Utcom Week 9 Antibiotics

Front 1

This drug works by inhibiting transcription in bacteria (i.e DNA --XXX--> RNA)

Back 1

Rifampin

Front 2

Sulfonamides & other anti-metabolites are often ______

Back 2

bacteriostatic (slow growth only)

Front 3

Sulfonamides are ____ and sulfanylmides are used to mimic ___ in _____ acid metabolism

Back 3

antimetabolites
PABA
folic

Front 4

Tetracyclines, chloramphenicol, and erythromycin are _____ while aminoglycosides are ____. They all work by ____.

Back 4

bacteriostatic
bactericidal
inhibiting protein synthesis.

Front 5

Factors that influence drug choice.

Back 5

1.)Sensitivity of the infecting organism to the drug
2.)Distribution of the drug within the body (will it get to the site of infection?)
3.)Relative toxicity of the drug
4.)Severity of the infection

Front 6

For most sites what is the major route of drug uptake?

Back 6

passive diffusion

Front 7

Active transport of anionic and cationic drugs leads to their accumulation in the ____, and their export from the _____.

Back 7

kidney
brain

Front 8

Factors which determine outcome of treatment?

Back 8

Condition of tissue,
status of the patient immune system,
development of microbial resistance

Front 9

When are you most likely to see suprainfection?

Back 9

1.)Prolonged treatment
2.)Use of broad spectrum antibiotics
3.)Immunocompromised patient

Front 10

When should you use drug combinations?

Back 10

Emergency treatment
Prevention of resistance
Synergism
Mixed infections

Front 11

What are the 3 types of beta-lactams?

Back 11

Penicillins
Cephalosporins
Other beta-lactams

Front 12

Most commonly prescribed beta-lactam?

Back 12

amoxicillin

Front 13

Bacteria resistant to penicillin G?

Back 13

Staph aureus (mostly resistant now)
Enterococcus faecalis
Gram Neg Bacilli
Bacteroides fragilis (other bacteroides are susceptible)
Chlamydia

Front 14

The beta-lactam ring is responsible for what properties of beta-lactams?

Back 14

a. essential for antimic. activity
b. responsible for drug allergy
c. responsible for neurotoxicity

Front 15

The weak acid group in beta-lactams is responsible for what properties of beta-lactams?

Back 15

a. renal tubular secretion
b. potential cation toxicity

Front 16

Combination with ____ decreases rate of renal secretion of _____

Back 16

probenicid
Penicillin G

Front 17

Phenoxymethylpenicillin also known as _____, is ____, and has good ______

Back 17

Pen V
acid stable
oral availability

Front 18

The two repoistory pencillins are?

Back 18

Procaine Penicillin G
Benzathine Penicillin G

Front 19

How should repository pencillins be administered?

Back 19

Intramusculary, because they are poorly soluble

Front 20

Which one, Pen G or Pen V should be used against Neisseria?

Back 20

Pen G

Front 21

The beta-lactamase resistant penicillins are?

Back 21

Methicillin (no longer used)
Oxacillin
Cloxacillin
Dicloxacillin
Nafcillin

Front 22

The beta-lactamase resistant penicillins should be used to treat ___?

Back 22

Penicillin G-resistant Staph. aureus
Methicillin (no longer used)
Oxacillin
Cloxacillin
Dicloxacillin
Nafcillin

Front 23

Methicillin is no longer marketed because of ______.

Back 23

renal toxicity (interstitial nephritis

Front 24

Nafcillin is eliminated by ______ – thus there is less chance of ___ in patients with compromised ______

Back 24

biliary excretion
CNS toxicity
renal function

Front 25

Aminopenicillin, Carboxypenicillins
Ureidopenicillins are examples of ___

Back 25

BROAD SPECTRUM PENICILLINS

Front 26

Better oral absorption? amoxicillin or ampicillin?

Back 26

Amoxicillin

Front 27

Available for both oral & parenteral use? amoxicillin or ampicillin?

Back 27

Ampicillin

Front 28

Effective against shigella and listeria? amoxicillin or ampicillin?

Back 28

Ampicillin

Front 29

This broad spectrum penicillin is useful against UTI's because it's concentrated in the urine.

Back 29

Carbenicillin indanyl

Front 30

None of the broad-spectrum penicillins are resistant to _____

Back 30

b-lactamases.

Front 31

B-lactamase inhibitors affect ____ class A b-lactamases but not _____ b-lactamase.

