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Pharmacology > Exam 2: Inhibitors Of Protein Synthesis 2 > Flashcards

Exam 2: Inhibitors Of Protein Synthesis 2 Flashcards

1
Q

What are the 5 aminoglycoside drugs?

A

Streptomycin, gentamicin, tobramycin, Amikacin, and Neomycin

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2
Q

What is the MOA for Aminoglycosides?

A

Irreversibly inhibit protein synthesis of susceptible microorganisms by inhibiting the function of 30s subunit.

Bactericidal- hits 3 different parts of the translation machinery

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3
Q

Why aren’t aminoglycosides effective against anaerobic species?

A

In order to be effective, aminoglycosides first must be actively transported (OXYGEN REQUIRING) into the bacteria and bind to the 30s subunit

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4
Q

What are Aminoglycosides used to treat?

A

Aerobic G- enteric bacteria or when there is suspicion of sepsis or endocarditis

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5
Q

Which aminoglycosides are effective against P. Aeruginosa?

A

Gentamicin, tobramycin, and amikacin.

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6
Q

What are the significant toxicities associated with aminoglycosides?

A

Ototoxicity and nephrotoxicity.

-Dependent on duration of time the concentration of the drug is above threshold.

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7
Q

Are Aminoglycosides have time or concentration dependent killing?

A

Concentration dependent killing.

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8
Q

Do aminoglycosides have. High or low post antibiotic effect and what does this mean for dosage?

A

High PAE.

A single large dose has better efficacy than multiple smaller doses which also reduces the toxic side effects.

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9
Q

How are aminoglycosides administed?

A

IM, IV, or topical

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10
Q

What are the methods of resistance for aminoglycosides?

A
  • Deficiency of ribosomal receptors
  • Lack of permeability of the drug molecule into the bacteria
  • Enzymatic modification by the bacteria
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11
Q

Do Aminoglycosides have cross resistance?

A

Bacteria that acquire resistance to one aminoglycoside may exhibit cross resistance to other aminoglycosides.

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12
Q

What type of antibiotic is chloramphenicol?

A

Broad spectrum

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13
Q

What is the significant side effect associated with chloramphenicol?

A

Fatal aplastic anemia

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14
Q

What is the MOA of chloramphenicol?

A

Reversibly binds to the 50s subunit and prevents the attachment of the amino acid containing end of the aminoacyl tRNA to the acceptor site on the ribosome.

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15
Q

Is Chloramphenicol bacteriostatic or -cidal?

A

Bacteriostatic, but can b bacteriocidal against certain common meningeal pathogens such as H. Influenzae, N. Meningitis, and strep pneumoniae at therapeutic concentrations

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16
Q

What does chloramphenicol also inhibit in mammalian cells and what can this lead to?

A

It can inhibit mitochondrial protein synthesis.

Many of the adverse side effects such as bone marrow depression and gray baby syndrome appear to be a result of this.

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17
Q

What is the spectrum of chloramphenicol?

A

G-, G+, anaerobes, aerobes, atypicals (spirochetes, rickettsial, and chlamydiae.

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18
Q

What is the therapeutic use of Chloramphenicol?

A

NOT FIRST CHOICE and restricted to life threatening infections.

-Typhoid fever, meningitis, ricketsia, bacterial conjunctivitis (topical)

19
Q

What is Chloramphenicol an inhibitor of?

A

Potent inhibitor of CYP34A and CYP2C19

20
Q

How is Chloramphenicol metabolized?

A

In the liver, conjugated with glucuronic acid to form chloramphenicol glucurnate, an inactive metabolite, which is then excreted in the kidney.

21
Q

Which drug has the best CNS penetration?

A

Chloramphenicol

22
Q

What are the hematopoietic problems that can arise from Chloramphenicol use?

A
  • Bone marrow depression (dose dependent and reversible upon discontinuation)
  • Fatal aplastic anemia (dose independent and can develop months after drug has been discontinued)
23
Q

Why is chloramphenical not recommended for babies?

A

They can develop gray baby syndrome from inadequate activity of glucuronyl transferase in newborn liver. Discontinuation at onset can lead to recovery- if not taken off they will die.

24
Q

How can resistance to chloramphenicol occur?

A
  • Acetyl transferase produced by the resistant organism acetylates and inactivates chloramphenicol.
  • Binding site may be modified
  • Efflux pumps
25
Q

What are the 3 tetracycline drugs and how are they administered?

A
  • Tetracycline (Oral or topical)
  • Doxycycline (oral)
  • Minocycline (Oral)
26
Q

What is the MOA of tetracyclines?

A

Bind reversible to the 30s subunit and prevent the access of aminoacyl tRNA to the receptor site on the mRNA ribosome complex. This prevents the addition of amino acids to the growing peptide chain.
-Bacteriostatic at therapeutic concentrations

27
Q

What is the spectrum of tetracyclines?

A

Broad spectrum (G-, G+, anaerobes, aerobes, atypicals)

28
Q

What organisms are resistant to tetracyclines?

A

B. Fragility, Proteus, and Pseudomonas

29
Q

What is the DOC for cholera?

A

Tetracyclines

30
Q

What is the DOC for mycoplasma pneumoniae?

A

Tetracyclines

31
Q

What is the DOC for chlamydia infections?

A

Tetracyclines

32
Q

What is the DOC for early Lyme disease?

A

Tetracyclines and amoxicillin

33
Q

What is the DOC for vibrio species?

A

Tetracyclines

34
Q

How does resistance to tetracyclines usually occur?

A

Efflux pumps

35
Q

Does cross resistance occur between the types of tetracyclines?

A

No.

36
Q

What ions does tetracycline chelate with?

A

Ca+, Fe+, and Al+

37
Q

What are the adverse reactions to tetracyclines?

A

-Inhibition of bone growth, teeth discoloration, photosensitivity, normal flora changes, liver damage.

38
Q

What are the long acting tetracyclines?

A

Doxycycline and Minocycline- longer plasma half life and require less frequent dosing

39
Q

Who should tetracyclines not be prescribed to?

A

Pregnant women or children under 8yo.

40
Q

What class of drug is tigecycline?

A

Glycylcyclines

41
Q

What is tigecycline?

A

A synthetic derivative of Minocycline envelop to circumvent resistance mechanisms

42
Q

What is the spectrum of Tigecycline?

A

Similar to tetracyclines, however shows activity against tetracycline resistant organisms

43
Q

What is the MOA of Tigecycline?

A

Binds to the 30s subunits, bacteriostatic

Pharmacology (25 decks)

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