E2L17: Chemical Methods - Disrupt Phospholipoprotein Membrane Flashcards
What part of the phospholipid is hydrophilic? Hydrophobic?
- hydrophilic head
- hydrophobic tail
Talk to me about things that disrupt phospholipoprotein membranes in general.
- disrupts cell/plasma membrane and its phospholipids
- are SURFACTANTS, which mimic phospholipids –> poke holes + dissolve membrane
- are CIDAL agents b/c membrane damaged
- toxic to us if used systemically b/c we have cell membranes!!!
What are some broad categories whose MOA is disrupt phospholipoprotein membranes? (disrupt cell wall synthesis)
Detergents (cationic, anionic, non-ionic), Polymyxins, Polyenes, Azoles
What are Cationic Detergents? MOA? Examples? Efficacy against TB, Hep B, spores? Disinfectant/Sterilant?
- detergents w/ + charge, most effective of detergents
- MOA: disrupt phospholipoprotein membranes
- ex: benzalkonium chloride (benzyl ammonium chloride), cetylpyridium chloride
- NOT v effective against TB, Hep B, nor spores
- -> disinfectant (not effective towards spores)
Why do hospitals and food industries use cationic detergents?
- low toxicity
- G+ org (ex: staph + strep) still problem in hospitals
- -> cationic detergents better for G+ bacteria
What are Quaternary Ammonium Cmpds?
- nitrogen w/ 4 alkyl groups attached
- 1 alkyl is long+non-polar = tail
- in most Lysol brands
Are cationic detergents more effective towards G+ or G- bacteria and why?
More effective towards G+ b/c G+ have murein and NO OUTER MEMBRANE. G-‘s outer membrane blocks cationic detergents. G-‘s cell wall still damaged (outer membrane portion), but not as vital as if the cell membrane itself was damaged.
What are Anionic Detergents? MOA? Examples? Typ. used for what org?
- detergents w/ - charge, not as effective as cationic
- MOA: disrupt phospholipoprotein membrane
- typ. used for weak org (ex: gonococcus [Neisseria gonorrhea], meningococcus [Neisseria meningitidis], pneumococcus [Strep. pneumo], syphilis [Treponema pallidum])
What is Benzalkonium Chloride?
- MOA: disrupt phospholipoprotein membrane
- quaternary ammonium cmpd
- cationic detergent
- -> good against G+ org (staph/strep)
What’s Cetylpyridium Chloride?
- MOA: disrupt phospholipoprotein membrane
- quaternary ammonium cmpd
- cationic detergent
- -> good against G+ org (staph/strep)
- preservative in mouthwashes, cosmetics, ophthalmic soln
What’s Sodium Lauryl Sulfate?
- MOA: disrupt phospholipoprotein membrane
- anionic detergent
- preservative in some mouthwashes
What are Bile Salts?
- MOA: disrupt phospholipoprotein membrane
- anionic detergent
- helps emulsify lipids in intestines
- found in MacConkey’s agar, which is selective for G- due to bile working against G+ org
- Taxo P discs have bile salts
What are the organisms that Anionic detergents normally treat against?
- gonococcus –> Neisseria gonorrhea
- meningococcus –> Neisseria meningitidis
- pneumococcus - Strep. pneumo.
- syphilis –> Treponema pallidum
What are Taxo P discs?
- have bile salts - MOA: detergent -> disrupt phospholipoprotein membrane
- “P” = strep. “P”neumo
- used for ID, there’d be zone of inhibition around disc
What are non-ionic detergents? MOA?
- only surfactants (mimic phospholipids)
- ex: “bland” soaps –> MOA: mechanical - scrubbing
- NO antimicrobial action
Talk about Polymyxins as a whole.
- they’re series of amino acids connected by polypeptides (peptide bonds)
- have polar, cyclic head + non-polar tail
- Bacillus species (ex: subtilis) make polymyxins for protection
- B and E (colistin) used clinically
- NOT DOC!!! b/c neurotoxic + nephrotoxic (kidney)
- narrow spectrum for G-
Okay, talk about Kirby-Bauer Technique.
