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Immuno > antibiotics > Flashcards

antibiotics Flashcards

1
Q

Beta-lactamase inhibitors

A

Clavulanic acid
Sulbactam
Tazovactam

peptidoglycan synthesis

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2
Q

Penicillin

A 
Penecillin
Ampicillin
Amoxicillin
 Methicillin
Oxacillin
Ticarcillin
piperacillin

peptidoglycan synthesis

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3
Q

Cephalosporin

A 
® 1st gens:
						◊ Cefazolin
						◊ cephalexin
					® 2nd gens:
						◊ Cefuroxime
						◊ cefoxitin
					® 3rd gens:
						◊ Ceftriaxone
						◊ ceftazidime
					® 4th gen:
cefepime
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4
Q

Carbapenem

A 
® Imipenem
					® Meropenem
					® Ertapenem
					® Doripenem
All the "penem" s

peptidoglycan synthesis

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5
Q

Monobactam

A

Aztreonam

peptidoglycan synthesis

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6
Q

Vancomycin

A

® Binds to d-ala-d-ala
® PBPs cannot find precursors
® Effective on gram +….not effective on gram -
◊ Permeability barrier of outer membrane
® Often used for beta-lactam resistant infections (MRSA) or in patients with beta-lactam hypersensitivity
□ Mechanism of resistance
® Modification of Antibiotic target
◊ Bacteria acquire genes encoding machinery to produce altered peptidoglycan structure….D-ala-D-Lac
◊ Vancomycin is unable to bind
◊ Plasmids, transposons
◊ Enterococci (VRE…vanco-resistant enterococci)
◊ Hydrogen bonds slide
Emergense of VRSA (cultures grew VRE and VRSA…HZT)

glycopeptides

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7
Q

Bacitracin

A

□ Neosporin…too toxic for systemic use
□ Binds to pyrophosphase on the lipid carrier for peptidoglycan precursors (bactoprenol-P) and blocks recycling
□ No available lipid carrier = no synthesis
□ Group A streptococci are 10x more sensitive
® “A Disks” diagnostic test

uppP (bacA, ybjG, pgpA)

peptidoglycan synthesis

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8
Q

Fosfomycin (??)
□ murA
D-cycloserine

A

□ Inhibits peptidoglycan crosslinking
□ Structurally similar to D-ala
□ 2nd line anti-TB
□ Competitive inhibitor of d-ala at 2 spots
® Has higher affinity for enzymes than d-ala (natural substrate)
a) Alanine racemase
D-alanyl-d-alanine synthetase

peptidoglycan synthesis

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9
Q

Tetracyclines

A 
® Tetracycline
					® Doxycycline
					® Minocyline
				□ Bacteriostatic, broadspectrum, overuse, widespread resistance
				□ Mechanism:
					® Bind to 30s
					® Interferes with binding of aminoacyl tRNA to ribosome
				□ Resistance:
					® Efflux pump (most common)
Mutations of target (ribosome)

Ribosomes and Protein Synthesis

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10
Q

Tigecycline

A

□ “new”….glycylamino modification of minocycline
□ Bacteriostatic
□ Mechanism: same as tetracyclines (30s)
® Binds additional unique sites on the ribosome
Does not exhibit cross-resistance with tetracyclines

Ribosomes and Protein Synthesis

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11
Q

Aminoglycosides

A

® Gentamicin
® Amikacin
® Tobramycin
□ Bactericidal (only cidal ribosomal inhibitors)
® Good in hard-to-kill Gram -‘s (pseudomonas aeruginosa)
® Does not penetrate gram + well
® Poor activity against anaerobes
□ Mechanism: bind irreversibly to 30s
® Stops initiation of protein synthesis
® Causes premature release of mRNA
® Causes misreading
□ Adverse effects:
® Ototoxic
® Nephrotoxic
□ Resistance:
Enzymatic modification of antibiotic: (transferases add adenyl, acetyl, or P)….prevent binding

Ribosomes and Protein Synthesis

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12
Q

Macrolides (only have mycin in names)

A

® Erythromycin
® Azithromycin
® Clarithromycin
□ Bacteriostatic, patients allergic to beta-lactam
□ Gram +
□ Mechanism: binds 50s to block elongation
□ Resistance:
a) modification of target: Enzymatic modification (methylation) of rRNA
◊ (ERM)
+Efflux pumps

