Inhibitors of the nucleic acid synthesis

Question 1

Discuss theenzymes involved in the process of dna synthesis

Answer 1

1.Double helix is separated by the helicase protein

2.Topoisomerase 2 relaxes the coil. Involved with removing DNA supercoils
– Separation of the replicated DNA into
respective daughter cells during replication

3.DNA polymerase is an enzyme that synthesizes DNA molecules from deoxyribonucleotides, which are the building blocks of DNA. The enzymes play an essential role in DNA replication, usually working in pairs to produce two matching DNA stranges from a single DNA molecule.

Question 2

Give examples of fluoroquinolones

Answer 2

Ciprofloxacin ,levofloxacin ,moxifloxacin , gemifloxacin

Question 3

True or false: Fluoroquinolones are synthetic antibiotics

Answer 3

true

Question 4

Discuss the spectrum of ciproflaxin

Answer 4

They are active against gram neg aerobic (streptococcus and pneumococci ) inhibited to a weaker extent

lacks activity against anaerobic bacteria

drugs of choice for typhoid fever

used for cystitis

LRI

Not recommended for genorrhea

Meningococcal prophylaxis

Question 5

Spectrum and uses of moxifloxacin ,gemifloxacin and levofloxacin

Answer 5

• More active against gram pos bacteria
• Not useful against pseudomonas
• LRI ,acute sinusitis ,skin & urinary infection

Mostly reserved in cases of beta lactam allergy

Question 6

Which drugs are used for M.tuberculosis

Answer 6

moxifloxacin and levofloxacin

Question 7

discuss the mechanism of action of inhibition of topoisomerase ( DNA gyrase)

Answer 7

-Prevent the relaxation of positively supercoiled dna required for normal transcripttion and replication

Inhibits the cutting and joining action of the enzyme on the dna double helix

Question 8

Mechanism of action for Topoisomerase IV inhibitors

Answer 8

Prevent the removal of supercoils by the
enzyme
– Interfere with the separation of replicated
chromosomal DNA into the respective
daughter cells during cell division
• Bactericidal

Question 9

What causes resistance of bacteria towards floroquinolone

Answer 9

1. 1 or more point mutations in quinolone binding site of the target enzyme
2. Change in permeability

Question 10

Pharmacokinetics of floroquinolone

Answer 10

Oral or IV

Best taken on an empty stomach

Ciprofloxacin is absorbed rapidly 70 -80%
Must be in adequate fluid
Absorption impaired by divalent cations (incl.
those in antacids)
• Excessive alkalinity of urine must be avoided
• It is widely distributed into tissues, especially in
bone, kidney, prostate and lung

T1/2 is 4 - 5 hours
• Metabolised via the liver cytochrome P450
enzyme system
• ± 40 - 50% excreted unaltered in the urine

Question 11

side effects of fluoroquinolone

Answer 11

1. Could cause seizures
   hallucinations
   photosensitivity
   hyperglycemia or hypoglycemia in diabetic and non diabetic patients

Hypoglycemia in patients rcieving oral hypoglycemic agents

Question 12

Discuss the drug interaction of fluoroquinolone

Answer 12

Ciprofloxacin/levofloxacin and theophylline →
ciprofloxacin/levofloxacin inhibit the cytochrome
P450 enzyme system
• Theophylline toxicity → in asthma patients
2. Warfarin
3. NSAIDs
4. Oral hypoglycemic agents (glibenclamide)
5. Some may interfere with agents that prolong QTc
interval
6. Antacids/minerals
7. Probenecid

Question 13

Cautions/Contraindications of fluoroquinolone

Answer 13

1. Epilepsy (strong caution bordering on C/I)
2. Hepatic failure
3. Pregnancy/lactation (strong caution bordering
   on C/I)
4. Babies/children (<18 years) (strong caution
   bordering on C/I)
5. Renal failure
6. Porphyria
7. Elderly patients
8. Allergy
9. G6PD deficiency

Question 14

What are the uses of metronidazole ?

Answer 14

1.Bactericidal
2, Effective against anaerobic bacteria
3. Has an antiprotozoal action against trophozoites of :
*Entamoeba histolytica ( Protozoa causing colon inflammation ,amoebic dysentery and liver abscesses
*Trichomonas Viginalis (protozoa that causes vaginitis and uretritis

Question 15

What are the uses of metronidazole?

Answer 15

Helicobacter pylori (treatment regimen) → peptic
ulcers
• Giardiasis
• Acute necrotising ulcerative gingivitis
• Pseudomembranous colitis

Question 16

What is the mechanism of action of metronidazole

Answer 16

1. Reaction intermediates are formed after the reduction of the drug eg f free radicles which interact with macromolecules eg DNA. Causing alterations in the dna helix and breaking of the dna chain

Question 17

True or false , The development of resistance is high in bacteria against metronidazole

Answer 17

false, development of resistance is low but increasing

Question 18

Discuss the pharmacokinetics of metronidazole

Answer 18

1. When given orally is nearly totally absorbed
2. It has almost 8 hours halflife
3. It can also be administered rectally , IV and topicalpreparations
4. Its is widley distributed in the body including the CSF
5. Metabolism occurs in the liver andd 10-20 % are excreted unaltered in the urine
6. Plasma clearance decrease with impaired liver function
7. Dose must be adjusted with patients with severe liver and renal disease

Question 19

What are the side effects of metronidazole?

Answer 19

1. Dry mouth
2. meralic taste
3. CNS effects
4. Inhibits metabolism of alcohol resulting in acetaldehyde plasma increase ultimately disulfiram-like effect

Question 20

How does metronidazole interact with other drugs ?

Answer 20

1. Cimetidine (antagonist ) result in decrease of metronidazole metabolism
2. Phenobarbitone (agonist) =(increase in metronidazole metabolism
3. Warfarin ( increases anticoagulant effect )
4. Alcohol ( decreases alcohol metabolism)

Question 21

What are the cautions and contraindications of metronidazole

Answer 21

C/I with alcohol use
2. Caution in patients with epilepsy, porphyria
3. Caution with CNS disease
4. Impaired hepatic function
5. Avoid if possible during 1st trimester of
pregnancy and breastfeeding