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Pharm Summer 2020 > Inhibitors of Cell Wall Synthesis > Flashcards

Inhibitors of Cell Wall Synthesis Flashcards

1
Q

Antibiotics that inhibit cell wall synthesis require what?

A

Require a cell that is actively dividing. Little to no effect if not growing.

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2
Q

Which antibiotics are cell wall inhibitors by peptidoglycan?

A

Bacitracin and vancomycin

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3
Q

What antibiotics are cell wall inhibitors by transpeptidase

A

Pencillins

Cephalosporins

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4
Q

Penicillins. Differences in drugs are due to

A

Structure. Side chain affects antimicrobial spectrum, stability to stomach acid, cross hypersensitivity and susceptibility to degradative enzymes.

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5
Q

What do all penicillins have in common?

A

All have the B-lactam ring.

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6
Q

MOA by penicillins

A

B lactam antibiotics form a covalent bond with the bacterial enzyme transpeptidase. This inhibits the catalytic activity of the enzymes.

  • Prevents elongation or cross linking of peptidoglycan.
  • Leads to autolysis
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7
Q

Transpeptidase enzymes

A

Group of bacterial enzymes that are anchored in the cytoplasmic membrane and extend into the periplasmic space.

responsible for the assembly, maintenance, and regulation of the peptidoglycan portion of the bacterial cell wall.

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8
Q

“easy to kill gram negative” and “hard to kill gram negative”

A

Gram negative are surrounded by outer envelope that acts as a barrier.
Easy to kill have channels that allow entry.
hard to kill have restrictive porins and are resistant to many antibiotics (pseudomonas)

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9
Q

Example of a hard to kill gram negative bacteria

A

pseudomonas

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10
Q

Natural penicillins are obtained from

A

mold fermentation. Susceptive to inactivation by enzymes that bacteria produce, called Beta lactamases. Beta lactamases can destroy penicillin molecule.

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11
Q

beta lactamase

A

Enzymes that bacteria produce to destroy penicillin molecule.
Same as penicillinase.

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12
Q

penicillinase.

A

Enzymes that bacteria produce to destroy penicillin molecule.
Same as beta lactamase.

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13
Q

When are penicillinase-resistant penicillins used?

A

For the treatment of penicillinase producing staph. Avoid over use to prevent resistance.

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14
Q

examples of penicillinase-resistant penicillin

A

Nafcillin

Oxacillin

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15
Q

Methicillin. When should it be used?

A

High toxicity. causes interstitial nephritis.

Used only to identify resistant strains of S. Aureus (MRSA.) MRSA is resistant to all available B-lactam antibiotics.

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16
Q

MRSA is susceptible to

A

Vancomycin.

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17
Q

Extended spectrum penicillins

A

designed to maintain Gram + and easy gram negatives

Resistance is a major problem. Often combined with a penicillinase inhibitor.

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18
Q

natural resistance vs acquired resistance

A

Natural: organisms that lack a cell wall or have a cell wall that is impermeable to the drug.

Acquired: occurs via plasmid transfer. Can encode for resistance to multiple agents.

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19
Q

Beta lactamase activity

A

Enzyme hydrolyzes the beta lactam ring in the antibiotic. Results in loss of the bactericidal activity.

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20
Q

3 methods of acquired resistance

A

Beta lactamase activity
Decreased permeability (efflux pump)
Altered penicillin binding proteins- newer acquired resistance. Cause of MRSA resistance. Lower affinity to antibiotics. Would need to increase conc to an impossible amount.

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21
Q

How are antibiotics absorbed

A

Most are INcompletely absorbed after oral administration. Reach intestine in sufficient amounts to affect intestinal flora (GI issues).

Amoxicillin is almost completely absorbed in stomach- not as much GI issues.

22
Q

Absorption of penicillinase-resistant penicillins.

A

Destroyed in acidic environments. Must be taken 30-60 minutes before food or 2-3 hours after. Need to decrease acidic environment of food.

23
Q

Distribution of antibiotics

A

All cross the placenta, but are not teratogenic.
Cannot penetrate bone or CNS unless inflammation.
Cannot reach prostate

24
Q

Hypersensitivities with antibiotics

A

5-10% of patients have reactions.

