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Pharm Exam 4 > Tetracycline and Aminoglycosides > Flashcards

Tetracycline and Aminoglycosides Flashcards

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1
Q

What is a ribosome?

A

A large nucleoprotein complex that catalyzes the ordered polymerization of amino acids

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2
Q

What directs the ribosome to order the amino acids?

A

An mRNA template (mRNA translation)

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3
Q

How can drugs target bacterial ribosomes while not affecting human ribosomes?

A

Structural difference (70s prokaryote vs. 80S Eukaryote)

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4
Q

What are the 3 steps of protein synthesis?

A
  1. Initiation
  2. Elongation
  3. Termination
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5
Q

Which step of protein synthesis do most current protein synthesis inhibitors target?

A

Elongation

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6
Q

How to aminoglycosides inhibit protein synthesis?

A

Promote premature termination

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7
Q

Tetracyclines are named according to what?

A

The number of fused rings
Tetra = 4
Doxy = 2
Mino = 1

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8
Q

How do tetracyclines inhibit protein synthesis?

A

Bind to the 30S ribosomal subunit and inhibit binding of amino acylated tRNA to A site of ribosome

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9
Q

What helps tetracycline along in its effect on bacteria?

A

Bacteria concentrate tetracyclines inside the cell, eukaryotes and resistant bacteria do not

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10
Q

Are tetracyclines bactericidal?

A

No, bacteria start to grow again once the patient stops taking tetracycline.

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11
Q

What is the spectrum of activity for tetracycline?

A

Broad Spectrum: G+, G-, aerobe, anaerobe, atypical bacteria (rickettsiae, mycoplasma, Chlamydia)

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12
Q

Of Tetracycline, Doxycycline, and Minocycline: which has the lower bioavailability and higher risk of superinfection in the gut?

A

Tetracyclines

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13
Q

What inhibits the absorption of Tetracyclines?

A

divalent cations (Ca, Mg, Al, Fe). Think of Tetracycline binding to bone. Do not take w/ milk. Take 1-2 hrs prior to a meal. Tetracycline is a potent chelator

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14
Q

Of tetracycline, doxycycline and minocycline: which are the most lipophilic and are therefore more easily distributed?

A

Tetracycline and Doxycycline

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15
Q

What is a characteristic of tetracyclines that is useful in the treatment of adults with periodontal disease?

A

Concentrate in gingival crevicular fluid

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16
Q

Of Tetracycline, doxycycline, and minocycline: which has the shortest halflife and therefore must be dosed more often during the day?

A

Tetracycline (4/day)

Minocycline and doxycycline (2/day)

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17
Q

Of tretracycline, doxycycline, and minocycline: which is eliminated unchanged in the urine?

A

Tetracycline (whereas minocycline and doxycyclines undergo hepatic
metabolism and excretion as well as renal excretion)

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18
Q

When is tetracycline contraindicated?

A

In pregnant women and children less than 8. Uptake and concentrates in developing bones and teeth.

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19
Q

What are 3 common side effects of tetracycline?

A

Staining of teeth and altered rates of bone growth
GI disturbances
Phototoxic skin reactions

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20
Q

Is teeth staining reversible or irreversible?

Is it dose dependent or non-dose dependent?

A

Irreversible/permanent and dose dependent

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21
Q

What is the superinfection and its symptoms that can be caused by tetracycline (doxycycline has reduced risk)?

A

Colitis due to superinfection by C.diff (main symptom: bloody stools)

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22
Q

What can be a rare side effect from treating a meningococcal infection with minocycline?

A

Vestibular toxicity: dizziness, vertigo

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23
Q

What do doxycycline and minocycline do in the blood and what consideration must be made?

A

Depress plasma prothrombin. If patient is on anticoagulation therapy, dosing may need to be reduced

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24
Q

Why not use a tetracycline with a penicillin?

A

Tetracycline is bacteriostatic. Will reduce amount of cell wall synthesis targets for penicillin reducing its bacteriocidal effectiveness

25
Q

Tetracyclines are Drugs of choice for the treatment of what infections?

A

Mycoplasma pneumonia
Rickettsia (Rocky Mountain Spotted Fever)
Borrelia (Lyme’s Disease)
Chlamydia (Chlamydia pneumonias/vaginitis)
Vibrip(Cholera)
Combo therapy for H.pylori ulcer
Acne
Gonorrhea and syphilis in penicillin allergic

26
Q

What drug is commonly used for the eradication of the meningococcal carrier state (treating people who have come in close contact with someone who has meningitis)?

A

Minocycline

27
Q

What is Periostat?

