Comparison and mode of action of antibiotics and chemotherapeutic agents.
This presentation include definition, comparison of antibiotics and chemotherapeutic, mode of action of antibiotics, role of antibiotics, types of chemotherapeutic agents.
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3. Outline
i. Definations
ii. Differance between Antibiotics and Chemotherapeutic Agents
iii. Antibiotics
iv. Mode of action of Antibiotics
v. Chemotherapeutic Agents
4. Definations
• Antibiotics
Antibiotics are medicines that fight infections caused by bacteria in humans and animals by either killing the bacteria or making it
difficult for the bacteria to grow and multiply. Bacteria are germs. They live in the environment and all over the inside and outside
of our bodies.
• Chemotheraputic Agents
The treatment of a disease with a chemical substance is called chemotherapy and the chemical substance used for the purpose is
known as a chemotherapeutic drug/agent (generally called therapeutic drug/agent).
5. Differance between Antibodies and Chemotheraputic agents
• Chemotherapeutic agents commonly refer to drugs used in the treatment of cancer.
These drugs aim at destroying or controlling cancer cells by damaging DNA or
interfering with cell division and growth.
• In contrast, antibiotics are a group of drugs used to treat bacterial infections by
killing or inhibiting the growth of bacteria.
• Both groups relate to medical treatments but chemotherapeutics cater specifically to
attack malignant cells mostly attributed with cancers whilst antibacterial targets any
microorganisms causing problematic infections/diseases without discrimination.
• Chemotherapeutic agents and antibiotics can also be differentiate on the basis of:
i. Target cells
ii. Mechanism of action
iii. Toxicity
6. Antibiotics
• Sources of Antibiotics
i. Natural: mainly fungi sources e.g Benzylpenicillin.
ii. Semi-synthetic: chemically altered natural compund e.g Ampicillin.
iii. Synthetic: chemically designed in lab e.g Moxifloxacin.
• Role of Antibiotics
i. Bactericidal effect
ii. Bacteriostatic effect
7. Mode Of Action Of Antibiotics
• There are six major modes of
action:
1. Interference with cell wall synthesis
2. Inhibition of protein synthesis
3. Interference with nucleic acid synthesis
4. Inhibition of a metabolic pathway
5. Inhibition of membrane function
6. Inhibition of ATP Synthase
8. Conti.
1. Interference with cell wall synthesis
Bacterial cells are surrounded by cell walls made of peptidoglycan. Peptidoglycan biosynthesis is essential to the integrity of the cell wall
structure, and it is the outermost layer and the main component of the cell wall. Specific antibiotics interfere with the biosynthesis of
peptidoglycans, thereby destroying the integrity of the cell wall. Since mammalian cells do not have the peptidoglycan wall structure,
inhibition of cell wall peptidoglycan biosynthesis is a preferred target for the discovery of antibacterial agents, and at the same time has
no significant negative impact on mammalian host cells.
2. Inhibition of protein synthesis
Protein synthesis is a complex, multi-step process involving many enzymes and conformational alignment. However, most antibiotics interfere with the
30S or 50S subunits of the 70S bacterial ribosome to block bacterial protein synthesis. For example, tetracyclines, including doxycycline, prevent the
binding of aminoacyl-tRNA by blocking the A (aminoacyl) site of the 30S ribosome. They are capable of inhibiting protein synthesis in both 70S and
80S (eukaryotic) ribosomes.
3. Interference with nucleic acid synthesis
Antibiotics can inhibit replication, transcription, and folate synthesis of microorganisms. Quinolone drugs can interfere with DNA synthesis by
inhibiting topoisomerase, an enzyme involved in DNA replication. For example, the second-generation quinolone drugs levofloxacin, norfloxacin, and
ciprofloxacin are active against both Gram-negative and Gram-positive bacteria. There are also antibiotics that interfere with RNA synthesis by
inhibiting RNA polymerases, such as doxorubicin and actinomycin D (dactinomycin). They interfere with bacterial and mammalian systems and are
therefore most commonly used as antineoplastic and antitumor drugs, attacking rapidly growing malignant cells as well as normal cells.
