microbio ch. 20 - antimicrobial medications

Define chemotherapeutic agents

a chemical/drug used to treat any disease

Define antimicrobial agents

chemical that inhibits or kills microbes

Define antibiotics

naturally produced compound that inhibits or kills microbes

What is the difference between an antibiotic and an antibody?

antibiotics are drugs that kill bacteria, antibodies are proteins produced by your immune system to fight various pathogens

What are the main microbial sources of antibiotics?

soil bacteria (bacillus or streptomyces species), or fungi (penicillium or cephalosporium species)

What is selective toxicity?

greater toxicity toward microbe than host

Why is selective toxicity advantageous to have an antimicrobial agent that is very selectively toxic?

it allows an antimicrobial drug to kill or inhibit a pathogen (like bacteria) without harming the host's (human) cells

What is therapeutic index?

ratio of toxic vs effective dose of a drug (and you want the effective dose to be a lot lower than toxic)

What does it mean that an antimicrobial agent is cidal?

it is going to kill the microorganism

What does it mean that an antimicrobial agent is static?

microorganism will only be inhibited from growing as long as the drug concentration is high enough

What is a broad spectrum antibiotic?

kills a lot of different species of microorganisms

What is a narrow spectrum antibiotic?

kills few microorganism species (targeting smaller group), typically because you want some to stay

Why is the distribution of an antimicrobial agent an important consideration when selecting an agent to treat a microbial infection? 

have to think about how it is going to spread throughout the body and make sure it reaches the site of infection

Why can some agents be used in combination while others cannot?

some drugs interact and cancel each other out, increase their effect or have an unintended effect

Why must adverse effects, cost and resistance be considered when choosing an antimicrobial agent?

have to think about the side effects, how much people can afford/how expensive the drug is, and how likely it is for the microorganism to become resistant

What are the targets on bacterial cells that antimicrobial agents affect? 

cell wall synthesis, nucleic acid synthesis, cell membrane integrity, metabolic pathways, and protein synthesis

What antibacterial agents target cell wall (peptidoglycan) synthesis?

b-lactam antibiotics, glycopeptide antibiotics (vacomycin), bacitracin

What antibiotics are considered B-lactam drugs?

penicillins, cephalosporins, carbapenems, monobactams

Penicillin is an example of what type of drug that targets on bacteria

b-lactam that targets cell wall synthesis

Cephalosporins are an example of what type of drug that targets on bacteria

b-lactam that targets cell wall synthesis

Carbapenems are an example of what type of drug that targets on bacteria

b-lactam that targets cell wall synthesis

Monobactams are an example of what type of drug that targets on bacteria

b-lactam that targets cell wall synthesis

What is the cellular target of β-lactam drugs? 

cell wall (peptidoglycan) synthesis

What is the mechanism of action of β-lactam drugs?

inhibits penicillin binding proteins and crosslinking: crosslink between NAM is formed by penicillin binding proteins and lactam binds to these causing a weak cell wall and eventually lysis

What is the target for vancomycin?

cell wall (peptidoglycan) synthesis

What is the target for bacitracin?

cell wall (peptidoglycan) synthesis

How does vancomycin inhibit/kill bacteria?

binds to peptide chain coming off of NAM and prevents crosslink forming = weak cell wall = lysis

Vancomycin is the drug of last resort to treat what?

methicillin-resistant staphylococcus aureus or MRSA infections

How does bacitracin inhibit/kill bacteria?

prevents transportation of peptidoglycan precursors (NAG and NAM) by blocking subunits of peptidoglycan from being transported out to where peptidoglycan is being synthesized

What is bacitracin used for?

ointment for cuts and scraps

What drugs inhibit bacterial protein synthesis? 

aminoglycosides, tetracyclines, macrolides, chloramphenicol, lincosamides, oxazolidinones

How does aminoglycosides inhibit bacterial protein synthesis. 

bind to 30S subunits, blocking translation initiation and causes misreading of mRNA (creating a faulty protein)

Give examples of aminoglycosides

streptomycin, tobramycin, gentamycin, amikacin

Streptomycin is an example of what type of drug that targets what on bacteria

aminoglycoside that targets protein synthesis

Tobramycin is an example of what type of drug that targets what on bacteria

aminoglycoside that targets protein synthesis

Gentmycin is an example of what type of drug that targets what on bacteria

aminoglycoside that targets protein synthesis

Amikacin is an example of what type of drug that targets what on bacteria

aminoglycoside that targets protein synthesis

How does tetracyclines inhibit bacterial protein synthesis. 

binds to 30S subunit, blocks tRNA from entering A and P sites (elongation stops)

What drugs that inhibit bacterial protein synthesis bind to the 30S subunit?

aminoglycosides and tetracyclines

How does macrolides inhibit bacterial protein synthesis. 

binds to 50S subunit, prevents translocation (when ribosome shifts)

Give examples of macrolides

erythromycin, axithromycin, clarithromycin

Erythromycin is an example of what type of drug that targets what on bacteria

macrolide that targets protein synthesis

Azithromycin is an example of what type of drug that targets what on bacteria

macrolide that targets protein synthesis

Clarithromycin is an example of what type of drug that targets what on bacteria

macrolide that targets protein synthesis

How does chloramphenicol inhibit bacterial protein synthesis. 