Ribosomes and Protein Synthesis

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13
Q

Clindamycin

A

□ Bacteriostatic
□ Inactive against gram - aerobes
□ Community-aquired MRSA&raquo_space; hospital acquired MRSA
□ Used for toxin-producing S. aureus
□ Mechanism
® Bind 50s blocks elongation
□ Resistance
® Modification of target: Enzymatic modification (methylation) of rRNA
® Exhibits cross resistance with macrolides: ERM

Ribosomes and Protein Synthesis

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14
Q

Chloramphenicol

A

□ Bacteriostatic, broadspectrum
□ Mechanism:
® Binds 50s to inhibit elongation (aka peptidyl transferase activity)
□ Adverse effects
® Toxicity (aplastic anemia)
◊ Lack of selectivity (targets mitochondria)
® Limited to severe infection
◊ Typhoid fever
◊ Rocky mountain spotted fever
□ Resistance
modification of antibiotic: CAT (bacterial enzyme, chloramphenicol acetyltrasferase) puts acetyl group on drug

Ribosomes and Protein Synthesis

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15
Q

Oxazolidinones (linezolid???)

A

□ Complicated skin and skin structure infections by S. aureus, S. pyogenes, or S. agalactiae
□ Not effective against most gram -
□ $$$$$$$ high cost$$$$$$$$
□ bacteriostatic
□ Mechanism
® Binds unique site of 50s (23S rRNA) preventing formation of 70s initiation complex
□ Negatives
® Rapid appearance of resistance bacteria
□ Resistance
® Modification of antibiotic target: SNPs in ribosomal components
No cross resistance

Ribosomes and Protein Synthesis

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16
Q

Trimethoprim

A 
□ Analog of dihydrofolate
					® Inhibits dihydrofolate reductase
				□ Resistance:
					® Acquisition of another gene encoding dihydrofolate reductase
overexpression

Key Metabolic Reactions

17
Q

sulfonamides

A

® Sulfamethoxazole
® Sulfadiazine
Metabolic analogues of p-aminobenzoic acid

Key Metabolic Reactions

18
Q

Polymyxins
® Polymyxin B
Colistin

A 
□ Lipopeptide antibiotic
				□ Gram -
				□ Bactericidal
				□ Narrow
				□ Mechanism:
					® Bind to LPS disrupts both outer membrane and cytoplasmic membrane
					® novel
				□ Adverse effects:
Toxicity limit

Cell Membrane

19
Q

Daptomycin (lipopeptide)

A

□ Gram +
□ Bactericidal
□ Narrow
□ Mechanism:
® Bind and disrupt the cytoplasmic membrane
® Possible loss of membrane potential
novel

Cell Membrane

20
Q

Rifampin (rifampicin)

A

□ Bactericidal
□ Mechanism
® Binds beta-subunit of bacterial RNA polymerase
□ Problem: rapid selection for resistance
® Never used on its own (?)
□ Resistance:
Mutations in beta subunit

RNAP AND RNA SYNETHESIS

21
Q

Fidaxomicin

A

□ Bactericidal
□ Mechanism
Binding to RNA polymerase: Noncompetitive inhibitor of RNA synthesis (different site from rifampin)

RNAP AND RNA SYNETHESIS

22
Q

Nalidixic acid

A

® “original”
® Mechanism: binds to DNA gyrase and/or topoisomerase to inhibit
Problems: narrow, rapid selection for resistance

DNA replication and Repair
Synthetic quinolone

23
Q

Fluoroquinolones (all the “floxacin”s) (clinically useful)

A 
◊ Norfloxacin
						◊ Ciprofloxacin
						◊ Moxifloxacin
						◊ Levofloxacin
					® Bactericidal, broad
					® SAME MECHANISM
					® Resistance:
						1) Modification of antibiotic target: Point mutation in DNA gyrase
Efflux pump

DNA replication and Repair
Synthetic quinolone

24
Q

Metronidazole

A

□ Anaerobic bacterial infections
□ C difficile pseudomembranous colitis
□ bactericidal
□ Mechanism
Anaerobic environment: radical is produced leading to toxic metabolites that damage DNA

DNA replication and Repair

Immuno (3 decks)

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