M5 PART 12 Flashcards
Drugs have been used for the treatment of infectious diseases since the ____ Century (e.g., quinine and emetine)
17th
introduced Salvarsan (for syphilis)
(Arsphenamine or Compound 606)
PAUL ERLICH
Accidental discovery of Penicillin
ALEXANDER FLEMMING
/
Discovery of the sulfonamides
GERHARD DOGMAK
Penicillin has been used clinically as an antibiotic
FLOREY & CHAIN
1940
An ideal antimicrobial agent exhibits ____, which means that the drug is harmful to a pathogen without being harmful to the host.
SELECTIVE TOXICITY
antibiotics act against a limited group of bacteria
NARROW SPECTRUM
antibiotics act against a larger group of bacteria
TETRACYCLINE
BROAD SPECTRUM
Bactericidal drug ____ bacteria
KILL
suiCIDAL
Bacteriostatic drug ____ of bacteria
INHIBITION
INHIBITION OF CELL WALL SYNTHESIS
- New peptidoglycan monomers are inserted by transglycosylase (transglycosidase)
- The final rigidity of the cell wall is imparted by cross-linking of the peptide chains by transpeptidase enzyme
- Penicillin-Binding Proteins (PBP) may act as transglycosylase or as transpeptidase
BACTERIAL CELL WALL SYNTHESIS
INHIBITION OF CELL WALL SYNTHESIS
BACTERIAL CELL WALL SYNTEHSIS:
New peptidoglycan monomers are inserted by ____
TRANSGLYCOSYLASE
INHIBITION OF CELL WALL SYNTHESIS
BACTERIAL CELL WALL SYNTHESIS:
The final rigidity of the cell wall is imparted by cross-linking of the peptide chains by ____ enzyme
TRANSPEPTIDASE
INHIBITION OF CELL WALL SYNTHESIS
BACTERIAL CELL WALL SYNTHESIS:
____ may act as transglycosylase or as transpeptidase
PENICILLIN-BINDING PROTEIN (PBP)
BACTERIAL CELL WALL SYNTHESIS
- All ____ are selective inhibitors of bacterial cell wall synthesis
- block the action of transpeptidase; no cell wall formed
β-lactam drugs
BACTERIAL CELL WALL SYNTHESIS
Destruction of bacterial ____ (destroys peptidoglycan)
AUTOLYSINS
only β-lactam drug that has one ring
MONOBACTAMS
active in non growing
β-lactam antibiotics
the only actively used monobactams
AZTREONAM
The penicillins are derived from molds of the genus
penicillium
They have the highest activity against Gram-positive organisms, spirochetes, and susceptible to β-lactamases
NATURAL PENICILLINS
NATURAL PENICILLINS
o Aqueous penicillin G (IV)
o Procaine penicillin G (IM)
o Benzathine penicillin G (IM)
PENICILLIN G (BENZYLPENICILLIN)
NATURAL PENICILLINS
phenoxymethylpenicillin
PENICILLIN V
NATURAL PENICILLINS
anesthetics combined with Pen G
Procaine penicillin G (IM)
Benzathine penicillin G (IM)
NATURAL PENICILLINS
stable in gastric acid, orally administered
PENICILLIN V
NATURAL PENICILLINS
gastric acid sensitive hence administered parenterally
PENICILLIN G
- Antistaphylococcal penicillins
-
Lower activity against Gram-positive organisms and inactive against Gram-negative organisms.
