Resp: Pharm 3 (Protein Synthesis Inhibitors)

Front 1

What are the bactericidal protein synthesis inhibitors?

Back 1

Aminoglycosides (except spectinomycin)
Streptogrammins

Front 2

What are the bacteriostatic protein synthesis inhibitors?

Back 2

1. Tetracyclines
2. Chloramphenicol
3. Erythromycins
4. Clindamycin
5. Linezolid

Front 3

How do aminoglycosides interfere w/ protein synthesis?

Back 3

Mess up INITIATION --> Bind to the 30S ribosome and prevent formation of the initiation complex

Front 4

How does linezolid interfere w/ protein synthesis?

Back 4

Mess up INITIATION --> Bind to the 30S ribosome and prevent formation of the initiation complex --> JUST LIKE AMINOGLYCOSIDES

Front 5

How do chloramphenicol, tetracyclines, and clindamycin interfere w/ protein synthesis?

Back 5

Prevent elongation

Front 6

How does erythromycin and spectinomycin interfere w/ protein synthesis?

Back 6

By preventing translocation (moving the peptidyl-tRNA from the A to the P site)

Front 7

When do you use aminoglycosides as a single agent?

Back 7

Against Gram - bacteria (except Staphylococci)

Front 8

Why do you combine aminoglycosides w/ beta-lactams?

Back 8

Because the initial event is penetration through the outer membrane, followed by binding to sites in the cytoplasm. They can't reach these sites on Gram + bacteria w/o a b-lactam

Front 9

Why are aminoglycosides ineffective against strict anaerobes?

Back 9

b/c uptake of aminoglycosides is through an O2-dependent active transport system

Front 10

Explain the post-antibiotic effect involving aminoglycosides.

Back 10

They have significant activity in vivo despite conc. falling below MIC --> allows for q daily dosing

Front 11

What is the therapeutic use of aminoglycosides?

Back 11

1. combined w/ b-lactam to treat severe aerobic Gram - bugs
2. combined w/ Pen to tx Enterococcus faecium

Front 12

Describe the pharmacokinetics of aminoglycosides.

Back 12

1. Parenteral administration (given IM)
2. Largely excluded from CNS and ocular fluid
3. Pre-mixing w/ b-lactam inactivates!!
4. Primarily excreted by kidneys

Front 13

What are the major toxicities of aminoglycosides?

Back 13

Ototoxicity and Nephrotoxicity

Front 14

What are the major resistance mechanism to aminoglycosides?

Back 14

1. Degredation by enzymes (adenylation, acetylation, phosphorylation)
2. Alteration of ribosomal binding site

Front 15

Which aminoglycoside is least susceptible to inactivating enzymes?

Back 15

Amikacin

Front 16

Give three tetracyclines

Back 16

1. Tetracycline
2. Doxycycline
3. Minocycline

Front 17

What are the therapeutic uses of tetracycline?

Back 17

1. Rocky Mtn. Spotted Fever (Rickettsia)
2. Cholera (Vibrio cholerae)
3. Lyme Dz (Borrelia)
4. Brucellosis (Brucella)

Front 18

Describe the pharmacokinetics of tetracyclines.

Back 18

1. Given orally or IV, distribute well except to CNS
2. Oral absorption inhibited by 2+ and 3+ cations (milk, antacids, etc.)

Front 19

What are the major toxicities of tetracyclines?

Back 19

1. GI irratation (oral admin)
2. Phototoxicity (rash after sun exposure)
3. Hepatic and renal toxicities
4. Deposition in bones and teeth (contraindicated in kids and pregnant women)
5. Fanconi syndrome (from using expired drugs) -- Nausea, vomiting, polyuria, proteinuria

Front 20

Give 4 examples of aminoglycosides

Back 20

Gentamycin, Amikacin, Tobramycin, Streptomycin

Front 21

True of False: Tetracyclines are bactericidal.

Back 21

FALSE

Front 22

What are the two major resistance mechanisms against tetracyclines?

Back 22

1. Increased efflux by an active transport pump
2. Protection proteins that prevent binding to ribosome

Front 23

What are the therapeutic uses of chlroamphinicol?

Back 23

USED FOR SERIOUS INFECTIONS FOR WHICH ALL OTHER ABX ARE CONTRAINDICATED.
1. Bacterial meningitis caused by H. influenzae or N. meningitidis in pts w/ Pen analphylaxis
2. Alternative for Rocky Mtn. Spotted Fever when tetracycline is contraindicated (preggers and kids)

Front 24

True or False: Vancomycin binds to Acyl-D-Ala-D-Lactate with high affinity?

Back 24

FALSE!! It binds to D-Ala-D-Ala

Front 25

Does Chloramphinicol penetrate the CNS?

Back 25

YES!!!

Front 26

What are the major toxicities of chloramphinicol?

Back 26

1. Aplastic anemia (destroys bone marrow) --> near-universally fatal
2. Dose-related, reversible bone marrow depression
3. Gray-baby syndrome from circulatory collapse (adjust dose for newborns)

Front 27

How do VISA and VRSA strains differ?

Back 27

VISA strains are resistant b/c of thickening of the cell wall that causes trapping of the abx in the outer layer. VRSA have vanA gene (from transposons) which confer resistance.

Front 28

What is the major resistance mechanism to chloramphinicol?

Back 28

Enzyme (chloramphinicol acetyl transferase) often found in drug-resistant plasmids

Front 29

Give 3 macrolides.

Back 29

Erythromycin, Clarithromycin, Azithromycin

Front 30

What is a major interaction w/ macrolides and other abx?

Back 30

Macrolides are antagonistic w/ both chloramphinicol and clindamycin

Front 31

What are the therapeutic uses of Macrolides?

