E2L18: Chemical Methods - Suppress Cell Wall Synth + Antimetabolites Flashcards
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?
- during log growth phase b/c mainly building cell wall
- G+ more murein
- G- outer membrane block out natural penicillins
What can break down beta-lactam rings? Name some organisms.
- beta-lactamases
- produced in org such as staph aureus, neisseria gonorrhea, since some strains have penicillinases, cephalosporinases, and carbapenemases
Talk about penicillins as a whole. What are some broad groups of penicillins?
- 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
All penicillins have a ___ w/ a _____ ring, but differ in their side chains/______
1) nucleus
2) beta-lactam ring
3) R-groups
What are some other antibiotic groups that also suppress cell wall synth (murein synth) that aren’t penicillins?
- cephalosporins (5 generations)
- carbapenems
- bacitracin
- vancomycin
Natural penicillin examples?
- benzyl penicillin (penicillin G)
- phenoxymethyl penicillin (penicillin V)
Benzyl penicillin?
- 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)
Phenoxymethyl penicillin?
- natural penicillin
- aka Penicillin V
- benzene ring w/ alkyl group + O
- better orally, resistant to stomach acid
- MOA: suppress cell wall synth (murein synth)
Repository penicillin examples?
- mix Penicillin G w/ either Procaine or Benzathine
- -> trying to wean off of procaine usage…
Benzathine Penicillin?
= 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)
Semi-synthetic penicillin examples? What are semi-synth penicillins?
- derived from penicillin g - modified penicillin g
- ex: ampicillin, amoxicillin, ticarcillin
Ampicillin?
- semi-synth penicillin - suppress CW synth (murein)
- extra amino group
- broad spectrum (can pass outer membrane)
- DOC for Proteus Mirabilis UTI
Amoxicillin?
- semi-synth - suppress CW synth (murein)
- extra OH group
- DOC for Proteus Mirabilis UTi
- broad spectrum (can pass outer membrane)
Ticarcillin?
- semi-synth - suppress CW synth (murein)
- has sulfur ring
- DOC for Pseudomonas Other Infections (which causes pneumo and osteomyelitis)
Talk about Pseudomonas aeruginosa infections and Pseudomonas Other Infections.
- 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
Beta-Lactamase Resistant Penicillin examples?
- methicillin, oxacillin, cloxacillin, augmentin
Methicillin?
- 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)
Oxacillin?
- beta-lactamase resistant penicillin - suppress CW synth
- parenteral (given IV or IM)
- systemic infections
Cloxacillin?
- beta-lactamase resistant penicillin - suppress CW synth
- oral
- v similar to oxacillin but for less severe infections
Augmentin?
- 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
MDRSA is resistant to… ____ b/c of efflux pumps.
Streptomycin (aminoglycoside)
Cephalosporins in general?
- look like penicillins, but w/ 2 side groups
- from cephalosporium molds
- contains 5 generations: cephalexin (keflex); cefotiam; ceftriaxone, cefotaxime; cefepime; ceftaroline
Why are cephalosporins penicillin substitutes?
- 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
What’s the 1st generation cephalosporin?
- Cephalexin (Keflex)
- narrow spectrum for G+ (staph/strep)
What’s the 2nd generation cephalosporin?
- Cefotiam
- not broad, more for G- (Entereobacter, Proteus, Haemophilus)
What’s the 3rd generation cephalosporins?
- Cetriaxone and Cefotaxime
- both broad spectrum
- DOCs for G- infections (Klebsiella pneumo)
What’s the 4th generation cephalosporin?
- Cefepime
- also DOC for G- infections (Klebsiella pnuemo)
What’s the 5th generation cephalosporin?
- Ceftaroline
- used for CAP (community acquired [bacterial] pneumo)
Carbapenems?
- 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
Carbapenem example?
- Primaxin
= Imipenem (carbapenem) + Cilastatin (blocks renal dipeptidase enzyme activity: dehydropeptidase I, which protects imipenem from kidney breaking it down) - DOC for Acetinobacter
Bacitracins?
- 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)
Explain all of the components of the triple ointment (Neosporin).
- Polymyxin B - fights G-
- Bacitracin - fights G+
- Neomycin - broad spectrum
Vancomycin?
- 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
What are some groups of antimetabolites? How do antimetabolites work?
- 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)
What’s the PABA metabolic pathway?
PABA (para animo benzoic acid) –> dihydropteroic acid (sulfa!!!) –> dihydrofolic acid (trimethoprim!!!) –> tetrahydrofolic acid
What are sulfanomides? (sulfa drugs) Examples?
- contain benzene group and amino group
- works on first step of PABA pathway (PABA to dihydropteroic acid)
- ex: sulfadiazine, bactrim
Sulfadiazine?
- sulfadiazine (antimetabolite)+ Ag (protein coag) = silver sulfadiazine
- for burn patients
- ex: sulfonamide
Bactrim?
= 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
What are Sulfones? Example?
- antimetabolites
- NOT sulfa drug, but works at same point
- -> (PABA –> dihydropteroic acid)
- ex: Dapsone
- -> DOC for Mycobact. leprae (leprosy)
Isoniazid?
- 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
PAS???
- 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)
Antibiotics based on pH change?
- 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
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
d) detergents - block synth of murein
detergents disrupt phospholipoprotein membrane
All of the following act by competitive inhibition except:
a) dapsone
b) isoniazid
c) lysozyme
d) sulfonamide
e) none
c) lysozyme
lysozymes digest murein!!! MOA not suppress murein synth
