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IPFC 2 > Antibiotics: Pharmacology > Flashcards

Antibiotics: Pharmacology Flashcards

1
Q

Which are the beta lactams

A

penicillins, cephalosporins, carbapenems, and beta-lactamase inhibitors

** all have the lactam ring

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2
Q

MoA of beta lactams : cell wall

A

impact cell wall synthesis via inhibition of the transpeptidation reaction

  • Bind covalently and block PBP so that it can no longer remove terminal alanine; no cross linking occurring + peptidoglycan synthesis

**only kill cells that are actively growing

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3
Q

T or F: B lactams oral absorption is impaired by food

A

T - all except amoxicillin

— rest needed to be dosed 1-2 hours before or after a meal

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4
Q

Which beta lactams are acid stable

A

penicillin, amoxicillin, ampicillin and cloxacillin: can be given orally

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5
Q

Main SEs of Beta lactams

A

GI: N/V/D
Secondary opportunistic infections
- skin rash or hypersensitivity (cross reaction in class and across classes)

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6
Q

How does B lactam hypersensitivity occur

A

penicillin Ags are presented during metabolism to immune cells when bound to protein

  • recognized as non-self and mount response against
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7
Q

What is the main mech of B-lactam R

A

Beta-lactamase: destroys beta lactam ring —- and therefore Abx activity

  • included for penicllins, cephalosporins, carbapenems
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8
Q

2nd mech of R for beta lactams

A

modification of PBP (ex/ Strep. pneumo)
—- responsible for MRSA too

impaired penetration: gram - (more layers); efflux pumps (gram -)

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9
Q

B lactamase inhibitors include…

A

clavulanic acid and tazobactam

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10
Q

T or F: beta lactamase inhibitors have strong antibacterial activity on their own

A

F - they act as a suicide molecule and used in combo with beta lactam
—- distracts B-lactamase while beta lactam actually does its shit

** extends the penicillin activity too to include those with R because of beta lactamase production —- Beta lactam producing strands of S. aureus

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11
Q

What penicillins are b-lactamase inhibitors used in combo with

A

amoxicillin, ticarcillin, piperacilin

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12
Q

T or F: penicillin G is oral and V is IV

A

F - G is IV and V is oral

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13
Q

What are the anti-staphylococcal penicillins

A

Cloxacillin
- food impacts its absorption

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14
Q

What are the anti-pseudomonal penicillins

A

ticarcillin, piperacillin

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15
Q

What makes cephalosporins different than penicillins (structure)

A

beta lactam ring + 6C ring

penicillins: beta lactam ring + 5 C ring

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16
Q

T or F: penicillins tend to have a broader spectra than cephalosporins

A

F - cephalosporins is broader

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17
Q

T or F: all cephalosporins are prodrugs

A

F - some are prodrug esters

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18
Q

T or F: you can get cross sensitivity bw penicillins and cephalosporins

A

T - 1-5%

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19
Q

Special ADRs of cephalosporins

A

nephrotoxicity - high doses

disulfiram-like reactions: inhibit alcohol dehydrogenase so if drink get build up of acetaldehyde

