E2L18: Chemical Methods - Suppress Cell Wall Synth + Antimetabolites Flashcards

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1
Q

What part of the bacterial growth curve are chemicals that suppress cell wall synthesis (murein synth) most effective? If the chemicals are derived from a natural source, which is it more effective against: G+ or G-? Why?

A
  • during log growth phase b/c mainly building cell wall
  • G+ more murein
  • G- outer membrane block out natural penicillins
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2
Q

What can break down beta-lactam rings? Name some organisms.

A
  • beta-lactamases
  • produced in org such as staph aureus, neisseria gonorrhea, since some strains have penicillinases, cephalosporinases, and carbapenemases
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3
Q

Talk about penicillins as a whole. What are some broad groups of penicillins?

A
  • effective against group A strep (pyogenes), Clostridium perfringens (gas gangrene in GI tract), Neisseria meningitidis (G- cocci, v contagious), treponema pallidum (syphilis, gram non-reactive)
  • found from penicillium mold growing on staph aureus
  • groups: natural, repository, semi-synthetic, beta-lactamase resistant
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4
Q

All penicillins have a ___ w/ a _____ ring, but differ in their side chains/______

A

1) nucleus
2) beta-lactam ring
3) R-groups

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5
Q

What are some other antibiotic groups that also suppress cell wall synth (murein synth) that aren’t penicillins?

A
  • cephalosporins (5 generations)
  • carbapenems
  • bacitracin
  • vancomycin
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6
Q

Natural penicillin examples?

A
  • benzyl penicillin (penicillin G)

- phenoxymethyl penicillin (penicillin V)

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7
Q

Benzyl penicillin?

A
  • natural penicillin
  • aka Penicillin G
  • has side group benzene ring w/ methyl
  • injection or IV
  • not good orally b/c stomach breaks it down
  • narrow spectrum for G+, only for G+
  • MOA: suppress cell wall synth (murein synth)
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8
Q

Phenoxymethyl penicillin?

A
  • natural penicillin
  • aka Penicillin V
  • benzene ring w/ alkyl group + O
  • better orally, resistant to stomach acid
  • MOA: suppress cell wall synth (murein synth)
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9
Q

Repository penicillin examples?

A
  • mix Penicillin G w/ either Procaine or Benzathine

- -> trying to wean off of procaine usage…

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10
Q

Benzathine Penicillin?

A

= benzathine + penicillin g (benzyl penicillin)

  • lasts 18 hrs in body, allowing slow release @ low dose
  • prophylactic for rheumatic fever from strep pyogenes
  • can also treat syphilis (treponema pallidum)
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11
Q

Semi-synthetic penicillin examples? What are semi-synth penicillins?

A
  • derived from penicillin g - modified penicillin g

- ex: ampicillin, amoxicillin, ticarcillin

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12
Q

Ampicillin?

A
  • semi-synth penicillin - suppress CW synth (murein)
  • extra amino group
  • broad spectrum (can pass outer membrane)
  • DOC for Proteus Mirabilis UTI
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13
Q

Amoxicillin?

A
  • semi-synth - suppress CW synth (murein)
  • extra OH group
  • DOC for Proteus Mirabilis UTi
  • broad spectrum (can pass outer membrane)
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14
Q

Ticarcillin?

A
  • semi-synth - suppress CW synth (murein)
  • has sulfur ring
  • DOC for Pseudomonas Other Infections (which causes pneumo and osteomyelitis)
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15
Q

Talk about Pseudomonas aeruginosa infections and Pseudomonas Other Infections.

A
  • in general, pseudomonas v resistant to many antiobiotics + opportunistic (ex: nosocomial)
  • 2 kinds: Pseudomonas aeruginosa UTI (in GI tract, comes out in feces) and Pseudomonas aeruginosa Other (causes pnemo and osteomyelitis
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16
Q

Beta-Lactamase Resistant Penicillin examples?

A
  • methicillin, oxacillin, cloxacillin, augmentin
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17
Q

Methicillin?

A
  • not used in US anymore
  • has extra side groups which penicillinases can’t break down
  • MSSA (penicillinase), MRSA (penicillinase + PBP), MDRSA (penicillinase + PBP + efflux pump)
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18
Q

Oxacillin?

A
  • beta-lactamase resistant penicillin - suppress CW synth
  • parenteral (given IV or IM)
  • systemic infections
19
Q

Cloxacillin?

A
  • beta-lactamase resistant penicillin - suppress CW synth
  • oral
  • v similar to oxacillin but for less severe infections
20
Q

Augmentin?

A
  • beta-lactamase resistant penicillin - suppress CW synth
    = Amoxicillan (semi-synth) + Potassium Clavulanate (competitive inhibitor, that allows amoxicillan to do its thang)
  • suicide substrate - inactivates enzymes
  • extends activity of amoxicillin to MSSA, but not MRSA
21
Q

MDRSA is resistant to… ____ b/c of efflux pumps.

A

Streptomycin (aminoglycoside)

22
Q

Cephalosporins in general?

A
  • look like penicillins, but w/ 2 side groups
  • from cephalosporium molds
  • contains 5 generations: cephalexin (keflex); cefotiam; ceftriaxone, cefotaxime; cefepime; ceftaroline
23
Q

Why are cephalosporins penicillin substitutes?

A
  • b/c similar to penicillins
  • good for the 5% Americans who are allergic to penicillin
  • cephalosporins resistant to penicillinase, but some might have both penicillinase + cephalosporinase
  • 10% ppl allergic to penicillin also allergic to cephalosporin
24
Q

What’s the 1st generation cephalosporin?

