Antimicrobial agents
I. Introduction
Pharmacognosy IV
PHG 423
Dr/ Abdulaziz Saeedan
Pharmacy College
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Antimicrobial agents
 Antimicrobial agents are compounds that either kills or prevents the growth and
multiplication of microorganisms such as bacteria, viruses, fungi or protozoa.
 They are used to prevent or treat infectious diseases.
 There are 2 groups of antimicrobial agents used in the treatment of infectious
diseases:
1- Antibiotics, which are natural substances produced by certain groups of
microorganisms.
2- Chemotherapeutic agents, which are chemical substances that are completely
synthesized.
NOTES:
o Penicillin was the first antibiotic to be discovered by Sir Alexander Fleming in
1928.
o Chemotherapeutic agents were originally those employed against infectious
microbes, but the term has been broadened to include anticancer drugs.
o In the medical and pharmaceutical fields, all these antimicrobial agents used in
the treatment of infectious diseases are referred to as antibiotics.
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Sources of Antibiotics
1- Natural – These are antibiotics that isolated from fungal and bacterial sources.
Ex: Benzylpenicillin (from penicillum notatum) and streptomycin (from
Actinomycetes sp)
2- Semi-synthetic – These are antibiotics that isolated from fungal or bacterial
sources then modified chemically in the Lab.
• Semi-synthetic drugs were developed to decrease toxicity and increase
effectiveness
Ex: Ampicillin and Amikacin
3- Synthetic – These are antibiotics that completely synthesized in the Lab.
• They are designed to have greater effectiveness and less toxicity.
Ex: Moxifloxacin and Norfloxacin
NOTES:
 Most of the natural antibiotics are isolated from soil microorganisms.
 Natural antibiotics are often more toxic than synthetic antibiotics.
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Antibiotic spectrum
•
It is the field of antibacterial activity of the antibiotic or the range of microorganisms that
affected by the antibiotic.
So there are 2 types of antibiotic spectrum:
1) Narrow spectrum antibiotics:
• These are antibiotics which act against limited range of microorganisms.
• Ex: Penicillin G is a narrow spectrum drug as it is only effective against Gram +ve
bacteria.
2) Broad (wide) spectrum antibiotics:
• These are antibiotics which act on wide range of microorganisms either Gram +ve or
Gram –ve bacteria.
• Ex: Tetracyclines are broad spectrum drugs as they are effective against Gram +ve and
Gram -ve bacteria.
NOTES:
o No antibiotic is effective against all microbes.
o There is no relation between spectrum of an antibiotic and its efficacy or potency (ie.
narrow spectrum antibiotics are weak and broad spectrum are strong is a not true thinking)
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Action of Antibiotics
1) Bacteriostatic antibiotics:
• These are antibiotics which prevent the growth and multiplication of bacteria.
• Bacteriostatic antibiotics give the chance for natural immunity to deal with the
microbes SO they are given to patients with good immune status.
• Ex: Sulfonamides, Tetracycline, Chloramphenicol.
2) Bactericidal antibiotics:
• These are antibiotics which kill bacteria.
• Bactericidial antibiotics may lead to release of toxins and other microbial
contents leading to subsequent illness and inflammatory responses.
• Ex: Penicillins, Cephalosporins, Streptomycine.
NOTES:
o Minimal Inhibitory Concentration (MIC) = The lowest concentration of antibiotic that
inhibits the growth of the bacterial population.
o Minimal Bactericidal Concentration (MBC) = The lowest concentration of antibiotic that
kills the bacterial population
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What is the Ideal Antibiotic?
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Antibiotic Targets
• Antibiotic targets can be divided into 5 major sites:
1- Bacterial nucleic acids
2- Bacterial metabolism
3- Bacterial ribosomes or bacterial proteins
4- Bacterial plasma membrane
5- Bacterial cell wall
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MOA of Antibiotics
1) Inhibition of nucleic acid synthesis:
Ex: Quinolones.
 Topoisomerase enzymes, especially topoisomerase II (DNA gyrase) relaxes the
supercoiled DNA molecules of the bacterial cell.
 Relaxation of the supercoiled DNA molecules allows the DNA strands to be
replicated by DNA polymerase enzyme.
► Quinolones acts by inhibition of DNA-gyrase enzyme, so prevent relaxation of
the supercoiled DNA molecules of the bacterial cell and consequently inhibit the
synthesis or replication of DNA.
NOTES:
 Topoisomerase enzymes are present in both prokaryotic (bacteria) and eukaryotic
(human) cells, but the quinolones are specific inhibitors of bacterial
topoisomerase II.
 Inhibitors that are effective against human topoisomerase enzymes, such as
etoposide, are used as anticancer drugs to kill cancer cells
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2) Interfering with the bacterial metabolism:
Ex: Sulfonamides



