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Walsh drugs Flashcards

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1
Q

macrolides structure

A

macrocyclic lactone ring of 14-16 carbons with deoxy sugars attached

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2
Q

macrolide mechanism

A

inhibits protein synthesis via binding to 50S ribosomal RNA which prevents elongation

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3
Q

metronidazole chemistry

A

a synthetic derivative of 5-nitroimidazole

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4
Q

metronidazole mechanism

A

selectively absorbed by anaerobic bacteria and sensitive protozoa in unionized form–> nonenzymatically reduced by reacting with ferredoxin–> results are toxic products that accumulate in cells–> taken up into bacterial DNA–> unstable molecules that are highly reactive–> bactericidal

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5
Q

sulfonamides chemistry

A

structurally related to p-aminobenzoic acid (PABA)

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6
Q

sulfonamides mechanism

A

as structural analogs of PABA, they inhibit dihydropteroate synthase and thus folate production

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7
Q

trimethoprim mechanism

A

inhibits dihydrofolate reductase

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8
Q

fluoroquinolones structure

A

synthetic fluorinated analogs of nalidixic acid

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9
Q

fluoroquinolones mechanism

A

block bacterial DNA synthesis by inhibiting topoisomerase II (DNA gyrase) and IV

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10
Q

nitrofurantoin structure

A

aromatic xenobiotic compound with 2 main pharmacophores: nitro group attached to furan ring at 5 position, hydrazone moiety

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11
Q

nitrofurantoin mechanism

A

undergoes rapid intracellular conversion to highly reactive intermediates by bacterial reductases–> these intermediates react non-specifically with many ribosomal proteins and disrupt the synthesis of proteins, RNA, DNA, and metabolic processes

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12
Q

fosfomycin structure

A

phosphoenolpyruvate analogue, contains a phosphonic group and an epoxide ring

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13
Q

fosfomycin mechanism

A

inhibits cytoplasmic enzyme enolpyruvate transferase (MurA) by covalently binding to the cysteine residue of the active site. blocks the addition of phosphoenolpyruvate–> UDP-N-acetylglucosamine (which is the first step in the formation of UDP-N-acetyluramic acid, the precursor to N-acetylmuramic acid, which is only found in bacterial cell walls). thus, inhibits a very early stage of bacterial cell wall synthesis

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14
Q

macrolides solubility

A

poorly soluble in water but dissolve in organic solvent (so they are dispensed as esters and salts)

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15
Q

macrolides preferred pH

A

enhanced activity at alkaline pH (inactivated in highly acidic environments)

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16
Q

macrolides renal

A

no renal dose adjustments; not removed by dialysis

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17
Q

macrolides distribution

A

distributed widely except CNS and CSF; traverses placenta

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18
Q

macrolides major ADE

A

GI intolerance due to direct motilin agonists/disrupt normal gut flora. also may prolong QT interval

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19
Q

which macrolide has the highest tendency of prolonging QT interval

A

erythromycin

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20
Q

which macrolide has the lowest tendency of prolonging QT interval

A

azithromycin

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21
Q

what side effect can erythromycin produce

A

acute cholestatic hepatitis (fever, jaundice, etc)

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22
Q

metronidazole distribution

A

wide; penetrates well into the CNS and CSF

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23
Q

how is metronidazole metabolized

A

hepatically; may accumulate in hepatic insufficiency

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24
Q

major ADE for metronidazole

A

disulfiram-like reaction due to accumulation of acetaldehyde: avoid alcohol also for 3 days after treatment

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25
3 major groups of sulfonamides
PO absorbable, PO nonabsorbable, topical
26
major groups within PO absorbable sulfonamides
short, intermediate, long acting
27
what classification is sulfamethoxazole
intermediate acting
28
sulfonamides renal
renal dose adjustments at severe reduction in kidney function
29
sulfonamides major ADE
cross allergy?, urinary tract disturbances: crystalluria, hematuria, urinary obstruction. fever, rash, photosensitivity, urticaria, n/v/d, SJS, nephrosis, allergic nephritis, hematopoietic disturbances
30
sulfonamides taken near end of pregnancy
increased risk of kernicterus in newborns (a type of brain damage secondary to high levels of bilirubin)
31
how to treat crystalluria from sulfonamides and why
sodium bicarb--> it alkalizes the urine, helps make it more soluble
32
trimethoprim important PK
it is more lipid soluble than sulfamethoxazole; higher volume of distribution
33
ratio of sulfa to TMP
5:1
34
renal dose adjustment in bactrim?
yes
35
TMP major ADRs
megaloblastic anemia, leukopenia, granulocytopenia. patients with AIDS and pneumocystis pneumonia experience high frequency of fever, rash, leukopenia, diarrhea, elevations of hepatic enzymes, hyperkalemia, hypernatremia
36
fluoroquinolones absorption
impaired by divalent and trivalent cations, including those found in OTC antacids like tums: dose 2 hours before or 4 hours after any products containing these cations
37
fluoroquinolones major ADE
GI events including antibiotic-associated colitis. QT prolongation. may damage growing cartilage and cause arthropathy: not rec. for <18 years. avoid in pregnancy. Peripheral neuropathy/CNS effects (concern for elders)
38
nitrofurantoin important PK
doesn't work systemically, is a urinary antiseptic
39
nitrofurantoin major ADR
anorexia, n/v, neuropathies, hemolytic anemia in patients with glucose 6 phosphate deficiency. hypersensitivity
40
Nitrofurantoin antagonizes the action of ____
nalidixic acid
41
fosfomycin major ADE
hematuria and dysuria, counsel patients to drink plenty of water
42
how does food impact clarithromycin absorption
ER form: increases. IR form: no effect
43
how does food impact azithromycin and erythromycin absorption
decreases
44
what is different about the chemistry of clarithromycin
the addition of a methyl group: improves acid stability and oral absorption.
45
how does clarithromycin compare to erythromycin in terms of antibacterial activity
it is more active against mycobacterium avium
46
what is different about the PK of clarithromycin
longer half life so twice daily dosing
47
dose adjustments for clarithromycin
reduce at CrCl< 30 ml/min
48
advantages of clarithromycin over erythromycin
lower incidence of GI intolerance, less frequent dosing, better tissue penetration
49
what is different about the chemistry of azithromycin
addition of a methylated nitrogen to the lactone ring
50
azithromycin is highly active against
chlamydia species
51
what is different about azithromycin PK
longest half life of all agents: once daily dosing and shortening duration of therapy
52
azithromycin with meals
1 hour before or 2 hours after
53
when is nitrofurantoin contraindicated
CrCL <60 mL/min
54
what is the difference between macrobid and macrodantin
macrobid contains 25% macrocrystal and 75% monohydrate. macrodantin contains only macrocrystal
55
erythromycin inhibits ____
CYP3A4, can increase concentrations of drugs. clarithromycin does this less, and azithromycin does not participate at all.
56
erythromycin increases serum concentration of ____
PO digoxin by increasing bioavailability
57
how is macrobid taken
bid
58
how is macrodantin taken
qid
59
which is the least active fluoroquinolone for gram + and -
norfloxacin
60
which fluoroquinolones have excellent gram - and good gram +
ciprofloxacin, levofloxacin, ofloxacin
61
which fluoroquinolones have improved activity against gram +
gemifloxacin and moxifloxacin

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