Back 31

plasmid
chromosomal

Front 32

Hypersensitivity, Neurotoxicity
Cation toxicity are all side effects seen with _____

Back 32

penicillins

Front 33

What is the Herxheimer reaction, what drug class associated with it, and what disease is usually being treated?

Back 33

chills, fever, headache, muscle & joint pain shortly after first penicillin injection in patients with syphilis. Rash develops at syphilitic lesions – disappears in a few weeks. Does not recur with subsequent penicillin injections. Usually not necessary to withhold treatment.

Front 34

High doses of penicillin can result in ___ and ___ loss

Back 34

Fluid and electrolyte loss – high doses of any penicillin: penicillin anion is concentrated in renal tubules and produces an osmotic diuresis: increases Na+ uptake by principal cells of collecting tubules & secretion of K+ and H+ into the luminal fluid. Thereby producing hypokalemic alkalosis.

Front 35

Doses of penicillin > 6 g/day can cause ___ anemia.

Back 35

Coombs-positive hemolytic anemia
Penicillin dose > 6 grams/day
About 10% of patients will show a positive Coombs test.
A few patients will become anemic

Front 36

____ was a side-effect that caused methicillin to be withdrawn from the market and often seen with other penicillins (>10g/day) as well.

Back 36

Interstitial nephritis

Front 37

Diarrhea, pseudomembranous colitis, maculopapular rash caused by which two drugs?

Back 37

Ampicillin, amoxicillin

Front 38

Prolonged bleeding caused by platelet inhibition are associated w/ these two drugs?

Back 38

Carbenicillin, ticarcillin

Front 39

Cephalosporins are b-lactams. What ring position substitution is associated with beta-lactamase resistance and spectrum?

Back 39

7

Front 40

Cephalosporins are b-lactams. What ring position substitution is associated with pharmokinetic profile and toxicity?

Back 40

3

Front 41

Which has a broader antimicrobial spectrum? Cephalosporins or penicillin G?

Back 41

Cephalosporins

Front 42

Should cephalosporins be prescribed to people with hypersensitivity reactions to penicillins?

Back 42

Hell no. There is an approximately 10% incidence of cross-hypersensitivity between penicillins and cephalosporins: cephalosporins are generally too risky for use in patients who have had an anaphylactic episode with a penicillin.

Front 43

Second generation cephalosporins are more active versus ____ or ____than 1st gen.

Back 43

Haemophilus
B. fragilis

Front 44

Of the 1st and 2nd generation cephalosporins, only _____ reaches CNS at therapeutic levels. Is it the drug of choice for treatment of meningitis?

Back 44

cefuroxime
no

Front 45

Unique property of 4th generation cephalosporins?

Back 45

Resistant to most beta-lactamases and doesn't induce their expression.

Front 46

Name the only 4th generation cephalosporin we talked about in class.

Back 46

Cefepime
(NOT stable to some extended spectrum b-lactamases )

Front 47

CEPHALOSPORIN used to treat gonorrhea? How is excreted? What generation?

Back 47

Ceftriaxone
biliary excretion (just like Nafcillin)
3rd generation

Front 48

CEPHALOSPORIN used to treat pseudomonas? What generation?

Back 48

Ceftazidime
3rd generation
(plus aminoglycoside for pseudomonal meningitis)

Front 49

Cephalosporins that can be administered orally have an _______

Back 49

alpha-amino group on the substituent attached to carbon 7. This structure allows uptake by a dipeptide transport system in the gut
CEPHALEXIN is an example.

Front 50

Group A 2nd generation cephalosporins used for

Back 50

H. influenzae

Front 51

Group B 2nd generation cephalosporins used for

Back 51

B. fragilis

Front 52

3rd generation cephalosporins use a ____ group to confer stability to b-lactamases of ____

Back 52

Oxime ether group
enterobacteriaceae

Front 53

3rd generation cephalosporins use a ____ group that affects binding to PBPs and entry into the periplasm

Back 53

Aminothiazole ring

Front 54

Cephalosporins are known to cause ___ damage EXCEPT for ____ (looking for a drug name here)

Back 54

Kidney damage (direct tubular necrosis).
Cephalexin and a few other cephalosporins.

