Treatment of Infections Flashcards
Superficial fungal infections usually give rise to what infections?
Tineas infections
Such as athletes foot (tinea pedis) and ringworm of the scalp (tinea capitis)
What is a carbapenem?
An inhibitor of cell wall synthesis
These are highly resistant to B-lactamases, and have a very broad spectrum of activity, including anaerobes
These are last resort!!
How do Azoles and Triazole (like Fluconazole and Itraconazole) work?
Block lanosterol 14(a)-demethylase
Which prevents ergosterol biosynthesis
What are the 2 major proteins that are in HIVs envelope?
gp120
gp41
What is the HAART therapy?
Highly Active Anti-Retroviral Therapy
Taking 3 different anti-retroviral drugs, with at least 2 different classes
This decreases the chance of resistance build up
What type of drug can be depositied into the teeth and bone of growing children/foetus?
Tetracyclines such as doxycycline
How do Polyenes (Nystatin and Amphotericin B) work?
Target ergosterol –> increasing membrane permeability
Are fungi eukaryotic or prokaryotic?
Eukaryotic
How do tetracyclines like doxycycline work?
How does resistance occur?
Bind reversibly to the A site on the 16rRNA unit. This interferes with translocation in the tRNA (A –> P)
Their effects are bacteristatic, and they have a great level of selective
The induction of efflux pumps…..
Intrinsic - The basal activity of the pumps
Acquired - The upregulation in the presence of the antibiotic
How do Allyamines and Thiocarbamates (like Terbinafine) work?
They block squalene epoxidase
And so prevents ergosterol biosynthesis
Explain the differences between a isomotic, hyper/hypo osmotic solutions
Isomotic - Where the osmolality of the solution is equal to that of the intracellular fluid
Hyper-osmotic - When the osmolality of the solution if greater than that of the intracellular fluid (so movement out)
Hypo-osmotic - When the osmolality of the solution if less than that of the intracellular fluid (so movement in)
What are NNRTIs, and how do they work?
Non-Nucleoside Reverse Transcriptase Inhibitors
These inhibit DNA replication by binding to the allosteric site of reverse transcriptase, causing a conformational change
How does the Varicella-Zoster Virus (VZV) work?
It gains entry via the respiratory tract, and moves through the lymph to the skin (its target organ) after 14 days incubation
This can stay latent after the initial infection in the cerebral/posterior root ganglia. Later on it can then move down a sensroy nerve and back to the skin
What is the difference with Endotoxin, and exotoxins?
Endotoxin - A structual feature of lipopolysaccharides
Exotoxins - These are toxins that are actively secreted during normal growth
How do Echinocandins (Caspofungin and Micafungin) work?
Block 1,3-(B)-D-glucan synthase
Which in turn prevents cell-wall biosynthesis
How does Nitrofuratonin work?
It is broken down into many different active metabolites
Broad spectrum of activity
Cannot be used on people with urinary cathaters, due to drug accumulation in the bladder
How do glycopeptides such as Vancomycin work?
And how does resistance build up?
These bind to the d-ala - d-ala on the peptide side chain of the peptidoglycan monomer, preventing this from being added to the peptidoglycan chain
Only work against gram positive bacteria
There is an alteration in the terminal AA of the peptide chain, reducing hydrogen bonding, and so prevents stable binding of vancomycin
What is the difference between osmolarity and osmolality?
Osmolarity - The number of osmoles (particles) per litre of solution
Osmolality - The number of osmoles (particles) per Kg of solvent (eg, water)
How does HIV enter the cell?
HIV approaches a CD4(+) T-cell
Their gp41 and gp120 proteins vind to the CD4 and chemokine receptors
Binding of co-receptors causes a conformational change in gp120, exposing gp41 which has two domains (HR1 and HR2)
Zipping occurs, which is where HR2 coils into the grooves that have been exposed on HR1
This punches a hole in the membrane, allowing the HIV capsid to pass through the cell membrane
Explain the 2 different types of acquired resistance with respect to antibiotics
Genetic - This is irreversible, and comes about due to mutations or plasmids
Phenotypic - This is reversible, eg, E.coli is more resistant to antibiotics in a biofilm than on its own
What are the 3 routes of parenteal administration?