A
  • Cephalexin (Keflex)

- narrow spectrum for G+ (staph/strep)

25
Q

What’s the 2nd generation cephalosporin?

A
  • Cefotiam

- not broad, more for G- (Entereobacter, Proteus, Haemophilus)

26
Q

What’s the 3rd generation cephalosporins?

A
  • Cetriaxone and Cefotaxime
  • both broad spectrum
  • DOCs for G- infections (Klebsiella pneumo)
27
Q

What’s the 4th generation cephalosporin?

A
  • Cefepime

- also DOC for G- infections (Klebsiella pnuemo)

28
Q

What’s the 5th generation cephalosporin?

A
  • Ceftaroline

- used for CAP (community acquired [bacterial] pneumo)

29
Q

Carbapenems?

A
  • not penicillin, also suppress CW synth (murein)
  • switch sulfur and put carbon in ring
  • adv: v effective against G-, even ones resistant to 3rd gen cephalosporins (ex: acetinobacter)
  • very broad spectrum
30
Q

Carbapenem example?

A
  • Primaxin
    = Imipenem (carbapenem) + Cilastatin (blocks renal dipeptidase enzyme activity: dehydropeptidase I, which protects imipenem from kidney breaking it down)
  • DOC for Acetinobacter
31
Q

Bacitracins?

A
  • sourced from Bacillus species
  • a polypeptide
  • not penicillin, still suppress CW synth (murein)
  • narrow spectrum for G+
  • part of triple ointment (polymyxin B, neomycin, bacitracin)
32
Q

Explain all of the components of the triple ointment (Neosporin).

A
  • Polymyxin B - fights G-
  • Bacitracin - fights G+
  • Neomycin - broad spectrum
33
Q

Vancomycin?

A
  • suppress CW synth (murein synth)
  • MOST POWERFUL ANTIBIOTIC, the REAL O.G. for G+
  • DOC for some MRSA strains
  • can lead to VRE (vancomycin resistant entereococci)
  • comes from streptomyces
  • LAST RESORT, v toxic!!!
  • IV or orally
34
Q

What are some groups of antimetabolites? How do antimetabolites work?

A
  • antimetabolites = competitive inhibitors = structural analogues
  • stop folic acid (tetrahydrofolic acid) synthesis
  • blocks activity of enzymes in metabolism of PABA (para amino benzoic acid)
  • only static or inhibitory, NOT cidal
  • groups (kinda): sulfonamides (sulfa drugs), sulfones, isoniazid, trimethoprim, PAS (para aminosalicylic acid)
35
Q

What’s the PABA metabolic pathway?

A

PABA (para animo benzoic acid) –> dihydropteroic acid (sulfa!!!) –> dihydrofolic acid (trimethoprim!!!) –> tetrahydrofolic acid

36
Q

What are sulfanomides? (sulfa drugs) Examples?

A
  • contain benzene group and amino group
  • works on first step of PABA pathway (PABA to dihydropteroic acid)
  • ex: sulfadiazine, bactrim
37
Q

Sulfadiazine?

A
  • sulfadiazine (antimetabolite)+ Ag (protein coag) = silver sulfadiazine
  • for burn patients
  • ex: sulfonamide
38
Q

Bactrim?

A

= sulfamethoxazole + trimethoprim

  • ex: of synergism
  • used for uncomplicated UTI (caused by E. coli)
  • used for pneumocystis (carinii) jiroveci pneumo (PCP)
  • -> AIDS patients susceptible to PCP
39
Q

What are Sulfones? Example?

A
  • antimetabolites
  • NOT sulfa drug, but works at same point
  • -> (PABA –> dihydropteroic acid)
  • ex: Dapsone
  • -> DOC for Mycobact. leprae (leprosy)
40
Q

Isoniazid?

A
  • ex: INH (isonicotinic hydrazide)
  • DOC for TB, typ. in initial treatment
  • looks like B vitamin
  • -> given together w/ Pyridoxine to avoid nerve damage
  • prevents mycolic acid (makes TB’s wall so waxy) from getting into cell wall
  • metabolite? who knows??? lmao
41
Q

PAS???

A
  • stands for para aminosalicylic acid
  • used for TB
  • -> for MDRTB (resistant to INH and Rifampin, common TB drugs)
  • -> for XDRTB (resistant to INH, Rifampin and any fluroquinoline ex: ciprofloxacin, along w/ at least 1 injectable aminoglycosides: amikacin, kanamycin, capreomycin)
42
Q

Antibiotics based on pH change?

A
  • ex: quinine, chloroquine, primaquine
  • quinine extracted from cinchona tree (basic, bitter)
  • -> treats malaria (most effective in blood, not so effective when it’s hiding in liver/organs)
  • -> malaria tries to digest hemoglobin
  • -> basic pH blocks activity of HEME POLYMERASE –> buildup of heme
  • -> heme buildup - toxic to malaria
43
Q

Effects of antimicrobial agents on cell walls of bacteria include blocking its synth, digesting it, or breaking down its surface. Which is mismatched?

a) penicillin g - block synth of murein
b) lysozyme - digest murein
c) benzalkonium chloride - breaks down surface of 2nd membrane
d) detergents - blocks synth of murein
e) alcohol - breaks down 2nd membrane

A

d) detergents - block synth of murein

detergents disrupt phospholipoprotein membrane

44
Q

All of the following act by competitive inhibition except:

a) dapsone
b) isoniazid
c) lysozyme
d) sulfonamide
e) none

A

c) lysozyme

lysozymes digest murein!!! MOA not suppress murein synth