Pharmacology 31 - Antibiotics Flashcards
Describe membrane properities of the three types of bacteria
- Gram positive bacteria have a prominent peptidoglycan cell wall. (e.g. Staphylococcus Aureus)
- Gram negative bacteria have an outer membrane with lipopolysaccharide, smaller peptidoglycan membrane (e.g. Escherichia Coli)
- Mycolic bacteria have an outer mycolic acid layer, with a reasonably prominent peptidoglycan layer (e.g. Mycobacterium Tuberculosis)
Describe prokaryotic nucleic acid synthesis
Dihydropteroate (DHOp)
- Produced from paraaminobenzoate (PABA)
- Converted into dihydrofolate (DHF)
Tetrahydrofolate (THF)
- Produced from DHF by DHF reductase
- THF is Important in DNA synthesis
Describe prokaryotic DNA replication
DNA glyrase - topoisomerase which releases tension
Describe prokaryotic RNA synthesis
- RNA polymerase produces RNA from DNA template
- Differ from eukaryotic RNA polymerase
Describe prokaryotic protein synthesis
- Ribosomes produce protein from RNA templates
- Differ from eukaryotic ribosomes (eukaryotic 40s and 60s, prokaryotic 30s and 50s subunits)
List the protein synthesis inhibitors and where they act
Nucleic acid synthesis
- Sulphonamides inibit dihydropteroate syntase
- Trimethoprim inhibits DHF reductase
DNA replication
- Fluoroquinoones (eg, ciprofloxacin) inhibit DNA gyrase and topoisomerase IV
RNA synthesis
- Rifamycins (eg. Rifampicin) inhibit bacteral RNA polymerase. Used in mycobacterium tuberculosis
Protein synthesis
- Ribosomes are inhibited by aminoglycosides (eg. gentamicin), chroamphenicol, macrolides (eg. ertythromycin) and tetracylines
Describe bacterial wall synthesis
Peptidoglycan (PtG) synthesis
- A pentapeptide is created on N-acetyl muramic acid (NAM)
- N-acetyl glucosamine (NAG) associates with NAM forming PtG
PtG transportation
- PtG is transported across the membrane into the periplasm by bactoprenol
PtG incorporation
- PtG is incorporated into the cell wall when transpeptidase enzyme cross-links PtG pentapeptides
List bacterial wall inhibitors
- Glycopeptides (e.g. Vancomycin) bind to the pentapeptide preventing PtG synthesis - less effective in E coli
- Bacitracin inhibits bactoprenol regeneration preventing PtG transportation
- B-lactams bind covalently to transpeptidase inhibiting PtG incorporation into cell wall
- Lipopeptide - (e.g. daptomycin) disrupt Gram +ve cell membrane
- Polymyxins - binds to LPS and disrupts Gram -ve cell membranes
List B-lactams
- Carbapenems
- Cephalosporins
- Penicillins
List causes of antibiotic resistance
- Unnecessary prescription
- Livestock farming (30% of UK antibiotic use is in livestock)
- Lack of regulation
- Lack of development
Describe and give examples of bacteria using production of destruction enzymes in resistance
- B-lactamases hydrolyse C-N bond of the B-lactam ring
Eg. - Penicillins G and V -> Gram +ve (variation within the penicillins)
- Flucloxacillin and Temocillin -> B-lactamase resistant
- Amoxicillin -> Broad spectrum (gram -ve activity, resistant when co-administered with Clavulanic acid.)
Describe the resistance mechanism of Bacteria using additional target
- Bateria produce another target that is unaffected by the drug
- Eg. E coli produce different DHF reductase enzyme making them resistant to trimethoprim
Describe the resistance mechanism of bacteria altering target enzymes
- Alteration to the enzyme targeted by the drug. Enzyme still effective but drug now ineffective
- Eg. S Aureus - Mutations in the ParC region of topoisomerase IV confers resistance to quinolones
Describe the resistance mechanism of bacteria performing hyperproduction
- Bacteria significantly increase levels of DHF reductase
- Eg. E Coli produce additional DHF reductase enzymes making trimethoprim less effective
Describe the mechanism of resistance by alterations in drug permeation
- Reductions in aquaporins and increased efflux systems (harder for the antibiotic to enter the cell, and the antibiotics in the cell are removed more quickly)
- Eg. important in gram negative bacteris
List the possible mechanisms of antibiotic resistance
- Alterations in drug permeation
- Hyperproduction
- Altering target enzymes
- Additional target
- Production of destruction enzymes
How are fungal infections classified?
Can be classified in terms of tissue/organs:
- Superficial - Outermost layers of skin
- Dermatophyte - Skin, hair or nails
- Subcutaneous - Innermost skin layers
- Systemic - Primarily respiratory tract
What are the two most common antifungal drug classes?
- Azoles (eg. fluconazole)
- Polyenes (eg. amphotericin)
How do azoles work? Give an example of their use
- Inhibit cytochrome P450-dependent enzymes involved in membrane sterol synthesis (inhibits ergosterol production)
- Fluconazole (oral) used in candidiasis and systemic infections
How do polyenes work? Give an example of their use
- Interact with cell membrane sterols forming membrane channels (binds to ergosterol to create pores)
- Amphotericin (I-V) used in systemic infections
