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pharm exam 3 > 02 Study guide: cell wall & membrane COPY > Flashcards

02 Study guide: cell wall & membrane COPY Flashcards

1
Q

What are the 4 major classes of beta lactam antibiotics, and how can one recognize names of drugs in each class?

A

Penicillins: (-cillin)
Cephalosporins: (-cef-)
Carbapenems: (-penem)
Monobactams (aztreonam)

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2
Q

What are the 4 major classes of penicillins?

A
  • Natural Penicillins:
    • Penicillin G
    • Penicillin V
  • Anti-staphylococcal:
    • Nafcillin and Oxacillin
    • Dicloxacillin
  • Amino/ Broad spectrum:
    • Ampicillin
    • Amoxicillin
  • Extended Spectrum:
    • Piperacillin + tazobactam
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3
Q

Name 4 examples of beta lactamase inhibitor drugs.

A
  • Clavulinic Acid
  • Sulbactam
  • Tazobactam
  • Avibactam
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4
Q

What feature is shared in the names of all glycopeptide antibiotics?

A

-van-

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5
Q

Name the classes (and the 2 additional “other” drugs) that target bacterial cell membranes.

A
  • Other cell wall antibiotics: fosfomycin, bacitracin
  • Lipopeptides: dapotomycin
  • Polymyxins (-myxin)
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6
Q

Name 2 drugs that primarily target bacterial cell membranes.

A

Daptomycin: disrupts cytoplasmic membrane

Polymyxins: disrupt the outer membrane + cytoplasmic membrane

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7
Q

What are the two major components of peptidoglycan?

A

Polysaccharides: 2 alternating sugars - N-acetylglucosamine (G) and N-acetylmuramic acid (M)

Peptides: five amino acid chain, linked N-acetylmuramic acid sugar

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8
Q

What are the 3 major steps in PG synthesis – what happens in each step?

A

Monomer synthesis & transport: in cytoplasm, building blocks are made from amino acids & sugar by enzyme (Mur enzyme), then transported to the cell surface by lipid carriers.

Glycan polymerization: at cell surface, N and M sugars are connected into strands via transglycosylation by penicillin binding proteins (PBPs)

Polymer cross-linking: strands are linked by transpeptidation, when penicillin binding proteins (PBPs) remove the peptide’s terminal D-alanine to cross-link it to another peptide

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9
Q

What are the roles of PBP (both roles), Mur enzymes, and flippase II enzymes?

A

PBP often have both transpeptidase domain and glycosyltransferase domain

Mur A enzyme: building blocks made from amino acids and sugar

_Flippase II enzyme_s: transport building blocks to cell surface

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10
Q

Which steps in the PG synthesis pathway are targeted by: β lactams, glycopeptides, fosfomycin and bacitracin - and to what target does each one bind?

A

Photo attached below

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11
Q

What are 2 drugs that target the cell membrane, and how does each work?

A

Daptomycin: disrupts cytoplasmic membrane

Polymyxins: disrupt the outer membrane + cytoplasmic membrane

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12
Q

What are the 4 primary mechanisms by which bacteria become resistant to β lactam drugs?

A
  1. Inactivation of antibiotic by bacterial beta-lactamase: these enzyme catalyzed opening of the antibiotic’s beta-lactam ring
  2. Reduced uptake of antibiotic: specific to gram-negative bacteria (impervious outer membrane)
  3. Antibiotic efflux: gram negative bacteria may produce drug efflux pumps which toss some beta-lactam antibiotics back out
  4. Alteration of the antibiotic’s target: bacteria produce slightly different PBPs that antibiotics can’t bind to: development of a new PBP (PBP2a) by S. aureus is how the “superbug” MRSA arose
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13
Q

Which of the 4 mechanisms of how bacterial resistance develops against cell wall / membrane-targeted agents is the most common?

A

Inactivation of antibiotic by bacterial beta-lactamase

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14
Q

What is the function of bacterial beta lactamase enzymes?

A

they protect beta-lactam antibiotics from ring-destruction (counter-defense)

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15
Q

What type of bacteria are more likely to develop antibiotic resistance by altering drug uptake / efflux – gram positive or negative (and why)?

A

Gram negative. They have an impermeable outer membrane.

Example: development of a new PBP (PBP2a) by S. aureus is how the “superbug” MRSA arose

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16
Q

Give 3 examples of how bacteria can develop antibiotic resistance by altering antibiotic binding targets.

