Fungal Infections Flashcards
1
Q
What type of cells are fungi
A
Eukaryotic
2
Q
What is their cell wall made of
A
Chitin
3
Q
Fungi are heterotrophic, what does this mean?
A
An organism that can’t manufacture its own food and instead obtains its food and energy by taking in plant and animal matter
4
Q
How does fungi ‘grow’
A
Produce spores which move through water and air
5
Q
Why is fungus so infectious
A
High reproductive rate
Slow death so can spread before numbers thin
Broad host range
6
Q
Yeast vs Mould
A
- Yeast - single celled
Mould - multicellular - Yeast divide by budding whilst moulds develop from hyphae
7
Q
What are dimorphic fungi
A
They can switch from being yeast to mould depending on the environment
8
Q
What is hyphae
A
Branching from the cell wall
9
Q
Example of a dimorphic fungus
A
Coccidiodes immitis
10
Q
Ideal conditions for C immitis
A
Warm, arid conditions
11
Q
When does C immitis grow as mould
A
ambient temperature
12
Q
How is C immitis spread
A
Light so by wind
13
Q
When do C immitis convert from mould to yeast
A
At body temperature after inhalation
14
Q
What disease does C immitis cause
A
Pneumonia
15
Q
Why do not many fungi cause human infection
A
- Denature at 37 degrees
2. Our strong immune responses
16
Q
How common are life-threatening fungal infections
A
Very uncommon
17
Q
What is Otitis Externa
A
Inflammation of external ear canal
18
Q
What is Onychomycosis
A
Final nail infection
19
Q
What is Tinea Pedis
A
Athlete’s foot
20
Q
Name five fungi which can cause life-threatening disease in immunocompromised hosts
A
- Candida
- Invasive aspergillosis
- Pneumocystis
- Cryptococcosis
- Mucormycosis
21
Q
What does candida commonly cause in the mouth
A
Thrush
22
Q
Why does Invasive aspergillosis take place
A
Cause the immune system can’t stope spores from reaching the bloodstream via the lungs
23
Q
What does invasive aspergillosis often cause
A
TB
24
Q
Two life-threatening fungal diseases in healthy hosts
A
- Fungal asthma
2. Travel associated fungal infections
25
Four characteristics of selective toxicity drugs for fungal infections
1. Target receptors not in humans
2. Target receptors is different to any human analogues
3. Drug is concentrated in organism cell
4. Increased permeability to compound
26
How do human cells survive selective toxicity drugs
1. They use alternative metabolic pathways
27
Why is selective toxicity more difficult for fungi than bacteria
Eukaryotic
28
Four components of the final cell wall
1. Mannoproteins
2. B1,3, gluons
3. B1,6 gluons
4. Chitin
29
What is the plasma membrane of fungus made of
Ergosterol
30
Difference in composition of plasma membrane in humans and fungus
1, Humans have cholesterol in wall whilst fungi have ergosterol
31
What is an amphoteric molecule
A molecule with both acid and alkaline properties
32
What do amphoteric drugs act on in fungal cells
Drugs bind to ergosterol in membrane forming pores in membrane, k+ leakage and death
33
Why are polyenes like amphoteric drugs selective
1. 10 times lower affinity for cholesterol in mammalian membrane s
34
Does this mean polyenes can't cause damage in host cells
No, they can (dose dependant)
35
What are side-effects of polyenes
1. Anaphylactic reactions, hypotension
2. Hyperkalemia
3. Hypokalaemia if distal renal uses are effected
36
Describe the ergosterol synthetic pathway
Acetyl CoA -> Farnesyl Pyrophosphate -> Squalene -> Squalene Eposide
-> Lanosterol -> 4,4-dimethylcholesta-8,14,24-trienol -> 4,4-dimethyltrymosterol -> Fecosterol -> Episterol -> Ergosta-5,7,24(28)-trienol -> Ergosterol
37
What type of drug is Terbinafine
Allylamines
38
How does Terbinafine work
Reversible inhibition of squalene epoxidase
39
What is the bioavailability of Terbinafine
45%
40
Where is Terbinafine usually metabolised
First pass metabolism in the liver
41
Where is Terbinafine distributed to
Poorly perfused sites (skin and nails)
42
What is Terbinafine usually used to treat
Dermatophytes (Candida, aspergillus)
43
Two side-effects of Allyamines
Taste disturbance, deranged LFT, increased CYP450 metabolism
44
What do azoles inhibit
Lanosterol
45
Role of triazoles
Inhibit secondary targets in synthetic pathways
46
