Pharm Block4 Pack3

Front 1

What is the structure of Aminoglycosides?

Back 1

Amino sugars attached by glycosidic linkages

Front 2

What are the only two topical Aminoglycosides?

Back 2

Neomycin and Gentamicin

Front 3

Aminoglycosides demonstrate ______-dept killing.

Back 3

CONCENTRATION-dept killing
*High levels of antibiotic facilitate entry thru cell wall and membrane

Front 4

Since Aminoglycosides demonstrate a post-antibiotic effect,
how often can they be administered?

Back 4

One or two large doses each day to achieve HIGH peak levels

Front 5

What are Aminoglycosides' toxicity related to?

Back 5

Trough levels and host tissue "recovery time"

Front 6

Aminoglycosides are polar compounds, how are they absorbed?
Oral or Parenteral?

Back 6

NOT absorbed orally
Mostly PARENTERAL

Front 7

What about the Aminoglycoside Neomycin negates parenteral use?

Back 7

SEVERE TOXICITY

Front 8

Since Aminoglycosides are excreted renally,
what needs to occur in tx of pts w/ renal insufficiency?

Back 8

Dose adjustments

Front 9

How well do Aminoglycosides penetrate protected sites
such as the CNS, sputum, bile, and prostate?

Back 9

POORLY

Front 10

Since Aminoglycosides' activity are pH dependent, what may decrease their activity?
Hint: 7.4>>7.0

Back 10

Acidosis may decrease activity

Front 11

What is the mechanism of action of Aminoglycosides? Static or cidal?

Back 11

Binds to 30S subunit
BACTERICIDAL

Front 12

What makes the Aminoglycosides' mechanism of action unique?

Back 12

One of the only bacterICIDAL inhibitors of ribosomal activity

Front 13

What are the 3 mechanisms of resistance against Aminoglycosides?

Back 13

1. Plasmid mediated formation of inactivating enzymes - group transferases
2. Inhibition of drug penetration (porin mutations)
3. Decreased affinity of 30S subunit target site

Front 14

What is the spectrum of Aminoglycosides?

Back 14

E. coli, Proteus, Klebsiella
Enterobacter and Serratia
Pseudomonas
*Moderate gram positive coverage as well

Front 15

Are Aminoglycosides used alone or in a combination?

Back 15

Less potent when used alone
--> commonly used in combination

Front 16

What are the 3 clinical uses of Aminoglycosides?

Back 16

1. Serious gram negative infections in hospitalized pts
2. Empirically for neonatal infections
3. 1st and 2nd line against mycobacterial infections!

Front 17

What class of drugs are Aminoglycosides synergistic with?

Back 17

Cell Wall Active drugs

Front 18

What are the 3 major toxicities of Aminoglycosides?

Back 18

1. Significant RENAL toxicity
2. Ototoxicity
3. Neuromuscular blockade

Front 19

What are 2 features of the acute tubular necrosis caused by Aminoglycosides?

Back 19

1. REVERSIBLE
2. Dose related

Front 20

What are 3 features of the ototoxicity associated w/ Aminoglycosides?

Back 20

1. Auditory or Vestibular
2. IRREVERSIBLE
3. Dose related

Front 21

Are Aminoglycosides approved for use in pregnancy?

Back 21

NO! - not approved for use in pregnancy

Front 22

What are the 4 major Aminoglycosides? 3 minor?

Back 22

STREPTOMYCIN, TOBRAMYCIN
AMIKACIN, GENTAMICIN

Kanamycin, Neomycin, Netilmicin

Front 23

What is the average half-life of Aminoglycosides?

Back 23

2-3 hours

Front 24

How are Aminoglycosides inactivated in bacterial resistance?

Back 24

Inactivating enzymes add a METHYL group to them

Front 25

Besides the prototype Tetracycline,
what are the other 3 Tetracyclines?

Back 25

OXYTETRAcycline
DOXYcycline
MINOcycline

Front 26

Tetracyclines' oral absorption is variable, what further impairs it?

Back 26

Impaired by FOOD

Front 27

After Tetracyclines undergo hepatic cycling, where are they excreted?
Hint: Tetra 1, Doxy 2

Back 27

Tetracycline in URINE
Doxycycline in POOP

Front 28

What are the half-lives like for Tetracyclines?
How do the half-lives of Tetracycline and Minocycline compare?

