Ch. 20 - Antimicrobial Drugs

Who discovered chemotherapy?

Ehrlich

What is penicillin made of?

Penicillium, which is from the growth of Staphylococcus aureus

Antimicrobial drugs

Interfere with growth of microbes within a host

Antibiotic

Substance produced by a microbe that in small amounts, kills/inhibits another microbe

What are naturally occurring antibiotic sources?

• Bacteria (Gram+ rods— endospore formers)

• Actinomycetes (Streptomyces)

  • 50% of all antibiotics

Semi-synthetic antibiotic sources

Naturally occurring which are then modified at a lab

• Ampicillin

• Amoxicillin

Synthetic antibiotics

Made in the lab

• Trimethoprim

Narrow spectrum

Affects only 1 type of microbe

Broad spectrum

Affects 2+ types of microbes

Extended spectrum

Originally narrow spectrum but are modified to become broad (unnatural)

Describe the therapeutic index

Measurement of the drugs safety (toxic dose/effective dose)

• Difference in the numbers shows how safe it would be for the general public

• Toxic dosage should be much higher than the effective dosage to avoid overdose

Antibiotic mechanisms of action

1. Inhibit cell wall synthesis

2. Inhibit protein synthesis

3. Inhibit nucleic acid replication

4. Damage plasma membrane

5. Inhibition of essential metabolic synthesis

What are the inhibitors of cell wall synthesis?

• b-Lactams

• Peptide antibiotics

• Antimycobacterials

Function of b-Lactams

Prevent cross-linking of peptidoglycans

Difference with penicillin G to penicillin V

Penicillin G is the original penicillin given via injection b/c it gets digested by stomach acid.

• Penicillin V is the improved version PO

Structure of b-Lactams

Contains a b-Lactam ring connected to a house-like structure

Why are penicillins used the most?

• Largest therapeutic index

• Cheapest

What is penicillinase?

Enzyme that breaks down the b-Lactam ring

What are penicillinase/lactamase resistant antibiotics?

Antibiotics resistant to the enzyme Penicillinase

• Outer ring becomes resistant due to ammonium

Describe cephalosporins

• Similar structure to penicillin

• Contains b-Lactam ring followed by a hexagon

What are the polypeptide antibiotics?

1. Bacitracin

2. Colistin

3. Vancomycin

Bacitracin

• Inhibits the synthesis of linear peptidoglycan

• Effective against gram +

Colistin

• Inhibits synthesis of cell wall

• Effective against gram -

What is vancomycin?

• Glycopeptide (carbohydrate)

• “Last line” against MRSA penicillin resistant S. aureus)

Antimycobacterial antibiotics

• Effective against TB

• Inhibits mycolic acid synthesis into cell wall

Why is it preferred to use synthetic antibiotics?

Growing in the lab ensures purity which is more difficult than isolation

Describe inhibiting protein synthesis

• Bindings to small/large ribosomal subunit

• Antibiotics end in “mycin”

Why are protein synthesis inhibitors usually broad spectrum?

Because protein synthesis takes place in many bacteria

What are the inhibitors of DNA/RNA synthesis

1. Rifamycin (antimycobacterial drug— tuberculosis)

2. Ciprofloxacin (CIPRO— UTI, anthrax)

What antibiotic damages the plasma membrane?

Polymyxin B

• Combined with bacitracin & neomycin (triple action)

• Effective against gram -

What are the inhibitors of enzymes?

Sulfonamides & trimethoprim

• Inhibits folic acid synthesis

How do bacteria develop resistance to enzyme inhibiting antimicrobials?

Starts to take pre-formed folic acid instead of creating it

Mechanisms of drug resistance

• Prevent entrance of drug

• Pump out drug

• Inactivation/degradation of drug

• Alteration of target enzyme

• Alternative pathways for metabolism

Overuse of antibiotics

Kills off susceptible microbes leaving the resistant microbes to reproduce

What are the drug resistant “superbugs”?

MRSA

• Methicillin-resistant S. aureus —given vancomycin

VRE

• Vancomycin-resistant