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20
Q

What are the carbapenems

A

Include imipenem. meropenem and ertapenem

— same MoA: beta lactam

** imipenem is co-adminned with cola statin to prevent its breakdown in the kidney

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21
Q

SEs of carbapenems

A

N/V
seizures
cross reactivity with penicillins

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22
Q

T or F: Vanco is orally available

A

F - only IV unless treating GI shit

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23
Q

T or F: vancomycin targets the cell wall like Beta lactams

A

F - cell wall targeting but different MoA

binds to ala-ala terminal of peptidoglycan chain and prevents building

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24
Q

T or F: Vanco can’t penetrate gram - bacteria’s outer membrane

A

T == only impact gram +

25
Unique SEs of Vanco
IV admin shit toxicities associated with ear and kidney - rare and not seen in humans ; just animal models
26
Main mech of R to Vanco
mutation of target site (Ala-Ala) to Ala-Serine or Ala-lactate
27
What is Fosfomycin
Non-beta lactam cell wall agent - inhibits the MurA enzyme that produces peptidoglycan by acting as a PEP analog ** inhibits earlier on the cell wall synthesis pathway
28
ADRs of fosfomycin
Nausea, diarrhea, headache, neutropenia, angioedema
29
What are the bacterial ribosomal parts
30S and 50S human : 40S and 60S - different enough that targeting is relatively selective for B
30
What is included in the protein synthesis inhibitors
Tetracyclines (doxy), marcolides, clindamycin
31
What is the general structure of tetracyclines
4 ring system that is hydrophilic
32
MoA of tetracyclines
inhibit protein synthesis by binding to the 30S subunit and blocking incoming tRNA * slow/stop translation
33
T or F: Doxy is excreted in urine but also can undergo enterohepatic recycling
T
34
Tetracycline SEs
GI photosensitivity liver toxicity: high doses renal toxicity: Fanconi syndrome (expired tetracyclines) Vestibular Rxn - minocycline
35
When is it not safe to use tetracyclines
kids and pregnant people — chelate and bind to Ca - accumulate in these areas and can impact bones and teeth rxn related to dose: weight (not duration ) Doxy- only exception to this because decrease AFF to Ca
36
Main Mech of R to Tetracyclines
Drug Efflux (pump shit out)
37
MoA: Macrolides
protein synthesis inhibitors - bind reversible to 50S unit and inhibit transpeptidation and translocation
38
What are the macrolides
azithromycin, clarithromycin and erthromycin
39
Which of the macrolides is the best absorbed
Clarithromycin - Azithromycin is best on empty stomach and shouldn’t be taken with antacids - Erythromycin: acid labile and needs enteric coat
40
What metabolizes the macrolides
CYP 3A4
41
Which macrolides inhibit P450 enzymes
Clarith + Erythro but not Az
42
SEs of Macrolides
GI: anorexia, N/V/D fever, eosinophilia, rash hepatotoxicity: erythromycin QT prolongation
43
Which macrolide has the highest risk of QT prolongation
E> C> A ** more risk when already have long QT interval
44
T or F: there is one main mech of R for macrolides
F - they have just a shit ton 1) Reduce permeability (gram -) or active efflux (gram +) 2) destroy them via esterases 3) modification of ribosomal site (mutate target)
45
What is Clindamycin? MoA
not a macrolide; acts like one but chemically different - MoA; binds to 50S and blocks (can have cross R bw macrolides and clindamycin; also will compete for same spot if coadmin)
46
SEs of Clindamycin
N, D skin rash impaired LFT neutropenia
47
MoR for Clindamycin
Ribosomal access - poor porin permeability (gram -) **no impact by efflux pumps in gram + — gram + can’t pump out*** decreased ribosomal binding: change target
48
What are the DNA targeting ABx
FQ
49
What are the FQs
Ciprofloxacin, norfloxacin, ofloxacin Resp FQ: levofloxacin, moxifloxacin, gemifloxacin — bactericidal
50
FQ: MoA
block DNA synthesis 1) Inhibt DNA gyrase/topoisomerase II: DNA can’t uncoil and relax 2) Block Topoisomerase IV: replicated DNA does’t separate properly into cells during division ** expressed in humans too but relatively selective for B>H by 100-1000
51
T or F: FQs are normally given orally
T
52
FQ: ADRs
GI photosensitivity headache, dizzy, drowsiness, insomnia skin rash, abnormal LFTs QT prolongation cartilage and tendon damage: only seen in animal models —— why not used in those younger 18 years or pregnant people
53
Main MoR for FQ
mutations in binding region of target enzyme - mutation of gyrA subunit of DNA gyrase others: change permeability, expression of proteins that protect DNA gyrase from FQ
54
MoA: Metronidazole
Nitro group on Abx is metabolized into toxic radical in anaerobic bacteria — ferrodoxins reduce nitro group to radical to react with DNA and cause damage ** only impacted by aerobic bacteria, inhibited by O2 levels that are high ** once done its shit, gets regenerated and can repeat
55
DF for Metronidazole
IV, oral or suppository
56
SEs of Metronidazole
headache N/V/D dry mouth disulfiram like effects increased prothrombin time Rare (CNS): ataxia and paresthesias - associated with duration of therapy
57
Main MoR: Metronidazole
mutation that impairs production of nitro anion - decrease O2 scavenging ability (can’t get rid of O2 as well in bacteria) - decreased levels of ferredoxin
58
What is Fidoxamicin? MoA
Thicc boi that works against gram + and anaerobic bacteria - binds to sigma subunit of RNA poly - inhibit it and transcription ** used for C. difficile

IPFC 2 (7 decks)

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