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PHARM/MHD EXAM - 3 > L2 Pharm: Penicillin > Flashcards

L2 Pharm: Penicillin Flashcards

1
Q

B- Lactam (Penicillins):

  1. What is the MOA?
A
  1. Inhibit cell wall synthesis
    - bind & inhibit PBPs in the bacterial cell membrane (penicillin binding proteins)

HYDROLYZES THE CYCLIC AMIDE BOND F THE B-LACTAM RING, inactivating the antibiotic

*Number, type and location of PBPs vary
between bacteria
- PBPs are only expressed during cell division

  • Inhibition of PBPs leads to inhibition of final transpeptidation step of peptidoglycan synthesis
    (inhibits cross-linking)
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2
Q
  1. What is the half life of B lactam?
  2. How is it eliminated?
  3. What are 4 drugs that are exceptions to this?
  4. True or False: Cross-Allergenicity is not present.
A
  1. SHORT - less than 2 hours
  2. Eliminated unchanged by KIDNEYS
  3. Except:
    - nafcillin
    - oxacillin
    - ceftriaxone
    - cefoperazone
  4. FALSE: CROSS-ALLERGENICITY
    - all except AZTREONAM
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3
Q

What structure do all penicillins share?

A
  1. Share a B lactam ring attached to a 5 membered thiazolidine ring
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4
Q

Penicillins:

What are the Mechanisms of Resistance? (3)

A
  1. a) B-lactamase degradation
    (more effective in gram -)

b) PBP alteration, decreased binding affinity (MRSA, PRSP)
c) Alteration of outer membrane porin proteins –> decreased penetration (gram -)

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5
Q

Are penicillins bactericidal or bacteriostatic? (exception)

What is the function of the transpeptidase?

A
  1. Bactericidal (kill bacteria)
    - EXCEPT against Enterococcus
  2. Transpeptidase - cross-links the peptides in the membrane (B- lactase inhibit the transpeptidase)
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6
Q

How do gram positive bacteria destroy the B-Lactams?

Gram negative?

A
  1. B-lactamase destroys the B-Lactam antibiotics EXTRACELLULARLY
  2. Gram Negative:
    - B - lactase produced in periplasmic space and inhibit the B-Lactam in this space

THEREFORE: cannot reach the PBP target due to poor penetration of the outer membrane

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7
Q 
What are the mechanisms of resistance for Staphylococcus
aureus (MRSA) and penicillin-resistant
Streptococcus pneumoniae (PRSP)?
A

2 mechanism:

Alteration in structure of PBPs leads to DECREASED BINDING AFFINITY

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8
Q

What mechanism of resistance is specific for gram NEGATIVE bacteria?

A

3 Mechanism:

Alteration of outer membrane PORIN PROTEINS leading to decreased
penetration
- or EFFLUX PUMPS that don’t
allow the bacteria to stay within the cell

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9
Q

Define Natural Penicillins.

What are some examples of natural penicillins?

  • Parenteral (3)
  • Oral (1)

Which is short acting?
Which is long acting?

A
  1. Aqueous penicillin G (IV)
  2. Benzathine penicillin G (IM, LONG-acting)
    * given once a week for latent syphillis
  3. Procaine penicillin G (IM)
    * SHORT acting
  4. Oral: Penicillin VK
    * more bioavailable and better absorbed
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10
Q

Natural Penicillins:
Penicillin G and Penicillin VK have excellent activity against which

  1. Gram positive Cocci & Bacilli (6)
  2. Gram negative Cocci (2)
  3. Gram Negative Anaerobe (1)
  4. Other (1)
A
  1. Gram positive Cocci & Bacilli:
  • Group Streptococci* (A, B, C, F, G)
  • Viridans Streptococci*
  • pen-susc. S. Aureus
  • pen-suss. S. Pneumoniae
  • Enterococcus spp.
  • Bacillus Spp.
  1. Gram negative Cocci
    - Neisseria Spp.*
    - Pasteurella multocida
  2. Gram Negative Anaerobe
    - Clostridium Spp. *
    - -> above the diaphragm
  3. Other
    - Treponema Pallidum (syphillis)
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11
Q

Penicillinase - Resistant Penicillins:

  1. Developed in response to the emergence
    of penicillinase-producing ________.
  2. Synthetic derivatives of natural
    penicillin - contain an _____ side chain
  3. What are some examples of Penicillinase resistance Penicillins?
    - Parenteral (3)
    - Oral (1)
A
  1. Staphylococcus
  2. Acyl
3. 
Parenteral:
- Nafcillin
- Oxacillin
- Methicillin
* Dicloxacillin (oral)
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12
Q

What is considered to be the drug of choice for the treatment of infections of the following bacteria? (7)

  1. Treponema Pallidum (syphillis)
  2. Neisseria Meningitidis
  3. Corynebacterium diphtheria
  4. Bacillus Anthracis (anthrax)
  5. Clostridium perfringens
    & Tetani
  6. Viridans
  7. Group Streptococci
A

Penicillin G

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13
Q

Why were Penicillinase Resistant Penicillins developed?

STATE 4.

A

To overcome the penicillinase enzyme of Staphylococcus Aureus, which inactivated NATURAL PENICILLIN

  • containg an acyl side chain that streakily inhibits the action of penicillinase by preventing opening of the B lactam ring
  1. Nafcillin
  2. Methicillin
  3. Oxacillin
  4. Dicloxacillin * (oral)
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14
Q

What are the 3 gram positive bacteria susceptible to Penicillinase Resistant Penicillins?

What do these drugs have no activity against?

A
  1. Methicillin - susceptible S. Aureus (MSSA)
  2. Group Streptococci
  3. Viridians Streptococci

No gram negative activity & limited anaerobic activity

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15
Q

Antibiotic Resistance in Staphylococcus aureus:

First report of methicillin-
resistant S. aureus (MRSA)
caused by PBP alteration
mediated by _____ gene which confers resistance to all beta- lactams except what drug?

A
  1. mecA
  2. ceftaroline
    - only antibiotic for Staph. Aureus
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16
Q

Aminopenicillins:

  1. were developed in response to what?
  2. Semisynthetic derivative of NATURAL penicillin by adding what?
  3. State 3 examples
    (1 parenteral, 2 oral)

WHAT ARE THEY INEFFECTIVE AGAINST BECAUSE OF PENICILLINASE?

A

AMINOPENICILLINS:

  1. Gram negative Aerobes
  2. Adding an amino group
  3. Parenteral: AMPICILLIN

Oral: Ampicillin
& Amoxicillin

  1. Staph Aureuas
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17
Q

What are gram positive bacteria that are susceptible to Aminopenicillins? (2 really important, 4 others)

Gram negatives? ( 5 )
**KNOW THESE **

A

AMINOPENICILLINS
(Ampicillin, Amoxicillin)

\_\_\_\_\_\_\_\_\_\_\_\_\_\_
Gram Positive:
1. Enterococcus Spp.*
2. Listeria Monocytogenes
- pen-susc. S. aureus
- pen- suss. S. Pneumo
- Group Streptococci
- Viridans Streptococci

_____________________
Gram negative:

  1. Proteus mirabilis
  2. some E. coli
  3. Salmonella
  4. Shigella
  5. βL- H. influenzae
    - (only B-lactamase negative strains)
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18
Q

CARBOXYPENICILLINS:

  1. Developed in response to the need for what?
  2. Semisynthetic derivatives of natural
    penicillin – addition of _____ group
  3. What is the only drug for this??
A
  1. Agents with ENHANCED activity against gram negative bacteria & increasing frequency of Pseudomonas Aeriginosa as a nosocomial pathogen
  2. Carboxyl
  3. TICARCILLIN
    - Parenteral ONLY

(not available anymore anyways)

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19
Q

Carboxypenicillins:

  1. state the activity against Gram Negative bacteria
  2. Are there any gram positives bacteria it eradicates?
A
  1. PSEUDOMONAS AERUGINOSA
    - Proteus mirabilis
    - Salmonella, Shigella
    - some E. coli
    - βL+ H. influenzae
    - Enterobacter spp
  2. Marginal activity for gram positives
  • streptococcus spp. (less active)
  • NOT ACTIVE against Enterococcus or Staphylococcus
  • NOT active against Klebsiella spp., Serratia spp., or Actinobacter spp.
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20
Q

UREIDOPENICILLINS:

  1. Developed in response to the need for agents with MORE enhanced activity against what?
  2. Semisynthetic derivatives of the amino-
    penicillins with ____.
  3. State an example (parenteral? oral?)
A
  1. In response to enhanced activity against GRAM NEGATIVE bacteria
  2. acyl side chain adaptations
  3. NO ORAL
    - Parenteral: PIPERACILLIN**
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21
Q

What class of penicillins are the broadest spectrum penicillins available without B-Lactamase Inhibitors?