Front 55

Adverse effects associated with the methythiotetrazole cephalosporins (e.g., Cefoperazone)

Back 55

Delayed blood clotting because of low prothrombin levels in blood
Alcohol intolerance

Front 56

These two other beta-lactams are Broad spectrum - useful in emergency treatment
No cross-resistance with other b-lactams: they are not recognized well by bacterial b-lactamases

Back 56

meropenem & imipenem - cilastatin

Front 57

This other beta-lactam is Only effective against aerobic Gram neg. bacteria, Not hydrolyzed by b-lactamases
Little cross-allergenicity with other b-lactams

Back 57

Aztreonam

Front 58

Cilastatin inhibits renal ______, an enzyme that inactivates ________

Back 58

dehydropeptidase-1
imipenem

Front 59

____ helps prevent kidney toxicity of imipenem by blocking its active uptake and accumulation by renal tubule cells

Back 59

Cilastatin

Front 60

Most serious side-effect of cilastatin and imipenem?

Back 60

CNS toxicity is the most serious adverse effect: decreased consciousness and myoclonic jerking. In part, this may result from cilastatin inhibition of imipenem transport out of the CSF.

Front 61

Not hydrolyzed by dehydropeptidase-1.
Decreased incidence of CNS toxicity compared with imipenem/cilastatin

Back 61

Meropenem ( an "other" beta-lactam)

Front 62

Binds to PBP-3 of aerobic Gram negative bacteria ONLY. Little cross-allergenicity w/ other beta-lactams

Back 62

Aztreonam

Front 63

Not hydrolyzed by plasmid or chromosomal b-lactamases, and does not induce expression of the latter.
If chromosomal b-lactamases have been induced by other b-lactams, they will bind _______ and prevent it from binding to PBP-3.

Back 63

aztreonam

Front 64

Single i.m. injection for urethral gonorrhea

Back 64

beta-lactam substitute
Spectinomycin (Trobicin®)

Front 65

Treatment of meth.-resistant Staph. aureus (MRSA)
Backup drug for C. difficile pseudomembranous colitis.
Little activity vs Gm- bacilli

Back 65

beta-lactam substitute
Vancomycin

Front 66

Side effects of vancomycin?? (there's a whole bunch)

Back 66

Ototoxic: deafness, sometimes irreversible
Nephrotoxic: Blood & protein in urine
Thrombophlebitis: (clots in bloodstream) occur in over 10% of patients
Hypotension & “red man” syndrome because the drug releases histamine. Administer antihistamines 2 hrs before infusing the drug slowly (over 1 hr) i.v..

Front 67

NEW AGENTS PRIMARILY FOR RESISTANT Gm+ ORGANISMS

Back 67

Quinupristin/dalfopristin (Synercid®)
Linezolid (Zyvox®)
Daptomycin(Cubicin®)

Front 68

A combination of two streptogramins: inhibitors of protein synthesis

Back 68

Quinupristin/Dalfopristin (Synercid IV®)

Front 69

Active against vancomycin-resistant and multidrug-resistant Enterococcus faecium.
NOT active against Enterococcus faecalis

Back 69

Quinupristin/Dalfopristin (Synercid IV®)

Front 70

Main adverse reaction is muscle and joint pain
Inhibits Cyp3A4.

Back 70

Quinupristin/Dalfopristin (Synercid IV®)

Front 71

Parenteral and oral formulations for treatment of vancomycin-resistant enterococci.
Binds to 23S ribosomal RNA – no cross-resistance with other protein synthesis inhibitors

Back 71

Linezolid (Zyvox®)

Front 72

Thrombocytopenia is possible. Platelet counts should be monitored if treatment exceeds two weeks.

Back 72

Linezolid (Zyvox®)

Front 73

_________inhibits MAO – patients should avoid foods rich in tyramine, or drugs metabolized by MAO.

Back 73

Linezolid (Zyvox®)

Front 74

A cyclic lipopeptide antibiotic.
Inserts in cell membrane and causes rapid depolarization

Back 74

Daptomycin(Cubicin®)

Front 75

Indicated for skin and skin structure infections caused by:
Staph. aureus (including MRSA)
Strep. pyogenes
Strep. agalactiae
Strep. dysgalactiae subsp. Equisimilis
E. faecalis (Vanco sensitive)
Toxicities:
Rhabdomyolysis: Monitor patients for muscle pain/weakness. Discontinue if blood CPK>1000 units/L. Consider temporary discontinuation of HMG-CoA reductase inhibitors (“statins”).
Paresthesias (at high doses).

