Microbio Lecture 16 - 5 modes of action (Antimicrobial drugs)

1. Cell Wall Synthesis

prevents the making of peptidoglycan

Natural Penicillins (mode 1)

Penicillin G (injection) = not resistant to stomach acid

Penicillin V (oral) = resistant to stomach acid

against gram-positive bacteria

Semisynthetic Penicillins (mode 1)

• Oxacillin = narrow spectrum ; resistant to pencillinase

• Ampicillin = broad spectrum

• Amoxicillin = broad spectrum ; combined with inhibitor of penicillinase

Cephalosporins (mode 1)

• cephalothin = injection ; activity similar to penicillin ; first generation

• ceftaroline

Polypeptide Antibiotics (mode 1)

• bacitracin = topical application ; against gram-positive bacteria

• blocks assembly of linear NAG/NAM strands

2. Protein synthesis (70S ribesome)

disrupts/inhibits the making of proteins

Chloramphenicol (mode 2)

• broad spectrum ; potentially toxic

• affects bone marrow + blood cell development ; because it harms mitochondria in cells that produce new blood cells in bone marrow

Aminoglycosides (mode 2)

1. Streptomycin = broad spectrum, including mycobacteria

Aminoglycosides (mode 2)

2. Neomycin = topical use ; broad spectrum

Aminoglycosides (mode 2)

3. Gentamicin = broad spectrum

Tetracyclines (mode 2)

tetracycline, oxytetracycline, chlortetracycline

• broad spectrum, including chlamydias + rickettsias

Macrolides (mode 2)

1. Erythromycin

2. Azithromycin

3. Telithromycin

3. Nucleic acid synthesis

inhibits the making of nucleic acids

Rifamycins (mode 3)

Rifampin = inhibits synthesis of mRNA ; treatment for tuberculosis ; blocks RNA polymerase, so no mRNA (intereferes with transcription) ; selective toxicity

Quinolones (mode 3)

Nalidixic acid = blocks topoisomerase (gyrase) ; interferes with DNA replication

Fluoroquinolones (mode 3)

Ciprofloxacin = targets topoisomerase but modifications allow broader spectrum ; selective toxicity

4. Targeting Cell Membranes

injuring the plasma membrane

Lipopeptides (mode 4)

Polymyxin B = topical use, gram-negative bacteria

Lipopeptide antibiotics

change membrane permeability and assault the inner/outer membranes of Gram - and cell membrane of Gram +

• antifungals = combine with membrane sterols to further disrupt membranes

• lack selective toxicity = have more side effects due to similarities between human/microbe cell membranes

5. Essenstial metabolite synthesis

inhibiting the synthesis of essential metabolites

Sulfonamides (mode 5)

sulfamethoxazole-trimethoprim = broad spectrum ; combination widely used

Antimetabolites

compete with normal substrates (PABA) for an enzyme

• antimetabolite = fake ingredient ; looks so much like the real ingredient that the enzyme grabs it instead

• this stops synthesis of folic acid = needed for nucleotide synthesis

• selective toxicity (humans lack this pathway = we get folic acid from food)

Semisynthetic penicillin

taking natural penicllin and changing its side chains

• makes penicillin (antibiotic) work better in certain situations

3 types of semisynthetic penicillin

1. Penicillinase-resistant penicllins

2. Extended-spectrum penicillins

3. Penicillin + B-lactamase inhibitors

Penicillinase-resistant penicllins

• Methicllin and Oxacillin = modified side chains for reduced penicillinase activity

• Methicillin resistance has developed though (MRSA)

Extended-spectrum penicillins

Ampicillin and Amoxicillin

• effective against Gram + and Gram -

• able to penetrate Gram - cell walls

Penicillin + B-lactamase inhibitors

B-lactamase = penicillinase

Augmentin = Amoxicillin + Clavulanic acid

• Clavulanic acid → a drug ; a non-competitive inhibitor of penicillinase = blocks activity ; protects Amoxicillin