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Pharm test #3 > Penicillins > Flashcards

Penicillins Flashcards

1
Q

β-Lactam Characteristics

A
  • Same MOA: Inhibit cell wall synthesis
  • Same MOR: β-lactamase degradation, PBP alteration, decreased penetration
  • Bactericidal in a time-dependent manner, except against Enterococcus spp.
  • Short elimination half-life of
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2
Q

Penicillins discovery

A

Penicillin was accidentally discovered by Dr. Alexander Fleming in 1928
First used in 1941 for the treatment of staphylococcal and streptococcal infections (gram +)

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3
Q

penicillin common structure

A

All penicillins share a β-lactam ring attached to a 5-membered thiazolidine ring

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4
Q

how do penicillins work?

A
  • Interfere with cell wall synthesis by binding to and inhibiting penicillin-binding proteins (PBPs) located in bacterial cell membranes
  • 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 (no cross-linking)
  • all are bactericidal (except against Enterococcus)
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5
Q

3 mechanisms of penicillin resistance

A
  1. Production of β-lactamase enzymes
  2. Alteration in structure of PBPs leading to decreased binding affinity
  3. Alteration of outer membrane porin proteins leading to decreased penetration
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6
Q

Production of β-lactamase enzymes

A
  • Most important and most common mechanism
  • the enzyme hydrolyzes the β-lactam ring inactivating the antibiotic;
  • over 100 β-lactamase enzymes have been identified
  • can be overcome by addition of β-lactamase inhibitors

ex. Penicillin-resistant Staphylococcus aureus (and many others)

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7
Q

gram + vs gram - use of β-lactamases

A

gram + bacteria release β-lactamase into the extracellular area to inhibit β-lactam

while gram - bacteria release β-lactamase into the periplasma space where β-lactam is distroyed

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8
Q

examples of Alteration in structure of PBPs leading to decreased binding affinity as a method of resistance

A

methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP)

β-lactamase inhibitors will not longer increase the effects of the drugs, bc the binding sites on PBP have changed so the drug cannot bind.

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9
Q

Natural Penicillins

A

First group of penicillins to be discovered and used clinically

Parenteral agents: Aqueous penicillin G (IV), Benzathine penicillin G (IM, long-acting), Procaine penicillin G (IM)
Oral agent: Penicillin VK (only one with high enough bioavailability to be given orally)

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10
Q

Penicillin VK

A

natural penicillin that can be given orally bc it is better absorbed therefore giving it a higher bioavailability

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11
Q

penicillin G

A

natural penicillin (the first one given to humans) must be given via IV

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12
Q

Benzathine penicillin G

A

natural penicillin given via IM, the only long lasting penicillin can be dosed once a week

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13
Q

natural penicillins are given for

A
  • Drugs of choice for:
 penicillin-susceptible S. pneumoniae, 
infections due to other streptococci, 
Neisseria meningitidis, 
syphilis**, 
Clostridium perfringens or tetani,
Actinomyces, 
Bacillus anthracis (anthrax)
  • Endocarditis prophylaxis; prevention of rheumatic fever
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14
Q

Penicillinase-Resistant Penicillins

A
  • Developed in response to the emergence of penicillinase-producing Staphylococcus
  • Semisynthetic derivatives of natural penicillin - contain an acyl side chain (prevent hydrolization by penicillinase)

Examples include:
Parenteral agents: Nafcillin *, Oxacillin, and Methicillin (not available)
Oral agent: Dicloxacillin

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15
Q

Penicillinase-Resistant Penicillins are used for

A

methicillin-susceptible S. aureus* (MSSA)

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16
Q

penicillinase is

A

a specific B-lactamase, that hydrolyzes the B-lactam ring

17
Q

3 ways to overcome penicillanase produced by MSSA

A
  1. penicillinase-resistant penicillins,
  2. beta-lactamases inhibitors, or
  3. changing to cephalosporin core [cefazolin]
18
Q

Carboxypenicillins


A

Developed to further increase activity against gram-negative aerobes. Lost some gram+ activity in the process

example: Ticarcillin

19
Q

Nafcillin

A

penicillinase-resistant penicillin used to treat MSSA

has a higher risk of Interstitial Nephritis than other penicillins

20
Q

Carboxypenicillins
 (ticarcillin) have increased potency against

A

gram - bacteria :
Enterobacter spp.
Pseudomonas aeruginosa*

21
Q

Ureidopenicillins

A

Developed in response to the need for agents with even more enhanced activity against gram-negative bacteria
• Semisynthetic derivatives of the amino-penicillins with acyl side chain adaptations

Examples include:
Parenteral agent: Piperacillin (not available)
Oral agents: None

22
Q

Ureidopenicillins are good to use against

A

anaerobes (target organism)
Pseudomonas aeruginosa*
Enterobacter sp.

