Tetracycline and Aminoglycosides

Question 1

What is a ribosome?

Answer 1

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

Question 2

What directs the ribosome to order the amino acids?

Answer 2

An mRNA template (mRNA translation)

Question 3

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

Answer 3

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

Question 4

What are the 3 steps of protein synthesis?

Answer 4

1. Initiation
2. Elongation
3. Termination

Question 5

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

Answer 5

Elongation

Question 6

How to aminoglycosides inhibit protein synthesis?

Answer 6

Promote premature termination

Question 7

Tetracyclines are named according to what?

Answer 7

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

Question 8

How do tetracyclines inhibit protein synthesis?

Answer 8

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

Question 9

What helps tetracycline along in its effect on bacteria?

Answer 9

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

Question 10

Are tetracyclines bactericidal?

Answer 10

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

Question 11

What is the spectrum of activity for tetracycline?

Answer 11

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

Question 12

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

Answer 12

Tetracyclines

Question 13

What inhibits the absorption of Tetracyclines?

Answer 13

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

Question 14

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

Answer 14

Tetracycline and Doxycycline

Question 15

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

Answer 15

Concentrate in gingival crevicular fluid

Question 16

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

Answer 16

Tetracycline (4/day)

Minocycline and doxycycline (2/day)

Question 17

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

Answer 17

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

Question 18

When is tetracycline contraindicated?

Answer 18

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

Question 19

What are 3 common side effects of tetracycline?

Answer 19

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

Question 20

Is teeth staining reversible or irreversible?

Is it dose dependent or non-dose dependent?

Answer 20

Irreversible/permanent and dose dependent

Question 21

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

Answer 21

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

Question 22

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

Answer 22

Vestibular toxicity: dizziness, vertigo

Question 23

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

Answer 23

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

Question 24

Why not use a tetracycline with a penicillin?

Answer 24

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

Question 25

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

Answer 25

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

Question 26

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)?

Answer 26

Minocycline

Question 27

What is Periostat?

Answer 27

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

Question 28

What is Arestin?

Answer 28

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

Question 29

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

Answer 29

ANUG

Question 30

Protein synthesis inhibitor that is isolated from streptomyces soil bacteria?

Answer 30

Chloramphenicol

Question 31

What is the major side effect associated with chloramphenicol?

Answer 31

Aplastic anemia

Question 32

Aplastic anemia associated with chloramphenicol is an example of what

Answer 32

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

Question 33

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

Answer 33

Binds to 50S bacterial ribosome and inhibits ribosomal peptidyltransferase

Question 34

What is the Gray Baby Syndrome?

Answer 34

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

Question 35

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

Answer 35

Lipophilic and crosses blood brain barrier

Question 36

What are 2 blood dyscrasias associated with chloramphenicol?

Answer 36

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

Question 37

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

Answer 37

it goes away once chloramphenicol is stopped

Question 38

When is chloramphenicol indicated for treatment?

Answer 38

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

Question 39

Aminoglycosides are important for treating what bacteria?

Answer 39

Gram negative bacilli aerobes | Pseudomona (P. aeruginosa)

Question 40

How must aminoglycosides be administered?

Answer 40

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

Question 41

Do aminoglycosides have a high or low therapeutic index?

Answer 41

Low Therapeutic Index, so monitoring.

Question 42

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

Answer 42

``` Narrow spectrum (focus on gram negative aerobes) Bacteriocidal ```

Question 43

Are aminoglycosides useful against anaerobes?

Answer 43

No

Question 44

What is the aminoglycoside mechanism of action?

Answer 44

Bind bacterial ribosome 30S subunit and inhibit protein synthesis

Question 45

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

Answer 45

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

Question 46

Why are Aminoglycosides poorly absorbed if taken orally?

Answer 46

Due to their large size

Question 47

Can aminoglycosides cross cell membranes?

Answer 47

No

Question 48

How are aminoglycosides excreted?

Answer 48

Unchaged, rapidly by kidney (glomerular filtration)

Question 49

What are 2 toxicities associated with aminoglycosides?

Answer 49

Ototoxicity | Nephrotoxicity

Question 50

How is aminoglycoside toxicity avoided?

Answer 50

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

Question 51

What makes bacteria resistant to aminoglycosides?

Answer 51

Aminoglycoside-metabolizing enzyme acquired from plasmids

Question 52

What are some systemic infections that are treated by aminoglycosides?

Answer 52

``` Klebsiella Proteus E.coli Enterobacter Pseudomonas aeruginosa Serratia ```

Question 53

Why are aminoglycosides NOT used at abscess sites?

Answer 53

Because abscesses have anaerobes against which aminoglycosides are ineffective

Question 54

Name 2 infections where aminoglycosides are administered along with penicillin?

Answer 54

Meningitis | Enterococcal endocarditis

Question 55

What is a prototype aminoglycoside?

Answer 55

Gentamicin

Question 56

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

Answer 56

Neomycin

Question 57

What aminoglycoside is used in pseudomonal infections?

Answer 57

Tobramycin

Question 58

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

Answer 58

Amikacin | Netilimicin