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PA20309 > Treatment of Infections > Flashcards

Treatment of Infections Flashcards

1
Q

Superficial fungal infections usually give rise to what infections?

A

Tineas infections

Such as athletes foot (tinea pedis) and ringworm of the scalp (tinea capitis)

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2
Q

What is a carbapenem?

A

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!!

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3
Q

How do Azoles and Triazole (like Fluconazole and Itraconazole) work?

A

Block lanosterol 14(a)-demethylase

Which prevents ergosterol biosynthesis

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4
Q

What are the 2 major proteins that are in HIVs envelope?

A

gp120

gp41

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5
Q

What is the HAART therapy?

A

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

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6
Q

What type of drug can be depositied into the teeth and bone of growing children/foetus?

A

Tetracyclines such as doxycycline

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7
Q

How do Polyenes (Nystatin and Amphotericin B) work?

A

Target ergosterol –> increasing membrane permeability

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8
Q

Are fungi eukaryotic or prokaryotic?

A

Eukaryotic

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9
Q

How do tetracyclines like doxycycline work?

How does resistance occur?

A

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

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10
Q

How do Allyamines and Thiocarbamates (like Terbinafine) work?

A

They block squalene epoxidase

And so prevents ergosterol biosynthesis

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11
Q

Explain the differences between a isomotic, hyper/hypo osmotic solutions

A

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)

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12
Q

What are NNRTIs, and how do they work?

A

Non-Nucleoside Reverse Transcriptase Inhibitors

These inhibit DNA replication by binding to the allosteric site of reverse transcriptase, causing a conformational change

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13
Q

How does the Varicella-Zoster Virus (VZV) work?

A

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

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14
Q

What is the difference with Endotoxin, and exotoxins?

A

Endotoxin - A structual feature of lipopolysaccharides

Exotoxins - These are toxins that are actively secreted during normal growth

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15
Q

How do Echinocandins (Caspofungin and Micafungin) work?

A

Block 1,3-(B)-D-glucan synthase

Which in turn prevents cell-wall biosynthesis

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16
Q

How does Nitrofuratonin work?

A

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

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17
Q

How do glycopeptides such as Vancomycin work?

And how does resistance build up?

A

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

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18
Q

What is the difference between osmolarity and osmolality?

A

Osmolarity - The number of osmoles (particles) per litre of solution

Osmolality - The number of osmoles (particles) per Kg of solvent (eg, water)

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19
Q

How does HIV enter the cell?

A

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

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20
Q

Explain the 2 different types of acquired resistance with respect to antibiotics

A

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

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21
Q

What are the 3 routes of parenteal administration?

A

Intravenous - Into a large proximal vein

Intramuscular - Small amount of liquid into the muscle

Subcutaneous - Liquid added to the subcutaneous tissue

22
Q

Describe the different herpes viruses

A

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

23
Q

How do macrolides, like erythromycin and clarithromycin, work?

A

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

24
Q

Explain Vapour Point Depression

Boiling point elevation and Freezing point depression

A

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

25
How are Benzylpenicillin (Pen G) and Amoxicillin similar and different?
Can pass through the BBB --\> can be used to treat meningitis Excreted in the urine Is absorbed and distributed quickly **Difference** = Amoxicillin is oral, whilst Pen G is given IV/IM
26
How does **Fluorinated pyrimidine analogues** (5-Flucytosine) work?
**Prevent RNA/DNA biosynthesis** by being incorportated instead during replication
27
What type of drugs are usually given IV?
Those with a low bioavaliability
28
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
29
What are the major **side effects of aminoglycosides** such as gentamicin?
**Nephrotoxicity** **Ototoxicity** So monitoring is very important
30
Define **Colligative Properties**
This is known as the properties of solutions that are dependent on the ratio of solute particles to solvent particles in the solution, not the identity of the solute
31
How do **fluoroquinolones** such as ciprofloxacin work? And how does resistance occur?
They bind and inhibit DNA Gyrase and Topoisomerase IV, and so DNA replication **DNA Gyrase** - Removes the DNA supercoils ahead of the replication fork **Topoisomerase IV** - Seperates the DNA after replication Oral absorption is decreased in the presence of cations (so dont take with milk) Alteration in these enzymes inhibit the binding of ciprofloaxacin
32
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
33
How do **intergrase inhibitors** work? With respect to HIV
They inhibit the key enzyme, enzyme intergrase This prevents the HIVs genetic information being incorporated into the hosts
34
What bond is used in protease inhibitors that allow them to be useful?
**Hydroxyethylene Bond**
35
What is the main difference between the **herpes virus**, and other viruses?
Herpes produces its own **DNA polymerase** as an early stage protein.....which other viruses do not
36
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
37
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**
38
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
39
How can Candida obtain resistance?
Can gain **azole resistance** via changes in the structure and function of the **Major Facilitator Superfamily (MFS)** --\> these are an antifungal **efflux transporter**
40
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
41
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
42
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
43
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
44
What are the **specific targets** for drugs in fungi?
**Ergesterol** **P-450-dependent 14-(a)-demethylase** (fungi version of mammal P450s) --\> From the _ERG11_ gene
45
What are **Oxazolidinones**, like linezolid, used for?
Used as a **last resort antibiotic** to highly-resistant **gram-positive bacteria**
46
What is **vaginal thrush** causes by? And when **uncomplicated**, what is the treatment?
C.albicans Treated with intravaginal azoles (eg, clotim**azole** and micon**azole**) Oral flucanazole can also be used (single dose) as well as intravaginal nystatin
47
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
48
What are the 2 co-receptors of HIV?
CCR-5 CXCR4
49
# 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
50
Explain **penicillins**
Broad spectrum Solubility can increase with the addition of Na/K+ salts Sensative to stomach acid
51
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
52
How does **Chloramphenicol** work? And how is it normally given?
Binds to the 50S subunit, preventing peptide bonds from being formed Given as an eye drop, as can cause large side effects if it reaches the systemic circulation

PA20309 (6 decks)

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