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Flashcards in Antibiotics (Nucleic Acid Synthesis Inhibitors) Deck (16):
1

ANTI-METABOLITES (ANTIFOLATE DRUGS -- Sulfonamides)
- weakly acidic compounds that have a common chemical nucleus resembling ______________
- solubility may be decreased in acidic urine
- Combination of three separate sulfonamides (triple sulfa) to reduce the likelihood that any one drug will precipitate.
Classification:
- short-acting: ...
- intermediate-acting: (3) ___________ (MNEMONIC: MDP)
- long-acting: (1)

ANTI-METABOLITES (ANTIFOLATE DRUGS -- Sulfonamides)
- weakly acidic compounds that have a common chemical nucleus resembling PABA (para-aminobenzoic acid)
- solubility may be decreased in acidic urine
- Combination of three separate sulfonamides (triple sulfa) to reduce the likelihood that any one drug will precipitate.
Classification:
- short-acting: ...
- intermediate-acting: sulfamethoxazole (SMX), sulfadiazine, sulfapyridine (MNEMONIC: MDP)
- long-acting: sulfadoxine (suldadoooooxine loooooooong-acting)

2

ANTI-METABOLITES (ANTIFOLATE DRUGS -- Trimethoprim)
- structurally similar to ____________
- weak ________ that is trapped in acidic environments
- reaches high concentrations in prostatic and vaginal fluids

ANTI-METABOLITES (ANTIFOLATE DRUGS -- Trimethoprim)
- structurally similar to folic acid
- weak base that is trapped in acidic environments
- reaches high concentrations in prostatic and vaginal fluids

3

ANTIFOLATES (Mechanism of Action)
Sulfonamides
- bacteriostatic inhibitors of folic acid synthesis
- competitive inhibitors of ________________
- selective toxicity of sulfonamides results from the inability of mammalian cells to synthesize folic acid (must use preformed folic acid that is present in the diet)
Trimethoprim (intermediate-acting)
- selective inhibitor of bacterial _____________________ (4-5x more sensitive to inhibition by trimethoprim)
Trimethoprim-Sulfamethoxazole
- when two drugs are used in combination, antimicrobial synergy results from the sequential blockade of folate synthesis
- drug combination is bactericidal

ANTIFOLATES (Mechanism of Action)
Sulfonamides
- bacteriostatic inhibitors of folic acid synthesis
- competitive inhibitors of dihydropteroate synthase (SS - sulfonamides synthase)
- selective toxicity of sulfonamides results from the inability of mammalian cells to synthesize folic acid (must use preformed folic acid that is present in the diet)
Trimethoprim (intermediate-acting)
- selective inhibitor of bacterial dihydrofolate reductase (bacterial dihydrofolate reductase is 4-5x more sensitive to inhibition by trimethoprim) (trimethopRim - Reductase)
Trimethoprim-Sulfamethoxazole
- when two drugs are used in combination, antimicrobial synergy results from the sequential blockade of folate synthesis
- drug combination is bactericidal

4

RESISTANCE TO ANTI-FOLATE DRUGS
Plasmid-mediated and results from:
- decreased intracellular accumulation of the drugs
- increased production of _______ by bacteria
- decrease in the sensitivity of dihydropteroate synthase to sulfonamides

RESISTANCE TO ANTI-FOLATE DRUGS
Plasmid-mediated and results from:
- decreased intracellular accumulation of the drugs
- increased production of PABA by bacteria
- decrease in the sensitivity of dihydropteroate synthase to sulfonamides

5

__________________
Drug of choice for burn wounds
SE: kernicterus, acute hemolysis in ______________, hypersensitivity (assume cross-reactivity to hypersensitivity, SJS/TEN), GI upset, nephrotoxicity (crystalluria, hematuria),
Displaces protein-binding of bilirubin and drugs (warfarin, methotrexate)

SILVER SULFADIAZINE
Drug of choice for burn wounds
SE: kernicterus, acute hemolysis in G6PD deficiency, hypersensitivity (assume cross-reactivity to hypersensitivity, SJS/TEN), GI upset, nephrotoxicity (crystalluria, hematuria),
Displaces protein-binding of bilirubin and drugs (warfarin, methotrexate)

6

Cotrimoxazole
- for UTI, respiratory infections, sinus infections, P. jiroveci pneumonia, toxoplasmosis, nocardiosis, typhoid fever, shigellosis, cholera (back-up)
SE: kernicterus, acute hemolysis in G6PD deficiency, hypersensitivity (assume cross-reactivity to hypersensitivity, SJS/TEN), GI upset, nephrotoxicity (crystalluria, hematuria),
Displaces protein-binding of bilirubin and drugs (warfarin, methotrexate)

Cotrimoxazole
- for UTI, respiratory infections, sinus infections, P. jiroveci pneumonia, toxoplasmosis, nocardiosis, typhoid fever, shigellosis, cholera (back-up)
SE: kernicterus, acute hemolysis in G6PD deficiency, hypersensitivity (assume cross-reactivity to hypersensitivity, SJS/TEN), GI upset, nephrotoxicity (crystalluria, hematuria),
Displaces protein-binding of bilirubin and drugs (warfarin, methotrexate)

7

Kernicterus
- bilirubin deposits in ______________ and ______________
- clinical presentation: hypo/hypertonia, lethargy, high-pitched cry, opisthotonos

Kernicterus
- bilirubin deposits in subcortical nuclei and basal ganglia
- clinical presentation: hypo/hypertonia, lethargy, high-pitched cry, opisthotonos

