuscualr block
-Intestinal roundworms
Tests to guide chemotherapy
-Disk-diffusion method
-Kirby-bauer test
-S, I, R- qualitative results
-Broth dilutions
-Minimal Inhibitory Concentration (MIC)
-quantitative method for determining the lowest concentration of an antimicrobial agent required to inhibit visible microbial growth
-Minimal amount in micrograms/mL that is going to inhibit growth of microorganism- quantitative
-Important in sepsis
Antibiotic resistance mechanisms
-Spontaneous mutations
-Hereditary drug resistance R factors on plasmids
-self-replicationing
-Transferred by conjunction
-Enzymatic destruction or inactivation of the drug
-Prevention of penetration to the target site w/in the microbe (porin- gram-(-) cell wall)
-Block entry
-Alteration of the drug’s target sits (modified penicillin-binding protein)
-Rapid efflux (ejection)
-Variations of Resistance Mechanism (resistant mutants)
Enzymatic Destruction
-Carbapenems-production
-Beta-lactamase production
Multidrug resistant pumps
-Efflux pumps actively transport drugs out of the cell
-P. aeruginosa, E. coli, S, aureus, S, pneumoniae
Resistance to Antimicrobial drugs
-Persister cells: microbes w/ genetic characteristic allowing for their survival when exposed to an antibiotic
-Superbuds: bacteria that are resistant to large #’s of antibiotics
-Resistance genes are often spread horizontally amount bacteria on plasmids or transposons via conjugation or transduction
Methicillin-Resistant S, aureus (MRSA)
-MRSA contain novel or altered Penicillin Bining Protein (PBP2a)
-Major nosomial pathogen
-Community acquired pathogen
Vancomycin Resistant Enterococci (VRE)
-Contain a vanA gene cluster on a plasmid encode for high level resistance to vancomycin
-Resistance genes have spread widely
-Major focus of infection control