o Nafcillin
o Methicillin
o Oxacillin
o Dicloxacillin - Staphylococci resistant to oxacillin and nafcillin have the mecA gene
β-lactamase resistant
β-lactamase resistant
Lower activity against Gram ____ organisms
positive
- Extended-Spectrum Penicillins
- They have high activity against both Gram-positive and Gram-negative organisms but are destroyed by β-lactamases
- Ampicillin
- Amoxicillin
Aminopenicillins
β-lactamase resistant
Staphylococci resistant to oxacillin and nafcillin have the ____ gene
mecA
β-lactamase resistant
inactive against Gram-____ organisms
negative
β-lactamase resistant drugs
Nafcillin
Methicillin
Oxacillin
Dicloxacillin
Aminopenicillins
They have high activity against ____ organisms
both gram-negative & gram-positive
Aminopenicillins
are destroyed by ____
β-lactamases
AMINOPENICILLINS
Ampicillin
Amoxicillin
MAJOR GROUPS OF CEPHALOSPORINS
Cefotaxime
Ceftizoxime
Ceftriaxone
Ceftazidime
Cefoperazone
Moxolactam
Cefixime
Cefpodoxime proxetil
Ceftibuten
Cefdinir
Cefditoren
THIRD GENERATION
Aminopenicillins + β-Lactamase Inhibitors
Ampicillin is commonly combined with what drug for β-Lactamase inhibition
SULBACTAM
- Ampicillin + Sulbactam (Sultamicillin)
- Amoxicillin + Clavulanic acid (Co-Amoxiclav)
Aminopenicillins + β-Lactamase Inhibitors
Aminopenicillins + β-Lactamase Inhibitors
Amoxicillin is commonly combined with what drug for β-Lactamase inhibition
CLAVULANIC ACID
Piperacillin is commonly combined with what drug for β-Lactamase inhibition
TAZOBACTAM
anti-pseudomonal
* Carbenicillin
* Ticarcillin
Carboxypenicillins
MAJOR GROUPS OF CEPHALOSPORINS
MRSA active
Ceftaroline
Ceftobiprole
- Piperacillin (anti-pseudomonal)
- Mezlocillin
Ureidopenicillins
Cephalosporins
Cephalosporins tend to be resistant to the
β-lactamases
- The mechanism of action is analogous to that of penicillins
- tend to be resistant to the** β-lactamases**
- have been arranged into major groups, or “generations”
Cephalosporins
MAJOR GROUPS OF CEPHALOSPORINS
FIRST GENERATION
Cephalothin
Cephapirin
Cefazolin
Cephalexin
Cephradine
Cefadroxil
first yr students - positive (gram +)
CEPH
Cephalosporins
Cephalosporins have been arranged into major groups, or
GENERATIONS
Ureidopenicillins
Piperacillin (anti-pseudomonal)
Mezlocillin
Cephalosporins
The mechanism of action is analogous to that of
PENICILLINS
Carboxypenicillins
- Carbenicillin
- Ticarcillin
Ticarcillin is commonly combined with what drug for β-Lactamase inhibition
CLAVULANIC ACID
MAJOR GROUPS OF CEPHALOSPORINS
SECOND GENERATION
Cefamandole
Cefuroxime
Cefonic acid
Cefaclor
Cefoxitin
Cefotetan
Cefprozil
Cefuroxime axetil
Cefmetazole
Lorocarbef
CEF + VOWEL
equal activity = not positive, not negative
MAJOR GROUPS OF CEPHALOSPORINS
Cefamandole
Cefuroxime
Cefonic acid
Cefaclor
Cefoxitin
Cefotetan
Cefprozil
Cefuroxime axetil
Cefmetazole
Lorocarbef
SECOND GENERATION
MAJOR GROUPS OF CEPHALOSPORINS
Cephalothin
Cephapirin
Cefazolin
Cephalexin
Cephradine
Cefadroxil
FIRST GENERATION
MAJOR GROUPS OF CEPHALOSPORINS
only 1st gen drug administered intravenously
CEFAZOLIN
MAJOR GROUPS OF CEPHALOSPORINS
the very first first generation drug
Cephalexin
MAJOR GROUPS OF CEPHALOSPORINS
very first second generation drug
Cefuroxime
MAJOR GROUPS OF CEPHALOSPORINS
THIRD GENERATION
Cefotaxime
Ceftizoxime
Ceftriaxone
Ceftazidime
Cefoperazone
Moxolactam
Cefixime
Cefpodoxime proxetil
Ceftibuten
Cefdinir
Cefditoren
CEF + CONSONANT
numbers/money
gram negative
MAJOR GROUPS OF CEPHALOSPORINS
FOURTH GENERATION
Cefepime
Cefpirome
Summary of Activity of Cephalospirins
Gram (+) cocci and PEcK (P.
mirabilis, E. coli, K. pneumoniae)
1st gen
Summary of Activity of Cephalospirins
Gram (+) cocci and HENPEcK (H. influenzae, E. aerogenes, N. gonorrhae, P. mirabilis, E. coli, K. pneumoniae)
2nd gen
Summary of Activity of Cephalospirins
Gram (+) cocci and HENPPEcK (H. influenzae, E. aerogenes, N. gonorrhae, P. aeruginosa, P. mirabilis, E. coli, K. pneumoniae)
3rd gen
Summary of Activity of Cephalospirins
Gram (+) cocci [MRSA] and E. coli, K. pneumoniae, P. mirabilis, and P. aeruginosa
4th gen
deactivates imipinem
inhibits cilastatin
RENAL DEHYDROPEPTIDASE
RENAL DEHYDROPEPTIDASE
deactives ____
imipenem
RENAL DEHYDROPEPTIDASE
inhibits ____
cilastatin
has good activity against many Gram-negative rods, Gram-positive organisms, and anaerobes.