A

Doxycycline (20mg tab bid, p.o.). Systemic therapy of advanced periodontal disease for up to 1 year?

28
Q

What is Arestin?

A

Topical minocycline to be placed in periodontal pocket for up to 3 weeks release

29
Q

What other periodontal problem can tetracyclines be used to treat (as an alternative to penicillin)?

A

ANUG

30
Q

Protein synthesis inhibitor that is isolated from streptomyces soil bacteria?

A

Chloramphenicol

31
Q

What is the major side effect associated with chloramphenicol?

A

Aplastic anemia

32
Q

Aplastic anemia associated with chloramphenicol is an example of what

A

idiosyncratic toxicity (characteristic peculiarity[internet definition for idiosyncratic])

33
Q

Though Chloramphenicol is similar to tetracycline in its spectrum of activity, how is it different (mechanism of action)?

A

Binds to 50S bacterial ribosome and inhibits ribosomal peptidyltransferase

34
Q

What is the Gray Baby Syndrome?

A

Neonate symptom that showed infants do not have mature hepatic drug metabolizing system (Chloramphenicol requires hepactic metabolism)

35
Q

What character of chloramphenicol makes it useful in treating bacterial meningitis?

A

Lipophilic and crosses blood brain barrier

36
Q

What are 2 blood dyscrasias associated with chloramphenicol?

A
  1. Predictable, dose dependent depression of bone marrow cell proliferation
  2. Non-predictable, non-dose dependent risk of aplastic anemia that can occur even months after off Chloramphenicol
37
Q

What is the good thing about the depressed bone marrow cell depression caused by chloramphenicol?

A

it goes away once chloramphenicol is stopped

38
Q

When is chloramphenicol indicated for treatment?

A

In severe systemic infections not treatable with less- toxic drugs. E.g. Cephalosporing resistant typhoid (S. typhi) or Meningitis and pneumonia caused by H.influenza or B. fragilis

39
Q

Aminoglycosides are important for treating what bacteria?

A

Gram negative bacilli aerobes

Pseudomona (P. aeruginosa)

40
Q

How must aminoglycosides be administered?

A

parenteral (outside alimentary, normally IV or IM [internet definition])

41
Q

Do aminoglycosides have a high or low therapeutic index?

A

Low Therapeutic Index, so monitoring.

42
Q

Aminoglycoside spectrum (broad vs narrow) and activity (bacteriostatic vs bacteriocidal) is what?

A 
Narrow spectrum (focus on gram negative aerobes)
Bacteriocidal
43
Q

Are aminoglycosides useful against anaerobes?

A

No

44
Q

What is the aminoglycoside mechanism of action?

A

Bind bacterial ribosome 30S subunit and inhibit protein synthesis

45
Q

What are 3 effects caused by aminoglycosides binding the 30S bacterial ribosome?

A
  1. Accumulation of initiation complexes (streptomycin monosomes)
  2. Misread mRNA = wrong amino acid inserted
    3 Premature protein release from mRNA
46
Q

Why are Aminoglycosides poorly absorbed if taken orally?

A

Due to their large size

47
Q

Can aminoglycosides cross cell membranes?

A

No

48
Q

How are aminoglycosides excreted?

A

Unchaged, rapidly by kidney (glomerular filtration)

49
Q

What are 2 toxicities associated with aminoglycosides?

A

Ototoxicity

Nephrotoxicity

50
Q

How is aminoglycoside toxicity avoided?

A

Longer interval, monitored dosing, not in patients with impaired kidney function

51
Q

What makes bacteria resistant to aminoglycosides?

A

Aminoglycoside-metabolizing enzyme acquired from plasmids

52
Q

What are some systemic infections that are treated by aminoglycosides?

A 
Klebsiella
Proteus
E.coli 
Enterobacter 
Pseudomonas aeruginosa 
Serratia
53
Q

Why are aminoglycosides NOT used at abscess sites?

A

Because abscesses have anaerobes against which aminoglycosides are ineffective

54
Q

Name 2 infections where aminoglycosides are administered along with penicillin?

A

Meningitis

Enterococcal endocarditis

55
Q

What is a prototype aminoglycoside?

A

Gentamicin

56
Q

What aminoglycoside is used in skin ointments or to sterilize bowel prior to GI surgery?

A

Neomycin

57
Q

What aminoglycoside is used in pseudomonal infections?

A

Tobramycin

58
Q

What 2 aminoglycosides that are back up drugs for gram negative drug resistant infections?

A

Amikacin

Netilimicin

Pharm Exam 4 (8 decks)

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