Intravenous - Into a large proximal vein
Intramuscular - Small amount of liquid into the muscle
Subcutaneous - Liquid added to the subcutaneous tissue
Describe the different herpes viruses
HSV1 - Oropharyngeal Sores in children, usually spread from kissing
HSV2 - Genital infections that are common in young adults, which can increase the chance of HIV infection
Both are part of the alpha sub-family of herpes, are enveloped, and have DS DNA
How do macrolides, like erythromycin and clarithromycin, work?
Bind to the 23S rRNA in the 50S subunit, inhibiting translocation
Mainly used in the treatment of gram-positive bacteria
Used for strep infections when penicillin allergies are present
Explain Vapour Point Depression
Boiling point elevation and Freezing point depression
Vapour Point Depression - Where the addition of a non-volatile solute to the solvent will decrease the vapour pressure…..so less moleucle will evaporate
Boiling Point Elevation - The dissolution of a non-volatile solute in a solvent will increase the boiling point
Freezing Point Depresson - The dossolution of a non-volatile solute in a solvent will decrease the freezing point
Explain how Acyclovir works
A pro-drug, that is phosphorylated 3 times, the first by viral thymidine kinase….which gives the drug specificity
ACV-TP is then incorporated into the DNA strand being created, acting as a chain terminator
What is Fuzeon?
And how does it work?
It is a peptide mimic of the HR2 domain and so binds to the HR1 domain in place
This prevents the natural HR2 from zipping down –> hense stopping the HIV from entering the cell
What bond is used in protease inhibitors that allow them to be useful?
Hydroxyethylene Bond
What are Cephalosporins? such as Cefalexin
And what are the differences between the 3 generations?
These are broad-spectrum antibiotics, that are resistant to B-lactamases
Isolated from natural fungi
Has a high C.difficile superinfection risk
Each generation has increased activity and resistance to B-lactamases
How do CCR5 entry inhibitors work?
They block the attatchment of HIV capsid to the CCR5 co-receptor
However this isn’t perfect as it does not prevent the strains of HIV that bind to CXCR4
How does sulphonamides, such as trimethoprim, work?
Inhibit nucleic acid synthesis
Cant be used in the first tri-mester of pregnancy
Commonly used in the treatment of UTIs
How do Rifamycins, such as Rifampicin work?
Semi-synthesised inhibitors of RNA polymerase, which are bactericidal
First line treatment for TB, when used with other antibiotics to reduce build up of resistance
How do polymyxins such as colistin work?
They target the outer membrane (on gram -ve) by binding to lipid A in lipopolysaccharides, causing the membrane to become leaky
Mainly used in the treatment of pseudomonas infections in CF patients
How do nitroimidazoles, such as metronidazole, work?
These are pro-drugs, that when activated, affect the DNA in the bacterial cell
Its given orally for anaerobic infections (eg, C.difficile), and other gential tract infections.
It can pass through the CSF
Cannot be taken with alcohol
How do B-lactams work?
And how does this differ with different types of bacteria?
And how does resistance build up?
Bind and inhibit Penicillin-Binding-Proteins (PBPs) which are transpeptidases
This therefore prevents cross-linking, killing the cell
To work on gram -ve, porins must be present in order to pass through the outer membrane
Alteration of the PBPs, and less porins being formed in the membrane, allowing less to pass through the outer membrane in gram negative
What are Oxazolidinones, like linezolid, used for?
Used as a last resort antibiotic to highly-resistant gram-positive bacteria
What are B-lactamases, and where do they accumulate?
They are molecules that hydrolyse the B-lactam ring
Gram +ve - They move through the medium, and around where B-lactam drugs are
Gram -ve - They accumulate in the periplasmic space, which is inbetween the two membranes
Define Osmotic Pressure
And what is the Van’t Hoff Factor?
Osmotic Pressure - The external pressure required to prevent the movement of solvent via osmosis
Van’t Hoff Factor (i) - This is a differing value that must be used when calcuating the osmotic pressure of solutions with electrolytes present
How do lipopeptides, such as daptomycin, work?
Intergrate themselves into the membrane, causing leakage and rapid depolarisation
Only active on gram-positive organisms
Given IV
