Principles of antibiotics -I

Introduction

Antibiotics are ligands whose receptor are microbial proteins that function on the biochemical difference that exists between microorganisms and humans, they have the ability to selectively injure or kill an invading microorganism without harming the cells of the host. They are one of the few drugs which can cure, and not just suppress the disease. These are the most frequently used as well as misused drugs.

Antibiotics or Antimicrobial agent (AMA): 

designate synthetic as well as naturally obtained drugs that selectively suppress the growth of or kill other microorganisms.

Classification: 

A. Biochemical Pathways:

B. Chemical structure:

C. Class:

1.  Antibacterial: Penicillins, Aminoglycosides, Erythromycin, Fluoroquinolones, etc.
2. Antifungal: Griseofulvin, Amphotericin B, Ketoconazole, etc.
3. Antiviral: Acyclovir, Amantadine, Zidovudine, etc.
4. Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole, Diloxanide, etc.
5. Anthelmintic: Mebendazole, Pyrantel, Niclosamide, Diethylcarbamazine, etc.

D. Spectrum of activity:

Narrow-spectrum   Extended-spectrum  Broad-spectrum

E. Type of action:

Bacteriostatic Drugs: Arrest the growth and replication of bacteria, thus hampering the spread of infection until the immune system attacks, immobilizes, and eliminates the pathogen.

e.g. Sulfonamides, Erythromycin, Tetracyclines, Clindamycin, Chloramphenicol, Linezolid, and Ethambutol.

Bactericidal Drugs: They kills the pathogenic microbes.

e.g. Penicillins, Cephalosporins, Aminoglycosides, Vancomycin, Polypeptides, Ciprofloxacin, Rifampin, Metronidazole, Isoniazid, Cotrimoxazole, and Pyrazinamide

(Note: static drugs may become cidal at higher concentrations)

Selection of Antimicrobial Agents:

A. Microbial Factors

Identification of the infection organisms- 

B. Determining antimicrobial susceptibility of infective organisms

Susceptibility tests for bacteria, fungi, parasites, and viruses have been developed to determine whether these shifts have acquired at a sufficient magnitude to warrant higher doses of the drug to achieve particular effects.

C. Pharmacokinetic Basis of Antibiotics

1. Patient Factors

Age: In the newborn and older, the mechanism for the elimination of drugs is erratic.
Kidney and liver function: If these organs are not functioning properly, drugs that require them for elimination should be avoided.
Allergy: If the patient has a history of allergy to an antibiotic, it should be avoided.
Pregnancy: as far as possible antimicrobial should be avoided.
Impairment of host defense: In intact host defense, a bacteriostatic is good enough but in an impaired situation, a bactericidal drug is suggested.

2. Drug Factors

Adequate levels of an antibiotic must reach the site of infection for the invading micro-organisms to be effectively destroyed.
Lipid solubility: higher the lipophilicity higher the penetration
Molecular weight: low molecular weight; higher the penetration
Protein binding of the drug: greater the distribution of the drug
Route of administration: oral or parenteral depend on the severity of the patient
Cost:  lower cost higher preference

D. Determinants of Rational Dosing

The potency of the antimicrobial agents: Successful antimicrobial therapy of an infection depends on the concentration of the antibiotic at the site of infection.
IC₅₀ /EC₅₀: The inhibitory concentration that is 50% effective, a measure of the antimicrobial agent's potency.
Minimum Inhibitory Concentration (MIC): The lowest antimicrobial concentration that prevents visible expansion of an organism after 24hrs of incubation.
Minimum Bactericidal Concentration (MBC): The lowest concentration of antimicrobial agents that results in a 99.9% decline in the count after the overnight broth dilution incubations.
Post-antibiotic effect: The time required for the retainment of logarithmic growth. It is generally calculated from the time required to attain a 10-fold increase in bacterial count in the culture for antibiotic exposed and unexposed tubes.

The topic will be further explained on the resistance and the risk factors of antibiotics in upcoming blogs. Stay tuned for more pharmacy blogs at @A-Z pharmascience