Penicillins, Cefalosporins Flashcards
(23 cards)
Background Information: Penicillins and Cefalosporins
Are inhibitors of cell wall therefore bactericidal
Are beta lactam ABs
Beta Lactam ABs
Drug Groups
Penicillins Cefalosporins Carbapenems Monobactams Beta Lactamase Inhibitors
Chemistry of beta lactam ABs
A ring
in penicillin: thiazoline ring
cefalosporins: dihydrothiazine ring
carboxylic group attached to it: to form water sol/insol
complexes
B ring
respo for antobacterial effect
AA bound to it; variations here resp for pharmacolo diff
Bacterial Cell Wall Structure
G+
Plasma membrane surrounded by thick peptidoglycan
–> lipophilic drugs better
G-
Plasma membrane surrounded periplasmatic place and
thin peptidoglycan layer
Porin proteins ‘bind’ peptidoglycan with outer
membrane–> hydrophilic drugs better
Peptidogycan
Polysaccharide rich chain with cont 2 alternating sugars
N Acetylglucosamine and N Acetylmuramic Acid
Mode of Action
Beta Lactam ABs inhibit proteins: Penicillin Binding protein = transpeptidase
–> inhibit cross linkage step of cell wall synthesis
Conformation of beta lactam AB is similar to that of
D-Ananyl-D-Alanine
–> beta lactams bind to active site of transpeptidase:
enzyme opens lactam ring and acetylates itself–>
modification–> irreversible inhibition
Synthesis of Bacterial Cell Wall
Stage 1
Synth of precursor molecules; incl conversion L-Alanine
into D-Alanine
Good: selective toxicity. L Alanine is encoded in
humans
Stage 2
Polymerisation of precursor molecules
Stage 3
Cross Linkage of Peptidoglycan fibers
Done by PBP
Constant Remodelling
–> point of attack for ABs
Mechanism of Resistance
Presence of beta lactamases
PBP Mutation (ex MRSA)
G-: can’t cross outer membrane-> needs porins
Mutation in porin or efflux mechanism (pumps)
Atypical bacteria that don’t have peptidoglycan layer
Slowly growing bacteria that don’t constantly remodel
IC bacteria–> protected
When do Penicillins not work?
Cell Wall less pathogens
IC bacteria
Slowly growing bacteria
Penicillins
Drug Groups
Early Penicillins with rel narrow spectrum
Penicillinase resistant with narrow spectrum
Aminopenicillins with medium spectrum
Antipseudomonal penicillins
Early Penicillins with Rel Narrow Spectrum
Pharmacokinetics
Spectrum
Penicillin G
IV or IM (decomp in acidic environment; acid labile)
3-4x daily
Well distributed in body; can’t pass BBB
Excreted unchanged renally–> good for UTIs
1st choice for meningococcus meningits
(inflammation destroys BBB)
Penicillin V
Acid stable–> orally; food delays absorption
IV: form salt with Na or K
Well distributed; can’t pass BBB
Excreted unchanged via urine–> good for UTIs
via OAT and OATP
Better for tonsillitis and other upper resp infections
Mainly G+: staphy (resistance); strep; enterocooci
Some G-: neisseria gonorrhea: Pen G only
Some spirochetes (treponema pallidum)
Some anaerobes (clostridium)
Early Penicillins with Rel Narrow Spectrum
Indications
Clostridium infections Neisseria meningitides Pneumococcus pneumoniae Endocarditis (Strepto- or enterococci) Osteomyelitis Soft tissue infections
Penicillinase Resistant with Narrow Spectrum
Only ones not sensitive to beta lactamases
Used for screening; otherwise not really in use anymore
Incompletely absorbed from GIT; food counters absorp
Evenly distributed in body
Low penetration of BBB
Extensively bind to PP
Elimination: unchanged renally
Nafcillin and Oxacillin mainly eliminated in bile
Narrow spectrum; mainly G+
Used in staphy infections with penicillin resistance
