Beta-Lactam & Other Cell Wall- & Membrane-Active Antibiotics Flashcards by Alyssa Abigail Fuentes

Q

____________ share features of chemistry, mechanism of action, pharmacology, and immunologic characteristics with cephalosporins, monobactams, carbapenems, and β-lactamase inhibitors.

A

Penicillins

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Q

All beta-lactam compounds contain a ____________ containing an amide group, which reacts with the active site of enzymes involved in building the bacterial cell wall.

A

4 membered lactam ring

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Q

The basic chemical structure of all penicillins consists of a:

A

thiazolidine ring (attached to)
β-lactam ring
secondary amino group (6-aminopenicillanic acid)

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Q

____________ of the β-lactam ring by bacterial β-lactamases yields ____________, which lacks antibacterial activity

A

Hydrolysis
yields: penicilloic acid

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Q

True or False

The penicillins are susceptible to inactivation by amidases and lactamases

A

True

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Q

T or F

Carbapenems have a the same stereochemical configuration in the lactam ring that imparts resistance to most common β-lactamases.

A

F

different stereochemical configuration

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Q

Substituents of the ________________ determine the essential pharmacologic and antibacterial properties of the resulting molecules.

A

6-aminopenicillanic acid moiety

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Q

What are examples of compounds that are relatively stable to gastric acid and suitable for oral administration

A

penicillin V
amoxicillin
dicloxacillin

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Q

Penicillins can be assigned to one of three groups which are?

A

Penicillins (eg. penicillin G)
Antistaphylococcal penicillins (eg. nafcillin)
Extended-spectrum penicillins (aminopenicillins and antipseudomonal penicillins)

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Q

What group of pencillin is this?

These have the greatest activity against gram-positive organisms, gram-negative cocci, and non-β-lactamase-producing anaerobes.

A

Penicillins
(eg. penicillin G)

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Q

What group of pencillin is this?

These have little activity against gram-negative rods

A

Penicillins
(eg. penicillin G)

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Q

What group of pencillin is this?

These are susceptible to hydrolysis by β-lactamases.

A

Penicillins
(eg. penicillin G)

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Q

What group of pencillin is this?

These penicillins are resistant to staphylococcal β-lactamases.

A

Antistaphylococcal penicillins
(eg. nafcillin)

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Q

What group of pencillin is this?

They are active against staphylococci and streptococci

A

Antistaphylococcal penicillins
(eg. nafcillin)

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Q

What group of pencillin is this?

They are not active against enterococci, anaerobic bacteria, and gram-negative cocci and rods

A

Antistaphylococcal penicillins
(eg. nafcillin)

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Q

What group of pencillin is this?

These drugs retain the antibacterial spectrum of penicillin

A

Extended-spectrum penicillins
(aminopenicillins and antipseudomonal penicillins)

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Q

What group of pencillin is this?

These drugs have improved activity against gram-negative rods

A

Extended-spectrum penicillins
(aminopenicillins and antipseudomonal penicillins)

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Q

Like penicillin, they are relatively susceptible to hydrolysis by β-lactamases

A

Extended-spectrum penicillins
(aminopenicillins and antipseudomonal penicillins)

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Q

T or F

The activity of penicillin G was originally defined in units.

A

T

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Q

The minimum inhibitory concentration (MIC) of any penicillin (or other antimicrobial) is usually given in ____________

A

mcg/mL

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Q

Most penicillins are formulated as the ________ or ____________ of the free acid

A

sodium or potassium salt

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Q

Potassium penicillin G contains about 1.7 mEq of ________ per million units of penicillin (2.8 mEq/g)

A

K+

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Q

Nafcillin contains ________, 2.8 mEq/g.

A

Na+

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Q

What compounds of salt of penicillin G provide repository forms for intramuscular (IM) injection.

A

Procaine salts
Benzathine salts

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In ____________ form, **penicillin salts** are **stable** for years at **4°C**

dry crystalline

**Penicillins**, like all β-lactam antibiotics, **inhibit bacterial growth by interfering** with the ____________ of **bacterial cell wall synthesis.**

transpeptidation reaction

The **cell wall** prevents cell ________ from **high osmotic pressure**

cell lysis

The **cell wall** is composed of a **complex**, **cross-linked polymer of polysaccharides** and **peptides** known as ____________

peptidoglycan

The polysaccharide of the cell wall contains **alternating amino sugars**, namely:

- N-acetylglucosamine - N-acetylmuramic acid

In the polysaccharide of the cell wall that contains an N-acetylmuramic acid sugar, a ____________ is linked to it

5-amino-acid peptide

In the MOA of Penicillin, the peptidoglycan in the cell wall terminates in ___________

D-alanyl-D-alanine

In the MOA of Penicillin, which enzyme is responsible for **removing the terminal alanine** in the process of **forming a cross-link** with a nearby peptide

Penicillin-binding protein (PBP)

What gives the cell wall its rigidity?