23
Q

β-Lactamase Inhibitors

A

Potent inhibitors of many bacterial β-lactamases
Protect penicillins from being hydrolyzed by some β-lactamases by irreversibly binding to catalytic site of β-lactamase enzyme
Very weak to no antibacterial activity
Examples include: Clavulanate, sulbactam, tazobactam, avibactam (used in combo with cephalosporins)

24
Q

β-Lactamase Inhibitor Combinations

A

Available only in fixed-dose combinations with specific penicillins

25
Q

efficacy of penicillins depends on

A

time above MIC (time dependent killing)

no post antibiotic effect (PAE) for gram - bacteria

26
Q

absorption of penicillins

A

Many penicillins are degraded by gastric acid
• Oral penicillins are variably absorbed; concs achieved PO are lower than IV
• Pen VK absorbed better than oral Pen G
• Amoxicillin absorbed better than ampicillin
• Dicloxacillin is absorbed the best of the PRPs

27
Q

aminopenicillins

A

Developed in response to the need for agents with gram-negative activity
• Semisynthetic derivative of natural penicillin – addition of amino group
• now commonly given with a B-lactamase inhibitor

Examples include:
Parenteral agent: Ampicillin
Oral agents: Amoxicillin

28
Q

Amoxicillin

A

aminopenicillin commonly given orally

29
Q

aminopenicillins commonly used against

A
  • Respiratory tract infections: pharyngitis, sinusitis, otitis media, bronchitis, urinary tract infections
  • Enterococcal* infections (often with an aminoglycoside) and infections due to Listeria monocytogenes*
  • Endocarditis prophylaxis in selected patients with valvular disease
30
Q

distribution of penicillins

A
  • Widely distributed into tissues and fluids
  • Adequate CSF concentrations achieved ONLY in the presence of inflamed meninges with high-dose parenteral administration
  • Variable protein binding
31
Q

elimination of penicillins

A
  • Most are eliminated unchanged by the kidney so that dosage adjustment is required in the presence of renal insufficiency; probenecid blocks tubular secretion
  • Nafcillin and oxacillin are eliminated primarily by the liver – do not require adjustment in renal insufficiency
  • ALL penicillins have short elimination half-lives (
32
Q

sodium load of penicillins

A

Sodium is contained in some preparations of parenterally-administered penicillins
• Must be used with caution in patients with CHF or renal insufficiency

Sodium content:
Sodium Penicillin G 2.0 mEq per 1 million units
Ticarcillin 5.2 mEq per gram
Piperacillin 1.85 mEq per gram

33
Q

Carboxypenicillins and Ureidopenicillins

A
  • Serious infections due to gram-negative aerobic bacteria such as pneumonia, bacteremia, complicated urinary tract infections, skin and soft tissue infections, peritonitis, etc
  • Empiric therapy for hospital-acquired infections
  • Infections due to Pseudomonas aeruginosa (esp piperacillin) *
34
Q

penicillin hypersensitivity

A
  • Higher incidence with parenteral administration
  • 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
35
Q

neurologic adverse affects of penicillin

A

direct toxic effect
Especially in patients receiving high IV doses in the presence of renal insufficiency

Irritability, jerking, confusion, seizures

36
Q

hemologic adverse effects of penicillins

A

Leukopenia, neutropenia, thrombocytopenia – usually during prolonged therapy (> 2 weeks)

Reversible upon discontinuation

37
Q

GI adverse effects of penicillins

A

Increased LFTs, nausea, vomiting, diarrhea, pseudomembranous colitis (Clostridium difficile diarrhea)

38
Q

renal adverse effects of penicillins

A

Interstitial Nephritis – Immune-mediated damage to renal tubules - characterized by an abrupt increase in serum creatinine, eosinophilia, eosinophiluria
Can lead to renal failure
Especially with nafcillin

Pharm test #3 (17 decks)

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