Name an azalole used to inhibit lanosterol
Fluconazole
47
What are clotrimazole and Ketoconazole active against
Candida
48
Adverse effects of azoles
1. Transaminitis
| 2. GI SEs
49
Adverse effects unique to itraconazole
Nausea, diarrhoea
| Liver failure
50
Adverse effects unique to Voriconazole
30% suffer from reversible visual disturbances
51
Why do azole drug-drug interactions occur
1. Result of CYPP450
52
Why are azole drug-drug interactions so rare for Fluconazole
1. Hydrophilic and easily excreted
53
What does Fluconazole inhibit
Warfarin, phenytoin, anxiolytics
54
Which is a stronger inhibitor, intra or post
Itra
55
What does Itraconazole and Posaconazole inhibit
CYP3A4
56
What does Voriconazole inhibit
CYP enzymes (some of the smaller ones)
57
Why are Candida displaying azole resistance
1. Mutations in ERG11 gene
2. Increased expression for ERG11
3. Causes efflux
58
What drugs are most effected by azole resistance in Candida
Fluconazole and Voricaonzole
59
What do Echinocandins inhibit
1,3 beta-glucan synthase
60
Define fungistatic
Inhibit growth of fungus
61
What type of cells are Echinocandins fungistatic towards
moulds at hyphen tip
62
What the of cells are Echinocandins fungicidal towards
Yeast
63
What cell are resistant to Echinocandins
1. Species with large amounts of 1,3 gluten in cell wall
64
What species are resistant to Echinocandins
1. Zygomycetes
2. Cryptococcus
3. Trichosporon
4. Fusarium
65
What is inconvenient about Echinocandins
1. Poor oral bioavailability (IV only)
| 2. Poor penetration in some parts of the body (CSF, eye)
66
What is a convenience of Echinocandins
Limited, and rare drug toxicity
1. Concentration dependant killing
2. Prolongues antibiotic effect
67
What fungal infection does this patient have
1. 60 yr old man has acute gallstone pancreatitis with pseudocysts
2. Stable on transfer
1 week later:
3. Febrile >38 despite antibiotics
4. Haemodynamics relatively stable
5. Fungal infection found in line tip and blood
Invasive Candida infection
68
How can we maximise sensitivity for fungi during diagnosis
1. Pick up from tissue and fluids if can be obtained (best place to pick up)
69
Blood culture efficiency for fungi vs bacteria
Blood culture only half as sensitive n fungi
70
Why can we detect if there is a fungal infection within the body by using blood
1. 1,3 gluten released by cell membrane into plasma
71
Inconveniences of blood samples for fungi
1. Prone to contamination
| 2. Non-specific for individual fungi
72
Most common Candida in hospital patients
1. Candida albicans
73
What two drugs are candida most susceptible to
1. Echinocandins
| 2. Polyenes (ampotericin B)
74
What fungal infection is this man suffering from:
1. 43 year old
2. Found unconscious
3. Lesion on CT in brain
4. Serum galactomanna found
Aspegillus
75
How do we know the 43 year old man is suffering from Aspergillus infection
Because Galactomannan is found in Aspergillus cell walls as an antigen
76
Two drugs that inhibit ergosterol synthesis
Azole
Allyamines
77
Drug that inhibits formation of cell wall gluten
Echinocandin
78
Drug that inhibits DNA and RNA synthesis
Pyrimidine (5-fluuorocytosine)
79
Drug that inhibits microtubule assembly
Grisan
80
How common is Onychomycosis
Very
81
What is Onchomycosis caused by
Dermatophyte moulds
82
When do dermatophyte moulds grow best
30 degrees
83
What species causes Onchymycosis
Trichopyton Rubrum
84
What is the most specific test for Onchymycosis
Microscopy (30% culture negative)
85
Two treatment options for Onchymycosis
1. Topical Amorolfine
| 2. Itraconazole and Terbinafine
86
What is Amorolfine
Morpholine
87
How does Amorolfine work
Stops production of ergosterol
88
What fungus has caused the following:
1. 75 yrs old
2. Admitted with onset respiratory failure
3. Pulmonary oedema was primary diagnosis
4. Beta gluten positive
Could be any cause every fungus has 1,3 gluten.
HOWEVER, since it effects the lungs it is pneumocystis
89
When is pneumocystis most common
Early in life
90
What patients usually get pneumocystis later in life
Immunocompromised
91
What clinical indication for pneumocystis is there
1. Hypoxia is more severe than tests are suggesting
