Micro Ch 12 Power Point/Notes

the spectrum of an antimicrobial drug-extended-spectrum

-ampicillin is effective on both gram-positive and gram-negative bacteria but not a wide range of them

chemotherapeutic drug

-any chemical used in the treatment, relief, or prophylaxis of a disease

-penicillin consist of three parts

-beta-lactam ring, thiazolidine ring, and a variable side chain that dictates microbicidal activity

-fluoroquinolones

-bind to DNA gyrase and topoisomerase -enzymes are essential for the replication of bacterial DNA -DNA gyrase tends to be the target in gram-negative bacteria -topoisomerase tends to be the target in gram-positive bacteria -broad spectrum and readily absorbed from the intestine

-rifampin

-blocks the action of RNA polymerase preventing transcription -prominent in treating mycobacterial infections (TB and leprosy) -usually given in combination with other drugs to retard resistance

-bacitracin

-blocks the elongation of peptidoglycan in gram-positive bacteria -major ingredient in antibiotic ointments (Neosporin) -topical application for gram-positive staphylococcal and streptococcal organisms -usually combined with neomycin and polymyxin

-antimicrobial drugs that disrupt the cell membrane

-cell with a damaged membrane invariably dies -disruptions in metabolism or complete breakdown and lysis -antibiotics that damage cell membranes have specificity for particular microbial groups based on differences on lipid types in the cell membrane -polymyxins cause leakage of proteins and nitrogen bases especially in gram-negative bacteria -amphotericin B and nystatin form complexes with sterols on fungal membranes -causes abnormal openings and seepage of ions -due to similarities of microbial and animal cell membranes these drugs can be toxic to human cells

-sulfonamides or sulfa drugs

-drugs function as metabolic analogs to block the synthesis of folic acid by bacteria -most are narrow-spectrum

semisynthetic drugs

-drugs that are chemically modified in a laboratory after being isolated from natural sources -examples include penicillin, cephalosporin, and tetracyclines

-antimicrobial drugs that affect nucleic acid synthesis

-drugs that interfere with nucleic acid synthesis block nucleotide synthesis, inhibit replication, or stop transcription -functioning DNA and RNA are also required for protein synthesis -broad-spectrum quinolones inhibit DNA unwinding enzymes or helicases stopping DNA replication -certain antiviral drugs are analogs of purines and pyrimidines which insert into viral nucleic acid like a normal base -the abnormal base stops synthesis and viral replication will be blocked

four generations exist of cephalosporins

-each group is more effective against gram-negative bacteria than the previous group -succeeding generations typically have improved dosing schedules and fewer side effects

the spectrum of an antimicrobial drug-narrow-spectrum

-effective on a limited range of cell types -usually target a specific component found only in certain bacteria -examples -bacitracin blocks elongation of peptidoglycan in gram-positive bacteria and has no effect on gram-negative bacteria -polymyxin breaks down the outer membrane of gram-negative cells but does not target gram-positive

-macrolides and related antibiotics

-erythromycin has a large lactone ring with attached sugars -blocks protein synthesis (prevents translocation from occurring) -administered orally for Mycoplasma pneumonia, legionellosis, pertussis, and diphtheria -clindamycin -tendency to cause adverse reactions in the GI tract limits its applications

interactions between drugs and microbes

-goals of antimicrobial drugs -disrupt the cell processes or structures of bacteria, fungi, and protozoa -inhibit the viral replication cycle

the spectrum of an antimicrobial drug-broad-spectrum

-greatest range of activity -work on most gram-negative and gram-positive bacteria, rickettsias, mycoplasmas, and spirochetes -usually exert their effects on common cell components such as ribosomes, which are found in all cells and within mitochondria

-cephalosporin group of drugs

-have a beta-lactam ring and a similar mode of action as compared to penicillins

-carbapenems and monobactams

-imipenem is a broad-spectrum carbapenem -mode of action is similar to penicillin but with greater resistance to beta-lactamases -aztreonam is a monobactam that is narrow-spectrum -used in treating pneumonia, UTIs, and septicemia by gram-negative aerobic bacilli -useful in treating patients that are allergic to penicillin

five major components that are useful drug targets in an actively dividing cell

-inhibition of cell wall synthesis -breakdown of cell membrane structure or function -inhibition of structures and functions of genetic material (DNA or RNA) -inhibition of protein synthesis -blocks on key metabolic pathways

