antibiotics
DESCRIPTION
Antibiotics. Learning objectives. Definitions Targets for antibiotic action Normal peptidoglycan & Protein synthesis in bacteria Mechanism of Action of Important Antibacterial and Antifungal Drugs. - PowerPoint PPT PresentationTRANSCRIPT
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Antibiotics
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Learning objectives
Definitions Targets for antibiotic action Normal peptidoglycan & Protein synthesis in
bacteria Mechanism of Action of Important
Antibacterial and Antifungal Drugs
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Antibiotic- Chemical agents produced by micro-organisms that kill or inhibit other micro-organisms.
Antimicrobial agents- agents of synthetic origin useful in the treatment of microbial or viral disease.
Probiotics- Live, nonpathogenic bacteria, which excludes the pathogen from binding sites on the mucosa (colonization resistance)
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selective toxicity; selective inhibition of the growth of the microorganism without damage to the host.
Basis is non-similarity of structure & function
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Actions
Bactericidal = kill bacteria Bacteriostatic = slow or interfere with growth
of bacteria
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Broad-spectrum antibiotics active against several types of microorganisms, e.g., tetracyclines are active against many gram -negative rods, chlamydiae, mycoplasmas, and rickettsiae.
Narrow-spectrum antibiotics active against one or very few types, e.g., vancomycin is primarily used against certain gram -positive cocci namely , staphylococci & enterococci
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Definition
Ideally, culture of suspect area should be done BEFORE starting antibiotic
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Uses
Treatment of existing infection Prevention of infection- Chemoprophylaxis in three circumstances:a. prior to surgery b. in immunocompromised patientsc. In people with normal immunity who have
been exposed to certain pathogens.
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In patients undergoing dental, GI tract, or GU tract surgery who have a damaged heart valve or a prosthetic heart valve.
Patients undergoing dental surgery are at risk for endocarditis caused by viridans streptococci should be given amoxicillin perioperatively . Patients undergoing GI tract or GU tract surgery are at risk for endocarditis caused by enterococci and should be given ampicillin and gentamicin perioperatively .
in patients with prosthetic joints or vascular grafts undergoing dental, GI tract or GU tract surgery
Prevention of infection of prosthetic joints or vascular grafts
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But there are far more antibacterial drugs than antiviral drugs.
WHY Because viruses use host cell in their growth
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Targets for antibiotic action
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4 majorTargets for antibiotic action
cell wall cell membrane protein synthesis nucleic acid
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Mechanism of Action of Important Antibacterial and Antifungal Drugs
Mechanism of Action DrugsInhibition of cell wall synthesis Penicillins, cephalosporins, imipenem
aztreonam(beta-lactams) , , vancomycin, Antifungals
Inhibition of protein synthesis 50S
30S
Chloramphenicol, erythromycin,clindamycin, linezolid, Tetracyclines and aminoglycosides
Inhibition of nucleic acid synthesis Sulfonamides, trimethoprim, Quinolones,(e.g.ciprofloxacin) Rifampin
Alteration of cell membrane function Polymyxin, daptomycin & Antifungals(Amphotericin B, nystatin)
Other mechanisms of action Isoniazid, metronidazole, Antifungals
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Classifications
Penicillins } Cephalosporins (ceftriaxone) } Beta-lactams Cabapenems } Glycopeptides ( vancomycin) Sulfonamides (septran) Tetracyclines Macrolides (Erythromycin, Azithromycin, &
clarithromycin) Aminoglycosides( Gentamicin) Quinolones ( ciprofloxacin)
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Antibiotics that Inhibit Cell Wall Synthesis
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Bacterial cell wall
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Prokaryotes differ from eukaryotes by having a cell wall that includes a peptidoglycan layer.
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Peptidoglycan consists of multiple amino-sugars that alternate NAG and NAM which are cross linked to form a lattice.
Cross-linking is essential to resist the high internal osmotic pressures
Peptidoglycan components manufactured intracellularly and transported across the cell membrane, where they link by transpeptidation.
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Penicillins
1.They bind to penicillin binding proteins (PBPs).on the bacterial cell wall
Inhibit transpeptidation of the peptidoglycan layer. 2.Autolytic enzymes called murein hydrolases
(murein is a synonym for peptidoglycan) are activated in penicillin-treated cells and degrade the peptidoglycan
Penicillin-treated cells die by rupture as a result of the influx of water
Act only on growing cells
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Other Beta -lactams
Cephalosporins,, carbapenems & Aztreonam are beta-lactam drugs that act in the same manner as penicillins; i.e., they are bactericidal agents that inhibit the cross-linking of peptidoglycan.
