Antimicrobial Pharmacology Flashcards
Microorganisms (+ examples)
Organisms of microscopic sizes, consisting of single or clustered cells
Eg. Virus, bacteria, fungi, protozoa, algae
Viruses
Microscopic, acellular, metabolically inert, intracellular organisms
COVID-19 Virus characteristics
- Single-stranded RNA virus with the largest genome among RNA viruses
- Has genomic proofreading mechanism to weed out mutations = resistant to antivirals
COVID-19 replication process
- Spike protein binds to ACE2 receptor, virus endocytosed
- Uncoating: RNA/genetic material enters
- Translation: mRNAs bind to ribosomes
- Genome replication
- Assembly of structural proteins to make new virus = excocytosed
Sotrovimab
Antiviral designed to attach to the spike protein of COVID-19
Prevents viral cell entry
Nirmatrelvir-ritonavir (Paxlovid)
Antiviral that inhibits the metabolism of Nirmatrelvir = prevent protein assembly
Ribavirin
Inhibits viral RNA-dependent RNA polymerase (RdRP)
Remdesivir
RdRP inhibitor
Remdesivir mechanism
Resembles ATP molecules and competes with nucleotides during viral RNA synthesis
Types of Vaccines
- Viral vector (doesn’t integrate virus DNA into host cell)
- mRNA
Bacteria
Microscopic, single-celled, prokaryotic, reproduce via fission/spores
Shapes of bacteria (3)
- Cocci (spherical)
- Bacilli (rod-shaped)
- Spiral
Gram positive bacteria (+example)
Thick cell wall
Eg. Staphylococcus
Gram negative bacteria (+example)
Thin cell wall, often pathogenic
Eg. E. coli
Anaerobe (+example)
Can survive without O2
Eg. Clostridium
Factors affecting antimicrobial efficacy
- Penetrating site of infection
- Achieving concentration above the minimum inhibitory concentration (MIC) during dosing interval
Expand on the factors within ‘penetrating site of infection’ that affects antimicrobial efficacy
- Physical barriers for the drug to travel (ex. Epithelial and endothelial cells, and the type of junction between cells)
- Chemical properties of the drug (ex. Hydrophilic or hydrophobic)
- Presence of multidrug transporters (ex. P-glycoprotein)
MIC
Minimum inhibitory Concentration:
Lowest concentration of antibiotic that inhibits visible growth of microorganism after overnight incubation
MBC
Minimum Bactericidal Concentration:
Lowest concentration of antibiotic required to kill microorganism
Ratio of MBC to MIC:
MBC:MIC <= 4 is?
MBC:MIC >4 is?
MBC:MIC <= 4 -> bactericidal (antibody kills bacteria)
MBC:MIC >4 -> bacteriostatic (antibody prevents further replication)
Rate of killing bacteria/inhibiting growth are:
- Time-dependent (length of time above MIC to kill/suppress growth)
- Concentration-dependent (increasing conc. above MIC to kill/suppress growth)
Β-lactam Antibiotics (ex + mechanism of action)
Ex. Penicillins
Inhibit synthesis of bacterial peptidoglycan cell wall
Macrolides (ex + mechanism of action)
Ex. Azithromycin
Inhibit bacterial protein synthesis by binding reversibly to 50S bacterial ribosome subunit
Aminoglycosides (ex + mechanism of action)
Eg. Gentamicin
Interfere with bacteria protein synthesis by binding irreversibly to 30S and 50S bacterial ribosome subunit. This creates fissures in bacteria outer membrane -> defective bacterial cell membrane
Tetracyclines (ex + mechanism of action)
Eg. Doxycycline
Inhibit bacteria protein synthesis by binding reversibly to 30S bacterial ribosome subunit. May also cause changes to cytoplasmic membrane
Sulfonamides (ex + mechanism of action)
Eg. Sulfamethoxazole
Interfere with folic acid synthesis (important for proteins) by inhibiting dihydropteroate synthetase + preventing addition of PABA into folic acid
Quinolones (ex + mechanism of action)
Eg. Ciprofloxacin
Inhibit DNA gyrase/topoisomerase -> inhibit relaxation of supercoiled DNA -> inhibit DNA replication
Glycopeptides (ex + mechanism of action)
Eg. Vancomycin
Binds to D-alanyl-D-alanine terminus of cell wall precursor units ->inhibit cell wall formation in gram positive bacteria
Oxazolidinone (ex + mechanism of action)
Eg. Linezolid
Inhibit protein synthesis by binding to P site of 50s ribosomal subunits
Antibiotic Side Effects (10)
- rash
- diarrhea
- abdominal pain
- nausea/vomiting
- drug fever
- hypersensitivity (allergic) reactions
- photosensitivity
- headache
- dizziness
- taste alterations
Mechanisms of Antibiotic Resistance (6)
- Decreasing entry of antibiotics into pathogen
- Increasing the export of antibiotic by efflux pumps
- Release of microbial enzymes that destroy antibiotic
- Alteration of microbial proteins that transform pro-drugs to effective moieties
- Alteration of target proteins (minimizes antibody binding)
- Development of alternative pathways to those inhibited by antibiotic