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Common Mechanisms Block 2 > Pharmacology -- Antimicrobial Agents > Flashcards

Pharmacology -- Antimicrobial Agents Flashcards

(72 cards)

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1
Q

What are the four major mechanisms of antibacterial resistance?

A

Alterations in receptor target, Decreased entry or efflux of drug, alterations in metabolic pathways, or drug inactivation

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2
Q

Penicillins are bactericidal or bacteriostatic? Bind ___ to crosslink NAM/NAG

A

Bactericidal; Transpeptidase

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3
Q

Penicillin-Binding Proteins are ____, _____, and ____

A

Transpeptidase, autolysins, and carboxypeptidases + endopeptidases

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4
Q

Resistance to Penicillins occurs in what 4 ways?

A

Modification of PBPs, Active pumping/efflux, cleavage of B-lactam by B-lactamases, and altered porins (prevent drugs from reaching target)

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5
Q

Why would the action of penicillin be antagonized if given alongside a bacteriostatic drug like tetracycline?

A

Need bacteria to actively grow in order to effectively inhibit cell wall synthesis

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6
Q

If penicillins are given in combo with an oral contraceptive, what will occur?

A

Less efficacy of oral contraceptive since antibiotics disrupt normal (gut) flora

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7
Q

What are the four classes of penicillins?

A

Natural penicillins, aminopenicillins, penicillinase-resistant penicillins, and antipseudomonal penicillins

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8
Q

What are the two natural penicillins? They are used to treat gram _____ (positive or negative).

A

Penicillin G, Penicillin V; positive

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9
Q

What are the two possible routes of administration of penicillin G? Why?

A

Intravenous or intramuscular; destroyed in acidic environments like GI tract

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10
Q

What is the route of administration of penicillin V? Timing?

A

Oral; 1 hour before meal or 2-3 hour after

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11
Q

What are the two aminopenicillins? They are primarily used to treat gram _____ (positive or negative)

A

Ampicillin, amoxicillin; negative

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12
Q

Aminopenicillins are administered ______ (enterally, parenterally, or both).

A

Both

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13
Q

What are the four penicillinase-resistant penicillins? They tend to be used to treat gram _____ (positive or negative).

A

Dicloxacillin, methicillin, oxacillin, and nafcillin; positive

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14
Q

Of the four penicillinase-resistant penicillins, which ones are given parenterally?

A

Methicillin, oxacillin, and nafcillin

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15
Q

Of the four penicillinase-resistant penicillins, which is given orally?

A

Dicloxacillin

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16
Q

What are the four antipseudomonal penicillins? They tend to be used to treat gram _____ (positive or negative).

A

Carbenicillin, Ticarcillin, Mezlocillin, and Piperacillin; negative

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17
Q

Antipseudomonal penicillins typically are administered _____ (enterally, parenterally, or both).

A

Parenterally

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18
Q

Which of the antipseudomonal penicillins can be administered orally? Its enteral utility is limited to what type of infections (location)?

A

Carbenicillin; Urinary tract/prostatic infections

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19
Q

What are the three B-lactamase inhibitors? Are they irreversible or reversible? What is their clinical use?

A

Clavulanic acid, sublactam, tazobactam; irreversible; not antimicrobial but provide expanded coverage to B-lactamase-producing organisms when combined w/ penicillin

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20
Q

Cephalosporins structurally resemble _____. What two ways do they differ from this other class of drugs?

A

Penicillins; differ from natural penicillins in their stability under pH change and ability to be taken with or without food

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21
Q

What are the adverse effects of cephalosporins?

A

Penicillin-allergic patients, GI irritation, Parenteral irritation, Renal toxicity, Disulfiram-like Reactions and hypothrombinemia, seizures, secondary infections

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22
Q

What are the carbapenems? Are they bactericidal or bacteriostatic? By what mechanism? Resistant or susceptible to B-lactamases?

A

Imipenem/cilastatin, doripenem, ertapenem, and meropenem; bactericidal; inhibit cell wall synth.; Resistant

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23
Q

What two drugs can interfere with cell wall synthesis by blocking polymerization and cross-linking of peptidoglycan by binding to D-Ala-D-Ala portion of cell walls? Which one also has other mechanisms involving disruption of membrane potential and changes in cell permeability?

A

Telavancin, Vancomycin; Telavancin

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24
Q

Which antimicrobial inhibits cell wall synthesis in both gram positive and gram negative organisms? Usually reserved for treating?

