Talaro - Chapter 12 - Antibiotics and Antivirals

antibiotics

compounds that block the growth and reproduction of bacteria

antibiotic producing microbes

Streptomyces, Bacillus, Penicillium, and Cephalosporium

selective toxicity

A drug that kills harmful microbes without damaging the host

mechanisms of drug action (antibioitics)

1) cell wall targeting

2) cell membrane targeting

3) DNA/RNA (nucleic acid) targeting

4) protein synthesis targeting

5) metabolic pathway targeting

narrow spectrum antibiotics

antimicrobials effective against a limited array or range of microbial types

broad spectrum antibiotics

affect a broad range of gram-positive or gram-negative bacteria

Cell Wall Targeting Antibiotics

penicillin and cephalosporins

beta lactam antimicrobials

- Block cell wall construction

- Contain a four-sided beta-lactam ring

- Bind to transpeptidase enzymes

- Prevent protein cross-links that bind peptidoglycan's carbohydrate chains together

activity of penicillin

destabilize the formation of the cell wall causing bacterial cells to lyse; inhibits transpeptidase

penicillinases

beta-lactamases that inactivate penicillins

cephalosporins generations

5 generations-depending on generation, all may be active

against gram positive, gram negative or anaerobic bacteria.

Basically, the level of gram negative coverage increases with each successive generation.

•First generation

•Second generation

•Third generation

•Fourth generation

•Fifth generation

vancomycin

narrow-spectrum, most effective in treatment of Staphylococcal infections in cases of penicillin and methicillin resistance or if patient is allergic to penicillin; toxic and hard to administer; restricted use

non beta-lactam cell wall inhibitors

vancomycin and bacitracin

bacitracin

narrow-spectrum produced by a strain of Bacillus subtilis; used topically in ointment like neosporin

polymixin

interact with phospholipids of the outer membrane- serious side effects; particularly affects gram negative

amphotericin B and Nystatin

form complexes with sterols on fungal membranes which causes leakage

aminoglycosides examples

streptomycin and gentamicin

aminoglycosides

type of protein synthesis blocking antibiotic; cause misreading of mRNA by changing the A-site conformation

tetracycline

type of protein synthesis blocking antibiotic; blocks the attachment of tRNA on the A-site; broad-spectrum; treats STDS, Rocky Mountain spotted fever, Lyme disease, typhus, acne and protozoan infections

competitive inhibition

substance that resembles the normal substrate competes with the substrate for the active site

synergistic effect

interaction of two or more medicines that results in a greater effect than when the medicines are taken alone

sulfonamides

are metabolic analogs of PABA and block folic acid synthesis

nucleoside

nitrogenous base + sugar

chloroquine

binds and cross-links the double helix

quinolones

inhibit DNA helicases

nucleotide analogs

disrupt DNA and RNA replication and cause point mutations

protease

enzyme that digests or breaks down protein

protease inhibitor

drug that treats AIDS by blocking the production of protease, a proteolytic enzyme that helps create new viral pieces for HIV

Antiviral agents that mimic the structure of nucleotides and compete for sites on replicating DNA

acyclovir, valacyclovir, famiciclovir, peniciclovir

interferons

proteins (cytokines) secreted by T cells and other cells to aid and regulate the immune response; second line of defense

amantadine and rimantidine

restricted almost exclusively to influenza A viral infections; prevent fusion of virus with cell membrane

relenza and tamiflu

slightly broader spectrum; blocks neuraminidase in influenza A and B

neuraminidase

helps release virions from the host cell after replication and assembly

ketolides

telitromycin (Ketek), new drug with different ring structure from Erythromycin; used for infection when resistant to macrolides

Oxazolidinones

linezolid (Zyvox); synthetic antimicrobial that blocks the interaction of mRNA and ribosome

Used to treat methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus (VRE)

Ways to acquire drug resistance

1) spontaneous mutations

2) conjugation and transformation

3) selective pressures

natural selection and drug resistance

Large populations of microbes likely to include drug resistant cells due to prior mutations or transfer of plasmids - no growth advantage until exposed to drug

If exposed, sensitive cells are inhibited or destroyed while resistance cells will survive and proliferate.

Eventually population will be resistant - natural selection