8

ANTIMETABOLITES (Quinolones)
- interfere with bacterial DNA synthesis by inhibiting:
--- topoisomerase ___ (DNA gyrase; blocks relaxation of supercoiled DNA) in gram (__) organisms
--- topoisomerase ___ (interferes with the separation of replicated chromosomal DNA during cell division) in gram (__) organisms
- usually bacteri_______ against susceptible organisms
- exhibit _______________ effect

ANTIMETABOLITES (Quinolones)
- interfere with bacterial DNA synthesis by inhibiting:
--- topoisomerase II (DNA gyrase; blocks relaxation of supercoiled DNA) in gram (-) organisms
--- topoisomerase IV (interferes with the separation of replicated chromosomal DNA during cell division) in gram (+) organisms
- usually bactericidal against susceptible organisms
- exhibit postantibiotic effect

9

RESISTANCE to FluoroQUINOLONES
- decreased intracellular accumulation of the drug via the production of ________ pumps
- changes in ________ structure
- changes in the sensitivity of target enzymes via point mutations in the antibiotic binding regions

RESISTANCE to FLUOROQUINOLONES
- decreased intracellular accumulation of the drug via the production of efflux pumps
- changes in porin structure
- changes in the sensitivity of target enzymes via point mutations in the antibiotic binding regions

10

Classification of FluoroQUINOLONES (across generations, increasing anti-Gram (__) activity)
1st Generation (Gram-negative; ____ infections)
- nalidixic acid, cinoxacin, rosoxacin, oxolinic acid
2nd Generation (gonococci, gram-positive cocci, mycoplasma)
- ciprofloxacin, ofloxacin, norfloxacin, lomefloxacin, enoxacin
3rd Generation (streptococci, enterococci )
- levofloxacin, gemifloxacin, moxifloxacin, sparfloxacin, grepafloxacin, gatifloxacin
4th Generation (broad-spectrum, including anaerobes)
- trovafloxacin, alatrofloxacin

Classification of FluoroQUINOLONES (across generations, increasing anti-Gram (+) activity)
1st Generation (Gram-negative; UTI infections)
- nalidixic acid, cinoxacin, rosoxacin, oxolinic acid
2nd Generation (gonococci, gram-positive cocci, mycoplasma)
- ciprofloxacin, ofloxacin, norfloxacin, lomefloxacin, enoxacin
3rd Generation (streptococci, enterococci )
- levofloxacin, gemifloxacin, moxifloxacin, sparfloxacin, grepafloxacin, gatifloxacin
4th Generation (broad-spectrum, including anaerobes)
- trovafloxacin, alatrofloxacin

11

Generation of ciprofloxacin, ofloxacin

2nd gen FQ

12

Generation of levofloxacin

3rd gen FQ

13

_______________
- 2nd gen FQ
- for UTI, GIT infections, atypical pneumonia, tuberculosis (2nd line)
- SE: ___________ and __________ rupture, GI distress, juvenile ________________ in children given this drug early in life
- Avoid use in young children and pregnant women
- Enhance toxicity of methylxanthines (_______________)

Ciprofloxacin
- 2nd gen FQ
- for UTI, GIT infections, atypical pneumonia, tuberculosis (2nd line)
- SE: tendinitis and tendon rupture, GI distress, juvenile osteoarthritis in children given this drug early in life
- Avoid use in young children and pregnant women
- Enhance toxicity of methylxanthines (theophylline)

14

______________
- 3rd gen FQ
- for lung infections caused by gram-(___), ___________ pneumonia (Chlamydia, Mycoplasma)
- SE: tendinitis, QTc prolongation, GI distress, CNS effects
- Avoid use in young children and pregnant women
- Enhance toxicity of methylxanthines (_______________)

Levofloxacin
- 3rd gen FQ
- for lung infections caused by gram-(+), atypical pneumonia (Chlamydia, Mycoplasma)
- SE: tendinitis, QTc prolongation, GI distress, CNS effects
- Avoid use in young children and pregnant women
- Enhance toxicity of methylxanthines (theophylline)
NOTE: GREPAFLOXACIN has been withdrawn due to severe cardiotoxicity (arrhythmias)

15

Miscellaneous Nucleic Acid Synthesis Inhibitors

___________________
- MOA: reactive reduction by _______________, forming free radicals that disrupt ETC. Bacteri________.
- for anaerobic or mixed intra-abdominal infections, vaginitis (Trichomonas, Gardnerella), pseudomembranous colitis, brain abscess, protozoal infections
- SE: GI irritation, metallic taste, headache, dark urine, ___________ reaction

Miscellaneous Nucleic Acid Synthesis Inhibitors

Metronidazole
- MOA: reactive reduction by ferredoxin, forming free radicals that disrupt ETC. Bactericidal.
- for anaerobic or mixed intra-abdominal infections, vaginitis (Trichomonas, Gardnerella), pseudomembranous colitis, brain abscess, protozoal infections
- SE: GI irritation, metallic taste, headache, dark urine, disulfiram reaction

16

Miscellaneous Nucleic Acid Synthesis Inhibitors

________________
- forms multiple reactive intermediates when acted upon by bacterial nitrofuran ___________. Bacteri_______.
- for UTI (except __________ and ___________)
- SE: skin rashes, pulmonary infiltrates, GI irritation

Miscellaneous Nucleic Acid Synthesis Inhibitors

Nitrofurantoin
- forms multiple reactive intermediates when acted upon by bacterial nitrofuran reductase. Bactericidal.
- for UTI (except Proteus and Pseudomomas)
- SE: skin rashes, pulmonary infiltrates, GI irritation

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