Meticillin, Oxacillin , Cloxacillin, Nafcillin
Aminopenicillins with Medium Spectrum
Group mainly used nowadays
Orally; acid stable
Good absorption from GIT: Amoxicillin best
Distribute evenly; low BBB penetration
Eliminated unchanged via urine
Spectrum: have AA side chain: + charged–> can easily cross G- membrane via porins
G+: staphy, strept, entero
G-: neisseria, proteus, salmonella, E.Coli
Uses Upper and lower resp tract infections UTIs H. Pylori eradication (in combo) Oseomyelitis Soft tissue infections Enterococcus endocarditis Surgical prophylaxis
Ampicillin, Amoxicillin
Augmentin: Amoxicillin + clavulanic acid
Antipseudomonal Penicillins
Poor absorption from GIT; require parenteral admin
Distribute evenly throughout body; low BBB penetration
Eliminated unchanged via urine
Rel. ineffective against G+
G-: proteus, pseudomonas
Used UTI Klebsiella infections Sepsis; endocarditis Hospital acquired pneumonia
Carboxypenicillins: obsolete due to resistance
Ureidopenicillins
Azlocillin
Piperacillin (combo with tazobactam)
Mezlocillin
Adverse Effects of Penicillins
Most common is HSR–> all four!
IgE–> anaphylaxis, angioedema
IgM and G–> vasculitis, neutropenia
Immune complex formation–> vasculitis, serum sickness
T Cell Med.–> Stevens Johnsons, urticaria
Reason: penicillins and breakdown products are haptens
Other Diarrhoea Decrease vit K--> inhibition of blood coagulation --> due to killing of gut flora Pseudomembranous colitis
Pseudoallergic Reaction: Measles like rash
Pseudo because no memory cells produced
High dose–> seizures; esp if kidney failure or meningitis +
Cross sensitivity
More fun facts: Penicillins
Practical strength >T1/2 due to irreversible inhibition
Some metabolised into penicilloic acid
Postantibiotic Effect
Persistent suppression of bacterial growth
Short in G+
Absent in G-
Cephalosporins
Drug Classification
1st - 4th Generation
Cephalosporins
1st Generation
Cefalexin: orally as well absorbed from GIT
Cefazolin: parenteral as not well absorbed
Narrow spectrum
Mainly G+ such as staphylo or strepto
G- minor: proteus; E Coli
–> uses quite limited
Skin and soft tissue infections (prophylactic pre surg)
UTIs
Upper and lower resp infection
Special SE
inhibition of
aldehyde dehydrogenase (inhib alcohol metab.)
disulfiram like reaction
vit K epoxide dehydrogenase
coumarin like effects
Cefalosporins
2nd Generation
G+: weaker than 1st gen
G-: broader: proteus, H. influenzae, E. Coli, Klebsiella
Some anaerobic bacteria
Good for gonorrhoea
Uses
Mainly upper resp tract infections
UTIs
Cefaclor (oral)
Cefuroxime (parenteral)
Cafamandol (also disulfiram and coumarin like effects)
Cefalosporins
3rd Generation
Broad spectrum
Many G+s except MRSA
Many G-s
Many Anaerobics
Uses UTI and resp TI Soft tissue infections Cross BBB--> 1st choice for H. Influenzae Meningitis 1st choice gonorrhoea (ceftiaxone) Antipseudomonal (ceftazidime)
Cefixime (oral)
Cefotaxime (parenteral)
Ceftriaxone (parenteral)=== GONORRHOEA
biliary excretion in up to 40%; can clog up bile ducts in
kiddies
Cefalosporins
4th Generation
Broad spectrum; similar to 3rd generation
Also good for MRSA (ceftobiprole)
Reserved for patients with life threatening infections by MDR
Cefepime Cefpriome Ceftobiprole Ceftraroline All parenterally given
Cefalosporins
SE
HSR; similar to that of penicillin
Show cross sensitivity
Biliary or uninary sludging–> stone formation
due to insoluble Ca complex formation by ceftriaxone
Nephrotoxic
Coumarin and Disulfiram like effects