Back 31

1. Legionnaire's Dz (Legionnella)
2. Mycoplasma pneumoniae
3. Chlamydia trachomatis
4. Whooping cough (Bordatella pertussis)

Front 32

Describe the pharmacokinetics of Azithromycin and Clarithromycin.

Back 32

They accumulate in phagocytes and are released at site of infection

Front 33

What are the major toxicities of Macrolides?

Back 33

They are well-tolerated w/ few side effects
1. GI distress
2. Hepatotoxicity from the estolate form

Front 34

What are the major interactions of Erythromycin and Clarithromycin?

Back 34

they potentiate the effects of corticosteroids, cyclosporine, digoxin, and warfarin (b/c of the inhibition of P450 enzymes that metabolize these drugs)

Front 35

True or False: Azithromycin has similar interactions w/ drugs metabolized by P450s like Erythromycin and Clarithromycin.

Back 35

FALSE

Front 36

What are the major mechanisms of resistance to macrolides?

Back 36

1. Decrease in permeability
2. Removal of drug by efflux pump
3. Modification of target site
4. Hydrolysis by an esterase

Front 37

How is clindamycin administered?

Back 37

orally

Front 38

What are the therapeutic uses of clindamycin?

Back 38

Used for opportunistic infections in AIDS pts
1. Severe anaerobic infections by Bacteriodes fragilis, among others
2. Alterative tx for toxoplasmosis (w/ pyrimethamine) and PCP (w/ primaquine)

Front 39

Describe the pharmacokinetics of clindamycin.

Back 39

metabolized by the liver and excreted in the bile (feces)

Front 40

What are the major toxicities of clindamycin?

Back 40

GI distress, skin rashes, hepatotoxicity --> all common
Possibility of C. difficile superinfection

Front 41

What is C. difficile (NAP1/027)?

Back 41

A particularly aggressive strain that has an increased production of toxins that damage the epithelial lining of the colon. It is resistant to all fluoroquinolones

Front 42

What is the most common resistance mechanism against clindamycin?

Back 42

Production of a methylase that modifies the binding site

Front 43

Name 2 streptogrammins

Back 43

Dalfopristin and Quinupristin. They are used together (16x more effective)

Front 44

What is the mechanism of the streptogrammins.

Back 44

They bind to the 50S subunit and constrict the exit channel of the nascent peptide

Front 45

What are the therapeutic uses of the streptogrammins?

Back 45

1. Vancomycin-resistant E. faecium (but NOT E. faecalis)
2. Pen^r-Strep pneumo
3. Can be used for MRSA

Front 46

Can streptogrammins be used to treat vanc resistant E. faecium?

Back 46

YES!!!

Front 47

Can streptogrammins be used to treat vanc resistant E. faecalis?

Back 47

NO!!! Only treats E. faecium.

Front 48

What are the major toxicities of streptogrammins?

Back 48

1. Hypersensitivity rxns
2. Abx-related pseudomembranous colitis

Front 49

What is the major drug-drug interaction caused by streptogrammins?

Back 49

Inhibits Cyp P450 enzymes --> increases conc. of cyclosporine, Ca++ blockers, etc.

Front 50

What is the major resistance mechanism to streptogrammins?

Back 50

Mutations in rRNA that decrease affinity for ribosome

Front 51

What is the mechanism of Oxazolidinones?

Back 51

binds the 50S subunit and prevents formation of the 70S initiation complex

Front 52

Give an example of an oxazolidinone.

Back 52

Linezolid

Front 53

What are the therapeutic uses of Linezolid?

Back 53

1. VRE
2. Pen^r-Strep. pneumo
3. MRSA
4. Groups A & B Strep

Front 54

What is the major resistance mechanism to linezolid?

Back 54

Mutations in rRNA that decrease affinity for the drug

Front 55

What are the major toxicities of linezolid?

Back 55

1. Increase bradycardia in pts taking beta blockers
2. Thrombocytopenia
3. Risk of superinfections

Front 56

What are the major drug-drug interactions of linezolid?

Back 56

1. It is a reversible MAOI, so don't give concurrently with another MAOI, tricyclic antidepressants, SSRI, or St. John's Wort
2. Avoid foods high in tyramine

Front 57

What is the mechanism of action of metronidazole?

Back 57

Taken up by anaerobes and converted to an active metabolite that disrupts DNA causing cell death

Front 58

What are the therapeutic uses of metronidazole?

Back 58

1. C. difficile
2. Bacteriodes fragilis
3. Trichomoniasis
4. Giardia
5. Amebiasis

Front 59

What are the major toxicities of metronidazole?

Back 59

1. Nausea, HA, dry mouth
2. disulfiram-like rxn w/ EtOH
3. Not good for pregnant women b/c of potential carcinogenic effects

Front 60

What is the major resistance mechanism to metronidazole?

Back 60

Decrease or loss of enzymes that activate the abx

Front 61

What is the mechanism of action of daptomycin?

Back 61

It is a lipophilic peptide that binds to cell membranes and causes depolarization, loss of potential and death

Front 62

What are the therapeutic uses of daptomycin?

Back 62

1. MRSA
2. VISA
3. VRSA
4. VRE
NOTE: VISA and VRSA have higher MICs

Front 63

Describe the pharmacokinetics of daptomycin

Back 63

Administered IV. 80% excreted in urine

Front 64

What is the major toxicity of daptomycin?

Back 64

Potential for skeletal membrane damage and peripheral neuropathy at high conc.

Front 65

What is the major resistance mechanism against daptomycin?

Back 65

Decrease or loss of enzymes that activate the abx