CH 10: Controlling Microbial Growth in the Body: Antimicrobial Drugs

Most antibiotics comes from what source?

Bacteria

The property of a chemical agent to be more inhibitory for a pathogen than for the pathogen’s host is referred to as

Selective toxicity

The mechanism of _____________ is to inhibit the formation of the peptidoglycan layer

Penicillin, Cephalosporin, Beta-lactams

What is one disadvantage associated with the use of broad-spectrum antibiotics?

They kill normal microbiota

What is the minimum inhibitory concentration (MIC)?

The smallest amount of drug that will inhibit the growth and reproduction of a pathogen

Which of the following is an example of a chemotherapeutic agent?

Sulfanilimide

Which of the following best describes why it is difficult to develop antiviral drugs?

iruses are difficult to target because they use the host cell’s enzymes and ribosomes to metabolize and replicate

Which of the following best describes the mechanism of action of aminoglycoside antimicrobials?

they inhibit protein synthesis by targeting the 30S ribosome

Which of the following does not describe the ideal antimicrobial agent?

chemically stable for long-term storage

Which of the following routes of administration results in the lowest drug concentrations in the body?

topical

Which of the following is not a way that microbes can acquire antimicrobial resistance?

changes in growth rate

Drugs

Chemicals that affect physiology in any manenr

Chemotherapeutic Agents

Drugs that act against disease

Antimicrobial agents (antimicrobials)

drugs that treat infections

Paul Ehrlich

Magic Bullets, arsenic compounds that kille dmicrobes

Alexander Fleming

Penicillin released from penicillum

Gerhard Domagk

Discovered sulfanilimide

Selman Waksman

Antibiotics, anitmicrobial agents produced naturally by organisms

Semi-synthetics

Chemically altered antibiotics that are more effective. longer lasting, or easier to administer than naturally occuring ones

Synthetics

Antimicrobials that are completely synthesized in a lab

Beta-lactams

Most prominent agent that prevents cross-linkage of NAM subunits. Binds to enzymes that cross link

Semi synthetic derivatives of beta-lactams

more stable in acidic environment, more readily observed, less likely to deactivate, more active against more bacteria types

Bacitracin

blocks transport of NAG and NAM from cytoplasm

Isoniazid and Ethambutol

disrupt mycolic acid formation in myobacterial species

Inhibition of synthesis of bacterial walls

Prevent bacteria from increasing amount of peptidoglycan layer. No effect on existig layer, effective only for growing cells

Inhibition of synthesis of fungal walls

Fungal cells composed of various polysacharides not found in mammalian cells

Echinocandin

inhibit the enzyme that synthesizes glucon

Aminoacyl

tRNA synthases, load amino acids onto tRNA molecules

Mupirocin

Selectively binds to isoleucyl tRNA synthase. Prevents loading of isoleucine only in Gram Positive Bacteria

Nystatin and Amphotericil B

attach to ergosterol in fungal membranes

Azoles and Allylamines

inhibit ergesterol synthesis

Polymixin

Disrupts cytoplasmic membranes of Gram - bacteria

Atovaquone

interferes with electron transport in protozoa and fungi

Antimetabolic Agents

can be effective when pathogen and host metabolic process differ

Heavy metals

inactivate enzymes

Trimethoprim

interferes with nucleotide synthesis

Amantadine, rimantadine, weak organic bases

prevent viral uncoating

Protease inhibitors

interfere with enzyme that HIV needs in replication cycle

Inhibition of Nucleic Acid Synthesis

several drugs, affect prokaryotic and eukaryotic, not used to treat infections, used in research and to slow cancer cell replication

Nucletide/nuceleoside analogs

interfere with function of nucleic acids, distort shape of molecules to prevent replication, transcription, translation

Reverse Transcriptase Inhibitors

act against enzyme that HIV uses to replicate, do not harm humans

Attachment antagonists

block viral attachment on receptor proteins

Pleconaril

blocks viral attachment

Arildone

Prevents viral uncoating

Ideal Antimicrobial agent

readily available, inexpensive, chemically stable, easily administered, non-toxic, non-allergenic

Narrow spectrum

effective against few organisms

Broad spectrum

Effective against many organisms. May allow secondary or superinfections to develop

Effectiveness ascertained by

Diffusion susceptibility test, min inhibtory + bacterial concentration test

Topical

application of drug for external infections

Oral

no needles, self administered

Intramuscular

Needle into muscle

Intravenous

Directly to bloodstream

Toxicity

Adverse reactions, poorly understood

Allergies

Rare, life threatening (anaphylactic shock)

Disruption of normal microbiota

result in secondary infections, overgrowth of normal flora causes superinfections

Resistance by bacteria acquired by

new mutations of genes, acquisition of R plasmids via transformation, transduction, or conjugation

Mycobacterium tuberculosis

produces MfPA proteins, binds DNA gyrase, prevents binding of Fluoroquinolone drugs

Slowing resistance

high concentration of drug for sufficient time

Synergism

one drug enhances effect of a second drug

Antagonism

Drugs interfere with each other