binds to 50S subunit, prevents peptide bond formation (can’t connect amino acids)

How does lincosamides inhibit bacterial protein synthesis. 

binds to 50S subunit, prevents elongation

Give examples of lincosamides

clindamycin

Clindamycin is an example of what type of drug that targets what on bacteria

lincosamide that targets protein synthesis

How does oxazolidinones inhibit bacterial protein synthesis. 

binds to 50S subunit, prevents initiation

What drugs that inhibit bacterial protein synthesis bind to the 50S subunit?

macrolides, chloramphenicol, lincosamides, oxazolidinones

What drugs inhibit bacterial nucleic acid synthesis? 

fluoroquinolones and rifamycins

How do fluoroquinolones inhibit the synthesis of nucleic acids?

inhibits topoisomerase (DNA gyrase, the enzyme that relieves supercoiling) = bacteria can’t replicate = nothing to stop supercoiling

Give examples of fluoroquinolones

ciprofloxacin and moxifloxacin

Ciprofloxacin is an example of what type of drug that targets what on bacteria

fluoroquinolone that targets nucleic acid synthesis

Moxifloxacin is an example of what type of drug that targets what on bacteria

fluoroquinolone that targets nucleic acid synthesis

How do rifamycins inhibit the synthesis of nucleic acids?

block prokaryotic RNA polymerase from initiating transcription

Give example of rifamycins

rifampin

Rifampin is an example of what type of drug that targets what on bacteria

rifamycin that targets nucleic acid synthesis

What metabolic pathway is targeted by the sulfonamides and trimethoprim? 

folic acid synthesis

How does blocking metabolic pathway inhibit bacterial growth?

inhibits PABA from entering pathway causing the pathway to be shut down or targets second enzyme further in pathway = can’t make nucleotides

What are drugs that inhibit metabolic pathways (specifically folic acid) used to treat?

UTI’s

Which drugs target the bacterial cell membrane? 

polymyxin B and daptomycin

How does polymyxin B effect cell membrane integrity?

binds to cell membrane of gram negatives and alters cell membrane permeability = cytoplasm leaks = death

How does daptomycin effect cell membrane integrity?

inserts into cell membrane of gram positives (not negatives = can’t penetrate outer membrane) and causes leakage of cellular contents

What is the minimum inhibitory concentration?

the lowest amount/concentration that prevents microbial growth

What is an antibiogram?

antibiotic susceptibility profile (know which antibiotic is most effective)

What are methods of determining drug susceptibility?

MIC values (panel), disc diffusions (incubate bacteria on plate with concentration of antibiotic and see if there’s growth), and e-tests (strip that contains gradient of antibiotic and diffuses out and you can see where zone of inhibition is)

What mechanisms can be used in acquired resistance? 

drug-inactivating enzymes, alteration of target, decreased uptake of drug, increased elimination of drug

How are drug-activating enzymes be used to acquire resistance?

enzyme modifies antibiotic, inactivating it

Examples of drug-inactivating enzymes

b-lactamases, chloramphenicol acetyltransferase

How is alteration of target used to acquire resistance?

antibiotic cannot bind target = causes mutation

How can decreased uptake of drug be used to acquire resistance?

porin proteins prevent antibiotic entry into the cell

How can increased elimination of drug be used to acquire resistance?

antibiotic enters cell but efflux pump ejects it

What is an efflux pump?

a protein in a cell's membrane that actively pumps harmful substances, like antibiotics or toxins, out of the cell, preventing them from reaching damaging concentrations, which is a major way bacteria develop antibiotic resistance and survive

What are some examples of diseases that have emerging resistance?

enterococci (systemic infections), staphylococci(), streptococci (strep throat), and mycobacteria (tb)

What method of acquisition of resistance is most responsible for resistance to aminoglycosides and resistance due to decreased uptake of drugs? 

spontaneous mutation

What resistance mechanisms are frequently acquired through gene transfer mechanisms?

What methods can be employed to slow the spread of antibiotic resistance?

limit non-medical use of antibiotics, selective and appropriate use of antibiotics, ensure dose and duration are adequate, combination therapy

 What steps in viral replication are targeted by antiviral drugs? 

viral entry, viral uncoating, nucleic acid synthesis, genome integration, assembly and release of viral particles

What antiviral drugs target uncoating?

amantadine and rimantadine

What antiviral drugs target nucleic acid synthesis?

analogs, reverse transcriptase inhibitors

What antiviral drugs target assembly/release of viral particles?

protease inhibitors

What are the targets for antifungal drugs? 

cell division, cytoplasmic membrane synthesis, nucleic acid synthesis, cell wall synthesis, protein synthesis

What drugs target ergosterol and how do these function to inhibit/kill fungi? 

polyenes, azoles, allylamines

How do griseofulvin and flucytosine inhibit/kill fungi? 

inhibits tubulin polymerization (prevents mitosis/meiosis); inhibits enzyme needed for nucleic acid synthesis

How does tavaborole inhibit fungal growth?

prevents charging of tRNA’s with AA - inhibits protein synthesis (only for onychomycosis)

Why are there so many more antibacterial agents compared to the number of antiviral or antifungal agents?

there are more difference between a human and bacterial cell that can be targeted. virus take control of own-cells (don’t wanna kill own cells)