Imipenem + Cilastatin
Imipenem + Cilastatin
Meropenem
Ertapenem
CARBANEPAMS
- Aztreonam
- It has antimicrobial activity directed primarily against the Enterobacteriaceae (Pseudomonas), including P. aeruginosa.
- No activity against Gram-positive organisms and anaerobes
MONOBACTAMS
ADVERSE EFFECTS
Hypersensitivity, Diarrhea, Nephritis, Neurotoxicity, Hematologic toxicities, Cation toxicity
PENICILLIN
ADVERSE EFFECTS
Allergic manifestations
CEPHALOSPORINS
ADVERSE EFFECTS
Imipenem/Cilastatin - N&V & diarrhea
Imipinem - may provoke seizures
CARBAPENEMS
ADVERSE EFFECTS
Aztreonam may cause phlebitis, skin rash, and occasionally abnormal liver function tests
MONOBACTAM
ADVERSE EFFECTS
fever, chills, and/or phlebitis at the infusion site
flushing (red man syndrome) and shock
Vancomycin
Mode of Action of Antibiotics That Inhibit Cell Wall Synthesis
ANTIBIOTIC: VANCOMYCIN, BACITRACIN
PROCESS INTERRUPTED: ____
mucopeptide synthesis
Mode of Action of Antibiotics That Inhibit Cell Wall Synthesis
ANTIBIOTIC: PENICILLIN, CEPHALOSPORINS
PROCESS INTERRUPTED: ____
cell wall cross-linking
Mode of Action of Antibiotics That Inhibit Cell Wall Synthesis
ANTIBIOTIC: CYCLOSERINE
PROCESS INTERRUPTED: ____
synthsis of cell wall peptides
Inhibition of Cell Membrane Function
If the functional integrity of the cytoplasmic membrane
is ____, macromolecules and ions escape from the cell, and cell damage or death ensues.
DISRUPTED
Inhibition of Cell Membrane Function
If the functional integrity of the cytoplasmic membrane is disrupted, macromolecules and ions ____ from the cell, and cell damage or death ensues.
ESCAPE
Inhibition of Cell Membrane Function
- Binds to cell membranes rich in phosphatidylethanolamine
- Active against gram-negative rods, especially P. aeruginosa, Acinetobacter baumannii, and carbapenemase-producing Enterobacteriaceae.
- Bactericidal
POLYMYXIN E (COLISTIN)
Inhibition of Cell Membrane Function | POLYMYXIN E (COLISTIN)
binds to cell membrane rich in ____
phosphatidylethanolamine
Inhibition of Cell Membrane Function
- Induces depolarization of bacterial membrane potential resulting to release of potassium
- This agent is given to organisms highly resistant to β-lactam agents and vancomycin.
- Bactericidal
DAPTOMYCIN
Inhibition of Cell Membrane Function | DAPTOMYCIN
Induces ____ of bacterial membrane potential resulting to release of potassium
depolarization
Inhibition of Cell Membrane Function | POLYMYXIN E (COLISTIN)
active against ____
gram negative rods
Inhibition of Cell Membrane Function | DAPTOMYCIN
Induces depolarization of bacterial membrane potential resulting to release of ____
potassium
Inhibition of Cell Membrane Function | DAPTOMYCIN
This agent is given to organisms highly resistant to ____ and ____
β-lactam agents and vancomycin
Amikacin
Gentamicin
Neomycin
Streptomycin
Tobramycin
AMINOGLYCOSIDES
antibiotics that targets 30s ribosomes
Aminoglycosdies
Tetracycline
Tigecycline
buy AT 30
blocks functioning of initiation complex & causes misreading of mRNA
Aminoglycosides
antibiotics that target the 50s ribosomes
Chloramphenicol
Erythromycin
Linezolid
Clindamycin
Macrolides
Quinupristin / Dalfopristin
CELL at 50
blocks tRNA binding to ribosome
tetracycline
type of activity: aminoglycosides
bactericidal
blocks protein translation
tigecycline
mycin source
streptomyces
ADVERSE EFFECTS
ototoxicity (vestibular & cochlear)
Nephrotoxicity (NTG)
Neuromuscular paralysis
Allergic reactions
AMINOGLYCOSIDES
Demeclocycline
Doxycycline
Minocycline
Tetracycline
TETRACYCLINES
ADVERSE EFFECTS
Gastric discomfort
Effects on calcified tissue
Fatal hepatotoxicity
Photoxicity
Vestibular problems
Pseudotumor cerebri
Superinfections
causes yellow tooth discoloration
Fancomi syndrome - acquired by taking an expired drug
TETRACYCLINES
blocks peptidyltransferase
Chloramphenicol
blocks translocation
macrolides
