Nucleic Acid Synthesis Inhibitors

Question 1

What is another name for sulphonamides?

Answer 1

antimetabolites

Question 2

What is the mechanism of action of sulphonamides?

Answer 2

Compete with p-aminobenzoic acid (PABA), as a false substrate for the enzyme dihydropteroate synthetase, in the synthesis of folic acid.

Question 3

What are Sulphonamides structural analogues of?

Answer 3

p-aminobenzoic acid (PABA)

Question 4

What is p-aminobenzoic acid (PABA) essential for in bacteria?

Answer 4

synthesis of folic acid

Question 5

What is the spectrum of activity of sulphonamides?

Answer 5

Wide, Gram + and - bacteria

Question 6

Where are most sulphonamides absorbed?

Answer 6

GIT

Question 7

After how long do sulphonamides reach maximum plasma concentrations?

Answer 7

4-6 hours

Question 8

Which sulphonamide is applied topically? (exception)

Answer 8

silver sulfadiazine

Question 9

What form of administration is not used with most sulphonamides?

Answer 9

topical

Question 10

Which organ metabolises sulphonamides?

Answer 10

liver

Question 11

How are sulphonamides excreted?

Answer 11

acetylated derivative is excreted in the urine

Question 12

What are the adverse effects of sulphonamides? (3)

Answer 12

• common: nausea, vomiting, headache
• crystaluria
• pregnancy: kernicterus in newborns

Question 13

What are the contraindications of sulphonamides?

Answer 13

Patients with porphyria

Question 14

What is the classification of trimethoprim?

Answer 14

diaminopyrimidine derivative

Question 15

What is the mechanism of action of trimethoprim?

Answer 15

Inhibits bacterial dihydrofolate reductase enzyme

Question 16

What does the enzyme dihydrofolate reductase do? (and what happens after this?)

Answer 16

converts dihydrofolic acid to tetrahydrofolic acid (active), a stage leading to the synthesis of purines and ultimately to DNA

Question 17

What is co-trimoxazole?

Answer 17

A combination of trimethoprim and sulfamethoxazole (sulphonamide)

Question 18

What are the therapeutic indications of co-trimoxazole? (5)

Answer 18

• Urinary tract, respiratory tract and prostatic infections
• prophylaxis
• Pneumocystis jirovecii (causes pneumonia in patients with AIDS)

Question 19

When is co-trimoxazole well absorbed?

Answer 19

After oral administration

Question 20

Describe the distribution of co-trimoxazole in body tissues and fluids

Answer 20

widely distributed

Question 21

What is the volume of distribution of trimethoprim and sulfamethoxazole?

Answer 21

100L

Question 22

What is the % of sulfamethoxazole bound to plasma proteins?

Answer 22

70%

Question 23

What is the % of trimethoprim bound to plasma proteins?

Answer 23

44%

Question 24

How is trimethoprim excreted and where?

Answer 24

unchanged in the urine

Question 25

Where is sulfamethoxazole metabolised?

Answer 25

liver

Question 26

What are the adverse effects of co-trimoxazole? (6)

Answer 26

- nausea, vomiting, blood disorders and skin rashes | - folate deficiency, with resultant megaloblastic anaemia

Question 27

What is the classification of ciprofloxacin?

Answer 27

Fluoroquinolone

Question 28

What is the mechanism of action of Fluoroquinolones?

Answer 28

Inhibits the function of topoisomerases, bactericidal

Question 29

What is the spectrum of action of Flouroquinolines?

Answer 29

Similar to aminoglycosides

Question 30

How are Flouroquinolines administered?

Answer 30

orally

Question 31

How is ciproflaxin administered?

Answer 31

IV, rapidly and well-absorbed orally

Question 32

Describe the distribution of ciproflaxin in body tissues and fluids

Answer 32

widely distributed

Question 33

Which parts of the body are penetrated by ciproflaxin?

Answer 33

tissues, bone, kidney, prostate, lung

Question 34

What is the half-life of ciproflaxin?

Answer 34

4-5 hours

Question 35

How is ciproflaxin metabolised?

Answer 35

In the liver by the cytochrome P450 enzyme system

Question 36

How is ciproflaxin excreted?

Answer 36

oral dose is excreted unchanged in the urine.

Question 37

What are the therapeutic indications of flouroquinolines? (4)

Answer 37

- Gram negative bacteria - Gram positive bacteria - Moxifloxacin more active against G+ and S. pneuomoniae - Useful in respiratory tract infections in patients with beta-lactam allergy

Question 38

What are the adverse effects of Flouroquinolines? (6)

Answer 38

- well-tolerated: GIT/skin rashes - theophylline toxicity in asthmatics - hepatotoxicity, prolonged QT interval, GIT disturbances, hypersensitivity reactions

Question 39

What are contraindications of flouroquinolines?

Answer 39

pregnancy and children under 18

Question 40

What is the classification of Metronidazole?

Answer 40

Nitroimidazole

Question 41

What is the mechanism of action of Metronidazole?

Answer 41

Selective toxicity against anaerobes

Question 42

What are the therapeutic indications of Metronidazole? (3)

Answer 42

- Antiprotozoal against trophozoites of Entermoeba histolytica and Trichomonas vaginalis - Eradicate H. pylori (peptic ulcer tx) - Potent antibacterial activity against anaerobes

Question 43

How is Metronidazole administered?

Answer 43

orally (rapidly and completely absorbed), rectal and IV

Question 44

When is a peak plasma concentration reached with Metronidazole?

Answer 44

1-3 hours

Question 45

What is the half-life of Metronidazole?

Answer 45

7 hours

Question 46

Describe the distribution of Metronidazole

Answer 46

distributed rapidly throughout the tissues including the cerebrospinal fluid

Question 47

In which organ is Metronidazole metabolised?

Answer 47

liver

Question 48

How is Metronidazole excreted?

Answer 48

unchanged in the urine

Question 49

What are the adverse effects of Metronidazole? (4)

Answer 49

- metallic, bitter taste in the mouth - GIT disturbances - When combined with alcohol: disulfiram-like reaction - Mutagenic, carcinogenic and teratogenic

Question 50

What are contraindication of Metronidazole?(3)

Answer 50

- cannot be used for more than 10 days - pregnancy/breastfeeding - alcohol consumption