10 antibacterial- nucleic acid synthesis inhibitor Flashcards
What are the two categories Nucleic Acid Synthesis Inhibitors
What are the two categories Nucleic Acid Synthesis Inhibitors
- Inhibitors of folic acid synthesis (indirect)
- folate is required as a donor of methyl group in the synthesis of nucleic acid precursors.
- Synthesis of tetrahydrofolate from dihydrofolate requires an enzyme called dihydrofolate reductase (DHFR)…which is the target of certain drugs (trimethoprim)
- Some drugs(sulfonamides) work by being an analog and compete with PABA (p-aminobenzoic) on an enzyme called (dihydropteroate synthase). p-aminobenzoic acid (PABA) is a precursor that allow bacteria to make their own folate
- Direct inhibitors of nucleic acid synthesis
Folic acid synthesis inhibitors
Folic acid synthesis inhibitors
(indirect nucleic acid inhibitor)
- Sulfonamides
- Inhibits dihydropteroate synthase
- Trimethoprim
- inhibit (dihydropteroate synthase) by acting as an anologue of PABA (precursor for bacterial folate synthesis).
- Pyrimethamine
- Both inhibit dihydrofolate reductase (DHFR)
what are Sulfonamides? mode of action and examples.
Sulfonamides
- How do they act (MOA):
- Structure similar to PABA
- Compete with PABA on enzyme (dihydropteroate synthase) , thus , impairing folate synthesis in microbes.
- Sulfonamide drugs:
-
Sulfamethaxazole*
- Short acting (4 hr)
-
Sulfadoxine*
- Long acting
-
Sulfadiazine*
- Intermediate acting (8-12 h)
- Silver sulfadiazine* (Topical)
- Sulfacetamide* (Topical)
-
Sulfamethaxazole*
Sulfonamides Uses
Sulfonamides Uses
Sulfonamides are active against:
- Sulfonamides are active against: Gram positive and negative organisms, chlamydia and some protozoa but not the rickettsiae**
- Sulfonamides: clinical uses
- Mild urinary tract infections
- Ulcerative colitis, rheumatoid arthritis : Sulfasalazine ****
- Nocardia and Chlamydia infections
- Conjunctivitis: Sulfacetamide eye drops
- Burns: Silver sulfadiazine 1% cream
- Toxoplasmosis (Toxoplasmosis is an infection due to the parasite Toxoplasma gondii) : Sulfadiazine + pyrimethamine
Sulfonamides side effects
Sulfonamides side effects
- Hypersensitivity reactions:
- Rashes → may be very severe → Steven-Johnson syndrome
- Clinically characterized by:
- peeling of skin and blisters all over the body
- Fever and respiratory symptoms
- Nephrotoxic
- Due to crystal formation in kidney → white urine
- Hemolysis
- In G-6-PD deficient patients
- Kernicterus (is a rare neurological condition that occurs in some newborns with severe jaundice) in new born:
- (if given in third semester) due to displacement of bilirubin from plasma proteins.
- Displacement of warfarin (Helps to prevent new blood clots from forming) from albumin → bleeding
What is trimethoprim? what is its mechanism of action and side effects cause for resistance?
What is trimethoprim? what is its mechanism of action and side effects
Trimethoprim is a folate synthesis inhibitor. Trimethoprim inhibits dihydrofolate reductase by acting as an anologue of PABA (precursor for bacterial folate synthesis) so that the baterial cannot produce it’s own folate.
- Mechanism of action:
- Trimethoprim (TMP), inhibits dihydrofolate reductase enzyme.
- Adverse Effect:
- Trimethoprim can produce the effects of folate deficiency in humans resulting in development of
- Megaloblastic anemia****
- RBC precursors in bone marrow require folate for DNA synthesis
- Deficiency of folate → nucleus does not mature → remains large → Megaloblasts (abnormal and enlarged RBC precursors
- Effects can be reversed by administration of folinic acid.
- Megaloblastic anemia****
- Trimethoprim can produce the effects of folate deficiency in humans resulting in development of
- resistance
- Resistance develops via mutations in the gene that codes for the dihydrofolate reductase.
What is Cotrimoxazole?
Cotrimoxazole
- A fixed dose combination of sulfamethaxazole (SMX) and trimethoprim (TMP) is called as Cotrimoxazole (=SMX+TMP)
- Causes sequential block of folate metabolism
- Sulfamethaxazole and trimethoprim individually they are bacteriostatic.
- Together they are Bactericidal & Synergistic
Uses of Cotrimoxazole
Uses of Cotrimoxazole (sulfamethaxazole (SMX) + trimethoprim (TMP))
- Drug of choice in****
- Pneumocystis jirovecii (carinii) pneumonia in AIDS patients (prevention and treatment)
- Urinary tract infection (uncomplicated)
- Toxoplasmosis (prevention and treatment)
- Other Uses:
- Respiratory tract infection
- Typhoid fever
- Chancroid
- Nocardiosis
what are Fluoroquinolones? explain its group classification.
what are Fluoroquinolones? explain its group classification.
- Are bactericidal drugs that block bacterial DNA synthesis
- By inhibiting DNA gyrase**** (topoisomerase II)
- Classification:
- 1st group:
- Norfloxacin*→least active
- used on Urinary Tract Infections (Ciprofloxacin too)
- 2nd group
- Ciprofloxacin*, Lomeflaxacin, Ofloxacin*, Levofloxacin*
- Mainly active against gram negative bacteria.
- 3rd group
- Sparfloxacin*, Moxifloxacin Travofloxacin Gatifloxacin
- Active b_oth against gram positive and negatives_
- 1st group:
Fluoroquinolones: Clinical Uses
Fluoroquinolones: Clinical Uses
- Urinary Tract Infections* →Ciprofloxacin/Norfloxacin
- **Typhoid (enteric fever)*. **Typhoid fever is an infection that causes diarrhea and a rash – most commonly due to a type of bacteria called Salmonella typhi
- treat typhoid( enteric fever) with Ciprofloxacin
- Gonorrhoea → Ofloxacin (DOC – ceftriaxone)
- Chancroid (Chancroid is a bacterial infection that is spread only through sexual contact.)
- treat chancroid with Ciprofloxacin (DOC- doxycycline)
- Chlamydia →Only Ofloxacin
- Pseudomonas infections* → Ciprofloxacin is the DOC (only give Piperacillin or cephalosporins in pregnant patients or children or elderly)
what drugs would you use for UTI’s
Ciprofloxain and norfloxacin Fluoroquinolones
Urinary Tract Infections* →Ciprofloxacin/Norfloxacin
What drug would you use for typhoid (enteric fever)
ciprofloxacin Fluroquinolones
Typhoid (enteric fever)* →Ciprofloxacin
Drug of choice for Pseudomonas infections
Ciprofloxacin fluoroquinolones
Pseudomonas infections* → Ciprofloxacin is the DOC (only give Piperacillin or cephalosporins in pregnant patients or children or elderly)
Urinary Tract Infections
Urinary Tract Infections
- Majority are caused by gram negative bacteria
- Most common cause is E. Coli
- Uncomplicated UTI –DOC is Cotrimoxazole*
- Complicated UTI– DOC is Ciprofloxacin*
Adverse effects of Fluoroquinolones
Adverse effects of Fluoroquinolones
- Fluoroquinolones
- should not be given to children and pregnant women.
- Get deposited in cartilage and damage its matrix.
- Danger of ruptured tendons (Arthropathy)***
