Exam 3 Tim Flashcards
1
Q
Classification of antibiotics based on (3)
A
- class and spectrum (gram + vs - vs both)
- biochemical pathway it interferes with
- chemical structure of the pharmacophere
2
Q
general steps of peptidoglycan biosynthesis (3)
A
- (in cytoplasm) sugar –> lipid –> lipid I –> lipid II
- translocation of lipid II from cytoplasm to periplasm
- (in periplasm) lipid II polymerization, PG-cross linking, lipid recycle
3
Q
Beta-lactams inhibit what step of peptidoglycan synthesis
A
- TPase step
- trans peptidase inhibition
- trans peptidation/crosslinking step
- comes after transglycosylation
4
Q
glycopeptides inhibit what step of peptidoglycan synthesis
A
- TGase step
- trans glycosylation inhibition
- ONLY WORK ON GRAM + (too large)
- work by forming complexes with uncrosslinked peptide (on D-ala-D-ala) strands –> block transglycosylation
5
Q
Transpeptidases are
A
- active site serine hydrolases
6
Q
Penicillin binding protein
A
- anything (protein) that binds penicillin
7
Q
Penicillin acts as a _____ unless attack of _____
A
- irreversible suicide inhibitor of TPase
- unless attack of water
8
Q
Unique characteristics of 5th generation cephalosporin and name
A
- 5th gen: unique aspects, broad spectrum, both bind to PBP-2a, which is responsible for resistance to methicillin (MRSA)
- ceftaroline
9
Q
PBP-2a
A
- PBP on staph aureus responsible for MRSA
- bifunctional transpeptidase/ transglycosylase
10
Q
1-4th gen of cephalosporin
A
- lead to diff penetration through porins (G (-))
- varied antibacterial and pharmacokinetic properties
- hypersensitivity most common adverse
11
Q
five gens of penicillin
A
- vary on narrow vs broad spectrum/ whether antipseudomonal (gram -) activity
- hypersensitivity most common adverse
12
Q
Which drug treats TB that was featured?
A
- Isonazid
- used in combo with other drugs for treatment (usually 4)
- as monotherapy for latent TB
- less freq used as comination regimen for nonTB mycobacterial infections
- MOA: acts as mimic of nicotinamide.. complex, isoniazid-NAD adduct inhibits INHa, best defined mech is inhibitor of mycolic acid biosynthesis (greasy outside layer)
Adverse: low in general, peripheral neuropathy and CNS toxicity
13
Q
Tetracyclines and glycylcyclines
A
- tigecycline
- A site 30S
- block incoming aminoacyl TRNA
- adverse: GI irritation, photosensitivity, discoloration of teeth
- bacteriostatic
14
Q
Tigecycline
A
- tetracycline resistant to efflux
15
Q
Aminoglycosides
A
- Gentamicin C
- A site 30S
- interfere with initiation
- primarily used gram (-), widely used b/c of BACTERICIDAL action and synergy with b-lactams
- adverse: nephrotoxicity and ototoxicity (damage to inner ear)
16
Q
Macrolides
A
- arithromycin, azithromycin, clarithromycin
- E site 50S
- block polypeptide exit tunnel
- bacteriostatic
17
Q
Synercid
A
- pristinamycins
- Qunupristin AND Dalfopristin together
- E site 50S at places partially overlapped by macrolides
- derived from streptogramins
18
Q
Linezolid
A
- only totally synthetic antibiotic that blocks protein synthesis (others that are still totally synthetic)
- binds to P site (peptidyl elongation) 50S
- most active against Gram +
19
Q
Retapulin
A
- analog of fungal natural product
- topical ointment approved for treating impetigo
- binds near P-site on 50S
20
Q
Telithromycin does not what?
A
- induce rRNA methylation resistance gene expression
- remember MLSb resistance phenotype
- this is a ketolide macrolide
- 3rd gen macrolide
21
Q
Tedizolid
A
- second gen oxazolidinone (other drug in this category is linezolid)
- active against linezolid resistant staphylococci
- 10x more potent than linezolid against MRSA
22
Q
Topo II
A
- DNA gyrase
- introduces negative supercoils, relaxes positive supercoils
- cuts both strands at once
23
Q
topo IV
A
- decatenates DNA (separating the DNA of daughter chromosomes once DNA replication is completed.)
- removes pos and neg supercoiling
24
Q
Quinolones induce the _____
A
- accumulation of double cut covalent DNA-enzyme intermediate by preventing DNA supercoiling
25
antibiotics that inhibit DNA gyrase and topo IV
- quinolones
| - ciprofloxacin, levofloxacin, gatifloxacin
26
Quinolones
- work best on gram neg but good for gram pos with new generations (THIS IS RIGHT)
- bactericidal
- generally well tolerated but can have CNS toxicity
- nalidixic acid worst toxicity (first gen)
27
Rifampin
- inhibits RNA polymerase to block RNA synthesis to kill bacteria
- blocks elongating RNA chain by binding DNA/RNA tunnel of b subunit (bottom jaw) of RNA pol
- bactericidal
28
Fidaxomicin
- binds to switch region and inhibits RNAP
- stays in GI where it needs to work (essentially zero systemic viability)
- specific to C. difficile
- bactericidal
29
Rifampin and Rivapentine
- both primarily used for treatment of TB
- major problem is compliance
- bactericidal agents
- G (+) over Gram (-)
- poor drug penetration
30
can bacteria use exogenous tetrahydrafolate?
- no
31
Cotimoxazole
- sulfamexothoxazole and trimethoprim
| - work synergistically to inhibit both steps of tetrahydrofolate synthesis
32
Sulfamethoxazole
- sulfa drug
- inhibits Dihydropteroate Synthase (not in humans) by mimicking PABA
- competitive inhibitor
- inhibits from GTP to Dihydropteroate
33
Trimethoprim
- diaminopyrimidine
- inhibits dihydrofolate reductase
- dihydrofolate to tetrahydrafolate
- great selectivity for bacterial DHFR over human
34
Which 3 drugs disrupt cell membranes?
- Gramicidin
- Polymyxin
- Daptomycin (complex with Ca)
35
Gramicidin and Polymyxins work on which gram and what're they used for?
- gram negative
- interact with lipopolysaccharide on surface of G(-)
- topical OTC ointments
36
Colistin
- high toxicity and used primarily for resistant gram - infections
- disrupts cell membranes
- last line of defense
37
Daptomycin primarily active against which gram?
- positive
- lipopeptide
- new drug, not much resistance yet
- complexes with Ca followed by membrane disruption
