E2L18: Chemical Methods - Suppress Cell Wall Synth + Antimetabolites

Question 1

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?

Answer 1

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

Question 2

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

Answer 2

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

Question 3

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

Answer 3

• 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

Question 4

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

Answer 4

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

Question 5

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

Answer 5

• cephalosporins (5 generations)
• carbapenems
• bacitracin
• vancomycin

Question 6

Natural penicillin examples?

Answer 6

• benzyl penicillin (penicillin G)

- phenoxymethyl penicillin (penicillin V)

Question 7

Benzyl penicillin?

Answer 7

• 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)

Question 8

Phenoxymethyl penicillin?

Answer 8

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

Question 9

Repository penicillin examples?

Answer 9

• mix Penicillin G w/ either Procaine or Benzathine

- -> trying to wean off of procaine usage…

Question 10

Benzathine Penicillin?

Answer 10

= 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)

Question 11

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

Answer 11

• derived from penicillin g - modified penicillin g

- ex: ampicillin, amoxicillin, ticarcillin

Question 12

Ampicillin?

Answer 12

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

Question 13

Amoxicillin?

Answer 13

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

Question 14

Ticarcillin?

Answer 14

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

Question 15

Talk about Pseudomonas aeruginosa infections and Pseudomonas Other Infections.

Answer 15

• 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

Question 16

Beta-Lactamase Resistant Penicillin examples?

Answer 16

• methicillin, oxacillin, cloxacillin, augmentin

Question 17

Methicillin?

Answer 17

• 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)

Question 18

Oxacillin?

Answer 18

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

Question 19

Cloxacillin?

Answer 19

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

Question 20

Augmentin?

Answer 20

• 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

Question 21

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

Answer 21

Streptomycin (aminoglycoside)

Question 22

Cephalosporins in general?

Answer 22

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

Question 23

Why are cephalosporins penicillin substitutes?

Answer 23

• 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

Question 24

What’s the 1st generation cephalosporin?

Answer 24

• Cephalexin (Keflex)

- narrow spectrum for G+ (staph/strep)

Question 25

What's the 2nd generation cephalosporin?

Answer 25

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

Question 26

What's the 3rd generation cephalosporins?

Answer 26

- Cetriaxone and Cefotaxime - both broad spectrum - DOCs for G- infections (Klebsiella pneumo)

Question 27

What's the 4th generation cephalosporin?

Answer 27

- Cefepime | - also DOC for G- infections (Klebsiella pnuemo)

Question 28

What's the 5th generation cephalosporin?

Answer 28

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

Question 29

Carbapenems?

Answer 29

- 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

Question 30

Carbapenem example?

Answer 30

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

Question 31

Bacitracins?

Answer 31

- 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)

Question 32

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

Answer 32

- Polymyxin B - fights G- - Bacitracin - fights G+ - Neomycin - broad spectrum

Question 33

Vancomycin?

Answer 33

- 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

Question 34

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

Answer 34

- 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)

Question 35

What's the PABA metabolic pathway?

Answer 35

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

Question 36

What are sulfanomides? (sulfa drugs) Examples?

Answer 36

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

Question 37

Sulfadiazine?

Answer 37

- sulfadiazine (antimetabolite)+ Ag (protein coag) = silver sulfadiazine - for burn patients - ex: sulfonamide

Question 38

Bactrim?

Answer 38

= 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

Question 39

What are Sulfones? Example?

Answer 39

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

Question 40

Isoniazid?

Answer 40

- 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

Question 41

PAS???

Answer 41

- 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)

Question 42

Antibiotics based on pH change?

Answer 42

- 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

Question 43

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

Answer 43

d) detergents - block synth of murein | detergents disrupt phospholipoprotein membrane

Question 44

All of the following act by competitive inhibition except: a) dapsone b) isoniazid c) lysozyme d) sulfonamide e) none

Answer 44

c) lysozyme | lysozymes digest murein!!! MOA not suppress murein synth