Nucleic Synthesis

Question 1

What are 5 ways to interfere with nucleic acid synthesis?

Answer 1

1. Alteration of base-pairing properties of the template
2. Inhibition of either DNA or RNA polymerase
   3.Direct effects on DNA itself
3. Inhibition of DNA gyrase
4. Inhibition of nucleotide synthesis

Question 2

How do Acridines work?

Answer 2

Intercalating agents - Produce frameshift mutations by sandwiching themselves between adjacent bases in DNA
Prevents bacterial reproduction

Question 3

What are they used against?

Answer 3

Topical against gram +ve bacteria
Surface disinfectant & superficial wounds

Question 4

What is an example of an acridine?

Answer 4

Proflavine - very toxic

Question 5

How does Actinomycin work?

Answer 5

Intercalates in minor groove of double helix between guanine cytosine base pairs
Interferes with RNA polymerase
Causes hairpin loops

Question 6

How is Actinomycin D administered?

Answer 6

I.V.

Question 7

How is actinomycin D distributed?

Answer 7

Widely bar BBB

Question 8

Where is actinomycin D absorbed?

Answer 8

poorly absorbed from GIT
Limited plasma binding
crosses placenta

Question 9

How is actinomycin D metabloised?

Answer 9

Minimally by the liver

Question 10

How is actinomycin excreted?

Answer 10

Via the biliary routes and urine

Question 11

What does actinomycin D inhibit?

Answer 11

Gram +ves/-ves and some fungi

Question 12

What are actinomycin D’s clinical uses?

Answer 12

Treatment of Wilm’s tumour
Combination chemotherapy
High antibacterial activity

Question 13

What are the adverse effects of Actinomycin D?

Answer 13

Hepatotoxicity, carcinogenicity, hematological toxicity, GIT distress and motility, hypersensitivity

Question 14

What is metronidazole?

Answer 14

Alkylating agent - forms covalent bonds with bases in DNA
Prevents replication and has cytotoxic effects

Question 15

What is an example of a metronidazole?

Answer 15

Falgyl (prodrug)

Question 16

What is metronidazole’s mode of action?

Answer 16

Reductive activation by intracellular trasnport proteins
Forms reduced cytotoxic compounds which binds to DNA
Loss of helical DNA structure and strand breakage - prevents nucleic acid synthesis

Question 17

What does metronidazole act against?

Answer 17

Anaerobic infections
Antiprotozoal infections

Question 18

What are metronidazole’s clinical uses?

Answer 18

Combination therapy against Helicobacter pylori
Oral infections
Amoebic dysentery

Question 19

How is metronidazole administered?

Answer 19

Oral
I.V.

Question 20

How is metronidazole absorbed?

Answer 20

Rapidly absorbed after oral admin.

Question 21

How is it distributed?

Answer 21

Bioavailability of almost 100%

Question 22

How is metronidazole metabolised?

Answer 22

Hepatic metabolism

Question 23

How is metronidazole excreted?

Answer 23

Kidneys in urine
some faecal elimination

Question 24

What are the side effects of metronidazole?

Answer 24

GIT distress and motility
Dermatological effects
Neurotoxicity
Stevens-Johnson syndrome

Question 25

What are the mechanisms of resistance proposed?

Answer 25

Specific resistance genes Reduced drug uptake Efflux systems Decreased activation

Question 26

What are Fluoroquinilones?

Answer 26

Bacterial enzyme (topoisomerases)

Question 27

What are fluoroquinolone's mechanism of action?

Answer 27

Catalyses ATP-dependent negative supercoiling of double stranded closed-circular DNA G-ve - inhibits DNA gyrase G+ve - inhibits topoisomerase IV Induce synthesis of exonucleases - breakdown of DNA

Question 28

What is an example of a fluoroquinolone?

Answer 28

Ciprofloxacin

Question 29

What does V act fluoroquinolone act against?

Answer 29

G-ve/+ organisms

Question 30

How are fluoroquinolones administered?

Answer 30

Oral I.V. Topical

Question 31

How are fluoroquinolones absorbed?

Answer 31

Well absorbed from GIT in oral admin

Question 32

How are fluoroquinolones distributed?

Answer 32

All tissues and body fluids Ofloxacin crosses BBB

Question 33

How are fluoroquinolones metabolised?

Answer 33

Hepatic metabolism - can inhibit cytochrome p450 enzymes

Question 34

How are fluoroquinolones excreted?

Answer 34

Renal excretion Some biliary elimination

Question 35

What are fluoroquinolones clinical uses?

Answer 35

Ciprofloxacin - G-ve organisms, UTIs, chlamydia Morfloxacin - UTIs

Question 36

What are common fluoroquinolones side effects?

Answer 36

GIT upset Alleregic reactions CNS effects Renal impairment

Question 37

What resistance mechanisms are used against fluoroquinolones?

Answer 37

Altered target - chromosomal mutations in bacterial genes Efflux pumps and porin channels cause decreased accumulation