J Letchford Lec 4 Inhibs of CW & NA synth Flashcards
Inhibitors of cell wall synthesis: G______
e.g ________, _______
These drugs are/aren’t toxic
______ is a large molecule
They are active against G_ve bacteria and not active against G_ve bacteria
Why is this?
They have issues with resistance espesh enterococci and VRSA (due to plasmid transfer)
Glycopeptides
Vancomycin
Teicoplanin
ARE toxic
Vancomycin
G+ve bacteria
Not active against G-ve bacteria as they can’t get through the outer membrane outside the peptidoglycan layer
Vancomycin is given bd by:
__ _____ for systemic infections as it’s not absorbed in the gut.
Orally for _.___ infections as it doesn’t need to be absorbed from the gut
IV infusion
Orally for C.diff
Teicoplanin is given:
__,__ _____ or ____ for systemic infections
IM, IV injection or infusion
Vancomycin and Teicoplanin are used in infections caused by B-lactam resistant…
G_ve cocci e.g _ _ _ _ , Staphylococcus epidermidis
G_ve rods e.g C.____ (in gut)
Growing resistance amongst VRSA, VISA (_____ intermediate SA, GRE (glycopeptide resistant) , VRE
G+ve e.g MRSA
G-ve e.g C.diff
Vancomycin intermediate Staph Aureas
Vancomycin and Teicoplanin PK:
- they can penetrate the ___.
- they are excreted by the _____ unchanged (not metab)
SE’s:
- Pain and _________ (swelling in vein where the inj is given) (1%)
- ____ toxicity (0.1-1%)
- ____toxicity
- Blood disorders (______, ______)
- Anaphylactoid reactions
CSF
Kidneys
Thrombophlebitis Renal toxicity Ototoxicity Blood disorders (neutropenia, pancytopenia) Anaphylactoid reactions
Antimicrobial inhibitors of cell wall synthesis: Cyclo____.
- _____ spectrum antibiotic
- Effective against T_____ (2nd line)
This drug is/isn’t toxic
This drug inhibits the ____ that converts L AA into _ AA in cell which is needed for ______ synthesis for use in the cell wall.
Cycloserine
Broad spectrum antibiotic
Tuberculosis
This drug is toxic so freq monitoring is needed
Antimicrobial inhibitors of cell wall synthesis: Baci____.
Active on G_ve bacteria
e.g Poly__ (Polymyxin B and Baci____)
Topically for skin and eye infections and prevention of wound infection
This drug can/can’t be used systemically
Why?
SE’s - contact allergic ______
Bacitracin
G+ve
Polyfax (Polymyxin B and Bacitracin)
This drug can’t be used systemically due to toxicity
SE = contact allergic dermatitis
How does Bacitracin work?
PG is synthesised in the cytoplasm and transported to outside of the cell
This is mediated by a carrier protein
This drug inhibits the carrier molecule so PG builds up in the cell
Antimicrobials affecting bacterial membranes: Polymyxins
e.g
Polymyxin _ (topical)
Polymyxin _
(Col____ IV or _____)
How do they work and do they work on G-ve or +ve bacteria?
Polymyxin B (topical)
Polymyxin E
Colistin IV or nebuliser
Work by disrupting the LPS on membrane of gram -ve bacteria by binding lipid A. This causes leakage of cytoplasm and cell dies
Polymyxins are given . for ____ infections cause by resistant G_ves e.g Ps. aeruginosa and E.coli
They are given topically (most often) for skin and eye infections.
SE’s:
N__toxic and N__toxic (I.V)
Local ____, dermatitis (Topical)
I.V for systemic
Neurotoxic and Nephrotoxic
Irritation
Antimicrobials affecting bacterial membranes: Lipo_____
e.g Dap____ (Cubicin)
Active against G_ve bacteria.
Causes rapid Ca2+ dependent _____ of cytoplasmic membrane leading to loss of function due to the formation of pores which cause leakage.
Lipopeptides
Daptomycin
G+ve
Depolarisation
Lipopeptides such as Dap_____ (Cubicin) are used:
. for skin and soft tissue infections, e_____ caused by resistant G_ves e.g _ _ _ _
SE’s include:
N___toxicity, my____, peripheral n_____ and col___ (as effects the bacteria in the gut leading to super infection)
Daptomycin
G+ves
MRSA
Nephrotoxicity
Myopathy
Peripheral neuropathy
Colitis
Metabolic inhibitors of nucleic acid synthesis:
e.g Sulphon____, Tri_____
Sulphonamides, Trimethoprim
Sulphon_____s inhibit the enzyme dihydropterate ______ which converts para-amino benzoic acid into Dihydro_____ acid.
This enzyme is/isn’t present in mammalian cells.
What does this mean?
Sulphonamides
Dihydropterate synthetase
Dihydropteroic acid
Isn’t present in mammalian cells
This gives the drug better selectivity for bacteria
Tri____ inhibits nucleic acid synthesis by inhibiting the enzyme dihydro____ re______ which converts dihydrofolic acid into t______ acid.
This normally then goes on to make p____/p_____
This enzyme is/isn’t present in mammalian cells.
Trimethoprim
Dihydrofolate reductase
Tetrahydrofolic acid
Purines
Pyrimidines
Is present in mammalian cells BUT better uptake in bacteria so still selectivity
