Nucleic Acid Synthesis Inhibitors Flashcards
What is another name for sulphonamides?
antimetabolites
What is the mechanism of action of sulphonamides?
Compete with p-aminobenzoic acid (PABA), as a false substrate for the enzyme dihydropteroate synthetase, in the synthesis of folic acid.
What are Sulphonamides structural analogues of?
p-aminobenzoic acid (PABA)
What is p-aminobenzoic acid (PABA) essential for in bacteria?
synthesis of folic acid
What is the spectrum of activity of sulphonamides?
Wide, Gram + and - bacteria
Where are most sulphonamides absorbed?
GIT
After how long do sulphonamides reach maximum plasma concentrations?
4-6 hours
Which sulphonamide is applied topically? (exception)
silver sulfadiazine
What form of administration is not used with most sulphonamides?
topical
Which organ metabolises sulphonamides?
liver
How are sulphonamides excreted?
acetylated derivative is excreted in the urine
What are the adverse effects of sulphonamides? (3)
- common: nausea, vomiting, headache
- crystaluria
- pregnancy: kernicterus in newborns
What are the contraindications of sulphonamides?
Patients with porphyria
What is the classification of trimethoprim?
diaminopyrimidine derivative
What is the mechanism of action of trimethoprim?
Inhibits bacterial dihydrofolate reductase enzyme
What does the enzyme dihydrofolate reductase do? (and what happens after this?)
converts dihydrofolic acid to tetrahydrofolic acid (active), a stage leading to the synthesis of purines and ultimately to DNA
What is co-trimoxazole?
A combination of trimethoprim and sulfamethoxazole (sulphonamide)
What are the therapeutic indications of co-trimoxazole? (5)
- Urinary tract, respiratory tract and prostatic infections
- prophylaxis
- Pneumocystis jirovecii (causes pneumonia in patients with AIDS)
When is co-trimoxazole well absorbed?
After oral administration
Describe the distribution of co-trimoxazole in body tissues and fluids
widely distributed
What is the volume of distribution of trimethoprim and sulfamethoxazole?
100L
What is the % of sulfamethoxazole bound to plasma proteins?
70%
What is the % of trimethoprim bound to plasma proteins?
44%
How is trimethoprim excreted and where?
unchanged in the urine
Where is sulfamethoxazole metabolised?
liver
What are the adverse effects of co-trimoxazole? (6)
- nausea, vomiting, blood disorders and skin rashes
- folate deficiency, with resultant megaloblastic anaemia
What is the classification of ciprofloxacin?
Fluoroquinolone
What is the mechanism of action of Fluoroquinolones?
Inhibits the function of topoisomerases, bactericidal
What is the spectrum of action of Flouroquinolines?
Similar to aminoglycosides
How are Flouroquinolines administered?
orally
How is ciproflaxin administered?
IV, rapidly and well-absorbed orally
Describe the distribution of ciproflaxin in body tissues and fluids
widely distributed
Which parts of the body are penetrated by ciproflaxin?
tissues, bone, kidney, prostate, lung
What is the half-life of ciproflaxin?
4-5 hours
How is ciproflaxin metabolised?
In the liver by the cytochrome P450 enzyme system
How is ciproflaxin excreted?
oral dose is excreted unchanged in the urine.
What are the therapeutic indications of flouroquinolines? (4)
- 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
What are the adverse effects of Flouroquinolines? (6)
- well-tolerated: GIT/skin rashes
- theophylline toxicity in asthmatics
- hepatotoxicity, prolonged QT interval, GIT disturbances, hypersensitivity reactions
What are contraindications of flouroquinolines?
pregnancy and children under 18
What is the classification of Metronidazole?
Nitroimidazole
What is the mechanism of action of Metronidazole?
Selective toxicity against anaerobes
What are the therapeutic indications of Metronidazole? (3)
- Antiprotozoal against trophozoites of Entermoeba histolytica and Trichomonas vaginalis
- Eradicate H. pylori (peptic ulcer tx)
- Potent antibacterial activity against anaerobes
How is Metronidazole administered?
orally (rapidly and completely absorbed), rectal and IV
When is a peak plasma concentration reached with Metronidazole?
1-3 hours
What is the half-life of Metronidazole?
7 hours
Describe the distribution of Metronidazole
distributed rapidly throughout the tissues including the cerebrospinal fluid
In which organ is Metronidazole metabolised?
liver
How is Metronidazole excreted?
unchanged in the urine
What are the adverse effects of Metronidazole? (4)
- metallic, bitter taste in the mouth
- GIT disturbances
- When combined with alcohol: disulfiram-like reaction
- Mutagenic, carcinogenic and teratogenic
What are contraindication of Metronidazole?(3)
- cannot be used for more than 10 days
- pregnancy/breastfeeding
- alcohol consumption
