20 Overview of Antimicrobial Drugs and Their Mechanisms

Chemotherapy

the use of a drug to treat a disease

Paul Ehrlich

research involved staining bacteria in blood samples, speculated about chemical agents with selective toxicity

Alexander Fleming (1928)

discovered the first presence of antimicrobial compound (Penicillium notatum mold on solid media)

Selective toxicity

killing/inhibiting harmful microbes without damaging the host

Antimicrobial drugs

A compound that kills or interferes with the growth of microbes within a host

Antibiotic

a substance produced by a microbe that, in small amounts, inhibits another microbe

Sulfanilamides

First antimicrobial drugs developed by a team of scientists at Bayer, known as 'Sulfa' (Prontosil Red).

Bactericidal

Directly kills microbes

Bacteriostatic

Inhibits bacterial growth

Inhibition of Cell Wall Synthesis

A mode of action for antibiotics that prevents the formation of the bacterial cell wall.

Inhibition of Protein Synthesis

A mode of action for antibiotics that prevents the production of proteins necessary for bacterial growth.

Targeting of Plasma Membrane

A mode of action for antibiotics that disrupts the integrity of the bacterial cell membrane.

Inhibition of Nucleic Acid Synthesis

A mode of action for antibiotics that interferes with the replication and transcription of bacterial DNA.

Inhibition of Key Metabolite Synthesis

A mode of action for antibiotics that blocks the synthesis of essential metabolites in bacteria.

Penicillin

Originally isolated from Penicillium mold, it prevents peptidoglycan crosslinking in bacterial cell walls.

Natural Penicillins

Penicillins that are derived from natural sources.

Synthetic Penicillins

Penicillins that are chemically manufactured.

structure of various penicillin

common nucleus, B-lactam ring

Penicillin G

An injectable form of penicillin effective against Gram-positive bacteria.

Penicillin V

An oral form of penicillin that is effective against Gram-positive bacteria.

Oxacillin

A synthetic penicillin

that resists destruction by penicillinase (a type of β-lactamase), but can still fit into penicillin-binding proteins (PBPs), blocking cell wall synthesis and killing bacteria.

Penicillinase

An enzyme produced by some bacteria that inactivates penicillin.

MRSA

Methicillin-resistant Staphylococcus aureus, a type of bacteria resistant to many antibiotics.

Potassium Clavulanate

A non-competitive inhibitor of penicillinase used to overcome bacterial resistance.

Dosage Characteristics of Penicillin G

Refers to the concentration of Penicillin G in blood over time after administration.

D-D transpeptidase

The bacterial enzyme responsible for crosslinking of peptidoglycan chains in the cell wall.

mechanism of penicillin

1. Binds to PBPs→ Penicillin binds to penicillin-binding proteins (PBPs), which help build the cell wall.

2. Blocks Peptidoglycan Cross-Linking→ Stops the cross-linking of peptidoglycan, a key cell wall component.

3. Weakens the Cell Wall→ The wall can't handle pressure → becomes unstable.

4. Bacteria Burst (Lysis)→ Water rushes in → the bacteria explode and die.

Evolution of Bacterial Resistance

The process by which bacteria develop the ability to resist the effects of antibiotics.

Augmentin

Combined with broad range synthetic penicillins.

Cephalosporins

Closely resembles penicillin and inhibits cell wall synthesis by the same mechanism.

First-generation Cephalosporins

Narrow spectrum; act against gram-positive bacteria.

Second-generation Cephalosporins

Extended spectrum includes gram-negative bacteria.

Third-generation Cephalosporins

Includes pseudomonads and is administered by injection.

Fourth-generation Cephalosporins

Administered orally.

Bacitracin

Inhibits cell wall synthesis and blocks transport of NAG and NAM building blocks across the cell membrane.

Vancomycin

Narrow spectrum that kills mostly Gram-positive bacteria by stopping their cell walls from being built properly and one of the last lines of defense against MRSA.

Steps of Protein Synthesis Inhibition by Antibiotics

1. Antibiotic attaches to bacterial ribosome→ It sticks to the ribosome, which is the bacteria's protein making machine.

2. Blocks ribosome function→ Prevents the ribosome from reading the bacterial RNA instructions.

3. Stops protein production→ No proteins get made, and bacteria can't grow or fix themselves

4. Bacteria stop growing or die→ Without proteins, bacteria cannot survive or multiply.

Chloramphenicol

Binds to 50S ribosomal subunit and inhibits formation of peptide bond; broad spectrum.