-isoniazid (INH)

-interferes with the synthesis of mycolic acid -found in the cell wall of acid-fast microorganisms (Mycobacterium) -treat infections of Mycobacterium tuberculosis -often prescribed with rifampin and other drugs in combination therapy to treat TB

Principles of Antimicrobial Therapy

-modern drugs to control infection have added to life span and health of humans

-antimicrobial drugs that block protein synthesis

-most drugs that inhibit protein synthesis react with the ribosome-mRNA complex -ribosomes of eukaryotes are different in size and structure as compared to ribosomes of prokaryotes -potential consequence of drugs that target prokaryotic ribosomes -damage mitochondrial ribosomes since they contain a prokaryotic type (70S) of ribosome

example of selective toxicity

-penicillin that blocks synthesis of the cell wall in bacteria (vertebrates do not have a cell wall) -among the most toxic to human cells are drugs that act upon a structure common to both the infective agent and host cell (such as a cell membrane)

-antimicrobial drugs that target the cell wall

-penicillins and cephalosporins react with enzymes involved in cell wall (peptidoglycan) synthesis -bind and block peptidases (enzymes) that cross-link the glycan molecules sensitive to osmotic pressure subject to lysis -vancomycin hinders the elongation of peptidoglycan

-antibiotics that damage bacterial cell membranes

-polymyxins -narrow-spectrum peptide antibiotics with a unique fatty acid component that contributes to their detergent activity -topical agent in Neosporin -indicated to treat drug-resistant infections caused by gram-negative rods -Pseudomonas aeruginosa and Acinetobacter baumanii

characteristics of an ideal antimicrobial drug

-selectively toxic to the microbe but nontoxic to host cells -microbicidal rather than microbistatic -remains potent long enough to act and is not broken down and excreted prematurely -does not lead to the development of antibiotic resistance -compliments or assists the activities of host defenses -relatively soluble; remains active even when diluted in body fluids and tissues -readily delivered to the site of infection -reasonably priced -does not disrupt the host's health by causing allergies or predisposing the host to other infections

-antimicrobial drugs that affect metabolic pathways

-some drugs act by mimicking the normal substrate of an enzyme through competitive inhibition -sulfonamides and trimethoprim are examples of competitive inhibitors

-drugs that block metabolic pathways

-sulfonamides -trimethoprim -silver sulfadiazine -sulfones

-norfloxacin and ciprofloxacin (Cipro)

-therapy for UTIs, STDs, GI infections, osteomyelitis, and respiratory infections -side effects can limit the use of the quinolones -include damage to tendons, increased risk of aortic aneurisms, and brain disturbances -FDA requires fluoroquinolones to carry a black box label to warn consumers of these serious side effects

synergy (synergistic effect)

-two drugs work together more efficiently as compared to the effectiveness of either drug alone

vancomycin

-used to treat staph infections in cases of penicillin and methicillin resistance -due to toxicity, usually restricted to the most serious, life-threatening conditions

-miscellaneous cell wall inhibitors (non-beta-lactam)

-vancomycin -bacitracin -isoniazid (INH) -ethambutol

affect metabolic pathways-sulfonamides and trimethoprim produce

a synergistic effect so a lower dosage can be used

antimicrobial chemotherapy

administer a drug to an infected person that destroys the infective agent without harming the host's cells

antibiotics come primarily from

aerobic spore-forming bacteria and fungi -bacteria include Streptomyces and Bacillus -fungi include the molds Penicillium and Cephalosporium

primary problems in therapy include

allergies and resistant strains

Aminoglycosides

are composed of amino sugars -subgroups and uses of aminoglycosides -inhibit protein synthesis (mRNA is misread) -streptomycin is the antibiotic of choice for treating bubonic plague and tularemia -also used as an anti-tuberculosis agent (combination therapy) -gentamycin is less toxic and administered for infections caused by gram-negative rods

Antibiotics

are naturally produced products that inhibit or destroy other microbes

synthetic drugs

are synthesized in the laboratory through chemical reactions

-tetracyclines

block the attachment of tRNA on the A site

-polymyxins

cause leakage of proteins and nitrogen bases especially in gram-negative bacteria