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Vancomycin
A glycopeptide that inhibits cell wall synthesis by blocking transpeptidation but by a mechanism different from that of the β-lactam drugs. It binds directly to the D-alanyl-D-alanine portion of the pentapeptide, which blocks the transpeptidase from binding, whereas the beta-lactam drugs bind to the transpeptidase itself.
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Vancomycin m.o.a
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Summary of antibiotics acting on cell wall
Could be due to - Inhibition of enzymes -Complexing with the growing part of peptidoglycan
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http://www.microbelibrary.org/images/spencer/spencer_cellwall.html
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Inhibition of fungal cell wall synthesis
By inhibiting the enzyme that synthesizes beta –glucan, a component of fungal cell walls
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Antimicrobial agents affecting Bacterial Protein Synthesis
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Normal protein synthesis in Bacteria
Transcription Translation
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Transcription occurs in the cell nucleus, where the DNA is held. The DNA is "unzipped" by the enzyme helicase, leaving the single nucleotide chain open to be copied. RNA polymerase reads the DNA strand , while it synthesizes a single strand of messenger RNA. The single strand of mRNA leaves the nucleus and migrates into the cytoplasm.
The synthesis of proteins is known as translation. Translation occurs in the cytoplasm, where the ribosomes are located. Ribosomes are made of a small and large subunit that surround the mRNA. In translation, messenger RNA (mRNA) is decoded to produce a specific polypeptide. This uses an mRNA sequence as a template to guide the synthesis of a chain of amino acids that form a protein.
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Protein synthesis
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Tetracyclines
They block protein synthesis by competing with tRNA for the A site of the ribosome/ mRNA complex.
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Aminoglycosides
Bind to 30S subunit and prevent complexing of the 50S subunit. ( compare with normal)
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Erythromycin
Inhibits translocation of ribosome along mRNA chain
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Chloramphenicol
Binds to the 50S subunit at same site as erythromycin, and inhibits transpeptidation
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Natural_Mirrors.lnkNatural_Mirrors.lnk
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INHIBITION OF NUCLEIC ACID SYNTHESIS
1.Inhibition of precursor synthesis e.g Sulphonamides & Trimethoprim inhibit synthesis of tetrahydrofolic acid which is required for synthesis of nucleic acid precursors A, G, T
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INHIBITION OF NUCLEIC ACID SYNTHESIS cont----
2. Inhibition of DNA synthesis by inhibiting DNA gyrase an enzyme which unwinds DNA strands for replication e,g Fluoro-Quinolones
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Alteration of Bacterial Cell Membranes
Few antimicrobial compounds act on the cell membrane because the structural and chemical similarities of bacterial and human cell membranes make it difficult to provide sufficient selective toxicity
E.g Polymyxins
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Alteration of Fungal Cell Membranes
Human cells have got cholesterol in their membranes while fungi have got ergosterol
E.g Amphotericin B -It disrupts the cell membrane of fungi because of its affinity for ergosterol
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Additional drug mechanisms
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Isoniazid
Bactericidal drug for Mycobacterium tube- rculosis (MTB) and other mycobacteria
Inhibits mycolic acid synthesis ( a part of Mycobacterial cell wall)
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Some important antibiotics
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Beta-Lactam Antibiotics So called because they
have a beta-lactam ring.
Penicillins, Cephalosporins, Carbapenems and monobactams.
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Penicillins
Available in 3 forms -Aqueous Pen.-rapidly metabolized -Procaine Pen- less painful -Benzathine Pen-very slowly metabolized(depot pen.)
