Antimicrobial Drugs and Drug Resistance Flashcards
1
Q
What is Antimicrobial Drugs?
A
- Used when immunization has not occurred and the immune system has
difficulty to eliminate infection- Useful against bacterial infection, very few antivirals are available
- These are compounds that kill or control the growth of microorganisms in
the host- These drugs must display selective toxicity or they will cause damage to the host
2
Q
What is the two broad categories of Antimicrobial Drugs?
A
- Synthetic and natural
- Large number of naturally occurring antibiotics with no clinical use
- Produced by bacteria and fungi
- Large number of naturally occurring antibiotics with no clinical use
- Can be described based on whether they are:
- Bacteriostatic or bacteriocidal
- Broad spectrum or narrow spectrum
3
Q
Cell Wall Active Antimicrobial Drugs
A
- Cell wall active agents offer excellent selective toxicity
- Most widely used class of antibiotics
4
Q
Beta Lactam Antibiotics
A
- Largest Class
- Common feature is the b-lactam ring
- Naturally occurring: produced by Penicillium and Cephalosporium fungi
- Example: penicillins and cephalosporins
- Can be modified in the lab to produce semi-synthetic drugs that have a modified spectrum of activity
- Susceptible to beta-lactamases
- Enzyme produced by some bugs to cut and inactivate beta-lactams
5
Q
Penicillins
A
- Narrow spectrum of activity
- Characterized by a five membered ring attached to the beta-lactam component
- Target transpeptidation in gram positive bacteria
- Cannot penetrate outer membrane of gram negative bacteria
- Semi-synthetic penicillin are modified to provide some activity against gram negative bugs
- Example: ampicillin
- Semi-synthetic penicillin are modified to provide some activity against gram negative bugs
6
Q
Cephalosporins
A
- Structurally distinct from penicillins
- Six membered ring is attached to the beta-lactam component
- Also target transpeptidation of peptidoglycan
- Many semi-synthetic examples
- Broader spectrum of activity than penicillin
- Better resistance against beta lactamases
- Grouped into generations
- 1st generation cephalosporin, 2nd generation cephalosporin etc.
7
Q
Growth Factor Analogs
A
- Growth factor analogs are structurally similar to growth factors but do not function in the cell
- Analogs similar to vitamins, amino acids, and other compounds
8
Q
Growth Factor Analogs (Example: Sulfa Drugs)
A
- Example: sulfanilamide
- Inhibit growth of bacteria by inhibiting folic acid synthesis and thus nucleic
acid synthesis (We can’t synthesis on out own) - Often used in combination with another analog→ trimethoprim
- Combination therapy minimizes the likelihood of resistance
9
Q
Growth Factor Analogs (Example: Isoniazid)
A
- Extremely narrow spectrum cell wall active agent
- Analog of mycolic acid component needed by Mycobacterium spp.
10
Q
Nucleic Acid Synthesis Inhibitors (Quinolones)
A
- Synthetic antimicrobials
- Inhibit DNA gyrase
- Prevents supercoiling of DNA
- Active against both Gram-negative and Gram-positive bacteria
- Example: ciprofloxacin a fluorinated quinolone (fluoroquinolone)
- Useful against life threatening infections
- Rifampin: binds to RNA polymerase preventing transcription
- Actinomycin: Binds to DNA template blocking transcription elongation
11
Q
Protein Synthesis Inhibitors
A
- Protein synthesis inhibitors target 70S ribosomes
- Good selective toxicity
- Some issues because human cells have 70S ribosomes in the mitochondrial matrix
12
Q
What are included in Protein Synthesis Inhibitors?
A
- Aminoglycosides
- Tetracycline
- Macrolides
13
Q
Aminoglycosides
A
- Bind to the 30S subunit of 70S ribosomes
- Block translation
- Narrow spectrum
- Useful against gram negative bugs
- Often used as a last resort drug
- Damaging to the kidneys and ears
- Examples include streptomycin, gentamycin and neomycin
14
Q
Tetracycline
A
- Broad spectrum
- Produced by species of the Streptomyces genus
- Bind to the 30S subunit
- Consist of both natural and modified semisynthetic
drugs - Binds to calcium damaging teeth and bone
- Shouldn’t be used in children and pregnant
women
- Shouldn’t be used in children and pregnant
- Used in veterinary medicine and to promote animal growth
- Creates problems with resistance
15
Q
Macrolides
A
- Broad spectrum of activity
- Bind to the 50S ribosomal subunit
- Only inhibits translation of some proteins
- Some proteins are preferential translated and others are not
- Creates a detrimental protein imbalance inside of the cell
- Useful to treat infection in patients with allergies to beta lactam antibiotics
- Example: erythromycin and azithromycin
- Produced by Streptomyces spp.