-aminoglycosides

cause misreading of the mRNA (streptomycin, gentamycin)

-first-generation

cephalosporins are most effective against gram-positive cocci and a few gram-negative bacteria

-semisynthetics have been

chemically altered with side chains; allows movement of the drug across the outer membrane of gram-negative cells -include ampicillin and amoxicillin -useful in treating many gram-negative infections

ribosome-mRNA complex

combination of ribosome and mRNA which must occur for translation to begin

-beta-lactam antibiotics

contain a reactive beta-lactam ring -primary mode of action is to interfere with cell wall synthesis resulting in cell lysis and cell death -most prominent are penicillins and cephalosporins

-third-generation

drugs are broad-spectrum -work well against gram-negative bacteria that produce beta-lactamases

narrow-spectrum

drugs are effective against a limited array of microbes

broad-spectrum

drugs are effective against a wide variety of microbial types

-fourth-generation

drugs are rapidly microbicidal -effective on both gram-negative and gram-positive bacterial infections

antimicrobial chemotherapy: ideal drug should be

easily administered, able to kill the infectious agent rather than just inhibit its growth, should remain active in the body as long as it is needed yet be safely and easily broken down and excreted

-drugs that act on DNA or RNA

fluoroquinolones rifampin

-amphotericin B and nystatin

form complexes with sterols on fungal membranes

-second-generation

forms are more effective (than first generation forms) in treating gram-negative bacteria

Chloramphenicol

has a unique nitrobenzene structure -blocks peptide bond formation during protein synthesis -broad-spectrum; toxic to human cells so use is limited -a small number of people undergoing long-term therapy incur irreversible bone marrow damage -aplastic anemia -administration limited to typhoid fever, brain abscesses, and rickettsial and chlamydial infections for which alternative therapy is unavailable

-penicillin V

has similar uses as penicillin G -has been modified to be stable in stomach acid and can be orally administered

Tetracycline Antibiotics

have four rings in their structure -block protein synthesis (tRNA is blocked from entering the A site of the ribosome) -broad spectrum -subgroups and uses of tetracyclines -tetracycline use can be limited by its side effects -GI disruption due to altering the normal flora -staining of teeth in children -ingestion during pregnancy can interfere with fetal bone development

-many bacteria produce beta-lactamases that target

he beta-lactam ring of penicillin -also called penicillinases

affect metabolic pathways-selective toxicity is derived from

he fact that mammals derive folic acid from their diet and do not have these bacterial enzyme systems

-erythromycin

inhibits translocation during translation

-ethambutol

is also an anti-tuberculosis drug -antibiotics that damage bacterial cell membranes

prophylaxis

is the use of a drug to prevent potential for infection of a person at risk

selective toxicity

kill or inhibit the growth of microbes without simultaneously damaging host tissues

antibiotic producers enjoy

less competition for space and nutrients

Antibiotics are produced by

natural metabolic processes of some microbes that can inhibit or destroy others (antagonism)

clavulanic acid is

often added to augment the drug's effectiveness

-oxazolidinones

prevent initiation and block ribosome assembly

-chloramphenicol

prevents the formation of peptide bonds

affect metabolic pathways-enzyme is no longer able to

produce a needed product so cellular metabolism slows or stops

Subgroups and Uses of Cephalosporins

relatively broad-spectrum and resistant to most penicillinases -cause fewer allergic reactions than penicillin -many are poorly absorbed from the intestine and must be given parenterally -injection into a muscle or vein

bacteria that possess beta-lactamases are

resistant to many penicillins

-antibacterial drugs that act on

the cell wall

cephalosporin-recognized by having

the root cef, ceph, and kef in their names

synthetic drugs-include

the sulfa drugs, antiviral drugs, quinolones, and azoles

combination therapy

utilizes two or more drugs at the same time to treat an infection -main rationale is to prevent the survival of drug-resistant microbes

-penicillin G

was the first antibiotic -parent compound for all the "-cillin" drugs -narrow-spectrum and cannot be given by mouth -drug of choice for infections by sensitive gram-positive bacteria

-drugs that interfere with protein synthesis

•Aminoglycosides •Tetracycline Antibiotics •Chloramphenicol •Macrolides and Related Antibiotics