Back 75

Daptomycin(Cubicin®)

Front 76

Bacterial Protein Synthesis Inhibitors
BROAD SPECTRUM? (name 2 classes)

Back 76

Chloramphenicol
Tetracyclines

Front 77

Bacterial Protein Synthesis Inhibitors
Intermediate SPECTRUM? (name 2 classes)

Back 77

Macrolides
Ketolides

Front 78

Bacterial Protein Synthesis Inhibitors
Narrow SPECTRUM? (name 3 classes)

Back 78

Lincosamides
Streptogramins
Linezolid

Front 79

Bacterial Protein Synthesis Inhibitors
All act on bacterial ___S ribosome except ____ which act on ____S

Back 79

50S
tetracyclines; 30S

Front 80

Describe tetracycline mode of action.

Back 80

Reversible binding to 30S ribosome subunit blocks aminoacyl-tRNA access to acceptor site (A site)

Front 81

What organisms are tetracyclines active against?

Back 81

Active against many Gram + and Gram – bacteria including anaerobes, rickettsiae, chlamydiae(intracellular things), mycoplasmae (no wall).
Some drugs act against protozoa
(e.g. doxycyline: Entamoeba and Plasmodium falciparum

Front 82

2 ways tetracycline gets taken in by cells?

Back 82

Both passive diffusion and active uptake by bacteria with intracellular concentration.

Front 83

3 modes of resistance developed to tetracyclines?

Back 83

1.)Upregulation of efflux pump
2.)Production of proteins interfering with ribosomal binding
3.)Can sometimes find
Impaired uptake via the active process
Enzymatic inactivation of the drug

Front 84

Tetracyclines are usually administered ___ except ___ which is administered by ___

Back 84

orally
tigecycline; IV

Front 85

What interferes with absorption of tetracyclines?

Back 85

Interference of uptake by food, divalent cations (Ca++, Mg++, Fe++ ) and antacids, dairy products.

Front 86

Tetracyclines Enter all body fluids well except ____

Back 86

CSF

Front 87

Tetracyclines are excreted in the ___ and ____ except these two drugs (__ and ___) which are only excreted in the _____

Back 87

bile and urine
doxycycline and tigecycline are exclusively in bile

Front 88

true or false? tetracyclines enter breast milk and cross placenta?

Back 88

true

Front 89

Side-effect of tetracycline discussed extensively in class

Back 89

Chelation with calcium causes binding to growing bones/teeth - damage.
Stained teeth

Front 90

Huge list of Tetracycline side effects

Back 90

Irritation of GI tract (diarrhea, vomiting, nausea)
Gastrointestinal effects due to microbial flora change
Effects on bones and teeth
Some minor liver toxicity but can be pronounced during pregnancy, in persons with liver dysfunction or with high I.V. drug doses
High does may cause dizziness etc (vestibular toxicity)

Significant urinary excretion of most drugs means accumulation to high dose and more toxicity can be found in persons with impaired kidney function (not for tigecycline/doxycyline which are excreted only via bile

Hypersensitivity (drug fever and skin rashes) is uncommon. Occasional cases of photosensitivity reported after i.v. tetracyclines

Front 91

____ has very broad spectrum of activity but NOT effective against ____ or ____ where the efflux pump is effective thereby causing intrinsic resistance.

Back 91

Tigecycline

Pseudomonas or Proteus

Front 92

Approx 30% patients develop nausea
IV admin
Excreted in bile.
Name the drug

Back 92

Tigecycline

Front 93

Class of drug w/ Macrocyclic lactone ring
with deoxy sugars
attached

Back 93

Macrolides

Front 94

Macrolides include:

Back 94

Erythromycin
Clarithromycin
Azithromycin
Kelotides (telithromycin)

Front 95

Macrolides mode of action

Back 95

block transpeptidylation; bind to 50S ribosomal subunit

Front 96

Macrolides: susceptible organisms

Back 96

Many Gram positive and negative organisms including Neisseria
Some mycobacteria
Intracellular bacteria, spirochetes (Treponema), Mycoplasmae, Legionella, Listeria, Helicobacter.

Front 97

Methylation of the binding site in the 50S ribosome
blocks all ___ plus ___ and _____

Back 97

macrolides
clindamycin (lincosamide)
streptogramin B
MLSb resistance

Front 98

Erythromycin Resistance is usually plasmid or chromonsomally encoded? What are some ways resistance is conferred?

Back 98

plasmid

Reduced intracellular concentration
Reduced cell permeability
Increase active efflux

Hydrolysis by esterases
Methylation of the binding site in the 50S ribosome

Front 99

Erythromycin is excreted in what?

