IC8 Flashcards
process of bacterial cell wall synthesis
1) NAM & NAG subunits come together
2) amino acid cross link chains of NAM and NAG
3) Tranglycosylation: subunits transported across to form cell wall
4) transpeptidation: transpeptidase cause cross linking of NAM-NAG chains
broad categories of cell wall inhibitors (2x)
1) beta lactams
2) glycopeptides - vancomycin
beta lactams general
- bactericidal to actively growing cells
- time dependent killing
MOA of beta lactams
- bind to active site of transpeptidase -> prevent cross linking of terminal peptide components of linear polymer chains -> weakening of cell wall structure -> intracellular osmotic pressure build up -> lysis
types of beta lactams (x4)
1) penicillin
2) cephalosporin
3) carbapenem
4) monobactam
beta lactams - penicillin - types (x4)
1) natural
2) penicillinase-resistant penicillin
3) aminopenicillin
4) anti-pseudomonal penicillin
beta lactams - penicillin - natural penicillin
- gram positive & gram negative
- X cover beta-lactamase producing microbes (majority of staph)
- types
1) Pen G: parenteral
2) Pen V: better oral bioavailability - renal clearance
beta lactams - penicillin - what is beta lactamase
destroys beta lactam ring
beta lactams - penicillin - penicillinase resistant penicillin
- ONLY GRAM POSITIVE
- cloxacillin
- penicillinase is a type of beta lactamase
- good coverage against MSSA
- bulky side chain prevent beta lactam ring from beta lactamase action
- oral/parenteral
- use natural if there are other gram positive microbes susceptible to natural penicillin
- renal clearance
beta lactams - penicillin - aminopenicillin
- gram pos & gram neg
- ampicillin, amoxicillin (better oral bioavailability)
- both oral/parenteral
- renal clerance
- X work if produce beta-lactamase (combi w beta-lactamase inhibitor)
- X cover pseudomona or klebsiella
beta lactams - penicillin - why aminopenicillin have better gram negative coverage?
hydrophilic groups allow better uptake by gram negative
beta lactams - penicillin - anti-pseudomonal penicillin
- piperacillin
- poor oral bioavailability so parenteral
- gram pos and gram negative btu better coverage against anaerobic
- X work if beta lactamase
- renal clearance
beta lactams - penicillin - beta lactamase inhibitors - general
beta lactam ring but weak anti-bacterial properties
beta lactams - penicillin - beta lactamase inhibitors - MOA
- suicide bomber
- stronger affinity for beta lactamase -> irreversibly bind to and inactivate beta lactamase -> protect other beta lactam Abx
beta lactams - penicillin - beta lactamase inhibitors - indications
MSSA that produce beta lactamase
beta lactams - penicillin - beta lactamase inhibitors - combinations
1) augmentin: clavulanate - amoxicillin
- oral, parenteral
- renal clearance
- MOA: bind to beta lactamase & restructure
2) subectam - ampicillin
- parenteral
- renal clearance
- MOA: irreversible binding
3) tazobactam - piperacillin
- parenteral
- broadest spectrum among penicillin
- renal clearance
- MOA: irreversible binding
beta lactams - penicillin - mechanism of resistance
- production of beta-lactamase
- MRSA: transpeptidase modified -> poor affinity for penicillin -> X bind
- downregulate porin channel = X take in Abx
- efflux pump pumps out Abx
beta lactams - penicillin - adverse reaction
1) hypersensitivity
2) safe and not too bad AE
3) N/V
4) neurotox if high dose + renal impairment
beta lactams - cephalosporin - general
X work against ESBL unless + beta lactamase inhibitor
beta lactams - cephalosporin - 1st gen
- cefazolin, cephalexin
- similar coverage to natural penicillin + penicillinase-resistant penicillin
1) gram pos, gram neg, MSSA
2) poor coverage if produce beta lactamase
3) X pseudomonas - cefazolin parenteral, cephalexin oral
beta lactams - cephalosporin - 2nd gen
- oral use
- improved gram negative coverage
- X pseudomonas
beta lactams - cephalosporin - 3rd gen
- ceftriaxone, ceftazidime
- better coverage against beta-lactamase producing bug
- better coverage to gram negative
- better penetration into CNS
- only ceftazidime cover pseudomonas
beta lactams - cephalosporin - 4th gen
- cefepime
- more resistant to beta lactamase
- cover pseudomonas
beta lactams - cephalosporin - 5th gen
- ceftaroline
- cover LAME
- X pseudomonas
beta lactams - cephalosporin - adverse reactions
1) hypersensitivity
- possible cross allergy between cephalosporin & penicillin
- X give cephalosporin if serious hypersensitivity to penicillin
2) GI
- kill normal gut flora = GI symp (N, D)
beta lactams - carbapenems - general
- 1st line against extended spectrum beta lactamases (ESBL)
- MRSA penicillin binding protein modified to resistant to carbapenem
beta lactams - carbapenems - indication
gram neg, anaerobic supp
X used when carbapenem resistance
beta lactams - carbapenems - types - imipenem + cilastatin
- cover pseudomonas
- why cilastatin?