9. Conti.
4. Inhibition of a metabolic pathway
Bacterial metabolism inhibitors are a class of antibiotics that target nucleic acid and amino acid synthesis pathways. Tetrahydro-folic Acid
(TH4) is a key coenzyme used to synthesize nucleic acids and certain amino acids in all life forms. Bacteria synthesize their folic acid
from the precursor para-aminobenzoic acid (PABA). Bacterial metabolism inhibitors affect bacterial metabolic pathways by interfering
with the bacterial TH4 synthesis.
5. Inhibition of membrane function
The bacterial membrane provides selective permeability for cellular homeostasis and metabolic energy-transduction. Several
antimicrobial agents interfere with multiple targets through the interaction of a lipophilic moiety with the bacterial membrane, leading to
the destruction of membrane structures and functional impairment. At present, antibacterial agents directed against the cytoplasmic
membrane components of bacteria have been reported, and they can act on both Gram-negative and Gram-positive bacteria.
6. Inhibition of ATP Synthase
ATP synthase is the principal energy-generating enzyme in all organisms from bacteria to vertebrates through oxidative phosphorylation
or photophosphorylation. Bacteria can produce ATP through substrate-level phosphorylation of fermentable carbon sources or oxidative
phosphorylation using respiratory chains and ATP synthase. Some antibiotics have been found to inhibit oxidative phosphorylation of ATP
synthase to affect the energy production of bacteria, which in turn kills bacteria.
10. Chemotherapeutic Agents
• Chemotherapeutic agents can be classified either by the
i. Effect of agents on the cell
ii. Pharmacological properties of the agent
• Chemotherapeutic agents can be divided into
i. Cell cycle-specific agents: These are agents effective at a specific phase (e.g S & M phase) in the cell cycle to prevent
cell replication by demaging cellular DNA and blocking production of protien important for RNA and DNA synthesis
ii. Cell cycle-non specific agents: These are the agents effective throughout all the phases of cell cycle, including the
resting phase.
• Chemotherapeutic agents on the basis of pharmacological
properties:
i. Alkylating agents
ii. Antimetabolites
iii. Antitumor antibodies
iv. Mitotic inhibitors
v. Hormones and hormone antagonists
vi. Miscellaneous agents
11. Alkylating agents
• Not a phase specific.
• Act on preformed nucleic acid by creating defects in tumor
DNA.
• Cause crosslinking of DNA strand and interfere with replication
and transcription
• Act with proliferating and non proliferating cells those in G0
phase.
12. Antimetabolites
• Phase specific.
• Work best in the S phase and having little effect in G0.
• Interefere with nucleic acid synthesis by displacing metabolities
at the regulatory site of key enzzyme.
13. Antitumor Antibodies
• Derived from natural sources that are generally too toxic to be
used as anti-bacterial agents
• Not phase specific
• Act in several ways:
-They disrupt DNA replication and RNA transcription
-Create free radicals which generate breaks in DNA
-Interfere with DNA repair
• These antibiotics include; Actinomycin-D, Mitomycin-C
14. Mitotic inhibitors
• Drugs that act to prevent cell division during the M phase.
• Include the plants alkaloids and taxoids
15. Hormones and Antagonists
• Main hormone used in cancer therapy are the corticosteroids
(phase specific).
• Act by binding to specific interacellular receptors, repressing
transcription of mRNA and thereby altering cellular function
and growth.
• Work with hormone binding tumors. They block hormon’s
receptor site on the tumor and prevent it from receiving normal
hormonal growth stimulation.
16. Miscellaneous Agents
• Act at different site in cell cycle;
-Cisplatin
-Carboplatin
-Mitotane
-Procarbazine