Antibacterial Agents 1: Introduction Flashcards
What is selective toxicity?
Selective Toxicity is where an antibiotic exerts its effect SELECTIVELY on the microbe and NOT on the host.
What are the 4 “types” of selective toxicity?
- Inhibition of a metabolic pathway found in bacteria but not in humans
- Inhibition of a Enzyme that is different in host and bacteria.
- Disrupt macromolecular structure that does not exist in humans
- Disrupt macromolecular structure that differs between microbes and humans
Give an example of Inhibition of a metabolic pathway found in bacteria but not in humans.
Folate Metabolism:
Mammals take up folate from environment whereas bacteria synthesize their own.
Give an example of inhibition of a Enzyme that has different structure in host vs bacteria.
- Ribosomal proteins (30/50S in bacteria vs 40/60 in eukaryotes)
- DNA Gyrase (bacteria) vs Topoisomerase (host)
Give an example of a Macromolecular structure that doesn’t exist in humans but does in bacteria:
Cell Wall: peptidoglycan synthesis does not occur in humans.
Give an example of a Macromolecular structure that differs in humans compared to microbes:
Cell Membrane:
Funguses have Ergosterol as the major CM component
Eukaryotes have cholesterol
What is the difference between Narrow (intrinsic) Resistance, Escape resistance, and Acquired Resistance?
Narrow- Microbe LACKS TARGET for drug action.
Escape- Microbe IS susceptible, but escapes consequences due to availability of certain biomolecules or failure to lyse.
Acquired- Selective pressure produces organisms that are increasingly resistant.
Within the realm of Escape resistance, what causes the “escape” ability?
- Purulent infection → release of purines, thymidine, serine, methionine → microbe escapes → sulfonimide resistance
*That’s why surgical drainage procedures are so important!
- Failure to “lyse” due to osmotic pressure difference → penicillin resistance
What are the two modes of Acquired resistance?
- Mutational (Chromosomal) Resistance
- Arises after multiple generations of replication
- Slight resistance
- Proper dosing and duration prevents - Plasmid Mediated Resistance
- Resistance may occur during single course of treatment
- Plasmid exchange via conjugation, transduction, or transformation
A drug that has only gram positive effectivity would be classified as a ____________ spectrum?
Narrow, Extended, or Broad
Narrow
Either Gram + OR -, but not both.
True or False: Extended and Broad spectrum antibiotics are effective against both gram + and - bacteria.
True
Extended = + and - Broad= + and - and atypical organisms
When would you use a broad spectrum antibiotic?
When the causative microbe is unknown in a severe infection. Switch to narrow spectrum as soon as possible
Broad spectrum therapy is aka Empiric therapy.
Definitive therapy=Known pathogens and Narrow therapy
What are the 5 types of mechanisms of resistance for bacteria?
- Decreased Entry (natural resistance)
- Bypass Pathway
- Altered Target Site (drug cant bind)
- Efflux Pump
- Enzymatic Degradation of drug
Dees Bacteria Are Effing Easy
How can we as physicians prevent increasing resistance to antibiotics?
- Use only when NEED IS ESTABLISHED
- Select antibiotic based on SUSCEPTIBILITY TESTS
- Adequate DOSE AND CONCENTRATION
What is the difference between a bactericidal and bacteriostatic drug?
Bactericidal drugs kill bacteria
Bacteriostatic drugs prevent bacteria from replicating. Later the immune system takes out the bacteria.
Which antibiotics mechanisms are generally bactericidal?
- Inhibition of cell wall synthesis
- Disruption of Cell Membrane fxn
- Interference with DNA fxn or synthesis.
Which antibiotic mechanisms are generally bacteriostatic?
- Inhibition of protein synthesis (except aminoglycocides)
2. Inhibition of intermediary metabolic pathways.
True or false: Bacteriostatic drugs can compensate for immunocompromised patients.
False
Bactericidal drugs compensate for immunocompromised patients.
What are some of the advantages of Bactericidal mechanisms?
- Good for Severe infections
- Act quickly + irreversibly
- Compensation of immunocompromised
- Can treat where normal immune system cannot (joint capsle, across blood brain barrier etc)
What are the 4 pharmacokinetic properties we are concerned about with antibiotic selection?
- Absorption
- Distribution
- Elimination
- Duration of Activity
What are 2 cons of oral antibiotics?
- Alteration of intestinal flora
2. Incomplete absorption of some drugs.
Some drugs exhibit selective distribution (accumulation). Which drug is used to treat osteomyelitis because it accumulates in bone?
Clindamycin
it goes in the “cylind”rical bone
Some drugs exhibit selective distribution (accumulation). Which drug is used to treat URIs-Pneumonia because it accumulates in pulmonary cells?
Macrolides
Macs help you when you hack (cough=pneumonia)
Some drugs exhibit selective distribution (accumulation). Which drug is used to treat periodontitis and acne because it accumulates in sebum and gingival crevicular fluid?
Tetracyclines
Some drugs exhibit selective distribution (accumulation). Which drug is used to treat UTIs and because it has rapid excretion in urine?
Nitrofurantoin
Nitrof-urine-toin
Some drugs exhibit selective distribution (accumulation). Which drug can cause abnormal bone growth and tooth discoloration?
Tetracycline because it binds Ca2+ in developing bone and teeth.
Some drugs exhibit selective distribution (accumulation). Which drug can cause ototoxicity and nephrotoxicity?
Aminoglycosides
Which type or metabolism do you need to wory about genetic polymorphisms?
Liver metabolism.
Some drugs may metabolize faster/slower based on polymorphisms.
What complication may arise if duration or dose of treatment is too low?
Resistance or recurrence of infection
What complication may arise if the duration is too long?
Superinfection
What complication may arise if the dose is too high?
Dose-related toxicities.
Which of the following is not an example of direct toxicity?
- Nausea and vomiting
- Liver failure
- Allergic reactions
- Neurotoxicity
- Bone marrow depression
- Allergic reactions
What’s the stupid mnemonic for Non-renal drug elimination (also may include drug-drug interactions, hepatotoxicity, or polymorphisms)?
DQ-CRIMES
- Doxycycline
- Quinolones: Ciproflaxin IS renal but CYP 450 Inhibitor
- Clindamycin
- Rifampin
- Isoniazid
- Metronidazole
- Erythromycin-like (Azi-Clar-Ery)
- Sulfonamides
What’s the stupid mnemonic for drugs that can cross the placental barrier?
Create A Totally Mutant Fetus:
Chloramphenicol AminoglycosidesT Tetracyclines Metronidazol Fluoroquinolones--
