Infection And Immunity Blagborough Flashcards

0
Q

How can metal chelation alter the pharmacokinetics of drugs?

A

Absorption can be severely reduced
Due to complexes formed from chelation having reduced water solubility
This means they can’t cross lipid membranes

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1
Q

What is metal chelation?

A

Interaction of a metal ion with a chemical molecule to form a heteroatomic ring

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2
Q

When metals chelate with a drug what’s the most stable ring size that could form?

A

6 membered ring

Followed by 5 or 7 membered ring (not aromatic)

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3
Q

When metals chelate with drugs, what’s the least stable ring size that may form?

A

4 membered ring (strained)

Or 8 membered (bond overlap)

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4
Q

Adriamycin, actinomycin, synthetic acridine and quinolone antimalarials are all intercalating cytostatic agents. What do they interfere with?

A

Bacterial DNA replication
These drugs bind strongly to the DNA of chromatin in the bacterial cell nucleus by slipping between 2 base pairs
Form charge transfer complexes with the nucleotides

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5
Q

What are nitrogen mustard cytostatic agents?

A

Alkylating agents

They interfere with DNA replication

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6
Q

Which two antibiotics are both aminoglycosides in the group of anthracycline antibiotics produced by some streptomyces species?
Hint: they differ in structure by one hydroxyl group!

A

Adrimycin and duanomycin

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7
Q

Adriamycin and duanomycin are both anti cancer antibiotics. A big problem is their cardiotoxcity. What can reverse this toxicity?

A

Calcium

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8
Q

Quinine is a common antimalarial.
It’s more toxic than others.
What’s it mainly used in combo with?

A

Pyrimethamine

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9
Q

Some drugs may be DNA topoisomerase inhibitors. What is topoisomerase?

A

Topoisomerase I and II
Enzymes
Bacterial DNA must first unwind to be replicated. Unwinding introduces a supertwist. Top I removes this supertwist and produces more relaxed DNA.
Top II further promotes strand separation.
Topoisomerase inhibitors interfere with these enzymes so stop replication.
Used in cancer

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10
Q

Some agents like adriamycin and actinomycin D can stabilise the Topiosomerase enzyme and DNA complexes and therefore make the breaks in the DNA permanent

A

This way they have made the topoisomerase enzymes (DNA Gyrases) LETHAL enzymes

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11
Q

What other drugs can act by inhibiting DNA Gyrases (topoisomerases)?

A

Quinolone antibacterial agents but not that active

Ciprofloxacin is highly active

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12
Q

How do tetracyclines exhibit their antibacterial effects?

A

Interfere with protein synthesis

By inhibiting binding of tRNA to the 30S subunit if ribosomes in bacteria

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13
Q

What two (aminoglycoside antibiotics) antituberucloctics are very important?

A

Streptomycin
Kanamycin
Both have a fairly wide antibiotic spectrum
Antituberucloctics: anti TB bacteria

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14
Q

Why do we have to warn people on tetracyclines about dairy products?

A

Several chances for the antibiotics to chelAte with the calcium ions
6 places where tertacyclines can chelate

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15
Q

How do streptomycin and kanamycin work?

A

Decrease translation in the bacteria by binding to the 30S subunit of the bacterial ribosome. Therefore stops any more addition of amino acids to the growing peptides

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16
Q

Streptomycin is more ______ than kanamycin, what does this mean?

A

More ototoxic
Damaging to auditory nerve in the ear so patient goes deaf
(Same with gentamicin)

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17
Q

What is the drug of choice in tuberculosis and leprosy?

A

Rifampicin

Much safer than others as it inhibits only bacterial RNA polymerase, not mammalian.

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18
Q

Chloramphenicol is the drug of choice against ______

By inhibiting the enzyme __________

A

Against typhoid
Inhibits peptidyl transferase

Chloramphenicol is Another product of the streptomyces species

19
Q

What antibiotic can compete with chloramphenicol for the same binding site?

A

Erythromycin
Acts in same way as chloramphenicol by inhibiting peptidyl transferase
It is the drug of choice to cure Legionnaires disease

20
Q

Are fungi more likely to be opportunistic or obligate?

A

Opportunistic

21
Q

Certain people are way more likely to suffer from Fungal infections. Can you think of the list of 5 patients more likely?

A
HIV / AIDS patients
Transplant patients (immunosupressed)
Those having radio and chemotherapy
Patients treated with powerful antibiotics 
Those with indwelling catheters
22
Q

One class of fungal infections is superficial

These are caused by the true dermatophytes.
What are these?

A

Trichophyton species
Epidermophyton species
Microsporum species

23
Q

What do the true dermatophytes give rise to?