Back 28

Half-lives --> 8 to 18 hrs
Tetracycline < Minocycline

Front 29

Do Tetracyclines have any synergism or antagonism?

Back 29

ANTAGONISTIC w/ Beta Lactams

Front 30

What is the mechanism of action of Tetracyclines?

Back 30

Binds to 30S subunit --> inhibits attachment of aminoacyl-tRNA

Front 31

Are Tetracyclines static or cidal?

Back 31

BacterioSTATIC

Front 32

What are 2 mechanisms of microbial resistance against Tetracyclines?

Back 32

1. Plasmid mediated facilitated efflux of the drug
2. Decreased entry into the bacterial organism (porin mutations)

Front 33

What is the spectrum of Tetracyclines?

Back 33

Gram positive Staph and Strep
Gram negative Enterics
Anaerobes
Atypical agents

Front 34

What 6 atypical agents are Tetracyclines effective against?

Back 34

Mycoplasma, Chlamydia, Chancroid
Rickettsia, Borrelia, Entamoeba

Front 35

What are the 6 clinical uses of Tetracyclines?

Back 35

1. Subacute Bronchitis due to H. influenzae and Strep pneumoniae
2. Atypical pneumonia
3. STDs (Chlamydia, Mycoplasma, Prostatitis)
4. Rocky Mountain Spotted Fever
5. Lyme Disease
6. Acne

Front 36

What are the 7 toxicities of Tetracyclines?

Back 36

1. Usual GI
2. Effects on bone & teeth
3. Hepatic necrosis (maybe fatal)
4. Renal tubular acidosis
5. Photosensitivity
6. CNS - headache
7. Vestibular - dose dept
8. Pseudotumor cerebri

Front 37

Which Tetracycline is especially toxic for the liver?

Back 37

Doxycycline - may be fatal!

Front 38

Who are Tetracyclines contraindicated in?

Back 38

FETUS and CHILDREN due to effects on bone and teeth

Front 39

What reaction may be triggered as a toxicity of Tetracyclines?

Back 39

Jarisch-Herxheimer reaction
(massive release of cytokines in response to rapid lysis of pathogens)

Front 40

Which tetracycline is Tigecycline a glycylcycline derivative of?
How is Tigecycline administered?

Back 40

Minocycline
IV use only

Front 41

What is the mechanism of action of Tigecycline ?

Back 41

HIGH affinity binding to 30S subunit --> blocks amino-acyl tRNA binding

Front 42

The half-life of Tigecycline is 42 hrs, so it is dosed q 12.
Is it static or cidal?

Back 42

BacterioSTATIC

Front 43

Tigecycline is well distributed into the tissues,
but how is it metabolized and where is it excreted?

Back 43

Metabolized in the LIVER
Excreted into BILIARY TRACT

Front 44

What organisms is Tigecycline effective against?

Back 44

MRSA, MRSE, VRE
Resistant pneumococci and enterococci
Acinetobacter and other gram negative aerobes and anaerobes

Some mycobacteria and mycoplasma
NOT PSEUDOMONAS

Front 45

What drug is Tigecycline synergistic with?

Back 45

Rifampin

Front 46

What 2 types of infections is Tigecycline used for clinically?

Back 46

1. Skin and skin structure infections
2. Intra-abdominal infections

Front 47

Is Tigecycline approved for children?

Back 47

NO - not approved for children

Front 48

What are the 4 toxicities of Tigecycline?

Back 48

1. Nausea and Vomiting
2. Headache and Pseudotumor cerebri
3. Possible bone and tooth discoloration
4. Transaminase elevation

Front 49

Does a cross hypersensitivity exist between Tigecycline and Tetracyclines?

Back 49

YES CROSS HYPERSENSITIVITY

Front 50

Which antimicrobial is rare, the only one in its class, and is rarely used in the US because of feared toxicity?

Back 50

CHLORAMPHENICOL

Front 51

Chloramphenicol has a half life of 2 to 3 hrs, by which ways is it absorbed?

Back 51

EXCELLENT oral absorption
Very effective when used IV too!

Front 52

Why is Chloramphenicol the single most effective antbiotic in terms of ease of distribution?

Back 52

Very LIPOPHILIC

Front 53

Chloramphenicol undergoes enterohepatic cycling, but which enzyme metabolizes it?

Back 53

Glucuronyltransferase

Front 54

Does Chloramphenicol inhibit or induce Cytochrome P450?

