Antibiotics (chapter 10)

Drug

chemical that affect physiology in any manner

Chemotherapeutic agent

drug that acts against disease

Antimicrobials

drugs that treat infectious diseases

penicillin is a ____ ______ antibiotic

naturally occurring

Majority of antibiotics are made from

Penicillium or Streptomyces

Semisynthetic

chemically altered antibiotics that have more benefits than naturally occurring ones

Synthetic

antimicrobials completely synthesized in a lab

Selective toxicity

drug will only affect microorganism without damaging host. also means mechanism of action will affect cell structure OR metabolism.

Inhabitation of cell wall synthesis

affects tetrapeptide bonds (prevent cross linkage of NAM subunits). Effective only for growing cells

Inhibition of protein synthesis

drugs target translation. can harm humans because we have some ribosomes that are 70S

Disruption of cell membranes

primarily effective in fungal infections. Drug attaches to ergosterol (cholesterol like) in fungal membranes. Don’t affect bacteria because they have hopanoid.

Inhibition of Nucleic Acid Synthesis

DNA gyrase and RNA polymerase. Affect both Eukaryotic and Prokaryotic cells, Humans are affected because we have the same enzymes

Inhibition of metabolic pathways

PABA required in metabolism of folic acid. Folic acid is involved in DNA/RNA production for bacteria. Shouldn’t hurt humans

Attachment antagonists

block viral attachment or receptor proteins. This is a new area of drug development

Beta lactams

inhibits cell wall synthesis. useful for gram positive cause they have thick cell walls. (Penicillin, its derivatives and cephalosporins)

beta lactam ring

A four-membered lactam ring found in beta-lactam antibiotics, essential for inhibiting bacterial cell wall synthesis.

Penicillin advantages

• inexpensive

• Usually not toxic

• good against gram positive

Penicillin disadvantages

• Narrow spectrum of activity

• Susceptible to penicillinase (beta lactamase)

beta lactamase

an enzyme that makes bacteria resistant to beta-lactam antibiotics, like penicillin

Pen V

stable with stomach acids and can be taken orally

Pen G

wont survive stomach acid

Semisynthetic derivates of beta-lactams

Oxacillin, Amoxicillin, Carboxypenicillin, Methicillin

benefits of semisynthetic derivatives of beta lactams

• more readily absorbed

• less susceptible to deactivation

• active against more types of bacteria

Methicillin

relates to Methicillin-resistant Staphylococcus aureus (MRSA)

Cephalosporins

• beta lactam (block tetrapeptide bonds)

• resistant to penicillinases

Bacitracin

• does not block tetrapeptide

• block transport of NAG NAM from cytoplasm'

• Topical gram positive bacteria

Vancomycin

• does not block tetrapeptide

• made from streptomyces

Isoniazid

Treats tuberculosis

Aminoglycosides

• good against gram negative

• can cause deafness and kidney failure

streptomycin

can be used in TB treatment

Neomycin

found in topical ointments

Gentamicin

effective against pseudomonas

Tetracyclines

• block A site on 50S subunit

• EX: Doxycycline

• Treats Lyme and RMSF

• can cause teeth discoloration in young people/animals

Chloramphenicol

• blocks polypeptide formation on 50S subunit

• broad spectrum

• easily diffuses into human tissues

• may cause bone marrow suppression

Macrolides

• 50S subunit blocking mRNA movement

• ED: Erythromycin and azithromycin

• may cause heart problems (rare)

polymyxin B

disrupts cytoplasmic membranes of gram negative bacteria

Azoles/Allylamines/Polyenes

• affect ergosterol

• potentially hepatotoxic (liver)

• Most end in AZOLE

Quinolones/Fluroquinolones

acts against prokaryotic DNA gyrase and has a broad spectrum

Ciprofloxacin

• is a quinolone

• can affect tendons, joints, muscle and nervous

• effective against anthrax

• DNA gyrase

Novobiocin

• affects DNA gyrase

• not a quinolone

• used in susceptibility testing

Rifampin

• disrupts RNA polymerase

Sulfonamides and Trimethoprim are

more effective together and they disrupt PABA formation of folic acid by blocking the needed enzyme

The ideal antibiotic is …

readily available, inexpensive, safe, and easy to administer

Clinical considerations of antibiotics

the two biggest are effectiveness and safety/side effects

narrow spectrum

only use if you know what you are dealing with and this is effective against only a few organisms

broad spectrum

only use when you don’t know what you are dealing with. May kill normal flora and has the potential to cause secondary or superinfections

Diffusion susceptibility test

determine which antibiotics are going to work

routes of administration

Topical, Oral, Subcutaneous, Intramuscular, Intravenous

Development of resistance

can be caused by mutations or the acquisition of R plasmids (resistance)

multiple-drug-resistant pathogens (superbug)

must be resistant to at least 3 microbial agents

Cross resistance

can happen when drugs are similar EX: Penicillin vs Amoxicillin

Synergism

one drug enhances the effect of a second drug EX: sulfonamides and trimethoprim

how can we prevent resistance

• use antimicrobials only when necessary

• develop new variations

• search for brand new antibiotics