Antibiotics and Anti-fungals Flashcards
Describe the distinctive features of: Gram positive bacteria, Gram negative bacteria and Mycolic bacteria
Gram +ve bacteria: Thick peptidoglycan cell wall
Gram -ve bacteria: Outer membrane contains lipopolysaccharide (LPS)
Mycolic bacteria: Outer mycolic acid layer
State the steps involved in the production of THF from PABA. What is THF important for ?
PABA –> DHOp (dihydropterase synthase)
DHOp –> DHF
DHF –> THF (DHF reductase)
THF important in nucleic acid synthesis
What is DNA gyrase?
A topoisomerase
Releases tension in DNA + is important in unwinding DNA to allow protein binding required for DNA replication
What does RNA polymerase do?
Produces RNA from a DNA template
What is the function of ribosomes? What is the key difference between ribosomes in eukaryotes and prokaryotes?
Produce protein from RNA templates
Eukaryote = 40S + 60S
Prokaryote = 30S + 50S
State 2 classes of drugs that interfere with nucleic acid synthesis and name the enzymes that they inhibit.
Sulphonamides: inhibits DHOp synthase
Trimethoprim: inhibits DHF reductase
Sulphonamides and Trimethoprim are sometimes used together. What is this preparation called?
Co-trimoxazole
Name a group of drugs that interfere with DNA replication and state its targets.
Fluoroquinolones inhibit bacterial DNA gyrase + topoisomerase IV
Name a group of drugs that interfere with RNA synthesis and state its main target.
Rifamycins inhibits bacterial RNA polymerase
Mainly used in tuberculosis
List 4 groups of drugs that inhibit ribosomes.
Macrolides e.g. Erythromycin
Aminoglycosides e.g. Gentamicin
Chloramphenicol
Tetracyclines
Describe how peptidoglycan is synthesized, transported to the cell wall and incorporated into the cell wall.
A pentapeptide is created on N-acetyl muramic acid (NAM)
N-acetyl glucosamine (NAG) associates with NAM forming peptidoglycan
PtG is transported across the membrane by bactoprenol
PtG is incorporated into the cell wall by transpeptidase enzyme, which cross-links PtG pentapeptides
Which groups of drugs interfere with peptidoglycan synthesis and how do they do this?
Glycopeptides (e.g. vancomycin): bind to pentapeptides + inhibit PtG synthesis
= a last resort for Gram+ve bacteria that are resistant to other antibiotics
Name a drug that interferes with peptidoglycan transport and state its target.
Bacitracin: inhibits bactoprenol regeneration, hence preventing PtG transport
Name a class of drugs that inhibit peptidoglycan incorporation and explain how they do this.
Beta lactams: bind covalently to transpeptidase, inhibiting PtG incorporation into the cell wall
What are the three subsets of beta lactams?
Carbapenems
Cephalosporins
Penicillins
Name two drugs that interfere with cell membrane stability and explain how they do this.
Lipopeptides: disrupt Gram +ve cell membranes
Polymyxins: bind to LPS + disrupt Gram -ve cell membranes
List five mechanisms of antibiotic resistance and give a brief description of each.
Additional target: bacteria produce another target that is unaffected by the drug
Hyperproduction: increase production of the target so the antibiotics are less effective (though energy inefficient)
Altered target: alteration in drug target so drug is no longer effective (though enzyme is still effective)
Alteration in drug permeation: reduction of aquaporins or increase of efflux systems
Destruction enzymes: beta-lactamases hydrolyse C-N bond of b-lactam ring rendering b-lactams inactive
What are penicillins G and V normally used to treat?
Gram-positive bacteria
Name two drugs that are relatively beta lactamase resistant.
Flucloxacillin
Temocillin
Name a broad-spectrum antibiotic that must be administered with another drug to become resistant to beta lactamases. What is this other drug?
Amoxicillin (no resistance on its own)
Clavulanic acid
What are the four types of fungal infection, characterised based on the tissues/organs affected?
Superficial: outermost layers of skin
Dermatophyte: skin, hair or nails
Subcutaneous: innermost skin layers
Systemic: primarily respiratory tract
What are the two main groups of anti-fungals? Give an example ofeach.
Azoles (fluconazole)
Polyenes (amphotericin)
Describe the mechanism of action of azoles.
Inhibit CYP51p (enzyme of the CYP450 system), which is involved in ergosterol production
Describe the mechanism of action of polyenes.
Interact with membrane sterols + form channels (punching holes in the membrane)
Give an example of Gram positive bacteria, Gram negative bacteria and Mycolic bacteria
Positive: Staphylococcus aureus
Negative: Escherichia Coli
Mycolic bactéria: Mycobacterium Tuberculosis
Give an example of when an azole and polyene would be used?
Azole: Candidiasis + Systemic infections
Polyene: Systemic infection