Streptomycin

Binds to 30S ribosomal subunit and interferes with proper reading of the mRNA codon; effective against Gram-/+ bacteria and Mycobacteria.

Tetracyclines

Binds to 30S ribosomal subunit and interferes with

docking of tRNA; blocking peptide synthesis, broad spectrum.

Erythromycin

Binds to 50S ribosomal subunit blocking the peptide tunnel; effective against Gram+ bacteria

Linezolid

Completely synthetic drug that binds to 50S ribosomal and prevents binding to 30S subunit; effective against Gram+ bacteria, may help delay bacterial resistance

Daptomycin

Attacks bacterial plasma membrane, changes membrane structure, and stops DNA, RNA, protein synthesis; effective against Gram+ bacteria.

Polymyxin B

Binds and destabilizes both outer and cytoplasmic membrane of Gram- bacteria; used topically.

Rifamycins

Inhibits synthesis of mRNA by binding to bacterial DNA-dependent RNA polymerase; used to treat tuberculosis and leprosy.

Aminoglycosides

Class of antibiotics including Streptomycin that interferes with protein synthesis.

Macrolides

Class of antibiotics including Erythromycin that binds to the 50S ribosomal subunit.

Inhibitors of Cell Wall Synthesis

Antibiotics that prevent the formation of bacterial cell walls.

Gram-positive bacteria

Bacteria that retain the crystal violet stain used in the Gram staining procedure.

Gram-negative bacteria

Bacteria that do not retain the crystal violet stain and are characterized by a thin peptidoglycan layer.

Ciprofloxin

Chemical synthesized (not isolated from microbe) that inhibits bacterial DNA Gyrase blocking DNA replication.

Quinolones and Fluroquinolones

A class of antibiotics that inhibit bacterial DNA replication.

Anthrax

An infectious disease that ciprofloxin is used to treat.

Sulfamethoxazole/Trimethoprim

Drug synergism (smaller dosage if two are combined), Inhibits synthesis of metabolic intermediates of Thymidine (eventually inhibiting DNA synthesis), often used to treat urinary tract infections (alternative to penicillin)

Drug Synergism

The phenomenon where smaller dosages are effective when two drugs are combined.

PABA (para-aminobenzoic acid)

competes with sulfamethoxazole to inhibit the synthesis of dihydrofolic acid in bacteria

Dihydrofolic acid

A precursor in the synthesis of tetrahydrofolic acid, which is inhibited by trimethoprim.

Tetrahydrofolic acid

A critical metabolite for the synthesis of proteins, DNA, and RNA.

Amphotericin B

An antifungal drug that binds ergosterols and leads to damage of the cell membrane.

Acyclovir

An antiviral drug that resembles the nucleoside deoxyguanosine and blocks DNA synthesis.

Chloroquine

An antiprotozoan drug used to treat and prevent malaria, targeting merozoites. (prevents inactivation of toxic metabolic

byproduct)

Artemisinin

An antiprotozoan drug used to treat and prevent malaria, targeting sporozoites.

Niclosamide

An antihelminthic drug that prevents ATP generation in tapeworms.

Praziquantel

An antihelminthic drug that alters membrane permeability in flatworms and flukes.

Ivermectin

An antihelminthic drug that causes paralysis in roundworms, some ticks, and mites.

Kirby-Bauer Test

A test used to identify antibiotic susceptibility.

E Test

A test used to determine Minimum Inhibitory Concentration (M.I.C.).

Misuse of Antibiotics

Includes using outdated antibiotics, using them for inappropriate conditions, and failing to complete the prescribed regimen.

Development of Antibiotic Resistance

A problem exacerbated by the misuse of antibiotics and large-scale antibiotic use in agriculture.

Blocking entry

One of the modes of bacterial resistance to antibiotics.

Inactivation by enzymes

A mode of bacterial resistance where enzymes inactivate antibiotics.

Alteration of target molecule

A mode of bacterial resistance where the target of the antibiotic is altered.

Efflux of antibiotic

A mode of bacterial resistance where bacteria pump out the antibiotic.