** imipenem hydrolysed by DHP1 in proximal renal tubule (Renal clerance)
** cilastatin DHP 1 inhibitor -> recover more active form but metabolite can be nephrotoxic so need dose adjustment if renal impairment
beta lactams - carbapenems - types - meropenem
- renal clearance
- cover pseudomonas
beta lactams - carbapenems - types - ertapenem
- renal clearance
- X pseudomonas
beta lactams - carbapenems - adverse reaction
1) hypersensitivity
2) GI symp
3) neuro tox esp if renal impairment
beta lactams - monobactam
- aztreonam
- only gram negative
- cover pseudomonas
- X gram pos & anaerobic
- poor oral bioavailability so parenteral
- renal clearance: dose adjustment if renal impairment
- adverse effect: little/no cross allergy so can still give if serious penicillin allergy
glycopeptides (Vancomycin) - indication
1) gram positive
- MRSA, penicillin resistant streptococcus, clostridium, enterococcus
2) serious infection in penicillin allergy individuals
3) CDAD 1st line oral
glycopeptides (Vancomycin) - MOA
prevent transglycosylation -> prevent NAM NAG coming together -> inhibit cell wall synthesis
glycopeptides (Vancomycin) - PK
- large molcule: X enter gram negative
- poor oral so parenteral UNLESS CDAD
- renal clearance, largely excreted unchanged (X use if renal impairment unless v jialat)
glycopeptides (Vancomycin) - adverse reaction
1) thrombophlebitis
- swelling at administration site
2) red man syndrome
- rash above nipple line (upper torso)
- prevent by prolonging vancomycin infusion
3) nephrotox, ototox (significant)
- X use unless bopz for renal tox
- careful if use w other nephrotox Abx
types of bacterial protein synthesis inhibitors (2x)
1) tetracyclines & glycylcycline
2) aminoglycosides
tetracyclines - general
- bacteriostatic
- avoid administration w beta lactams because beta lactam active against actively growing cells but tetracycline stop growth
tetracyclines - indications
broad spectrum.
- gram pos
- gram neg
- atypical (mycoplasma, chlamydia, legionella) -> community acquired pneumonia
- X PSEUDOMONAS
tetracyclines - MOA
bind reversibly to bacterial ribosome 30s subunit -> prevent binding of tRNA to A site of mRNA-ribosome complex -> inhibit bacterial protein synthesis
tetracyclines - PK
- good oral bioavailability, sometimes parenteral
- administration instruction
1) best empty stomach + water
2) X take w diary product cuz form non-absorbable chelates w divalent/trivalent -> X absorption - cross placental barrier -> bind to tissue undergoing calcification -> concentrate in fetal bone & dentition -> permanent staining of teeth & affect child growth
tetracyclines - types
1) tetracycline
- renal clearance
2) doxycycline
- skin & soft tissue infections caused by MRSA
- excreted unchanged in bile & urine
3) minocycline
- hepatic clearance
glycylcycline (tigecycline) - compared to tetracycline
- broader spectrum
- less susceptible to resistance development because overcome bacteria resistance mechanism:
1) bacterial efflux pump mediator
2) bacterial ribosomal protection
** higher affinity for ribosome -> displace Tet (O) and Tet (N) protection proteins -> Abx bind to ribosome
glycylcycline (tigecycline) - indication
1) Gram pos
- MRSA, resistant streptococci, vancomycin-resistant enterococci
2) gram neg
- ESBL
- carbapenem resistant
3) X for pseudomonas
glycylcycline (tigecycline) - MOA
bind to 30s subunit
glycylcycline (tigecycline) - PK
- poor oral, parenteral
- low plasma conc
- biliary clearance
- dose adjustment for hepatic dysfunction X for renal impairment
adverse effect for both tetracycline and glycylcycline
1) GI discomfort
- epigastric distress esp oral tetracycline
- drink more water & empty stomach
2) effect on calcified tissue
- deposition in bone & primary dentition
- avoid in pregnancy & children
3) tox
- hepatotox
- phototox: avoid sun exposure, use sun screen
4) superinfection if prolonged
- gut flora change = other bug proliferate
5) CDAD uncommon w tetracycline unless prolonged use
tetracycline & glycylcylcine CI
X pregnant/lactating, X > 8 yo
aminoglycosides - general
bactericidal cuz interact w cell membrane = more leaky
aminoglycosides - indication
- broad spectrum
1) gram pos need beta lactam (3rd gen cephalosporin)
2) gram neg (Esp aerobic)
3) multi drug resistance microbe
4) tb
5) empiric for serious infection - synergistic w beta lactam inhibitor
- X anaerobe
aminoglycosides - MOA
1) bind to 30s -> change ribosomal structure
- block formation of initiation complex
- wrong amino acyl tRNA bind to A site wo matching codon = misread codon
- inhibit translocation
2) entry into cell
- outer membrane: diffusion through aq porin channels
- inner membrane: active transport (inhibit by anaerobic, drop in pH, hyperosmolarity)
3) synergistic w cell wall synthesis inhibitor
- prevent emergence of resistance
- expand empiric spectrum
aminoglycosides - PK
- concentration dependent killing
- poor oral so parenteral
- renal clearance (nephrotox if renal impairment, X give w vancomycin)
aminoglycosides - types
1) gentamycin
- parenteral, renal clearance
2) tobramycin
- parenteral, renal clearance
3) amikacin
- parenteral, widest spectrum, renal clearance
4) Streptomycin
- parenteral, renal clearance, Tb
5) neomycin
- only oral one because parenteral severe nephrotox
aminoglycosides - AE
1) nepthrotox
2) ototox
3) neuromuscular paralysis: affect neuromuscular transmission
4) hypersensitivity reactions
aminoglycosides - monitoring
1) X renal impairment, hearing defect, myasthenia gravis (neuromuscular problem)
2) avoid + nephrotoxic drug
3) TDM to ensure X accumulation
aminoglycosides - resistance mechanism
1) efflux pump
2) Acetylation of aminoglycoside
3) alter 30s subunit
4) X bacteria aminoglycoside uptake