- a disc diffusion technique
- antibiotic discs on streaked agar plate
- measure zones of inhibition
- qualitative
- break points: R (resistant), I (intermediate), S (sensitive)
- -> R/I/S measurement depends on antibiotic
What are some advantages of Kirby-Bauer? Disadvantages?
- adv: can test multiple antibiotics simul. + can possible approx. MIC
- dis: not good for anaerobes or slow-growing bacteria (ex: mycobacterium - takes 2-4 weeks to grow)
- -> b/c disc diffuses quick, if slow-grow, only small [] over long period of time –> ineffective
Okay, talk about Tube Dilution Technique.
- dis: test only 1 at a time
- serial dilution, take certain dilution (ex: 128 micrograms/ml), 1/2 that dilution each time until 0 (- control)
- can determine MIC (quantitative)
- break points: S/I/R defined in micrograms/ml
- can also test for MBC (minimum bactericidal [])
What do the S/I/R break points relate to?
- relates to breakpoints in blood, [able to be achieved in blood] must be higher than MIC
- [] in blood relates to optimal therapy
- optimal therapy (method): topically, oral, intramuscular (IM), intravenous (IV)
How would you find an MBC? (minimum bactericidal []) What are the benefits to finding an MBC?
- perform MIC 1st
- inoculate all clear tubes onto fresh plates w/o antibiotics
- MIC should grow out b/c only inhibitory
- MBC typ 1-2 dilutions higher than MIC
- good to know for immunocompromised patients, adv b/c related to [blood] + measured in micrograms/ml
Talk about E-Tests.
- strip w/ gradient of [antibiotic]’s placed on culture plate lawn
- easier, more fool-proof way of finding MIC than serial tube dilution – more $$$ tho, lmao
Talk about Polymyxin B.
- ex: polymyxin - disrupts phospholipoprotein membrane
- narrow spectrum for G-
- LAST CHOICE for Acinetobacter + Pseudomonas systemic infections
- EXTERNAL use for:
- -> otic (ear) infections - otitis externa (outer ear), swimmer’s ear
- -> ophthlamic (eye)
- -> triple ointment (polymyxin b + bacitracin + neomycin)
How and where would you get Acetinobacter baumannii + Pseudomonas aeruginosa infections?
- affects immuno compro. patients in hospitals (nosocomial infections)
- these develop resistance easily, so polymyxins might required
Talk about Polymyxin E.
- AKA colistin
- ex: polymyxin - disrupts phospholipoprotein membrane
- narrow spectrum for G-
- very toxic
- EXTERNAL use - otitis externa
- for LAST CHOICE systemic infections Acetinobacter + Pseudomonas
- used in Thayer Martin Selective Agar
What’s in Thayer Martin Selective Agar? What’s it used for?
- used to ID gonorrhea in patients, by selecting for it
- includes: vancomycin (inhibits G+) + colistin (polymyxin E, for G- rods) + nystatin (inhibits yeasts)
- -> selects for G- cocci like gonorrhea
Talk about Polyenes as a whole.
- cyclic, multiple 2x bonds
- bind to sterols in cell membrane (ex: cholesterol in humans, ergosterol in fungi)
- antifungal –> binds to sterol in membrane –> CIDAL
- most bacteria lack sterols, but fungi have ‘em
- can be toxic to us b/c we have cholesterol (ex: of sterol)
Name some Polyenes.
nystatin and amphotericin B
Talk about Nystatin.
- ex: polyene - binds to sterols - disrupt membrane
- NOT a DOC nor an alternate, but still commonly used
- used for dermatophytes + superficial fungal infections by Candida albicans
- kinds of superficial fungal infections (vulvovaginal candidiasis - yeast infection; oropharyngeal candidiasis - thrush)
When can Candida albicans be a threat to us? (Threat to whom?)
- immuno compro.
- extreme youth
- pregnant women
- ppl w/ nutritional disorders (ex: diabetes)
Is Nystatin absorbed in the stomach? What uses come out of this?
- NO, not absorbed by stomach –> doesn’t go systemically when taken orally
- used to reduce yeast #’s in patients before surgery
- used in mouth rinses, lozengers to clear out Candida
Talk about Amphotericin B.
