Terminologies on anti infective agents

Terminologies on Anti-infective Agents 1

Terminologies on Anti-infective Agents

Kyaw San Lin (RN. 22)Khin Kant Kaw Gyi (RN. 47)


TerminologiesAntibiotic antimicrobialsSpectrumResistanceBactericidalBacteriostaticPost-antibiotic effect (PAE)Time-dependent killingDose-dependent killing


Anti-microbial chemotherapy the drug treatment of parasitic

infections in which parasites (bacteria, viruses, protozoa, fungi, helminths) are destroyed or inhibited without injuring the host, by a process known as “selective toxicity”


Selective Toxicity

interfering with some metabolic processes that exist only in the infectious organisms (not in the cells of the host) by the anti-infective agents at concentrations tolerated by the host (may be complete or rela tive)


Antibiotics

chemical substances originally produced by various species of mi cro-organisms (bacteria, fungi, actinomycetes), that in high dilution suppress the growth or cause death of other microorganisms.


Antibacterial spectrum

List of bacteria which are normally susceptible to antibacterial action of particular agents.


Narrow-spectrum antibiotics Antibiotics that act only on a single

or a limited group of microorganisms.

E.g., isoniazid is active only against mycobacteria. Mycobacteria

OtherChlamydia

Mycoplasma

Spirochetes G (-) rods

G (+) bacilli

Anaerobic organisms

G (+) cocci

G (-) cocci


Extended-spectrum antibiotics Antibiotics that are effective against

G (+) & also against a significant number of G (-) bacteria.

E.g. Ampicillin

OtherChlamydia

MycoplasmaSpirochetes G (-) rods

G (+) bacilli

Anaerobic organisms

G (+) cocci

G (-) cocci

G (+) bacilliListeria monocytogenes

G (-) rodsE. coliH. influenzaeProteusSalmonella typhi


Broad-spectrum antibiotics Antibiotics that are effective against

G (+), G(-), aerobic & anaerobic bacteria.

E.g., tetracyclineOther

Chlamydia

Mycoplasma

Spirochetes G (-) rods

G (+) bacilli

Anaerobic organisms

G (+) cocci

G (-) cocci

ActinomycesRickettsiaeAmoebae

Chlamydia

Mycoplasma

SpirochetesAnaerobic organisms

G (-) rods


Superinfection

Drug therapy, particularly with broad-spectrum antimicrobials or combination of agents, can lead to alteration of normal flora of respiratory, GI & GU tracts, permitting the overgrowth of opportunistic organisms.

Resistance to anti-microbial drugsMicroorganisms produce enzymes which destroy the active drugs.Microorganisms change their permeability to the drug.Microorganisms develop an altered structural target for drug.Microorganisms development an altered metabolic pathway that bypasses the reaction inhibited by drug.Microorganisms develop an altered enzyme that can still perform its metabolic function but is much less affected by drug than the enzyme in susceptible organisms.Terminologies on Anti-infective Agents 11


Cross-resistance Microorganisms resistant to certain

drug may also be resistant to other drugs that share mechanism of action or attachment.

Such relationships exist mainly between agents that are closely related chemically (Erythromycin – Oleandomycin, Neomycin – Kanamycin), but they may also exist between unrelated chemicals (Erythromycin – Lincomycin).


Bactericidal Vs Bacteriostatic


Bacteriostatic

Bactericidal

No antimicrobial agent

Bacteriostatic Inhibiting the growth or

multiplication of bacteria Number of bacteria remains relatively

constant. Immunologic mechanisms are

required to eliminate organisms. Examples:

drugs that usually inhibit a metabolic reaction that is needed for bacterial growth but is not necessary for survival (e.g., sulfonamides block the synthesis of folic acid)

Drugs that reversibly inhibit bacterial protein synthesis (e.g., tetracyclines)Terminologies on Anti-infective Agents 15


Bactericidal Lethal effect on mature bacteria (kill

the bacteria) Number of organisms falls rapidly

after exposure to the drug. Induce lethal changes in microbial

metabolism or block activities that are essential for microbial viability.

Examples:• drugs that inhibit the synthesis of the

bacterial cell wall (e.g., penicillins)• drugs that irreversibly inhibit

protein synthesis (e.g., streptomycin)


Pharmacodynamic interactions Bacteriostatic + Bacteriostatic

Different binding site Synergism Same binding site Indifference

Bactericidal + Bactericidal Synergism

Bactericidal + Bacteriostatic Antagonism Bactericidal drugs are usually more

effective against rapidly dividing bacteria.

Their effect may be reduced if bacterial growth is slowed by a bacteriostatic drug.


Minimum inhibitory concentration (MIC) minimum concentration that

will inhibit growth of a pathogen.


Dose-dependent Killing Some drugs kill better when the

maximum concentration of the drug is very high compared with MIC.

1 x MIC

2 x MIC

3 x MIC4 x MIC


Examples

Vancomycin Fluoroquinolones Aminoglycosides


Time-dependent Killing Killing effect of some drugs depend

on the percentage of time that blood concentrations of a drug remain above the MIC.

1 x MIC

4 x MIC


Examples

Penicillins Cephalosporins

Post-antibiotic effect (PAE) Persistent suppression of microbial

growth that occurs after levels of antibiotic have fallen below the MIC.

Antimicrobial drugs exhibiting a long PAE (several hours) often require only one dose per day.

For example, aminoglycosides and fluoroquinolones, exhibit a long PAE.

Proposed mechanisms by which the PAE occurs include both nonlethal damage induced by the antimicrobial agent & a limited persistence of the antimicrobial agent at the bacterial binding site.


References Department of Pharmacology: Lecture

notes on Pharmacology Volume 2, 4th ed. Universities of Medicine 1 & 2 (Yangon), Mandalay, Magway, Defense Services Medical Academy, 2013.

Clark MA, Finkel R, Rey JA, Whalen K: Lippincott’s Illustrated Reviews of Pharmacology, 5th ed. Lippincott Williams & Wilkins, 2012.

Bennett PN, Brown MJ, Sharma P: Clinical pharmacology, 11th ed. Churchill Livingstone, 2012.

Brenner GM, Stevens CW: Pharmacology, 4th ed. Saunders, 2012.Terminologies on Anti-infective Agents 24


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Terminologies on anti infective agents