A

UREIDOPENICILLINS

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22
Q

Ureidopenicillins have fairly good activity against ___

State the Gram Negative Bacteria it works against.

A
  1. Anaerobes
  2. a) Pseudomonas Aeriginosa*
    b) Enterobacter sp
    c) Klebsiella spp.
    d) Serratia Marcescens

+

  • Proteus Mirabilis
  • Salmonella
  • Shigella
  • E.Coli
  • Bl+ H influenza

Gram Positives:
-Viridians strep
-Group strep
Enterococcus

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23
Q

B- Lactamase Inhibitors:

  • Combination product of B-Lactamase & Penicillins
  1. Protect penicillins from being hydrolyzed by
    some β-lactamases by doing what?
  2. Very weak to no _______ activity
  3. Examples? (4)
A
  1. by irreversibly binding
    to catalytic site of β-lactamase enzyme
  2. Antibacterial
    • Clavulanate (+Amoxi)
    • Sulbactam (+Ampic)
    • Tazobactam (+Piperacil.)
    • Avibactam (used in combo with cephalosporins)
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24
Q
  1. Why were B- Lactamase Inhibitor Combinations developed?
Examples?
Parenteral 
a) What makes Unasyn
b) What makes Timentin
c) what makes Zosyvn

Enteral (1)

A
  1. To enhance the activity of Penicillins against B lactase produce bacteria
    a) Ampicillin- Sulbactam (Unasyn)
    b) Ticarcillin - Clavulunate (Timentin)
    c) Piperacillin/Taxobactam (Zosyn)

Oral: Amoxicillin - Clavulanate (Augmentin)

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25
Q

What Gram positive bacteria is killed by B-Lactamase Inhibitor combos? (1)

Gram Negative? (2 important, 4 others)

Anaerobe? (1)

What is ticarcillin/clavulanate extremely active against?

A
  1. S. Aureus (NOT MRSA)*
  2. H. Influenzae *
    Moraxella Catarrhalis*

E. Coli
Proteus Spp.
Klebsiella Spp.
Neisseria Gonorrhea

  1. Anaerobe:
    - Bacteroides spp. *

** TICARCILLIN/CLAVULANATE is active against STENOPHTROPHOMONAS MALTOPHILIA

Anaerobes:
- increased activity against B. Fragilis & B. Fragilis group (DOT) organisms

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26
Q
  1. Penicillins display ____ dependent bacterial killing
  2. Time above MIC correlates with what?
  3. All penicillins are bactericidal, but display bacteriostatic activity against ENTEROCCOCUS & STAPHYLOCOCCUS with the addition of what?
  4. What can this be used in the treatment of?
A
  1. Time dependent
  2. Efficacy
    - no significant PAE for gram negative bacteria
    (post-antibiotic effect)

HOWEVER significant for gram +

  1. AMINOGLYCOSIDE
    (gentamicin, streptomycin)
  2. used in treatment of Enterococcal Endocarditis
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27
Q

Absorption:

  1. Many penicillins degraded by _____
  2. Oral penicillins variable absorbed; since concentrations achieved with oral dosing are lower than those with parenteral dosing, oral therapy should only be used for what type of infections?
A
  1. Gastric acid – unsuitable for oral admin.
  2. MILD to MODERATE
    - Pen VK absorbed better than oral Pen G
    - Amoxicillin absorbed better than ampicillin
    - Dicloxacillin is absorbed the best of the PRPs
28
Q

DIstribution:

Widely distributed into tissues/fluids

  1. Adequate CSF concentrations achieved ONLY when?
A
  1. presence of INFLAMED meninges with high-dose parenteral

2.

