L31- Nucleic Acid Synthesis Inhibitors Flashcards
list the nucleic acid synthesis inhibitors
- fluoroquinolones
- sulfonamides
- trimethoprims
list the fluoroquinolones (by generation)
2nd: Ciprofloxacin
3rd: Levoflozacin
4th: Gemifloxacin, Moxifloxacin
Fluoroquinolones:
- (narrow/broad) spectrum
- bacterio-(static/cidal)
- earlier generations effective against (3) bacteria
- later generations are more effective against (4) in addition to (3)
1- broad
2- bacteriocidal
3- Gram- bacteria
4- Gram+ bacteria (and anaerobes); even broader spectrum
Fluoroquinolone MOA:
- (1) entry
- binds to (2) to interfere with (3)
1- porins
2- topoisomerase II (DNA gyrase) and IV
3- bacterial DNA replication
Fluoroquinolones:
- (1) mechanism of resistance
- effects (2) generation most
- (presence/absence) of cross-resistance
1- chromosomal mutations:
- encoding subunits of topo. II/IV
- regulation of efflux pumps
2- 2nd (Ciprofloxacin)
3- present
2nd generation Fluoroquinolones:
- (1) agents
- effective against (2) bacteria, especially when paired with (3)
- drug of choice for (4)
- treats (5) in CF patients
- for (6) prophylaxis
1- Ciprofloxacin
2- Gram- mostly, some Gram+ / atypicals
3- β-lactams (allows entry into bacteria)
4- Traveler’s diarrhea
5- P. aerugosa
6- meningitis
3rd generation Fluoroquinolones:
- (1) agents
- effective against (2) bacteria, especially (3)
- (4) is the main clinical use
- (5) are the other uses
1- levofloxacin
2- Gram- (improved), expanded Gram+/atypical activity
3- S. pneumoniae
4- CA-pneumonia
5- prostatitis, STD (not syphilis), skin infections, sinusitis, bronchitis, Tb
4th generation Fluoroquinolones:
- (1) agents
- effective against (2) bacteria
- (3) is the main clinical use
1- gemifloxacin, moxifloxacin
2- Gram- + even more expanded Gram+ / anaerobic activity
3- CA-pneumonia
discuss the criteria or guidelines for use of Respiratory Fluoroquinolones (indicate agents)
Levofloxacin (3rd), Gemifloxacin (4th), Moxifloxacin (4th)- for most common causes of pneumonia in the following situations:
- 1st line agents have failed
- other co-morbidities
- in-patient Tx
Fluoroquinolone Pharmacokinetics:
- (1) route of administration- (2) may disrupt absorption (similar to what other antibiotic)
- (3) discuss distribution
- dosage may be adjusted in (4) Pts
1- oral, good F
2- divalent cations (Ca, Fe, Zn)- like with tetracyclines
3- all tissues including bones- like tetracyclines
4- renal dysfunction (not moxifloxacin)
______ is the black box warning for Fluoroquinolones
CT issues (tendon ruptures, Achilles mostly) —> avoid in:
- Pregnancy, Lactation
- Children <18y/o (unless benefits outweigh risks)
Fluoroquinolone AEs:
- (1) are minor and common
- (2) are more serious
- (3) may occur post-therapy
1- GI distress, rash, photosensitivity + CNS (?)
2- peripheral neuropathy; QT prolongation (except Cipro)
3- Superinfection: C. diff, C. albicans, Strep. spp.
list the Sulfonamides
- sulfamethoxazole
- sulfadiazine
- sulfisoxazole
Sulfonamides:
-(1) structure which is used to inhibit (2) process in bacteria, affecting (3) enzyme
-effective against (4) bacteria
1- PABA (p-aminobenzoic acid) analog
2- folic acid synthesis
3- competitive inhibition of Dihydropteroate synthase (PABA –> DHF)
4- Gram+, Gram- bacteria
describe the mechanisms of resistance for Sulfonamides
Plasmids or Mutations:
- altered dihydropteroate synthase
- enhanced PABA production
- dec permeability
- dec intracellular drug accumulation
discuss the common clinical uses for Sulfonamides
In combination due to high resistance:
- Topical agent for ocular or burn infections
- Oral agent for simple UTIs (+ trimethoprim)
Sulfonamide AEs:
- (1) minor and common AEs
- (2) is the major concern, explain mechanism
- (3) and (4) reactions are also concerns before prescribing
1- GI distress, fever, rash, photosensitivity
2- Crystalluria — nephrotoxicity via accumulation in renal failure Pts
3- hypersensitivity (allergy)
4- G6PD def. Pts => hemolysis
Sulfonaminde contraindications
- <2mo old (neonates) –> may cause Kernicterus
- many drug interactions —> displaces drugs from albumin binding
Trimethoprim:
- (1) structure allows it to be an inhibitor of (2) enzyme to inhibit (3) synthesis)
- bacterio-(static/cidal) activity, effective against (5) bacteria
1- folic acid analog
2- dihydrofolate reductase (DHF –> THF)
3- purine, pyrimidine, amino acid synthesis
4- bacteriostatic
5- Gram+/- bacteria
describe the distribution, elimination of Trimethoprims and how it related to the clinical uses for Trimethoprim
- 80-90% excreted via kidney
- high concentrations reach prostatic and vaginal fluid
Uses:
- UTIs
- bacterial prostatitis
- bacterial vaginitis
Trimethoprim AEs:
- (1) are the common AEs
- (2) is the main contraindication
1- rash, pruritus
2- pregnancy –> antifolate effects
Cotrimoxazole = (1):
- bacterio-(static/cidal)
- (3) basic MOA
1- trimethoprim + sulfamethoxazole
2- bacteriocidal
3- inhibits sequential steps of THF synthesis and then nucleic acid synthesis
Cotrimoxazole:
- drug of choice for (1)
- commonly used in (2) Pts for (3) infections
- (4) are other common infections
(trimethoprim + sulfamethoxazole)
1- uncomplicated UTIs
2- immuno-compromised / opportunistic infections:
- PCP (drug of choice)
- Nocardiosis (drug of choice)
- Toxoplasmosis (alternative)
3- URI, ear / sinus infections
Cotrimoxazole Pharmaokinetics:
- (1) route of administration
- (2) discuss distribution
1- oral (sometimes IV)
2- well distributed, including CSF
Cotrimoxazole AEs:
- (1) are common
- (2) is the major concern
- (3) inc risk of AEs (what Pts)
- (4) contraindications
1- dermatological or GI issues
2- hemolytic anemia (especially G6PD)
3- AIDS
4- pregnancy / 1st trimester due to folate analog
