(LE2) Antimicrobial Drugs Flashcards
Describe antibiotics
- naturally occurring
- common in soil, fungi, and bacteria (competitive environment)
Describe synthetic Drugs. Give an example
- Laboratory derived
e.g. sulfa
Describe semisynthetic drugs
Antibiotics that are modified in the lab
What is selective toxicity?
Harms or kills the pathogen without causing significant harm to the host (magic bullet)
What properties are required for antimicrobial agents?
- selective toxicity
- soluble in body fluids
- biological half-life
Why is body fluid solubility important for antimicrobial agents?
Needs water-soluble molecules so that it can be used by the body
Why is half-life important for antimicrobial agents?
affects dosing
What is a broad spectrum drug?
Works on two or more groups of bacteria
What is a narrow spectrum drug?
Works on less than or equal to one group of bacteria
What is the spectrum of activity for Penicillin?
G+, narrow spectrum
What is the spectrum of activity for Isoniazid?
Very narrow spectrum
- Works on M. tuberculosis only
What is the spectrum of activity for Tetracycline?
Very broad spectrum
G+, G-, intracellular bacteria
What is the spectrum of activity for Streptomycin?
broad spectrum, acid-fast and G-
What is the mode of action for the following drugs: penicillins, cephalosporins, bacitracin, and vancomycin?
Inhibition of cell wall synthesis (peptidoglycan, mycolic acid)
-antibacterial
What is the mode of action for the following drugs: chloramphenicol, erythromycin, tetracyclines, and streptomycin?
Inhibition of protein synthesis (70S ribosomes)
- antibacterial
What is the mode of action for the following drugs: quinolones and rifampin?
Inhibition of nucleic acid replication and transcription (DNA or RNA)
- antibacterial (DNA gyrase)
- mostly antivirals
What is the mode of action for polymyxin B?
Injury to plasma membrane (ergosterol)
- antifungal
What is the mode of action for the following drugs: sulfanilamide and trimethoprim?
Inhibition of essential metabolite synthesis (competitive or non-competitive inhibitors)
- synthetic antibacterials
What category of side effects is most crucial to understand when developing an antimicrobial drug?
- Toxicity - determined by selective toxicity of drug (e.g. vancomycin req monitoring of liver & kidney function)
- Allergies - more common in some drugs than others (e.g. penicillin and sulfa)
- Disruption of normal microflora - problem with broad-spectrum drugs
- can lead to yeast infections and C. diff infections
What are ideal antimicrobial attributes?
- water-soluble
- selective toxicity
- biological half-life
- narrow spectrum
- low allergenicity
- tissue stability
- long shelf-life
- low cost
- low/no resistance acquisition
Sulfonamides & Trimethoprim
Type: Synthetic
MOA: competitive protein inhibition. PABA analog
Preferred use: broad spectrum
Side effects:
Interesting features:
Isoniazid (INH)
Type: Synthetic
MOA: inhibits mycolic acid in AF cell wall
Preferred use: Narrow spectrum; M. tuberculosis
Side effects: X
Interesting features: req 6 mo to 2 yr regiment compliance
Quinolones (e.g. Ciprofloxacin)
Type: Synthetic
MOA: inhibits DNA gyrase used in DNA replication
Preferred use: Gram broad spectrum
Side effects: weakening of tendons
Interesting features: newer drug -> no resistance yet
Penicillins
Type: Antibacterial
MOA: Cell wall inhibitor
Preferred use: narrow spectrum G+ Staphylococcus, Streptococcus, and some spirochetes (syphilis)
Side effects: X
Interesting features: Penicillin G (requires injection), Penicillin V (Orally, resists stomach acid)
Susceptible to beta-lactamase produced by MRSA. (carried on R plasmid)
Semi-Synthetic Penicillins
Type: antibacterial
MOA: cell wall inhibitor
Preferred use: Broader spectrum than penicillin
Side effects: X
Interesting features: Still has beta-lactam ring. Combined with Clavulanate to inhibit beta-lactamase
e.g. Augmenten = Amoxicillin + Clavulanate, Methicillin
Cephalosporins
Type: Antibacterial
MOA: cell wall inhibitor
Preferred use: broad spectrum
Side effects: X
Interesting features: more resistant to beta-lactamase; beta-lactam ring protected by 6-point ring structure
Vancomycin
Type: antibacterial
MOA: cell wall inhibitor
Preferred use: last resort; Broad spectrum MRSA & TB
Side effects: High toxicity, req kidney & liver function monitored
Interesting features: VISA - Vancomycin intermediate S. aureus