29
Q

Elimination:

  1. Most are eliminated primarily by the ____ unchanged.
  2. Require dosing adjustments in the presence of what?
  3. What blocks tubular secretion?
  4. Nafcillin & Oxacillin are eliminated primarily by what?
  5. What about Pipercillin?
A
  1. KIDNEYS
    - unchanged by glomerular filtration & tubular secretion
  2. dosage adjustment is required in the presence of renal insufficiency;
  3. Probenacid!
  4. LIVER
  5. Pipercillin does BOTH

** ALL penicillins have short elimination half-lives (

30
Q

SODIUM is contained in some preparations of parenterally-administered penicillins

Must be used with caution in patients with
what conditions? (2)

A
  1. CHF
  2. Renal insufficiency
    - ticercillin contains 5.2 mEq per gram
31
Q

Drugs of choice for the following is?:

  1. pen susc. S. penumo, 2. streptococci,
  2. N. meningitides,
  3. syphilis****
  4. C. perfringens and tetani
  5. Actinomyces
  6. B. antracis
  7. Endocarditis prophalaxis and
  8. prevention of rheumatic fever
A

NATURAL PENICILLINS

  • used for serious infections in hospitalized patients due to ts rapid effect & high serum concentrations
  • lower serum concentrations are achieved with oral penicillin VK so its use is limited to treatment of mild to moderate infections such as PHARYNGITIS or prophylaxis in some circumstances
32
Q

What is the drug of choice for the following:

Infections due to MSSA such as skin and soft
tissue infections
septic arthritis - osteomyelitis
-bacteremia endocarditis

A

Penicillinase-Resistant Penicillins

33
Q

Aminopenicillins can be used for what 3 types of situations?

What is it often used for the prophylaxis of?

A
  1. Respiratory tract infections
    - pharyngitis
    - sinusitis
    - otitis media
    - bronchitis
    - UTI
  2. Enterococcal infections
  3. Listeria Monocytogenes
  4. Endocarditis Prophylaxis for pts. with valvular disease
34
Q

Carboxypenicillins & Ureidopenicillins:

Used for infections with
what type of bacteria?

What are some examples of the clinical presentations of these infections?

What antibiotic is used for infections due to Pseudomonas Aeriginosa?

A
  1. gram-negative bacteria
  2. serious infections such as bacteremia, pneumonia, complicated urinary tract infection, peritonitis, intraabdominal infections,
    skin and soft tissue infections,
    bone and joint infections,
    and meningitis caused by gram-negative bacteria (hospital-acquired infections).
  3. PIPERACILLIN
35
Q

State which drugs would be used for the following categories of infections:

  1. sinusitis, otitis media, upperand lower respiratory tract infections, human or
    animal bite wounds
  2. polymicrobial infections such as polymicrobial
    pneumonia (aspiration), intra-abdominal infections, gynecologic infections, diabetic foot
    infections (3)
  3. Empiric therapy for febrile neutropenia or hospital acquired infections
A
  1. AUGMENTIN (oral)
  2. UNASYN, ZOSYN, TIMENTIN (IV)
  3. ZOSYN
36
Q

What is the major adverse effect of Penicillins?

A

HYPERSENSITIVITY

  • high incidence with parenteral admin

- Mild to severe allergic reactions ranging from
rash to anaphylaxis and death
- Antibodies produced against metabolic by-
products (penicillin degradation products) or
penicillin itself

  • Cross-reactivity exists among all penicillins and
    even some other β-lactams
  • Desensitization is possible
37
Q

What are examples of Neurologic adverse effects of PCN?

Of hematologic?

Which of the 2 is reversible?

A

Neurologic:

  • direct TOXIC effect
  • especially in IV w/ renal insufficiency patients

** Irritability, jerking, confusion, seizures **

Hematologic:

  • leukopenia
  • neutropenia
  • thromocytopenia
  • during PROLONGED therapy (>2weeks)

REVERSIBLE**

38
Q

What are examples of GI adverse effects of PCN?

What about Renal?
most with Which drug??