causes premature release of peptide chain
Quinupristin / Dalfopristin
blocks peptide bond formation
Clindamycin
blocks early step in ribosome formation
Linezolid
ADVERSE EFFECTS
hemolytic anemia
gray baby syndrome - cyanosis, not administered to babies
CYP450 inhibitor
rare: aplastic anemia - fatal
Chloramphenicol
ADVERSE EFFECTS
epigastric distress
cholestatic jaundice - bilirubin
ototoxicity
enzyme inhibitor
MACROLIDES
ADVERSE EFFECTS
Pseudomembranous colitis
Clindamycin
Erythromycin
Azithromycin
Clarithromycin
Telithromycin
MACROLIDES
erythromycin was named
Ilosone
Ilotycin
THERAPEUTIC APPLICATIONS
some anaerobes & certain gram negative bacteria
STREPTOGRAMINS
ADVERSE EFFECTS
Phlebitis
arthralgias
myalgias
STRETOGRAMINS
Quinupristin / Dalfopristin
ADVERSE EFFECTS
Gastrointestinal - N&V, diarrhea
Linezolid
THERAPEUTIC APPLICATIONS
Vancomycin-resistant
Linezolid
THERAPEUTIC APPLICATIONS
gram positive bacterias
Macrolides
THERAPEUTIC APPLICATIONS
bacteroides & other anaerobes
Clindamycin
THERAPEUTIC APPLICATIONS
Salmonellae, Meningococci, H. influenzae
Chloramphenicol
INHIBITION OF NUCLEIC ACID SYNTHESIS
Inhibition of bacterial DNA synthesis by blocking of DNA gyrase and topoisomerase IV
FLUOROQUINOLONES
topoisomerase produced by gram negative
tropoisomerase II
topoisomerase produced by gram positive
topoisomerase IV
QUINOLONE | GENERATION
Nalidixic acid
1st gen
a quinolone that has no fluorine in its structure
nalidixic acid
QUINOLONE | GENERATION
Ciprofloxacin
Ofloxacin
Norfloxacin
2nd gen
QUINOLONE | GENERATION
Levofloxacin
3rd gen
QUINOLONE | GENERATION
Moxifloxacin
4th gen
QUINOLONE | GENERATION
- used less often today
- have moderate gram-negative activity
- achieve minimal serum concentrations
- restricted to the treatment of uncomplicated urinary tract infections
FIRST GEN
QUINOLONE | GENERATION
- have expanded gram negative activity
- have some activity against gram positive and atypical organisms such as Mycoplasma pneumoniae and Chlamydia pnuemoniae
2nd gen
QUINOLONE | GENERATION
- retain expanded gram negative activity
- show improved activity against atypical organisms and specific gram positive bacteria
3rd gen
QUINOLONE | GENERATION
- shows improved gram positive coverage
- maintains gram negative activity
- gains anaerobic coverage
4th gen
ADVERSE EFFECTS
N&V, diarrhea
HA or dizziness
Phototoxicity - sensitivity to light
Cartilage erosion (arthropathy) - not advisable for <18 y/o, affects tendon
Contraindicated to patients with arrythmia
Drug interactions with antacids and cations
FLUOROQUINOLONES
ADVERSE EFFECTS
- Toxic effects are manifested by fever, skin rashes, gastrointestinal disturbances, depression of the bone marrow leading to anemia or agranulocytosis, hemolytic anemia, and liver and kidney function abnormalities
- SJS - Stevens Johnson Syndrome
- crystalluria
- jaundice
- kernicterus
SULFONAMIDES
Drugs for Tuberculosis
- binds to DNA-dependent RNA polymerase and thus inhibits RNA synthesis in bacteria
- has different mechanism, targets nucleic acid synthesis
- ADVERSE REACTION: orange color to urine, saliva, and sweat (harmless)
RIFAMPIN
Drugs for Tuberculosis
- inhibits mycolic acid synthesis
- targets cell wall of the MO
- ADVERSE REACTION: Liver toxicity, Peripheral neuritis (nerves)
ISONIAZID
+ VIT B6
Drugs for Tuberculosis
- inhibits mycolic acid synthesis
- targets the cell wall of the MO
- ADVERSE REACTION: Hepatoxicity, N&V, hypersensitivity, hyperuricemia
Pyrazinamide
Drugs for Tuberculosis
- inhibits the synthesis of arabnogalactan
- targets the cell wall of the MO
- ADVERSE REACTIONS: Optic neuritis w/ blurred vision, red-green color blindness
Ethambutol
o Leprosy
o SE: hemolytic anemia, gastrointestinal intolerance, fever, itching, and rashes
DAPSONE
o Antiprotozoal and for bacterial anaerobic infections
o SE: Stomatitis, diarrhea, and nausea
METRONIDAZOLE