A
  1. these enzymes catalyze opening of the antibiotic’s beta-lactam ring
  2. most but not all bacteria produce beta-lactamase enzyme to defend themselves from antibiotics
  3. bacteria make hundreds of different beta-lactamase enzymes, each degrades a particular range of beta-lactam antibiotics
17
Q

What is the mechanism by which MRSA developed resistance to penicillins?

A

Alteration of the antibiotic’s target: bacteria produce slightly different PBPs that antibiotics can’t bind to

  • all available beta lactam antibiotics (except two new cephalosporins) fail to bind to MRSA’s new PBP (PBP2a)
  • MRSA is currently treatable with vancomycin, daptomycin and ceftaroline
18
Q

Which class of beta lactam antibiotics has the broadest spectrum of activity?

A

Carbapenems (-penem): Imipenem, Meropenem

19
Q

Which 1 class of beta lactams antibiotics has activity against gram negative bacteria only?

A

Monobactams: Aztreonam (gram negative only)

20
Q

Among the 4 categories of penicillins, which 2 have a narrow spectrum of activity, and which 1 has the broadest spectrum of activity?

A
  1. Narrow spectrum:
    1. Natural Penicillins: Penicillin G (IV), Penicillin V (PO)
    2. Anti-Staphylococcal: Naficillin and Oxacillin (IV), Dicloxcillin (PO)
  2. Broadest spectrum:
    1. Extended Spectrum: Piperacillin + tazobactam (IV/IM)
21
Q

All penicillins have activity against which type of bacteria – gram positive or gram negative?

A

Gram Positive!

22
Q

Name 6 antibiotic classes / subclasses / drugs that can be used to treat MDR strains of bacteria

A
  1. Cephalosporins (5th generation, IV): Ceftaroline, ceftolozane + tazobactam
  2. Carbapenems: Imipenem (combine with beta-lactam inhibitor to provide activity against MDR bacteria)
  3. Glycopeptide: Vancomycin (more use recently due to rise in MDR bacteria)
  4. Other cell wall agents: Fosfomycin
  5. Cell membrane agents: Polymyxins
23
Q

Which of the β lactams is least likely to have cross-reactivity in patients with penicillin allergy?

A

Monobactams: Aztreonam (NO CROSS REACTIVITY)

24
Q

Which β lactam drug class is associated with the highest risk of C difficile colitis?

A

Cephalosporins (3rd generation): cefituten (PO), cefotaxime, ceftriaxone (-one, -ten, -ime)

25
Q

Which antibiotic drug produces a classic constellation of side effects including histamine-mediated flushing, ototoxicity and nephrotoxicity?

A

Glycopeptides: Vancomycin

26
Q

Which β lactam subclass can cause alcohol intolerance, hemolysis, impaired coagulation and C diff. colonic overgrowth?

A

Cephalosporins (3rd generation): cefituten (PO), cefotaxime, ceftriaxone (-one, -ten, -ime)

27
Q

Which β lactam drug is mainly cleared by renal metabolism?

A

Carbapenems (-penem): Imipenem, Merapenem, Doripenem, Ertapenem

28
Q

Which one of the 4 classes of beta lactam antibiotics is only available IV (and why)?

A

Carbapenems (-penem): Imipenem, Merapenem, Doripenem, Ertapenem

29
Q

Give examples of 2 antibiotics that are more likely to cause concentration-dependent risk of seizures?

A
  1. Natural Penicillins: Penicillin G (IV or IM)
  2. Carbapenems (-penem): concentration-dependent seizure risk (Imipenem, Merapenem, Doripenem, Ertapenem) [Imipenem highest risk]
30
Q

How can one recognize the names of beta lactamase inhibitor drugs, and what is the one exception to this rule?

A
  1. Beta Lactamase inhibitor (usually-bactam):
    1. Sulbactam, Tazobactam, Avibactam

Exception: Clavulanic Acid

31
Q

What is the purpose of beta lactamase inhibitor drugs?

A

Combined with beta lactam antibiotics to overcome bacterial drug resistance

32
Q

Are beta lactamase inhibitors generally administered with non-beta lactam antibiotics?

A

No, it is usually administered with beta lactam antibiotics

33
Q

Which antibiotic must be administered in combination with cilastatin, and what is the purpose of cilastatin in this combination?

A

Carbapenems: Imipenem (must combine with cilastatin (DHP-1 inhibitor) to achieve therapeutic concentration because DHP-1 metabolizes carbezenems

pharm exam 3 (9 decks)

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