A
  1.  Increased LFTs, nausea, vomiting, diarrhea,
    pseudomembranous colitis
    (Clostridium difficile diarrhea)
  2. Interstitial Nephritis
    * *most with nafcillin**

[NAFCILLIN is NOT for Nephrons]

- Immune-mediated damage to renal tubules -
characterized by an abrupt increase in serum
creatinine, eosinophilia, eosinophiluria

  • •  Others: phlebitis, hypokalemia, Na overload
39
Q

What causes Interstitial nephritis?

It is most commonly associated with which drugs?

What are initial manifestations?

What are some other adverse affects to the following:

  1. Nafcillin
  2. Ticarcillin
  3. Ticarcilin & Piperacillin
A
    • associated with immune mediated damage to renal tubules where the penicillin acts as a HAPTEN when bound to renal tubular cells
  2. Methicillin, Nafcillin
  3. Eosinophiluria, and an abrupt increase in serum creatinine
    * may progress to renal failure
  4. Nafcillin - Phlebitis
  5. Ticarcillin - Hypokalemia
  6. Ticarcilin & Piperacillin - Na overload and fluid retention
40
Q

How are the following eliminated:

  1. Dicloxacillin
  2. Nafcillin
  3. Oxacillin
    4, Piperacillin
  4. Pip/tazo
A
  1. Dicloxacillin - Renal & hepatic
  2. Nafcillin - HEPATIC
  3. Oxacillin - HEPATIC
    4, Piperacillin - Renal AND Hepatic
  4. Pip/tazo - Renal & Hepatic
41
Q

What antibiotic works great for the following bacteria:

(KNOW THESE) GRAP POSITIVE

  1. Group A,B,D,F
  2. Streptococci
  3. Viridans Strep.
  • susc. Staph Aureus
  • S. pneumoniae
  • some enterococcus
  • bacillus
  • Corynebacterium
A

NATURAL PENICILLINS

  1. Aqueous Pen G
  2. Benzathine
  3. Penicilling IM
  4. Procaine
  5. Penicillin G (IM)
  6. Penicillin VK (PO)
42
Q

What is the main gram negative bacteria the Natural Penicillins kill?

Main Anaerobes?

Other?

A
  1. Neisseria Meningitis
  2. Clostridium spp.
  3. Treponema Pallidum (OTHER –> SYPHILLIS)
43
Q

Penicillinase Resistance Penicillins (Nafcillin & Dicloxacillin)
kill what major gram positive bacteria?

A

Methicillin - Susceptible Staph. Aureus

  • limited activity for Anaerobes
  • no activity for gram negative
44
Q

Aminopenicillins (ampicillin & amoxicillin) kill what major Gram positive Bacteria? (2)

A
  1. ENTEROCOCCUS

2. Listeria Monocytogenes

45
Q

What drug can kill Pseudomonas spp. & STENOTROPHOMONAS MALTOPHILIA ?

A

Carboxypenicillins

  • TICARCILIN (IV)
46
Q

_____ is used for broad gram negative coverage including P. aeriginosa

A

Piperacillin (IV)

47
Q

What drugs can be used against B-Lactamase producing strains of : (3 total)

E. Coli, Proteus app, Klebsiella, H. Influenzae, M. Catarrhalis, N Gonorrhea.

A

B - Lactamase INHIBITORS

  1. Ampicillin/Sulbactam ( unasyn)
  2. Amoxicillin/Clavulanate (Augmentin)
  3. Piperacillin/Tazobactam (Zosyn)
48
Q

What drugs make up the following:

  1. Unasyn
  2. Augmentin
  3. Zosyn
A

B - Lactamase INHIBITORS

  1. Ampicillin/Sulbactam ( unasyn)
  2. Amoxicillin/Clavulanate (Augmentin)
  3. Piperacillin/Tazobactam (Zosyn)
49
Q

Describe how the production of B - Lactamase enzymes function as a mechanism of resistance against Penicillins.

What gram positive bacteria produces B-Lactamase Enzymes? (1)

A

Enzyme hydrolyzes the B lactic ring inactivating the antibiotic

Produced by:

Gram +
1. Penicillin Resistance Staph. Aureus

50
Q

What gram NEGATIVE bacteria produces B-Lactamase Enzymes? (6)

A

Gram (-):

  1. H. Influenza
  2. Moraxella Catarrhalis
  3. Neisseria gonorrhoeae
  4. E.Coli
  5. Klebsiella Pneumoniae
  6. Enterobacter Spp.
51
Q

What is the only gram NEGATIVE anaerobe that produces B-Lactamase Enzymes?

