Page 96 - Review of Medical Microbiology and Immunology ( PDFDrive )

mebooksfree.com
mebooksfree.com
mebooksfree.com

mebooksfree.com mebooksfree.com mebooksfree.com CHAPTER 10 Antimicrobial Drugs: Mechanism of Action 85 mebooksfree.com
mebooksfree.com
mebooksfree.com
mebooksfree.com
mebooksfree.com
mebooksfree.com
• Quinolones inhibit DNA synthesis in bacteria by blocking DNA
• Caspofungin is a lipopeptide that inhibits fungal cell wall
gyrase (topoisomerase)—the enzyme that unwinds DNA
synthesis by blocking the synthesis of β-glucan, a polysac-
strands so that they can be replicated. Quinolones are a family of
charide component of the cell wall.
drugs that includes ciprofloxacin, ofloxacin, and levofloxacin.
Inhibition of Protein Synthesis
• Rifampin inhibits RNA synthesis in bacteria by blocking the
RNA polymerase that synthesizes mRNA. Rifampin is typically
• Aminoglycosides and tetracyclines act at the level of the
used in combination with other drugs because there is a high
30S ribosomal subunit, whereas chloramphenicol, erythro-
rate of mutation of the RNA polymerase gene, which results
mycins, and clindamycin act at the level of the 50S ribo- Alteration of Cell Membrane Function
in rapid resistance to the drug.
mebooksfree.com mebooksfree.com mebooksfree.com • Antifungal drugs predominate in this category. These drugs mebooksfree.com
mebooksfree.com
mebooksfree.com
somal subunit.
• Aminoglycosides inhibit bacterial protein synthesis by bind-
ing to the 30S subunit, which blocks the initiation complex.
No peptide bonds are formed, and no polysomes are made.
have selective toxicity because fungal cell membranes con-
Aminoglycosides are a family of drugs that includes gentami-
tain ergosterol, whereas human cell membranes have choles-
cin, tobramycin, and streptomycin.
terol. Bacteria, with the exception of Mycoplasma, do not
• Tetracyclines inhibit bacterial protein synthesis by blocking
have sterols in their membranes and therefore are resistant to
the binding of aminoacyl tRNA to the 30S ribosomal sub-
these drugs.
unit. The tetracyclines are a family of drugs; doxycycline is
used most often.
at the site of ergosterol in the membrane. It is used to treat
• Chloramphenicol inhibits bacterial protein synthesis by
the most serious systemic fungal diseases but has significant
blocking peptidyl transferase, the enzyme that adds the • Amphotericin B disrupts fungal cell membranes by binding
side effects, especially on the kidney.
new amino acid to the growing polypeptide. Chlorampheni-
mebooksfree.com mebooksfree.com mebooksfree.com Additional Drug Mechanisms mebooksfree.com mebooksfree.com
mebooksfree.com
• Azoles are antifungal drugs that inhibit ergosterol synthesis.
col can cause bone marrow suppression.
The azole family includes drugs such as ketoconazole, flucon-
• Erythromycin inhibits bacterial protein synthesis by block-
azole, itraconazole, and clotrimazole. They are useful in the
ing the release of the tRNA after it has delivered its amino
treatment of systemic as well as skin and mucous membrane
acid to the growing polypeptide. Erythromycin is a member
infections.
of the macrolide family of drugs that includes azithromycin
and clarithromycin.
• Clindamycin binds to the same site on the ribosome as does
• Isoniazid inhibits the synthesis of mycolic acid—a long-
erythromycin and is thought to act in the same manner. It is
chain fatty acid found in the cell wall of mycobacteria. Isoniazid
effective against many anaerobic bacteria. Clindamycin is
is a prodrug that requires a bacterial peroxidase (catalase) to
one of the antibiotics that predisposes to pseudomembra-
activate isoniazid to the metabolite that inhibits mycolic acid
nous colitis caused by C. difficile and is infrequently used.
synthesis. Isoniazid is the most important drug used in the
treatment of tuberculosis and other mycobacterial diseases.
Inhibition of Nucleic Acid Synthesis
mebooksfree.com mebooksfree.com mebooksfree.com Chemoprophylaxis mebooksfree.com mebooksfree.com
mebooksfree.com
• Metronidazole is effective against anaerobic bacteria and
• Sulfonamides and trimethoprim inhibit nucleotide synthe-
certain protozoa because it acts as an electron sink, taking
sis, quinolones inhibit DNA synthesis, and rifampin inhibits
away the electrons that the organisms need to survive. It also
RNA synthesis.
forms toxic intermediates that damage DNA.
• Sulfonamides and trimethoprim inhibit the synthesis of
tetrahydrofolic acid—the main donor of the methyl groups
that are required to synthesize adenine, guanine, and thymine.
• Antimicrobial drugs are used to prevent infectious diseases
Sulfonamides are structural analogues of p-aminobenzoic
as well as to treat them. Chemoprophylactic drugs are given
acid, which is a component of folic acid. Trimethoprim inhibits
primarily in three circumstances: to prevent surgical wound
dihydrofolate reductase—the enzyme that reduces dihydro-
folic acid to tetrahydrofolic acid. A combination of sulfa-
promised patients, and to prevent infections in those known to
methoxazole and trimethoprim is often used because bacteria
be exposed to pathogens that cause serious infectious
resistant to one drug will be inhibited by the other. infections, to prevent opportunistic infections in immunocom-
diseases.
mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com

mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com