Para-aminobenzoic acid (PABA) is utilized by bacteria and converted into dihydrofolic
acid by dihydropteroate synthetase enzyme.
Dihydrofolic acid converted by dihydrofolate reductase enzyme into tetrahydrofolic acid,
then to purines which are essential for synthesis of nucleic acids (DNA) of the bacterial
cell.
Due to the chemical similarity between sulfonamides and PABA, bacteria utilize
sulfonamides instead of PABA, so prevent the synthesis of dihydrofolic acid and block
the synthesis of DNA of bacterial cell.
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3) Inhibition of protein synthesis:
 Proteins that synthesized by ribosomes are needed for growth, multiplication &
other vital activities of bacteria.
 Antibiotics act at different sites on bacterial ribosomes.
o Aminoglycosides (Streptomycin, neomycin, gentamicin) and tetracycline bind to
the 30S ribosome causing misreading of mRNA.
o Chloramphenicol, Macrolides (Erythromycin) and Lincosamides (Clindamycin)
binds to the 50S ribosome so interfere with the process of amino acids
polymerization and result in synthesis of non-functional or defective protein.
 Defective protein fails to function correctly.
NOTE:
The selective toxicity of these antibiotics is low as bacterial ribosomes are similar to
the mitochondrial ribosomes of human cells.
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4) Interfering with the permeability of cell membrane:
o Ex: Polymyxin.
 The cell membrane of bacteria have a certain permeability to control and protect
the internal composition of the bacterial cell.
 Polymyxin attached to the cell membrane and interfere with its permeability, so
the bacterial contents can escape causing bacteriolysis.
 Polymyxin is very toxic as there is little differences between human and
bacterial cell membrane.
► So, it used as the last option.
NOTE:
Antibiotics that interfere with cell membrane function show the least degree of
selective toxicity.
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5) Inhibition of cell wall synthesis:


The bacterial cell wall is located outside of the cell membrane.
This wall is tough and rigid giving protection to the bacterial cell against the possible
osmotic damage.
 The cell wall is made up of the peptidoglycan molecules: NAG and NAM.
o NAG = N-acetylglucosamine
o NAM = N-acetyl muramic acid


At the final step of cell wall synthesis, cross-linking of NAG and NAM is completed
through the activity transpeptidase enzyme.
β-Lactam antibiotics (Penicillins and cephalosporins) inhibit the transpeptidase enzyme
so interfere with the process of cross-linking between NAG and NAM leading to rupture
of the bacterial cell due to osmotic damage.
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NOTES:
o Cell wall is absent in human cells, so antibiotic which destruct the cell wall
has high selective toxicity i.e toxic only to the bacteria and is non toxic to
human.
o Drugs that affect the bacterial cell wall are active only against young, actively
growing microbes.
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Failure of antibiotic therapy
 Antibiotic treatment is considered a failure if no response is seen within 3 days.
 Failure may be due to various causes:
1. Wrong diagnosis (a viral infection does not respond to antibiotics).
2. Wrong choice of antibiotic.
3. Wrong dosage .
4. Development of resistance during therapy.
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Side (adverse) effects of antibiotics
 Antibacterials are screened for any negative effects on humans before approval
for clinical use SO they are usually considered safe.
 However, some antibacterials have been associated with a range of adverse
effects.
 Side effects of the antibiotics are the unwanted reactions that occur during the
medication period.
 Antibiotic side effects are extremely variable from patient to patient and from
antibiotic to antibiotic.
Side-effects include:
І. Allergic reactions
ІІ. Toxic reactions
ІІІ. Superinfection
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I- Allergic reactions
 Allergic reactions may be mild or serious.
1. Mild allergic reactions:
a- Allergic dermatitis:
 Occurs by using of topical antibiotics.
 The treated area of skin appears red, swollen and itchy.
b- Urticaria:
 Urticaria is raised itchy rashes that appears on the skin
after using of systemic antibiotics.
 The rashes are often red and can be limited to one part of
the body or spread through large areas.
 In addition, some blisters may appears around the mouth.
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2. Serious allergic reactions:
a- Angioedema:
 It is the swelling of the body tissues.
 Lips, tongue, and eyelids may also swell.
b- Anaphylaxis: (Anaphylactic shock)
 It is the most severe form of allergic reactions and
is potentially life threatening.
 Usually occurs within 20 minutes to 2 hours of
exposure to the drug due to massive release of
histamine.
 The symptoms include hypotension, bronchial
asthma and skin rash.
 Anaphylaxis is an emergency case so it must be
treated immediately.
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How is an allergic reaction treated?
a- Simple rashes are treated with antihistamines and/or corticosteroids to reduce
itching and redness.
b- Anaphylactic shock is generally treated with injectable epinephrine and/ or
antihistaminics.
ІІ. Toxic reactions
a- Nephrotoxicity
• Antibiotics that are metabolized and excreted in the kidney most frequently
cause kidney damage.
b- CNS toxicity
• When drugs can pass through the brain barrier and accumulate in the nervous
tissues, they can interfere with neuronal function.
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III. Superinfection
 Broad-spectrum antibiotics may change the normal balance of
microflora in the GIT and vagina leading to overgrowth of certain
pathogens.
1- Antibiotic-associated diarrhea:
 5 to 25% of patients may develop diarrhea following antibiotic
medication due to destruction of the normal gut flora by the antibiotic
and results in overgrowth of Clostridium sp.
 The most common antibiotics implicated in antibiotic-associated
diarrhea are amoxicillin and ampicillin.
2- Vaginal and Oral thrush: (Candidiasis)
 Candida albicans is a fungus present normally in small populations in
the vagina and mouth and does not normally induce disease or
symptoms.
 Using of some broad-spectrum antibiotics kills bacterial species
leading to overgrowth of Candida albicans in vagina and oral cavity
causing thrush.
o The symptoms of vaginal thrush include itching, pain and vaginal
discharges.
o In oral thrush, some white patches are visible.
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