Lecture 8 - Med Chem Antibiotics 3 Flashcards

Question

Trimethoprim works by...

Answer 1

inhibition of action of dihydrofolate reducatase Bacterostatic mainly used in prophylaxis and treatment of UTI

Answer 2

subtle but significant architectural difference between the two enzymes

Answer 3

Flagyl, antibiotic + antiprotozoal comes in oral, cream or IV

Answer 4

Nitroimidazole class inhibits nucleic acid synthesis by disrupting the DNA of microbial cells only occurs in anaerobic cells

Answer 5

acts as bactericidal by affecting the synthesis of lipids, NA and Mycelia acid of cell wall of these species

Answer 6

Bio activation of INH 1. INH = prodrug, activated by oxidation via KatG to reactive species capable of acylating enzyme system found exclusively in M.Tuberculosis 2. mycelia acid important part of mycobacterial cell well. inhaler important enzyme 3. activating intermediates from INH interact with NADH bound within active site of inhaled to form acylated NDA which is no longer capable of catalyzing reduction of unsaturated fatty acids which are essential for synthesis of mycloic acids.

Answer 7

loss of catalyst activity is associated with the deletion of catalase gene, katG as well as over expression of of InhA

Answer 8

1. readily absorbed from GI 2. extensively metabolized to inactive metabolites 3. Acetylhydrazine serves as CYP450 substrate resulting in formation of reactive intermediate which capable of acylating liver protein resulting in liver necrosis **

Answer 9

N-acetylisoniazid, formed by action of N-acetyltransferase

Answer 10

Acetylhydrazide

Answer 11

inhibit bacterial DNA-dependent RNA polymerase by strongly binding to B-subunit of enzyme. Inhibition of DDRP leads to blocking of initiation of chain formation in RNA synthesis ** No effect once polymerization has begun ***

Answer 12

Significant benefit over prev investigated rifamcyins in that they're orally active, highly effective, and high clinical efficacy in oral txm of TB

Answer 13

1. suggested that naphthalene ring of rifamycins pi-pi bonds to an aromatic amino acid ring in DDRP protein 2. DDRP metalloenzyme which contains 2 zinc atoms 3. C1/C8 of rifamycin chelate to zinc atom, inc binding to DDRP and O at C21/C23 form strong H bond to DDRP 4. binding to DDRP results in inhibition of RNA synthesis

Answer 14

1. Free OH groups req at C1/C8/C21/C23 + appear to lie in plane 2. Acetylation at C21/C23 = inactive compounds 3. reduction of double bond in ring results in dec activity 4. opening macro ring = inactive compound

Answer 15

1. bioisostere of nicotinamide, possess bactericidal action 2. activity is pH depending w// good in vivo activity at pH 5.5 but nearly inactive at neutral pH*** 3. especially beneficial active against semi dormant intracellular tubercle bacilli that are not affected by other drugs.

Answer 16

1. prodrug, converted into active form Pyrazinoic acid (POA) by bacterial nicotinamidase/pyrazinamidase (PZase)

Answer 17

1. readily absorbed after oral admin, little excreted unchanged 2. major metabolic route consists of hydrolysis by PZase to pyrazinoic acid then oxidized by Xanthine oxidase to 5-hydropyrazinoic acid

Answer 18

1.Bacterostatic for TB + enantiomer is 200-500X moe active than - enantiomer usually given in combo w/ other TB drugs

Answer 19

1. not completely known 2. exerts bacteriostatic activity by inhibition of arabunosyl transferase, an enzyme that polymerizes arbinose into Arabian and then arabinogalactan, a mycobacterial cell wall constituent

Answer 20

involves gene over expression of arabinosyl transferase

Answer 21

1. majority oral admin excreted unchanged, no more than 15% appear as Metabolite A/B 2. both metabolites are devoid of biologic activity

Answer 22

1. Plasma membrane 2. Peptidoglycan layer 3. AG 4. Layer of mycolylates 5. LAM

Answer 23

``` Ethionamide Para-aminosalicyclic acid cycloserine capreomycin kanamycin ``` usually less well tolerated or higher incidence of ADE usually used in case of resistance

Answer 24

1. Bactericidal 2. MOA: similar to INH, prodrug converted to active acylating agent, which inactivates inhaled 3. orally active, but single large dose (>500mg) not well tolerated. SE = GI,CNS, sensitivity

Answer 25

used as 2nd line due to resistance and SE thought to act as antimetabolite interfering with in crop of para-amino benzoic acid into folic acid When co-admin w/ INH found to reduce acetylation of INH, thus increasing plasma lvls of INH

Lecture 8 - Med Chem Antibiotics 3 Flashcards

(49 cards)