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Disadvantages of Penicillins
Limited effect against G-ves Hydrolysis by gastric acid- no oral use Inactivation by beta lactamase enzymes Hypersensitivity (1-10%), Anaphylaxis(0-5%)
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Cephalosporins
Cephalosporins are beta-lactam drugs that act in the same manner as penicillins. The structures, however , are different:
Cephalosporins have a 6-membered ring adjacent to the beta-lactam ring ,while penicillins have a 5-membered ring
Bactericidal Products of the mould cephalosporium Five generations. 1st active against GPCs, 2, 3, 4
more against G-ves
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Cephalosporins cont---
Few allergic reactions Some are oral, but most are given parentally. Wide distribution after absorption E.gs Cefuroxime, cefotaxime and
ceftriaxone Broadspectrum, active against most Gram
+ve’s, some Gram –ve activity
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Carbapenems
Carbapenems are β-lactam drugs that are structurally different from penicillins and cephalosporins
Wide bactericidal activity against many gram -positive, gram -negative, and anaerobic bacteria
Eg. Imipenem, Meropenem etc
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Glycopeptides
E.gs Vancomycin Bactericidal for Gram positives esp MRSA
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Tetracyclines
Broad spectrum, originally derived from Streptomyces. More recent compounds are semi-synthetic or synthetic
Bacteriostatic action against gram +ve/-ve and some protozoa
Absorbed orally Tetracycline, Vibramycin, Minocycline
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Tetracyclines
Effectiveness reduced by Dairy products Antacids Iron
Contraindicated in pregnancy & children (discolor teeth ,may slow fetal skeletal development
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Aminoglycosides
Poor oral absorption No oral forms, only IV TOXICITY cautions
Nephro oto
Bactericidal action against GNRs like Pseudomonas, E.coli, Klebsiella
Poor entry into CSF
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Aminoglycosides
Gentamicin Kanamycin Neomycin Streptomycin Amikacin
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Chloramphenicol
Active against many gram +ve & gram-ves Inhibits protein synthesis to some extent in
mitochondria of human cells Bone marrow depressant (dose dependant) Aplastic anemia (idiosyncratic)
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Fluoro-Quinolones
5 generations Newer forms (ciprofloxacin, ofloxacin and
levofloxacin) have wider activity Used for RTI, UTI, GIT, Skeletal & soft tissue
infections Contraindicated in pregnancy & young child -ren, as it damages growing cartilage
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Sulphonamides & Trimethoprim
Bacteriostatic, good against gram –ve’s Sulphonamides & Trimethoprim are two drugs but
are used together for synergistic effect. E.g Septran Side Effects=Anemia, thrombocytopenia,
Photosensitivity( Avoid tanning , Avoid sunlight)
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Sulfonamides
Bacteriostatic Used to Treat: UTI Pneumocystis jiruveci pneumonia (PCP) URIs Otitis media Often in combination
Bactrim, Septra
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Macrolides
Bacteriostatic drugs with a wide spectrum of activity .
Erythromycin, Azithromycin, Clarithromycin Given in Strept. infections in Penicillin
allergic pts.
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Clindamycin
Bacteriostatic drug against anaerobes Important side effect of clindamycin is
pseudomembranouscolitis (suppression of the normal flora of the bowel by the drug and overgrowth of a drug-resistant strain of Clostridium difficile) causing severe bloody diarhea
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Rifampicin
Used in Tuberculosis & close contacts of meningitis
Not given alone as rapid resistance develops
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Isoniazid
Bactericidal drug for (MTB) and other mycobacteria
Effective against the organisms residing within macrophages
Side effect = Liver toxicity
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Metronidazole (Flagyl)
Bactericidal against anaerobic bacteria. It is also effective against certain protozoa
such as Giardia and Trichomonas .
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Antifungals
Amphotericin B has significant renal toxicity; measurement of serum creatinine levels is used to monitor the dose
Nystatin, Azoles (Fluconazole, ketoconaz-ole,voriconazole, posaconazole, and itraconazole) used in local and systemic fungal diseases
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Nursing
Instruct pt to take meds for full length of time – do not stop when feeling better
Assess for s/s of superinfection
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Definitions
Antibiotic chemical agents produced by micro-organisms that kill or inhibit other micro-organisms. Antimicrobial agentsAgents of synthetic origin useful in the treatment of microbial or viral disease.
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Bactericidal kill bacteria Bacteriostatic slow or interfere with growth of bacteria
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selective toxicity selective inhibition of the growth of the microorganism without damage to the host.
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Broad-spectrum antibiotics are active against several types of microorganisms Narrow-spectrum antibiotics are active against one or very few types of microorganisms
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Probiotics live, nonpathogenic bacteria. Provide colonization resistance by which the nonpathogen excludes the pathogen from binding sites on the mucosa.
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Targets for antibiotic action
cell wall cell membrane protein synthesis nucleic acid
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Mechanism of Action of Important Antibacterial and Antifungal Drugs
Inhibition of cell wall synthesis Penicillins, cephalosporins, imipenem , aztreonam , vancomycin, Antifungals Inhibition of protein synthesis 50S Chloramphenicol, erythromycin, clindamycin, linezolid, 30S Tetracyclines and aminoglycosides
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Normal protein synthesis in Bacteria-Steps
Transcription
mRNA is formed from DNA in the nucleus
Translation
The synthesis of proteins is known as translation. Translation occurs in the cytoplasm
www.elmhurst.edu/~chm/vchembook/584proteinsyn.html Micro exam 3 quizlet
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