MICRO LECTURE: 4

Who is Paul Ehrlich?

Wanted a magic bullet

What is the “magic bullet”?

A chemical that causes little to no harm to the patient but eradicate the pathogen

Who is Alexander Fleming?

Accidentally discovered the mold Penicillum

What came from the mold Penicillum?

Penicillin

Who is Selma’s Waksman

Coined the term “antibiotic”

What does the term “antibiotic” mean?

Natural product of or derived from the metabolism of living organisms

Who discovered streptomycin from soil?

Selman Waksman

Who is Gerard Domagk?

Discovered Prontosil

What did Prontosil do?

Had an inhibitory effect on staphylococci, streptococci, and other gram (+) species

What did Chain and Florey do?

Isolated + conducted clinical trails on penicillin

What did the clinical trails on penicillin find?

Proved effective on gonorrhea, meningitis, tetanus, + diphtheria

What does a antibiotic that is “natural” mean?

Products of metabolism of living microbes

What is an example of a “natural” antibiotic

Penicillin

What does an antibiotic that is “synthetic” mean?

Made completely in the lab

What is an example of “synthetic” antibiotic

Antiviral drugs

What does an antibiotic that is “semisynthetic” mean?

Natural products chemically modified/enhanced

What is good about semisynthetic

More effective than synthetic, less toxic than natural

What is “selective toxicity”

When a drug harms the pathogen but not the host

What is a “therapeutic dose”

Drug concentration effective as either microbicidal or microbiostatic

What is “toxic dose”

Concentration of drug that causes harm to host

What is a “therapeutic window”

Dosage of drug that is tolerated by host + effective against pathogen

What makes the “therapeutic window”

Therapeutic dose + toxic dose

What is “synergistic effect”

Combing drugs that lower therapeutic dose + be more effective treatment

What is “broad” spectrum drugs mean

Drugs that are effective to a wide range of pathogens

What is bad about “broad” spectrum drugs

May destroy the microbiome of patient

What is it called when a microbiome is disrupted/ destroyed?

Dysbiosis

What is “narrow” spectrum drugs mean

Drugs that specific pathogens or family of microbes

Why do organisms produce chemicals that can be used as antibiotics in human

It is used for survival when there is fierce competition for limited nutrients, giving the organism selective advantage for nutrients + space

What are the four major targets of antimicrobial agents in the pathogen

Translation, nucleic acid synthesis, cell wall synthesis, and metabolic pathways

What agents inhibit DNA synthesis

Quinolones and Rifampin

What does quinolones do?

Synthetic, Inhibits DNA replication

What are some drug examples of quinolones

Levofloxacin + Ciprofloxacin

What does Rifampin do?

Semisynthetic, inhibits RNA transcription

What are some drug examples of Rifampin

Rifampin

What inhibits Cell Wall synthesis

Penicillin, Cephalosporin, Carbapenems, Glycopetides, + Polypeptide

What does penicillin do

Inhibits an enzyme that catalyzes the last step of wall synthesis

What are some drug examples of penicillin

Penicillin G + V; Natural, Ampicillin, Amoxicillin, Methicillin, + Carbenicillin; semisynthetic

What does Cephalosporin do

Semisynthetic; Fight pathogens resistant to penicillin

What are some drug examples of Cephalosporin

Cephalothin + Cephalexin

What does Carbapenenms do

“Drug of last resort” ;Broad-spectrum bactericidals from Streptomyces cattleya

What are some drug examples of Carbapenems

Imipenem + Meropenem

What do Glycopeptides do

Treats gram (+), Severe staphylococcal diseases when patient is allergic or resistance to penicillin is found

“Last resort drug”

What are some drug examples of Glycopeptides

Vancomycin

What is the key treatment against MRSA (staph resistant to antibiotics)?

Vancomycin

What do polypeptides do

Affect the cell envelope(cell wall + cell membrane)

What is a drug example of Polypeptide

Bacitracin

What inhibits metabolism

Sulfonamides

What do Sulfonamides do

Synthetic; Interfere w/ folic acid metabolism

What is a drug example of Sulfonamides

Sulfamethoxazole

What disrupts the cell membrane

Polypeptide

What are some drug examples of Polypeptides that disrupt the cell membrane

Polymyxin B + Bacitracin

What does polymyxin B do

Acts like a detergent, disrupts the integrity of the cell membrane of gram (-) bacteria

What inhibits protein synthesis (translation)

Aminoglycosides, Tetracyclines, Chloramphenicol, Macrolides, Streptogramins, Oxazolidinone

Which protein synthesis inhibitors bind to 30S of the ribosome

Aminoglycosides + Tetracyclines

What does Aminoglycosides do

Cause a misreading of the genetic code on mRNA

What are drug examples of Aminoglycosides

Gentamicin + tobramycin

What do Tetracyclines do

Block attachment of tRNA

What are drug examples of Tetracyclines

Doxycycline

Which inhibitors that disrupt translation attach to 50S portion of the ribosome

Chloramphenicol, Macrolides, Lincosamides, Streptogramins, + Oxazolidinone

What does Chloramphenicol do

Blocks peptide bond formation between amino acids

What do Macrolides do

Prevent chain elongation

What is a drug example of Macrolides

Erythromycin

What does Lincosamides do

Prevent chain elongation, Limited to serious infections because use can trigger dysbiosis and opportunistic  C. diff infection

A drug example of Lincosamides

Semisynthetic clindamycin

What do Streptogramins do

Cause premature chain termination

Drug example of Streptogramins

Synercid (quinupristin-dalfopristin)

What do Oxazolidinones do

Interfere with chain initiation; “drugs of last resort”

Drug example of Oxazolidinones

Zyvox (effective against MRSA)

What side effects are associated with tetracycline

Causes discoloration on developing teeth + stuns bone growth in children

What drugs are used to treat TB (tuberculosis)

Aminoglycosides; Streptomycin + Rifampin

How do antiviral drugs work by interfering in with replication system

They block penetration (virus from attaching), inhibit biosynthesis (virus DNA replication), and prevent new viruses being built (assembly/release)

Why is it harder to fight fungal and parasitic infection compared to bacterial infections

It is harder to fight because the antimicrobial used to treat fungal infection lack selective toxicity because the fungal metabolism mimics human metabolism

What does antifungal target? Is there any structures similar to the human metabolism

Antifungal targets: plasma membrane, cell wall, nucleic acids, and cytoskeleton microtubules

Human metabolism