Back 54

INHIBITS Cytochrome P450

Front 55

What is the mechanism of action of Chloramphenicol?

Back 55

Binds 50S subunit --> inhibits peptidyl transferase

Front 56

Is Chloramphenicol static or cidal?

Back 56

BacterioSTATIC

Front 57

What are the 2 mechanisms of bacterial resistance against Chloramphenicol?

Back 57

1. Plasmid mediated production of antibiotic inactivating enzyme
2. Reduced membrane permeability (porin mutations)

Front 58

What is the spectrum of Chloramphenicol?

Back 58

Fairly broad
H. influenza, N. meningitides
Salmonella, Anaerobes, Rickettsia

NOT Staph, NOT Pseudomonas

Front 59

Chloramphenicol is usually not used because of its toxicity, except for which 3 clinical uses?

Back 59

1. Brain abscess
2. Typhoid Fever
3. Rocky Mountain Spotted Fever

Front 60

What are the 3 major toxicities of Chloramphenicol?

Back 60

1. Idiosyncratic Aplastic Anemia
2. Dose related Aplastic Anemia
3. GRAY BABY SYNDROME

Front 61

What is Gray Baby syndrome, which is caused by Chloramphenicol?

Back 61

Inability to conjugate Chloramphenicol because of immaturity/ decreased levels of glucuronosyl transferase

Front 62

What are the 4 Macrolides/Ketolides?

Back 62

ERYTHROmycin
CLARITHROmycin
AZITHROmycin
TELITHROmycin

Front 63

What are Macrolides?

Back 63

Large cyclic lactone rings w/ attached sugars

Front 64

Which Macrolide has the longest half life?
Hint: 72 hrs

Back 64

Azithromycin

Front 65

Which Macrolides has the best oral absorption?

Back 65

Clarithromycin

Front 66

Which Macrolides has the shortest half-life?
Hint: 1.4 hrs

Back 66

Erythromycin

Front 67

Macrolides are generally used orally, and have a good
tissue distribution, except where?

Back 67

Except CNS and EYE

Front 68

Where do Macrolides become concentrated?

Back 68

Concentrates in respiratory secretions

Front 69

Where does Azithromycin specifically become concentrated?

Back 69

Phagocytic cells and other tissues

Front 70

Macrolides are mostly metabolized and excreted in the liver, but they also have some urinary excretion. Which one has the most?

Back 70

Azithromycin

Front 71

What is the mechanism of action of Macrolides?

Back 71

Bind to 50S subunit --> prevent ribosomal translocation down mRNA

Front 72

Are Macrolides static or cidal?

Back 72

BacterioSTATIC

Front 73

What are the 4 mechanisms of resistance against Macrolides?

Back 73

1. Plasmid mediated target alteration by a methylase (eg. Strep pneumo)
2. Production of inactivating enzymes (eg. enterobacteriaceae)
3. Decrease in organism permeability
4. Increased efflux (mef A gene)

Front 74

What gene encodes for the HIGH level resistance against Macrolides that results in target alteration?

Back 74

Methylase encoded by the ERM BETA gene

Front 75

Which gene encodes for the LOW level resistance against Macrolides that results in increased efflux?

Back 75

Mef A gene

Front 76

What is the spectrum of Macrolides?

Back 76

Gram positive organisms; NOT ENTEROCOCCUS
Some anaerobes, Salmonella (Typhoid Fever)
Legionnaire's disease, Mycoplasma, Chlamydia,
Bordetella pertussis, Campylobacter, Atypical Mycobacteria

Front 77

Which infections is Azithromycin the DOC for?

Back 77

Salmonella (Typhoid Fever)
Bordetella pertussis

Front 78

Which infections is Clarithromycin the DOC for?

Back 78

Atypical Mycobacteria

Front 79

What are the clinical uses of Macrolides?

Back 79

1. Penicillin substitute for respiratory bacterial infections
2. Atypical pneumonia; Whooping cough
3. Atypical TB (MAI)
4. Resistant Salmonella

Front 80

Which Macrolides is used for Atypical TB (MAI)?

Back 80

Clarithromycin

Front 81

Which Macrolides is used for resistant Salmonella infections?

Back 81

Azythromycin

Front 82

All the Macrolides are contraindicated in pregnancy except?

Back 82

Azithromycin

Front 83

Besides abdominal pain and nausea, what other toxicity occurs in Macrolides?