- DOC for systemic/deep mycoses (fungal infection)
- CIDAL, toxic tho
- also used for severe candida albicans infections
- immuno compro @ most risk
- zygomycosis: rhizopus (black bread mold)
- aspergillosis: common soil org
- dimorphic fungi –> grow as yeast (large cocci w/ bud) @ 37C (body temperature), grow as mold @ 25C (RT) + looks like mold (hyphae) –> v pathogenic
What do Azoles do? What are some broad categories of Azoles?
- interfere w/ sterol synthesis (ergosterol)
- inhibitory/static
- complex, ringed structures
- broad categories: imidazoles, triazoles
What are some examples of Imidazoles? What are imidazoles?
- 2 nitrogens in a ring
- INSOLUBLE in H2O
- ex: clorimazole and miconazole, ketoconazole
Talk about Clorimazole and Miconazole
- used similarly, both for mild dermatophyte infections (candida), good for vulvovaginal infection
- used for ringworm and its 3 causes
What are the 3 causes of ringworm? What’s a common name for a kind of ringworm? What can you use to treat these ringworm infections? Is there a genetic predisposition for ringworm?
- 3 causes: microsporum, trichophyton, epidermophyton
- -> microsporum: skin, most common
- -> trichophyton: skin-nails-hair, NASTIEST
- -> epidermophyton: skin-nails
- ringworm on feet = athlete’s foot (tricho. or epidermo.)
- generally genetic predisposition
Talk about Ketoconazole.
- ex: imidazole (H2O insoluble) - azole - disrupt membrane
- TOPICALLY, alternate for systemic mycoses (zygomycosis, aspergillosis, dimorphic)
- alt. b/c more toxic
- if aspergillosis gets to brain, can’t use Ketoconazole b/c can’t pass BBB
What are the 3 causes of systemic mycoses?
- zygomycosis
- aspergillosis
- dimorphic fungi
What are Triazoles? Examples?
- azoles that are more H2O soluble
- MOA: disrupt membrane
- ex: fluconazole (diflucan) and voriconazole
What’s fluconazole? Other name? Used for…? DOC?
- aka Diflucan
- ex: triazole - azole - disrupt membrane
- DOC for systemic mycoses, including those of nervous system (can pass BBB)
Which of the following isn’t true about quaternary ammonium cmpds?
a) greater activity against G+
b) outer membrane of G- decreases effectiveness
c) viricidal against Hep
d) ineffective against tubercule bacillus
c) viricidal against Hep
Which of the following statements is TRUE regarding use of non-germ. soaps over 4 day period?
a) show a persistant reduction of microbes on skin over time
b) reduce bacterial count by 1/2 over 4 days
c) just as effective as germicidal soaps in reducing microbial contamination
d) microbial count actual increases 2x using non-germ
e) no sustained effect of non-germ. on reduction of microbial contam.
e) no sustained effect of non-germ. soap on reduction of microbial contamination
Which of the following antibiotics are used to treat fungal infections?
1 - penicillins, 2 - cephalosporins, 3 - triazoles, 4 - polyenes, 5 - nystatin
a) 1,2,3
b) 3, 4
c) 3,4,5
d) 4,5
e) all of ‘em
c) 3,4,5 (triazoles, polyenes, nystatin)
These agents work as microbicidal agents b/c they lower surface tension of cell membranes.
a) penicillin
b) surfactants
c) lysozyme
d) metallic ions
e) dry heat
b) surfactants
Which of the following statements regarding antifungal agents is incorrect?
a) amphotericin B - systemic fungal infections
b) nystatin - superficial candidiasis
c) ketoconazole - infections of the nervous system
d) fluconazole - yeast infections
e) none of these
c) ketonazole - infections of the nervous system
b/c can’t pass the BBB!!! voriconazole can pass BBB tho
Treatment of severe superficial candidiasis includes?
a) cetylpyridinium chloride
b) sodium lauryl sulfate
c) amphotericin B
d) polymyxin E
e) miconazole
c) amphotericin B
note: it’s a DOC for systemic/deep mycoses!