A

Cycloserine; M. tuberculosis when infection resistant to first-line anti-tubercular drugs

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25
Which antimicrobial acts as a cationic detergent that disrupts lipoproteins in bacterial cell wall? It is _____ (bactericidal or bacteriostatic) against nearly all Gram _____ (positive or negative, cocci or bacilli) with exception of Proteus.
Polymyxin B; Bactericidal; Gram negative bacilli
26
What are the 7 aminoglycosides?
Amikacin, gentamicin, kanamycin, netilmycin, streptomycin, tobramycin, and neomycin
27
Aminoglycosides bind to ____ of the ribosome interfere with protein synthesis in what 3 ways? Reliably used only in treating gram ____ (positive or negative) infections.
Formation of initiation complex, misread mRNA/miscoding of AA, and cause ribosome to separate from mRNA; negative
28
Aminoglycosides are usually given _____ (enterally, parenterally, or both). Their toxic effects are _____ and _____. They exhibit what is known as the _____ effect, where they continue to have effects after the antibiotic has been eliminated.
Parenterally; Nephrotoxicity, ototoxicity; Postantibiotic
29
_____ (anaerobes or aerobes) acquire resistance to aminoglycosides by alteration in receptor proteins on ribosomes. Others can enzymatically or posttranslationally alter through _____, _____, or _____.
anaerobe; phosphorylation, acetylation, or adenylation
30
What are the six tetracyclines?
Tetracycline, minocycline, doxycycline, demeclocycline, oxytetracycline, and tigecycline
31
Tetracyclines inhibit protein synthesis through _____ (reversible or irreversible) binding to ____ (30S or 50S) ribosomal subunit, thus making them _____ (bactericidal or bacteriostatic).
Reversible; 30S; Bacteriostatic
32
Glycyclines are antibiotics derived from tetracycline designed to overcome what two common mechanisms of resistance?
Resistance mediated by efflux pumps and ribosomal protection
33
Tigecycline is most closely related to what other tetracycline?
Minocycline
34
Tetracyclines penetrate gram negative bacteria by _____ (passive diffusion or active transport), and they penetrate gram positive bacteria by _____ (passive diffusion or active transport).
Passive diffusion; active transport
35
Gastric absorption of tetracyclines is inhibited by chelation to ____ or ____. Tetracyclines are best administered on a _____ (full or empty) stomach.
divalent cations, bile acid resins; empty
36
Which tetracycline is the safest option for patients with renal dysfunction? Why?
Doxycycline; because it is metabolized hepatically and excreted via the feces
37
Gram positive bacteria acquire resistance to tetracyclines via _____, while gram negative organisms acquire resistance to tetracyclines via _____. Which tetracycline is not affected by resistance mechanisms?
Efflux Pumps; Outer membrane proteins; Tigecyline
38
Chloramphenicol is a _____ (bactericidal or bacteriostatic) agent. It binds to the ____ (30S or 50S) ribosomal subunit and blocks linkage of incoming AA to growing peptide chain by interfering with _____.
Bacteriostatic; 50S; Peptidyl transferase
39
Chloramphenicol is metabolized via _____. Accumulation due to inefficiency in this process in both adults and children can result in what is known as _____
Glucuronidation; Gray Baby/Gray adult
40
The common lincosamide drug is known as _____, and it acts to interrupt protein synthesis by binding to the ___ (30S or 50S) ribosomal subunit and preventing the _____.
Clindamycin; 50S; translocation of incoming AAs from A site to P site
41
What are the 6 macrolides we need to know?
Erythromycin base, erythromycin estolate, erythromycin stearate, erythromycin ethylsuccinate, clarithromycin, and azithromycin
42
Macrolides act to inhibit protein synthesis by binding the same site on prokaryotic ____ (30S or 50S) ribosomal subunits as _____ and ____ bind, thus preventing _____.
50S; clindamycin, chloramphenicol; translocation of AA from A to P site
43
How might macrolides develop cross-resistance?
Share same binding site as clindamycin and chloramphenicol and may interfere with one another
44
What is unique about the toxic effects of macrolides on bacteria?
Can be both bacteriostatic or bactericidal depending on drug concentration
45
By what 3 mechanisms does resistance to macrolides occur?
Permeability alteration, methylation of bacterial 50S ribosomal subunit, development of mechanisms to enzymatically destroy the drug
46
Which macrolides are most associated with GI distress? Which one may cause cholestatic hepatitis? What are two other important adverse effects?
Erythromycins; Estolate salt; Inhibition of CYP3A4; QT prolongation
47
What other macrolide other than the erythromycins can cause QT prolongation?
Clarithromycin
48
Which macrolide does not cause QT prolongation or inhibition of CYP3A4
Azithromycin
49
The ketolide drug we need to know is ____. It acts to inhibit the ___ (30S or 50S) ribosomal subunit. What is unique about its action? Is it a good or poor substrate for efflux pumps?
Telithromycin; 50S; it binds to two separate domains; Poor