A

Tineas

That is athletes foot and ringworm

24
Q

Other than dermatophytes what’s the other kind of fungus that cause superficial fungal infections?

A

Candida species

C.albicans gives rise to oral and vaginal thrush

25
Q

Superficial (localised) fungal infection can establish themselves into systemic infection, more like when the patient is?

A

More seriously ill

26
Q

What ointment is commonly used to treat UNcomplicated vulvovaginal candidiasis (thrush)?

A

Ticonazole 6.5% Vaginal ointment

Uncomplicated means healthy, non pregnant women who have have previously been diagnosed by a doctor.

Other options: clotrimazole, miconazole, terconazole
Oral fluconazole as a single dose also commonly used

27
Q

Why is identifying candida by culture in the absence of any symptoms NOT an indication that someone needs antifungal treatment?

A

Because approximately 10-20% of women have candida or other yeasts in their vagina! therefore symptoms have to be present to start treatment

28
Q

How do we treat complicated thrush?

A

A longer duration of therapy with a intravaginal ointment or oral azole (fluconazole)

29
Q

What is complicated vulvovaginal candidiasis ?

A

Infections that are recurrent or severe
Caused by Candida’s OTHER than Candida albicans
Occur in women with underlying medical conditions such as pregnancy, diabetes, immunosuppression

30
Q

Voriconazole is now the antifungal medicine of choice and is always superior to?

A

always superior to amphotericin B

31
Q

What is caspofungin used for?

A

For systemic fungal infections
Given as an IV infusion for adults for invasive aspergillus or invasive candidiasis that aren’t responsive to amphotericin or intraconazole, or for intolerant patients

32
Q

What does Candida albicans use to aquire resistance to Azole treatments ?

A

CaMdr1p
An antifungal Efflux transporter protein
A MFS (major facilitator superfamily)
Transports drug out of fungi so it can’t accumulate

MFS multidrug transporter CaMdr1p is relevant to azole resistance in Candida

Other way: alteration to the Azole target protein Erg11p

33
Q

The multidrug transporter CaMdr1p shows selective substrate selectivity. Therefore what could we do to avoid it ? (And therefore avoid C albicans resistance)

A

Change a functional group in our drug so that the caMdr1p is no longer specific to our drug

34
Q

Griseofulvin is a SYSTEMIC antifungal.

What’s its mode of action?

A

Accumulates in keratin cells in host
Prevents transmission of fungi into unexfolidated skin cells

Prevents the correct functioning of micro-tubules assembly.

It stops the GROWTH and MOVEMENT of fungus through the cells

35
Q

What are two examples of Polyene antifungal agents?

A

Nystatin and amphotericin B

These are for systemic fungal infections

36
Q

How do the Polyene antifungals work?

A

Punch holes in cells
They’re pore forming
Which allows lipid permeation

Remember polyENES: fungi
Polymyxins: bacteria
But both work at cell membrane

37
Q

What are the major targets for Azoles, allyamines and morpholines?

A

Enzymes in the ergosterol biosynthetic pathway of fungus

Amorolfine clotrimazole fluconazole itraconazole ketoconazole terbinafine and Voriconazole all target these

38
Q

How does amorolfine (nail lacquer) exert it’s anti fungal action?

A

Results in depletion of ergosterol and accumulation of ignosterol in fungal cytoplasmic membranes

39
Q

Are fungicides selective?

A

Yes

They have higher affinity for fungal ergosterol than mammalian cholesterol

40
Q

How do miconzaole and ketoconazole (systemic) have their antifungal effects?

A

They inhibit synthesis of essential fungal cell membrane components such as ergosterol

41
Q

How do miconzaole and ketoconazole differ?

A

Miconzaole can exert direct physicochemical cell membrane damage at relatively high levels
Ketoconazole can’t do this

42
Q

What is the mode of action of Azoles?

A

They are fungistatics

Inhibit oxidative enzymes in fungus especially P450 14a demthylase and C4-demthylase

43
Q

Which of the triazoles are topical use only?

A

Clotrimazole
Econazole
Tioconzaole

Fluconazole and itraconazole can be used systemically

44
Q

Terbinafine and naftifine are both allylamines

How can they be used?

A

Topical and systemically

They have low mammal toxicity as allylamines have a far lower affinity for mammalian over fungal squalene epoxidases

45
Q

What could reduce affinity for allylamine drugs?

A

Mutations in their target enzyme : fungal squalene epxidase

46
Q

Why aren’t pseudomonas bacteria sensitive to beta lactam antibiotics?

A

They have inactive porins

So beta lactams can’t pass through the outer membrane into the cell wall