VRSA
VRE - Vancomycin-resistant Enterococcus
Streptomycin
Type: Antibacterial
MOA: Protein synthesis inhibitors
Preferred use: Broad spectrum; last resort for G- and TB
Side effects: Fairly toxic
Interesting features: Neomycin (Neosporin) topical variant
Tetracycline
Type: Antibacterial
MOA: protein synthesis inhibitor
Preferred use: broad spectrum; G+, G-, intracellular pathogens (chlamydia)
Side effects: High toxicity
Interesting features: Doxycycline common for acne, STDs, and malaria (intracellular protozoan) prophylactic
Chloramphenicol
Type: antibacterial
MOA: protein synthesis inhibitor
Preferred use: broad spectrum (G+/-)
Side effects: high toxicity. high penetrating power can enter bone marrow causing aplastic anemia, a type of leukemia
Interesting features: Topical use only for diabetic ulcers
Erythromycin
Type: antibacterial
MOA: protein synthesis inhibitor
Preferred use: narrow spectrum, G+
Side effects: X
Interesting features: -macrocyclic ring blocked by G- cell wall
- best alternative to penicillin
Rifampin
Type: antibacterial
MOA: Nucleic acid synthesis inhibitor
Preferred use: broad spectrum (G+/-)
Side effects: red/orange body fluid secretions
Interesting features: not super common
Amphotericin B
Type: antifungal
MOA: cell membrane inhibition
Preferred use: Systemic fungal infections
Side effects: fairly toxic
Interesting features: polyene ring disrupts ergosterol
Imidazoles
Type: antifungal
MOA: cell membrane inhibition
Preferred use: topical use; cutaneous fungal infections (athlete’s foot, yeast infection)
Side effects: X
Interesting features: Lamisil (pill form)
Griseofulvin
Type: antifungal
MOA: mitosis inhibition (targets microtubule formation)
Preferred use: under-the-nail fungal infections
Side effects:
Interesting features: targets keratinized tissues only
Acylovir
Type: antiviral
MOA: Inhibit viral DNA replication (nucleotide analog)
Preferred use: Herpes (HSV, shingles, etc.)
Side effects: non-selectively toxic
Interesting features: e.g. Valtrex
Anti-HIV drugs
Type: antiviral
- MOA: reverse transcription inhibitor (AZT)
Preferred use: HIV
Side effects: high mutation rate, toxic in high doses
Interesting features: nucleotide analog (adenine) - MOA: protease inhibitor. inhibit last step of HIV maturation
Preferred use: HIV
Side effects: high mutation rate
Interesting features: used in combination with AZT to reduce HIV replication
Quinine derivatives
Type: anti-protozoan
MOA: Toxin buildup
Preferred use: antimalarial
Side effects: vivid dreams
Interesting features: Chloroquine and Mefloquine; given as prophylactic prior to travel to high-risk areas
Metronidazole (Flagyl)
Type: anti-protozoan
MOA: interferes with anaerobic metabolism
Preferred use: Trichomonas (intestinal protozoan) & C. diff
Side effects:
Interesting features:
Mebendazole (Vermox)
Type: anti-helminth
MOA: inhibits microtubules -> motility
Preferred use: Ascaris and pinworm
Side effects: X
Interesting features: not absorbed by our cells
Niclosamide
Type: anti-helminth
MOA: inhibits aerobic respiration
Preferred use: tapeworms
Side effects: X
Interesting features: X
Pyrantel Pamoate (Antiminth)
Type: anti-helminth
MOA: causes paralysis of worm
Preferred use: hookworm, pinworm, Ascaris
Side effects: X
Interesting features: X
Antibiotic resistance is selected for by exposure to the drug. What habits/actions facilitate this?
- non-compliance
- incorrect dosage (self-medication)
- Use in animal foods
- Lack of prescription control
- use for non-bacterial infections
- overuse of broad-spectrum drugs
What mechanism of drug resistance is shown? Give an example
Inactivate the drug with enzyme
e.g. beta-lactamase for penicillin resistance
What mechanism of drug resistance is shown? Give an example
Alterations in membrane permeability
e.g. Tetracycline kept out and can’t reach target
What mechanism of drug resistance is shown? Give an example
Alterations in drug target
e.g. Erythromycin - AA change in ribosome
What mechanism of drug resistance is shown? Give an example
Active transport of drug back out of the cell
e.g. Pseudomonas
What mechanism of drug resistance is shown?
Horizontal gene transfer
- R plasmid
How can we limit drug resistance?
- effective drug concentrations: compliance and no drug “holidays”
- simultaneous drug administration (synergism/antagonism)
- restricting drug prescriptions
