Antibiotics and antifungals Flashcards
Describe the membrane properties of bacteria
Gram + or Gram - -> different
Gram + = large exterior peptidoglycan cell layer, then double cell membrane. eg: Staph Aureus
Gram -=LPS exterior, outer membrane, peptidoglycan and inner membrane
eg: e.coli
Mycloic-M.tuberculosis
Like gram +, with extra outer layer of mycolic acid-change properties
Explain how nucleic acid synthesis differers in bacteria? What Abx target it
Need 2 enzymes-dyhydropteroate (DHOp) and tetrahydrofolate (THF)-very important in producing DNA
targets for Abx:
DHOp=Sulfonamides-
THF-trimepthprim
used in combination
Explain how DNA replication and RNA synthesis differers in bacteria? What Abx target it
No same as human Topiosomerase enzyme but instead DNA gyrace for opening DNA to replicate
RNA synthesis-has RNA polymerase to form RNA –different from eukaryotes
Quinolones-target topiosomerase of prokaryotes
Rifamycins-target RNA polymerases -nearly only used for TB
Explain how protein synthesis differers in bacteria? What Abx target it
Ribosome is 70S and quite different from the eukaryotic 80S ribosomes
Amninoglycoisdes, Choramphenical, MACROLIDES, tetracyclins (REMEMBER MOSTLY MACROLIDES)
How do bacteria make their cell wall?
Peptidoglycan is the most important part–
made intracellularly in cytoplasm with NAM joining NAG and a pentapeptide (forms a peptidoglycan) (NAM and NAG are types of glycans)
Then the PtG is transported across the membrane to periplasm (bewteen cell wall and membrane) by bactoprenol
Then cross likned with the others with Transpeptidase
What Abx target cell wall synthesis in bacteria>
PtG synthesis- Glycopeptides (eg Vancomycins)-binds the pentapeptide binding NAM and NAG
Transport-Bacitracin-inhbits bactroprenol
Ptg incorporation
B-lactams inhbit transpetidase and prevent incorporation
Carbapenems, cephalosporins and penicillins
Extra–affect cell WALL stability
Lipopeptide-disrupts gram + cell MEMBRANE
Polymyxins-disrupts LPS layers in gram -
What are the 5 ways do bacteria resist Abx?
1) Destruction enzymes
Additional target, alteration of target, alteration of drug permeation and hyperproduction
WHat is the destruction enzyme mechanism of ABx resistance?
1) Destruction enzymes- eg: B-lactams. Bacteria developed B lactamases which degrade the ring
some B-lactams are lactamase resistant-steric protection of ring (temocillin (gram + specific)
Amoxicillin-co-administered with Clavulanic acid (together resist blactamase)
dont remember specific drugs-just be aware differences exists (in peniccilins groups
WHat is the additional target mechanism of ABx resistance?
Bacteria produce another enzyme/protein that can do the same role but cannot be targetted by Abx
eg: E.coli can produce a different DHF reductase-and become resistant to tripethoprim
WHat is the alteration target mechanism of ABx resistance?
Original enzyme/protein is modyfied so that Abx cannot bind to it/inhbit it
(not producing a different
S.aureus produced different Topoisomerase-resist quinolones
WHat is the alteration of drug permeation of ABx resistance?
Reduction of transport channels to allow the Abx in (eg: aquaporins) AND increase of efflux systems to kick the Abx out (removed faster)
=> reduce how much get in and reduce how long they stay in
quite a lot gram- bacteria have this
WHat is the hyperproduction leading to of ABx resistance?
Bacteria produce increase amounts of the enzymes being targetted by the Abx–
Abx still working, and inhbiting some, but there are still so much more around to work
eg: E.coli-produce more DHF reductase
not ideal for bacteria because need to work a lot harder-can kill them
How can you classify fungal infection? What are the 2 most common antifungals and how do they work
Superficial, dermatophytes, subcutanous, systemic (deeper=worse)
2 classes: Azoles and Polyenes
Azoles: Inhbit p450 dependent enzymes involved in membrane syntehsis in fungi. Eg; Flucoazole
Polyenes-interact with cell membrane Steroles forming the channels in fungi -perfors the membrane-cell becomes leaky and dies
eg: Amphotericin
