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What is metal chelation?

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

1

How can metal chelation alter the pharmacokinetics of drugs?

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

2

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

6 membered ring
Followed by 5 or 7 membered ring (not aromatic)

3

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

4 membered ring (strained)
Or 8 membered (bond overlap)

4

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

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

5

What are nitrogen mustard cytostatic agents?

Alkylating agents
They interfere with DNA replication

6

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!

Adrimycin and duanomycin

7

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

Calcium

8

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

Pyrimethamine

9

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

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

10

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

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

11

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

Quinolone antibacterial agents but not that active

Ciprofloxacin is highly active

12

How do tetracyclines exhibit their antibacterial effects?

Interfere with protein synthesis
By inhibiting binding of tRNA to the 30S subunit if ribosomes in bacteria

13

What two (aminoglycoside antibiotics) antituberucloctics are very important?

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

14

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

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

15

How do streptomycin and kanamycin work?

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

16

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

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

17

What is the drug of choice in tuberculosis and leprosy?

Rifampicin

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

18

Chloramphenicol is the drug of choice against ______
By inhibiting the enzyme __________

Against typhoid
Inhibits peptidyl transferase

Chloramphenicol is Another product of the streptomyces species

19

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

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

20

Are fungi more likely to be opportunistic or obligate?

Opportunistic

21

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

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

22

One class of fungal infections is superficial

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

Trichophyton species
Epidermophyton species
Microsporum species

23

What do the true dermatophytes give rise to?

Tineas
That is athletes foot and ringworm

24

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

Candida species
C.albicans gives rise to oral and vaginal thrush

25

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

More seriously ill

26

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

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

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

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

28

How do we treat complicated thrush?

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

29

What is complicated vulvovaginal candidiasis ?

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

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