A

Gram (-) Anaerobe:

1. Bacteroides Fragilis

52
Q

What drugs can be used for

  1. Group Streptococci
  2. Viridian Strep

** little activity for Staph due to penicillinase activity**

A

Natual Penicillins

53
Q

What gram negative bacteria can be killed by Natural penicillins? (2)

What anaerobes? (1)

EXCEPT?

Other?

A
  1. Neisseria Meningitidis
  2. Non -B lactam producing Neisseria gonorrhea

Anaerobes:
1. CLOSTRIDIUM

EXCEPT: Clostridium DIfficile

Other: Treponema pallidum

54
Q

What are some of the clinical uses of natural penicillins?

A
  1. Pen G in serious infections in hospitalized patients due to rapid effect & high serum concentrations
  2. Oral Pen VK for moderate infections
  3. Endocarditis prophylaxis in patients with valvular heart disease in dental procedures
  4. Prevention of rheumatic fever
55
Q

What are the penicillinase resistant drugs?

Why were they developed?

A
  1. Nafcillin - hepatic elimination
  2. Oxacillin
  3. Dicloxacillin (BEST ORAL)

** developed because of Penicillinase producing STAPH**

56
Q

What gram positive bacteria is susceptible to Penicillinase Resistant Penicillins?

A

methicillin susceptible staph aureus

  • no action for gram -

LIMITED for anaerobes

57
Q

Which is better orally: Amoxicillin or Ampicillin?

What 2 gram positive bacteria are killed by Aminopenicillins?

A

AMOXICILLIN

  1. ENTEROCOCCUS
  2. Listeria Monocytogenes
58
Q

What gram negative bacteria is killed by aminopenicillins? (5)

A
  1. H. Influenzae
    (only B lactase strains)
  2. E. Coli
  3. Proteus Mirabilis
  4. Salmonella
  5. Shigella
59
Q

Which drug is best for the following syndromes:

  1. skin & soft tissue infections
  2. septic arthritis
  3. Osteomyolitis
  4. Bactermia
  5. ENdocarditis

What is used for mild to moderate skin & soft tissue infections?

A
  1. PENICILLINASE RESISTANT PENICILLINS for anti-staph

2. ORAL dicloxacillin (for mild to moderate)

60
Q

____ drugs are NOT active against Klebsiella or Serratia.

But active against what??

A

Carboxypenicillins (ticarcillin)

  • PSEUDOMONAS
61
Q

Carboxypenicillins are best used clinically for what type of infections/patients?

A
  1. Hospital acquired infections

2. Immunocompromised patients

62
Q

Ureidopenicillinl are eliminated how?

What gram negative bacteria do they kill? (3)

A

DUAL
- hepatic & renal (piperacillin)

  1. Kill PSEUDOMONAS AURUGINOSA
  2. Klebsiella
  3. Serratia Marcescens
63
Q

What is the most active penicillin for pseudomonas aeriginosa?

A

PIPERACILLIN

64
Q

What gram negative is killed by B-lactamase inhibitor combos? (2)

Anaerobes?

A
  1. H. Influenzae
  2. Morazella catarrhalis
  3. Bacteoides (B fragilis)
65
Q

ENTEROCOCCAL infections are best treated with what?

A

Aminopenicillins (amp/amoxicillin)

66
Q

Penicillins and Cephalosporins Are Very Cidal For Microbes

What is this a pneumonic for?

A 
Penicillins and Cephalosporins Are Very Cidal For Microbes
Are  Aminoglycosides
V  Vancomycin 
C  Carbepenams
F  Fluoroquinolones
M  Metronidazole
67
Q

AMINO/AMOXI H.H.E.L.P.S.S

What is this pneumonic?

A

HHELPS

Gram negative bacteria susceptible to Aminopenicillins (Amoxi/Ampicillin)

H - H. Influenzae
H - H. Pylori
E - E.Coli
L - Listeria
P - Proteus
S - Shigella
S - Salmonella

PHARM/MHD EXAM - 3 (21 decks)

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