Antimicrobial Drug

Antimicrobial Drugs

Dr. Mejbah Uddin Ahmed

Antimicrobial Agents: Antimicrobial are the agents, they either kill or prevent growth of micro-organisms. Two categories: 1. Antibiotics: Antimicrobial drugs produced from biological agents (microorganisms). 2. Synthetic drugs: Antimicrobial drugs are synthesized in the laboratory.

Antibacterials: Relatively easy to develop and find with low toxicity because procaryotic cells are very different from host cells. Antihelminthic, antiprotozoan, and antifungal drugs: More difficult to develop because eucaryotic cells resemble human cells. Antivirals: Most difficult to develop because virus reproduces using host cell enzymes and machinery.

Selective toxicity A

drug should selectively kill or prevent growth of a microorganism, but not host cells.

Selective toxicity is achieved by:  They

act at specific site

 Bacterial

cell wall

 Inhibition

of an enzyme unique to bacteria

 Inhibition

of bacterial protein synthesis

 Bacterial

nucleic acid

 Selective

toxicity is better incase of antibacterial agents than antiviral or antifungal drug

Classification 1. According to source of originA) Antibiotics- natural products of fungi, & bacteria which kill the microbes e.g. Penicillins, B) Synthetic compound- e.g. trimethoprim, Sulfonamides.

Classification 2. Either kill or inhibit bacteria: A) Bactericidal- kills organisms: penicillin, cephalosporin, aminoglycoside. B) Bacteriostatic - Inhibit organisms from multiplying, but does not kill: tetracycline, chloramphenicol and erythromycin.

4. According to target site A. Inhibition of cell wall synthesis B. Inhibition of protein synthesis C. Inhibition of nucleic acid synthesis D. Inhibition of metabolic pathways E. Interference with cell membrane integrity

Classification 5. According to spectrum of activity: A) Narrow spectrum: Drugs that affect only Gram-positive organisms or only Gramnegative organisms: Vancomycin, Nalidixic acid. B) Broad spectrum: Drugs that affect both Gram-positive and Gram-negative organisms: Tetracycline, Ciprofloxacin.

A. cell wall synthesis Inhibitors: Beta-lactam

drugs

Penicillins Cephalosporins Carbapenems The

others

Cycloserine Vancomycin bacitracin

Penicillin: ● Act by binding to Penicillin Binding Proteins. ● Inhibit transpeptidase activity & peptide cross linking in cell wall. ● Cause the bacterial wall to weaken and take up water and burst

B. Inhibition of protein synthesis: ♦ Irreversibly binds to 30S ribosomal subunit: Aminoglycoside, Tetracycline ♦ Reversibly binds to 50S ribosomal subunit: Chloramphenicol, Erythromycin, clarithromycin, azithromycin

C. Inhibition of Nucleic Acid Synthesis: Quinolones: Inhibits DNA synthesis by affecting DNA gyrase . Rifamycins: inhibits bacterial DNA - dependent RNA polymerase blocks mRNA. Metronidazole: Breaks the strands of DNA

Inhibition of metabolic pathways: Most useful are folate inhibitors: Sulfonamides & Trimethoprim. Pteridine + PABA + Glutamic acid Sulfonamide HAH2 Trimethoprim

dihydropteroate synthatase Dihydrfolate reductase

HAH4 Purine

Pyrimidine

Amino acids

E. Injury to cell membranes ◆ Changes ◆

in membrane permeability.

Result in loss of metabolites and/or cell lysis.

◆ Many

polypeptide antibiotics.

◆ E.g.:

Polymyxin, Colistin, Daptomymycin, miconazole, Polyenes (anti-fungal agents)

Combinations

of Drugs

 Indications Severe

and mixed infections

Prompt

treatment

To To

delay emergence of drug resistance

achieve bactericidal action or synergism

 Disadvantages    

False sense of security High cost of treatment No more than effect of a single drug Possibility of antagonism (rarely)

 Combinations: Sulphonamide β

+ Trimethoprim,

lactams + aminoglycosides

Amoxycillin Anti

+ Clauvlinic acid

tubercular drugs.

Safety Concerns with the Use of Antimicrobials: ♦Toxicity: Kidney, Liver damage, Bone marrow (Chloramphenicol and aplastic anemia). ♦ Interactions with other medications ♦ Hypersensitivity reactions ♦ Fetal damage/risk to pregnant women: Tetracyclin causes discoloration of teeth in children. ♦ Kills host’s normal beneficial flora. ♦ Antibiotic Resistance.