50
Which inhibitor of antimicrobial protein synthesis is available as a topical ointment and is structurally considered to be a pleuromutilin antibiotic? It inhibits protein synthesis by interfering with ____ by binding to a site on the ___ (30S or 50S) ribosomal subunit. This binding allows what three results?
Retapamulin; Peptidyl transferase; 50S; Prevention of formation of active subunit, inhibition of peptidyl transferase, and blockage of P-site interactions
51
Which antimicrobial is available as a topical cream and ointment, results in no cross-resistance, and inhibits the tRNA that transports isoleucine?
Mupirocin
52
Which antimicrobial protein synthesis inhibitor interferes with synthesis by binding to a unique RNA site on the 50S subunit, thus preventing formation of functional 70S?
Linezolid
53
Streptogramins are a combination of what two compounds? They ____ (reversibly or irreversibly) block ribosomes and inhibit ____ (early or late) phases of protein synthesis.
Quinupristin, dalfopristin; Irreversibly; late
54
What are the 6 sulfonamides we need to know?
Sulfadiazine, silver sulfadiazine, sulfisoxazole, sulfamethoxazole, sulfacetamide, and sulfasalazine
55
Sulfonamides act to compete with _____ at the first step of the folic acid synthesis pathway and inhibit _____.
Para-aminobenzoic acid (PABA); Dihydropteroate Synthetase
56
What is important about the pharmacokinetics of sulfonamides? Metabolized hepatically by _____, _____, and/or _____. Genetically slow metabolizers are at increased risk for what? Which biotransformation is likely responsible for many of the adverse effects. After biotransformation, how are the sulfonamides excreted?
Highly bound protein that can have DDI with warfarin, NSAIDs, and sulfonylureas; acetylation, oxidation, and/or glucuronidation; acetylators at inc. risk for hypersensitivity reaction; oxidation; Renally
57
What drug inhibits folic acid synthesis by inhibiting dihydrofolate reductase? What mechanisms do bacteria use to develop resistance to this drug?
Trimethoprim; Reduced uptake, alteration or mutation of dihydrofolate reductase, or overproduction of dihydrofolate reductase
58
What are the 8 fluoroquinolones that we need to know?
Besifloxacin, norfloxacin, gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, and ofloxacin
59
Fluorquinolones are _____ (bactericidal or bacteriostatic) and interfere with ____ by inhibiting one of two enzymes: ____ or ____. Which fluoroquinolone is effective at inhibiting both?
Bactericidal; DNA synthesis; DNA gyrase; Topoisomerase IV; Gemifloxacin
60
____ or ____ may impair absorption of fluoroquinolones. ____ also interferes with absorption. Distributes to _____.
Food, cations; Sucralfate; Nearly all body compartments
61
The lipopeptide drug we need to know is ____. Acts by binding to bacterial membrane and causing what? Does it develop cross-resistance? It is primarily eliminated ____.
Daptomycin; rapid depolarization; No; unchanged in urine
62
Metronidazole is selectively absorbed by what microbes: ____ and ____? It is _____ (enzymatically or nonenzymatically) reduced by reacting with _____, thus causing what? Does it distribute to CNS?
anaeobic bacteria, sensitive protozoa; nonenzymatically; reduced ferredoxing; production of metabolites toxic to anaerobic cells; Yes
63
Which antimicrobial interferes with pyruvate/ferredoxin oxidoreductase enzyme-dependent electron transfer essential for anaerobic metabolism?
Nitazoxanide
64
Which antimicrobial is believed to cause cytotoxicity by damaging DNA and further inhibiting synthesis?
Tinidazole
65
Which antimicrobial is an inhibitor of RNA synthesis by binding to bacterial DNA-dependent RNA polymerase? What drug is it related to? How does it differ from that drug?
Rifaximin; Rifampin; Not absorbed from GI/excreted unchanged from feces and does not interfere with CYP450
66
Mycobacteria are ____ (morphology), ____ (gram positive or negative), ____ (anaerobic or aerobic) bacteria.
Rodlike; Gram positive; aerobic
67
Why are mycobacterial infections difficult to treat (5 reasons)?
Grow slowly, can lie dormant, thick/impermeable cell walls, can reside in host cells, and develop resistance quickly
68
Which anti-mycobacterial inhibits synthesis of mycolic acids?
Isoniazid
69
Isoniazid distributes to ____ (location), ____ (excluding or including CNS). It is metabolized via ____.
Total body water; including; acetylation
70
Which anti-mycobacterial agent inhibits bacterial RNA polymerase and prevents transcription by suppressing initiation of RNA chain formation? What is unique about its pharmacokinetics?
Rifampin; potent inducer of drug metabolism/DDI is a major concern
71
Which anti-mycobacterial agent inhibits RNA synthesis and acts to decrease replication of tubercle bacilli? (Vague, I know)
Ethambutol
72
Which anti-mycobacterial agent acts by binding to mycobacterial DNA and inhibiting RNA polymerase reactions? Is it bactericidal or bacteriostatic?
Clofazimine; bactericidal

Common Mechanisms Block 2 (5 decks)

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