  • Rash
  • Angioedema
  • Anaphylaxix
25
Q

Adverse reactions to antibiotics

A

Diarrhea due to disruption of flora
Nephritis (inflamed kidney) especially with methicillin.
Neurotoxicity
Hematologic toxicities causes decreased coagulation in blood. Be aware if they are on blood thinner!!
Cation toxicity

26
Q

Why you should be aware if your patient is on blood thinners and you want to rx an antibiotic

A

Antibiotics adverse effects include hematologic toxicities- causes decreased coagulation in blood. Will thin blood even more.

27
Q

Why can cephalosporins be given by itself more often?

A

Because they tend to be more resistant to certain beta lactamases.

28
Q

Spectrum of cephalosporins

A

First generation: Gram positive coverage. Little gram negative.

Second: Extended coverage. Same gram positive and improved gram negative with anaerobic coverage.

Third: Less gram positive. Gram negative.

4th: Borad spec. Gram positive like first gen and gram negative like 3rd gen with pull coverage against cefepime. No anaerobic coverage.
5th. Similar to 3rd. Also against MRSA and pneumonia. And against anaerobic. Advanced. Injection only.

29
Q

Which gen to use of cephalosporins.

  1. Skin infections
  2. Intra-abdominal infections
  3. Pneumonia
  4. Serious infections for immunocompromised patients
A
  1. 1st
  2. 2nd
  3. 3rd
  4. 4th
30
Q

What cephalosporin to treat MRSA

A

Ceftaroline

31
Q

Which cephalosporin to treat pseudomonas

A

Ceftazidime
Cefepime
Ceftolozane

32
Q

Are cephalosporins susceptible to staph penicillinase?

A

NO.

33
Q

If patients are allergic to penicillin, what generation of cephalosporins should be used

A

3rd gen.

34
Q

If patients are allergic to penicillin, which gen of cephalosporins should you avoid

A

1st gen

35
Q

Beta lactamase inhibitors

A

Do not have significant antibacterial activity by themselves.
They bind to penicillinases and inactivate. This protects the antibiotic from resistance mechanisms.

36
Q

Examples of Beta lactamase inhibitors

A

Clavulanic Acid

37
Q

Sulbactam

A

Tazobactam

38
Q

Bacitracin is only available

A

Topically. When given systemically, will cause nephrotoxicity.

39
Q

Mechanism of action of Vancomycin

A

Inhibits cell wall synthesis. Binds to alternative proteins in the cells all- weakens peptidoglycan polymerization and damages underlying cell membrane.

Not effective against gram negative cell wall synthesis. Very effective against gram positive.

Restrict use to treatment with serious infections. Don’t want to develop resistance.

40
Q

Administration of Vancomycin

A

Slow IV fusion
Oral absorption poor

Orally? Minimal metabolism and eliminated via kidneys.

41
Q

Adverse effects of Vancomycin

A

Fever
Chills
Phlebitis at injection site (inflammation at vein)
Flushing or shock if rapid infusion.

42
Q

Telavancin

A

Synthetic derivative of vancomycin. No evidence that it is more effective than vancomycin. Basically same thing. Inhibits cell wall synthesis.

43
Q

Telavancin adverse effects

A 
Taste disturbances
Nausea 
Vomitting
Insomnia 
Foamy urine 
Not be used during pregnancy 
Caution in cardiac conditions
44
Q

Bacitracin MOA

A 
Interferes with peptidoglycan synthesis 
great gram positive coverage 
Rare toxicity and allergic reactions 
Safe on pregnancy 
Only available topically. Very nephrotoxic when given systematically.
45
Q

What infections do you use bacitracin on

A

Infectious blepharitis and overnight coverage in treatment of bacterial corneal ulcers.

46
Q

Daptomycin MOA

A

Induces rapid depolarization of the cell membrane. Not a true cell wall antibiotic.

47
Q

Daptomycin spectrum

A

Limited to gram positive. Used for skin infections. Inactivated by pulmonary surfactants- never use for pulmonary infection.

48
Q

Daptomycin pharmacokinetics

A

90% bound to protein

No hepatic metabolism

49
Q

Adverse effects of daptomycin

A 
Constipation 
Nausea 
headache 
Myalgias - muscle aches 
Insomnia
50
Q

Most commonly prescribed cell wall antibiotics

A

Augmentin (500mg bid for 5-7 days)
Reflex (500 mg bid for 5-7 days)
^good for eyelid infections.

Bacitracin ophthalmic ointment for overnight coverage.

Pharm Summer 2020 (18 decks)

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