Back 99

bile

Front 100

Erythromycin base is destroyed by ______

Back 100

stomach acid (enteric coating needed).
Esters and salts can provide acid resistance.
Food interferes with uptake
i.v. preparations also used

Front 101

What drug for
Corynebacterium sp infections including erythrasma & diphtheria (to eradicate the organism)

Chlamydial infections

Community acquired pneumonia (because it covers both Strep pneumoniae and Legionella)

Used for susceptible Staph and Strep infections with penicillin-allergic persons

Back 101

erythromycin

Front 102

_______metabolites inhibit cytochrome P450 enzymes (increased theophylline, oral anticoagulants, cyclosporine, methylprednisone)
Increases bioavailability of oral digoxin

Back 102

erythromycin

Front 103

Similar to erythromycin but also works on
Mycobacterium avium and M. leprae, Toxoplasma gondii

Back 103

Clarithromycin

Front 104

Similar to clarithromycin but does not interact with cytochrome P450 enzymes (smaller macrocyclic ring)
Very active against Chlamydia
Penetrates tissues to high concn with in slow release, 3 day half life.
Once a week dosing – very useful for STDs

Back 104

Azithromycin

Front 105

For macrolide-resistant strains where efflux pumps give resistance. Doesn’t work with resistance due to methylated target in ribosome.
Useful for community acquired pneumonias (Mycoplasma, Chlamydia, Legionella, Strep pneumoniae).
Interacts with cytochrome P450 3A4

Back 105

Ketolides (Telithromycin) small macrocyclic ring

Front 106

High risk of inducing Clostridium difficile pseudomembranous colitis
Mainly used for acne (as lotion) and in antibiotic combinations for treating and preventing mixed anaerobe infections
(penetrating abdominal wounds,
endocarditis prophylaxis in dental procedures
pelvic abscess & septic abortion)

Back 106

Clindamycin

Front 107

Chloramphenicol mode of action?

Back 107

Chloramphenicol Binds 50S subunit and blocks transpeptidation

Front 108

Active against rickettsiae
Not active against chlamydiae

Back 108

Chloramphenicol

Front 109

Clinical resistance mainly associated with plasmid encoded acetyltransferase which inactivates the drug

Back 109

Chloramphenicol

Front 110

May be taken orally – absorbed very well
Provided as a succinate salt for i.v. use
as base is insoluble - hydrolyzed in vivo.
Distributes into all body fluids and tissues
including CNS
Inactivated in liver
Metabolites and free drug mainly excreted in urine

Back 110

Chloramphenicol

Front 111

Inactivation is via conjugation with glucuronic acid
Conjugate excreted mainly in urine

If liver dysfunction present, dosage must be reduced greatly since drug metabolism is mainly in the liver.

Back 111

Chloramphenicol

Front 112

Dose-related suppression of red cell production – can lead to aplastic anemia (rare)

Is bacteriostatic so may antagonize b-lactams where killing of bacteria depends on bacterial growth

Inhibits liver metabolism of several drugs (including warfarin, phenytoin)

Back 112

Chloramphenicol

Front 113

Name the drug:
Newborn infants have poor glucuronic acid conjugation activity - develop gray baby syndrome
gray color, flaccidity, hypothermia, shock

Back 113

Chloramphenicol

Front 114

Toxicity limits routine use of ______ in spite of extremely good bioavailability and range of microbes inhibited.

Back 114

Chloramphenicol

Front 115

Largely restricted to serious rickettsial infections and for bacterial meningitis when beta-lactams cannot be used.

Topical use in eye infections (but not effective for Chlamydia)

Back 115

Chloramphenicol

Front 116

Drug combination of a streptogramin A with a streptogramin B

Back 116

Quinupristin-dalfopristin

Front 117

Treatment of staphylococcal infections including VRSA and MRSA

Back 117

Quinupristin-dalfopristin

Front 118

Treatment of vancomycin-resistant Enterococcus faecium (but not E. faecalis)

Back 118

Quinupristin-dalfopristin

Front 119

Active against Gram-positives (including anaerobes) – including MRSA, VRSA, enterococci (both E. faecium & E. faecalis)

Back 119

Linezolid (an oxazolidone)

Front 120

Binds at a unique site on the 50S ribosome subunit causing protein synthesis inhibition. No cross-reactivity of resistance with other antibiotics

Back 120

Linezolid (an oxazolidone)

Front 121

Adverse effects include mild thrombocytopenia and bone marrow suppression

Back 121

Linezolid (an oxazolidone)