Back 83

Cholestatic hepatitis (Erythromycin estolate)

Front 84

What are Macrolides associated with an increased incidence of in infants?

Back 84

Pyloric stenosis

Front 85

Which Macrolide doesn't cause multiple drug interactions secondary to inhibition of hepatic cytochrome enzymes?

Back 85

Azithromycin

Front 86

Which 2 CYP enzymes metabolize Telithromycin in the liver?

Back 86

Half by CYP450
Half by CYP 349

Front 87

What organisms does Telithromycin work against?

Back 87

PCN resistant pneumococci
H. influenza, M. catarrhalis, B. pertussis
Mycoplasma, Legionella, Chlaymdia

Front 88

What are the 5 toxicities of Telithromycin?

Back 88

1. Blurred vision
2. GI disturbances
3. Prolonged QT interval
4. Exacerbation of Myasthenia gravis
5. Multiple drug interactions

Front 89

What type of antibiotic is Clindamycin? Static or cidal?

Back 89

Lincosamide antibiotic
BacterioSTATIC

Front 90

Which drug class does Clindamycin have a similar mechanism of action to?
Cross-resistance?

Back 90

Macrolides
Leads to cross-resistance mediated by increased efflux

Front 91

How good is the tissue absorption of Clindamycin?

Back 91

GOOD oral absorption (90%!!) and tissue penetration
BUT NOT CNS or EYE

Front 92

Clindamycin has a half-life of 2.5 hrs, is it static or cidal?

Back 92

STATIC

Front 93

Which 2 groups does Clindamycin have excellent activity against?

Back 93

1. Gram positive infections (Staph aureus, severe invasive Strep)
but NOT ENTEROCOCCI
2. Anaerobes

Front 94

Besides the usual toxicity profile, what is unique about Clindamycin?

Back 94

Pseudomembranous colitis secondary to C. difficile overgrowth

Front 95

What is Synercid a streptogramin combination of?

Back 95

Quinupristin and Dalfopristin

Front 96

Which organ metabolizes and excretes Synercid?
Oral or IV use?

Back 96

LIVER
Only for IV use
*half-life = 1 to 3 hrs

Front 97

What is the mechanism of action of Synercid?
Hint: binds to unique sites

Back 97

Binds to 50S subunit --> prevents ribosome from translocating down the mRNA & prevents protein synthesis at elongation step

Front 98

Is Synercid cidal or static?

Back 98

BacteriCIDAL

Front 99

What are the 3 mechanisms of resistance against Synercid?

Back 99

1. Induction of inactivating enzymes
2. Increased efflux
3. Drug target modification

Front 100

What is the spectrum of Synercid?

Back 100

Staph aureus and Staph epidermidis
Strep pyogenes and Strep agalactiae, some enterococci

Front 101

Synercid toxicity prevents widespread use, what are the 4 major toxicities?

Back 101

1. Drug interactions
2. Phlebitis (40%)
3. Jaundice (30%)
4. Arthralgia and Myalgia (20%)

Front 102

The oxazolidione Linezolid is well absorbed orally and also available by IV,
what is the half-life?

Back 102

5 hours

Front 103

Linezolid is metabolized in the ___________ and excreted by the ___________.

Back 103

Metabolized in LIVER
Excreted by KIDNEY

Front 104

Which drug does Linezolid have a better penetration into the lung than?
(specifically for tx of pneumonia)

Back 104

Vancomycin!

Front 105

Is the AUC of Linezolid altered by food intake?

Back 105

NO - oral bioavailability is 100%
*low protein binding (31%), indpt of drug concentration

Front 106

What is the mechanism of action of Linezolid?

Back 106

Binds to 50S subunit --> inhibits initiation complex and translocation of tRNA

Front 107

Is Linezolid static or cidal?

Back 107

BacterioSTATIC

Front 108

What is the mechanism of resistance to Linezolid?

Back 108

Decreased target site affinity (target alteration)

Front 109

What is the spectrum of Linezolid?

Back 109

All aerobic gram positive bugs especially
Resistant Staph, Strep and Enterococci

Front 110

What are the 3 major toxicities of Linezolid?

Back 110

1. Thrombocytopenia
2. Neutropenia
3. Weak MAO inhibition

Front 111

Is the bone marrow suppression caused by Linezolid reversible or irreversible?

Back 111

REVERSIBLE bone marrow suppression