Antibiotics and antifungals Flashcards
Describe the membrane properties of a gram positive bacteria
Thick peptidoglycan cell wall
eg in staph aureus
Describe the membrane properties of a gram negative bacteria
Outer membrane has LPS (liposaccarides)
Describe the membrane properties of a mycolic bacterai
They have an outer mycolic acid layer eg mucobacterium tuberculosis
What are the steps of protein synthesis by antibiotics
- nucleic acid synthesis
- DNA replication
- RNA synthesis
- Protein synthesis
What are examples of drug intracellular targets in antibiotics that are involved in nucleic acid synthesis
- dihydropterate synthase converts PABA to DHOp
Sulphonamide inhibits DHOp synthase - dihydrofolate (DHF) reductase converts DHF -> THF
Trimerthoprim inhibits DNF reductase
What are examples of drug intracellular targets in antibiotics that are involved in DNA replication
DNA gyrases (topoisomerases) release the tension in DNA Fluoroquinolones inhibit DNA gyrases and topoisomerase IV
What are examples of drug intracellular targets that are involved in RNA synthesis
a. RNA polymerase produces RNA from DNA template
b. Prokaryotic RNA polymerase differs to eukaryotic ones
Rifamycins inhibit bacterial RNA polymerase
What are examples of drug intracellular targets that are involved in protein synthesis
a. ribosomes produce the protein from RNA templates
b. prokaryotic ribosomes differ from eukaryotic ribosomes.
What are examples of drugs that inhibit the ribosome
aminoglycosides
chloramphenicol
macrolides
tetracyclines
What are the different targets for extracellular gram +ve drug antibiotics
- peptidoglycan synthesis
- PtG transportation
- PtG incorporation
- Cell wall stability
What happens in peptidoglycan synthesis and what antibiotics target this step?
Pentapeptide is created on NAm and NAG associates with NAM forming the peptidoglycan
Glycopeptides bidn to pentapeptide and prevent PtG synthesis
What happens in PtG transportation and what antibiotics target this step
Bacteroprenol transports the PtG across the membrane
Bacitracin inhibits Bactoprenol regeneration
What happens in PtG incorporation and what antibiotics target this step
Transpeptidase enzyme cross links PtGs and creates wall
Beta lactams eg carbapenems, cephalosportins bind covalently to transpeptidase and inhibits it’s action
What antibiotics target the cell wall stability step of peptidoglycan synthesis
Lipopeptides disrupt the gram +ve walls
Polymyxin binds to liposaccarides and disrupts gram -ve membranes
What are causes of antibiotic resistance
Unnecessary prescription
Livestock farming
Lack of regulation
Lack of developmenet
What are different antibiotic resistance mechanisms
- additional targets - different DHFR enzyme
- hyperproduction - more DHFR enzyme
- alternations in target enzymes - alterations to enzyme to make drugs ineffective whilst the enzyme still works
- alterations in drug permeation - reductions in AQAs and increased efflux systems to reduce AB entry
- Production of destruction enzymes eg beta lactamases that hydrolyse C-N bonds of beta lactam ring
What are examples of antibiotics that are resistant to production of destruction enzymes therefore are an example of antibiotic resistance
Flycloxacillin and temocillin
Amoxicillin combats gram -ve bacteria and is resistant to beta lactamases only when co administered with clavulanic acid
What are different classifications of a fungal infection
- superficial (outer most layer of skin)
- dermatophyte (skin, hair or nails)
- subcutaneous (inner most skin layers)
- systemic (primarily respiratory tract)
What are examples of antifungal drugs used
Azoles eg fluconazole
Polyenes eg amphortericin
What does fluconazole do
Inhibit CYP450 enzymes involved in membrane ergosterol synthesis
What does amphortericin do
Binds to ergosterol and creates channel pores
What does fluconazole treat
Candidiasis, systemic infections
What does amphortericin treat
Systemic infections
