Antibiotics & Anti-fungals Flashcards
General information about the membrane proteins of the 3 types of Bacteria
Gram +ve bacteria:
• thick peptidoglycan cell wall
• e.g. Staph. Aureus
Gram –ve bacteria:
• outer membrane with LPS
• e.g. E. coli.
Mycolic bacteria
• outer mycolic acid layer
• e.g. Mycobacterium Tuberculosis
Broadly state the different steps of prokaryotic protein synthesis and the drug targets?
(1) Nucleic Acid Synthesis
(a) DHOp
(b) THF
(2) DNA Replication
• DNA gyrase
(3) RNA synthesis
• RNA Polymerase
(4) Protein Synthesis
• Ribosomes
Explain the drugs associated with (1) of prokaryotic protein synthesis in regards to the drug targets
(1) Nucleic Acid Synthesis
(a) Dihydropteroate (DHOp)
• produced from paraaminobenzoate (PABA) via. DHOp synthase
• converted into hihydrofolate (DHF)
= SULPHONAMIDE
• inhibits DHOp synthase
(b) Tetrahydrofolate (THF)
• Produced from DHF via. DHF reductase
• THF –> important in DNA synthesis
= TRIMETHOPRIM
• inhibits DHF reductase
Explain the drugs associated with (2) of prokaryotic protein synthesis in regards to the drug targets
(2) DNA Replication
o DNA gyrase
• Topoisomerase that helps release tension in DNA
= FLUOROQUINOLONES
• e.g. Ciprofloxacin
• inhibits DNA gyrase & topoisomerase IV
Explain the drugs associated with (3) of prokaryotic protein synthesis in regards to the drug targets
(3) RNA synthesis
o RNA Polymerase
• produces RNA from DNA template
• differs from eukaryotic RNA polymerase
= RIFAMYCINS
• e.g. Rifampicin
• inhibits bacterial RNA polymerase
Explain the drugs associated with (4) of prokaryotic protein synthesis in regards to the drug targets
(4) Protein Synthesis
Ribosomes
• produce protein from RNA templates
• differ from eukaryotic ribosomes
= (1) Aminoglycosides
• e.g. Gentamycin
= (2) Chloramphenicol
= (3) MACROLIDES
• e.g. Erythromycin
= (4) Tetracyclines
ALL INHIBIT the ribosome
Briefly state the steps to bacterial wall synthesis
(1) Peptidoglycan (PtG) synthesis
(2) PtG transportation
(3) PtG incorporation
Explain (1) of bacterial wall synthesis and drugs associated with it
(1) PtG synthesis
• A pentapeptide is created on N-acetyl muramic acid (NAM)
• N-acetyl glucosamine (NAG) associates with NAM forming PtG
= GLYCOPEPTIDES
• e.g. Vancomycin
• BINDS to pentapeptide = prevents PtG synthesis
Explain (2) of bacterial wall synthesis and the drugs associated with it
(2) PtG transportation
• Bactoprenol transports PtG across the membrane
= Bacitracin
• inhibits Bactoprenol regeneration
Explain (3) of bacterial wall synthesis and the drugs associated with it
(3) PtG incorporation
• Transpeptidase enzyme cross-links PtGs = creates wall (incorporated in)
= BETA-LACTAMS • e.g. Carbapenems • e.g. Cephalosporins • e.g. Penicillins • bind COVALENTLY to Transpeptidase & INHIBITS its action
What is the unofficial (4) of bacterial cell wall synthesis and the drugs associated with it?
(4) Cell wall stability
= LIPOPETIDE
• e.g. Daptomycin
• DISRUPTS gram +VE walls
= POLYMYXIN
• binds to LPS & disrupts gram -VE membranes
Causes of AB resistance
o Unnecessary prescription
•50% not required
o Livestock farming
• 30% of AB use
o Lack of regulation
o Lack of development
Broadly state the 5 types of AB resistance mechanism
(1) Destruction enzymes
• production of beta-lacatase
(2) Additional target
• different DHF Reductase enzyme produced
(3) Alteration of target
• Mutations in DNA gyrase enzyme
(4) Alteration in drug permeation
• drug influx REDUCE
• drug efflux INCREASE
(5) Hyperproduction
• over-production of DHF Reductase
Explain (1) of AB resistance mechanism
(1) Destruction enzymes
BETA-lactamases hydrolyse C-N bond of the BETA-lactam ring
Penicillins are NOT resistant to BETA-LACTAMSE
• combat gram +VE
Examples:
• Flucloxacillin & Temocillin –> RESISTANT to BETA-lactamase
• Amoxicillin –> broad spectrum AB combats gram -VE
o resistant to BETA-lactamse ONLY when co-administered with Clavulanic acid
Explain the 2nd resistance mechanism to AB - Alterations in target
Alteration in target ENZYMES:
Alterations to enzyme to make the drug ineffective whilst the enzyme still works
• e.g. S.Aureus has mutations in ParC region of topoisomerase IV = confers resistance to quinolones
