Term
1st generation quinolone
DOESN'T HAVE F IN POSITION 6 |
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Definition
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Term
1st generation quinolone
DOESN'T HAVE F IN POSITION 6 |
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Definition
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Term
1st generation quinolone
DOESN'T HAVE F IN POSITION 6 |
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Definition
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Term
2nd generation quinolone
F AT POSITION 6
NO SUBSTITUENT AT POSITION 8
PIPERAZINE RING |
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Definition
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Term
2nd generation quinolone
F AT POSITION 6
NO SUBSTITUENT AT POSITION 8
PIPERAZINE RING |
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Definition
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Term
2nd generation quinolone
F AT POSITION 6
EXCEPTION TO THE RULE: substituent at position 8
ONLY TRI-CYCLIC QUINOLONE
PIPERAZINE RING |
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Definition
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Term
2nd generation quinolone
F AT POSITION 6
NO SUBSTITUTION AT POSITION 8
PIPERAZINE RING
EXCEPTION TO THE RULE: N at position 8 |
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Definition
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Term
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Definition
| numbering of the fluoroquinolone ring |
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Term
3rd generation quinolone
F AT POSITION 6
SUBSTITUENT AT POSITION 8 |
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Definition
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Term
3rd generation quinolone
F AT POSITION 6
SUBSTITUENT AT POSITION 8 |
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Definition
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Term
4th generation quinolone
F AT POSITION 6
EXTRA N IN THE NUCLEUS
NO PIPERAZINE RING |
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Definition
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Term
4th generation quinolone
F AT POSITION 6
EXTRA N IN THE NUCLEUS
NO PIPERAZINE RING |
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Definition
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Term
reversibly inhibit DNA replication through the interaction with Type II topoisomerases: DNA gyrase and Topo IV
quinolone interact with each other to form a tetramer and these will interact with DNA gyrase
[image]
this drug-drug stacking maximizes the interaction of the carbonyl groups with the enzyme and maximizes the interactions of position 7
interaction with the enzyme:
[image]
another propsed MOA:
[image]
no drug-drug interaction, only one drug molecule. Mg is helping the interaction of the drug with the enzyme at the keto group and carboxyl group |
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Definition
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Term
topoisomerases are responsible for unlinking the parental strands during DNA replication
they transport another segment of DNA through the cleaved DNA segment
DNA gyrase remove the positive supercoils: alters the degree of DNA twisting, releases tension/stress on the molecule
Topo IV decatenates and precatenates behind the replication fork
selectivity of quinolones = our DNA gyrase is different than bacterial DNA gyrase
[image]
DNA gyrases form tetramers |
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Definition
| actions of topoisomerases |
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Term
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Definition
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Term
mutations in genes encoding for Topo II and Topo IV
drug efflux
multi-drug resistance: resistant to several classes of drugs, multiple efflux pumps that expel quinolones and other antibiotics as well
decreased drug uptake only in Gram - by porin change
resistance is common in hospital acquired infections |
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Definition
| bacterial resistance to quinolones |
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Term
BROAD SPECTRUM
bactericidal agents
intracellular bacteria inhibited |
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Definition
| antimicrobial activity of quinolones |
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Term
substituent at position 8
an F is responsible for the INCREASE in photosensitivity and OCH3 is responsible for the REDUCTION in photosensitivity (but it is still present)
ALL QUINOLONES ARE PHOTOTOXIC
[image]
high incidence of photosensitivity
[image]
reduces photosensitivity |
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Definition
| what may be the cause of photosensitivity of some quinolones? |
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Term
well absorbed, they differ with each other in their bioavailabilities
they penetrate well into fluids and tissues except CNS (only very lipophilic drugs can penetrate the BBB and quinolones are charged)
they are eliminated by the kidneys (also hepatic elimination)
metabolized by CYP450
metabolites and unchanged drug found in urine, bile, feces
tubular secretion and glomerular filtration
probenacid blocks tubular secretion
metabolites have significantly less antibacterial activity |
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Definition
| pharmacokinetics of quinolones |
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Term
GI upset
neurotoxic effects: seizures may be antagonized by NMDA antagonists, headache, dizziness, psychotic reactions, hallucinations, depression, convulsions, start a few days after and stop with medication
skin reactions: hypersensitivity (erythmema, pruritus, urticaria, rash), phototoxicity (exaggerated sunburn due to fluoroquinolones and its metabolites absorbing light to produce oxygen radicals that cause damage to the lipids of cell membranes), all quinolones are phototoxic
arthropathy: mechanism unknown, Mg deficiency, production of reactive oxygen, contraindicated for children, pregnant and nursing women
hypotension and tachycardia |
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Definition
| adverse effects of quinolones |
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Term
forms chelates with metal ions: reduces absorption, contraindicated with antacids, multivitamins, calcium supplements or dairy products
[image]
xanthine derivatives: inhibition of CYP450 system decreases clearance of theophyoline, N/V, convulsion, they interfere with caffeine metabolism, sleep disturbances and upper GI symptoms may result
NSAIDs: synergistic inhibition of central nervous system GABA receptors, neuroexcitatory phenomena may occur, dose dependent, convulsions with enoxacin and fenbufen |
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Definition
| drug interactions of quinolones |
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