Cross-links

In the MOA of Penicillin, what binding **inhibits** the **transpeptidation reaction** and halts peptidoglycan synthesis, and the cell dies

Covalently binding of D-Ala-D-Ala substrate to the active site of PBPs

# T or F Beta-lactam antibiotics kill bacterial cells **only when they are actively growing** and **synthesizing cell wall**

T

The cell envelope of a gram-negative bacterium has an outer membrane that is ___________

lipid bilayer

# T or F The **lipid bilayer** in a cell envelope of a bacterium is **only present in a gram-negative** and **not in gram-positive organisms**

T

The lipid bilayer of a cell envelope of a gram-negative bacterium is penetrated by ________, which are **proteins** that form channels **providing hydrophilic access to the cytoplasmic membrane**

porins

The cell envelope of a bacteria also has a ________ layer that is unique to bacteria and is **much thicker in gram-positive** organisms than in gram-negative ones.

peptidoglycan layer

What are the layers that constitutes the cell wall of a bacteria?

- outer membrane (lipid bilayer in gram-negative) - peptidoglycan

What enzymes/membrane proteins are responsible for cross-linking peptidoglycan

Penicillin-binding proteins (PBPs)

If **Beta-lactamases are present** where do they reside in the cell wall, where they may **destroy β-lactam antibiotics that penetrate the outer membrane**

periplasmic space or outer surface of cytoplasmic membrane

# T or F In order to halt the peptidoglycan synthesis, the Beta-lactam works by **binding the transpeptidase at the penicillin-binding protein site**, resulting in inhibition of transpeptidation

T

Resistance to penicillins and other β-lactams is due to one of four general mechanisms namely:

1. **inactivation** of antibiotic by **β-lactamase** 2. modification of **target PBPs** 3. **impaired penetration** of drug to target PBPs 4. **antibiotic efflux**

What is the most common mechanism of penicillin resistance?

production of beta-lactamase

Other β-lactamases, like **AmpC β lactamase** produced by ***Pseudomonas aeruginosa*** and ***Enterobacter*** sp and **extended-spectrum β-lactamases (ESBLs)** in Enterobacteriaceae,** hydrolyze both** ____________ and ___________

cephalosporins and penicillins

________________ are ***highly resistant*** to **hydrolysis** by **penicillinases** and **cephalosporinases**

Carbapenems

____________ are **hydrolyzed** by **metallo-β-lactamases** and **carbapenemases**, instead of hydrolysis of penicillinases and cephalosporinases

Carbapenems

What are the basis of **methicillin resistance in staphylococci** and of **penicillin resistance in pneumococci** and most resistant **enterococci**.

Altered target PBPs (These resistant organisms produce PBPs that have low affinity for binding β-lactam antibiotics)

Resistance due to **impaired penetration** of antibiotic occurs only in ____________ because of the impermeable outer membrane (lipid bilayer) of their cell wall, which is absent in gram-positive bacteria.

gram-negative species

**Beta-lactam antibiotics** cross the outer membrane and enter **gram-negative** organisms via **outer membrane protein channels** called ____________

porins

Gram-negative organisms also may produce an ____________, which consists of **cytoplasmic** and **periplasmic** protein components that efficiently transport some β-lactam antibiotics

efflux pump

**Gastrointestinal absorption** of ____________ is **erratic**, so it is **not suitable for oral administration**

nafcillin

What penicillin drugs are **acid-stable** and **relatively well absorbed**, producing serum concentrations in the range of 4–8 mcg/mL after a 500-mg oral dose

- Dicloxacillin - Ampicillin - Amoxicillin

**Absorption of most oral penicillins** *(amoxicillin being an exception)* is **impaired by food**, and the drugs should be administered at least ____________ **before or after a meal**

1–2 hours

________________ of **penicillin G** is preferred to the **intramuscular route** because of **irritation** and **local pain** from **intramuscular (IM) injection** of large doses.

Intravenous administration (IV)

**Highly protein-bound penicillins** like ____________ generally **achieve lower free-drug concentrations** in serum than less protein-bound penicillins

nafcillin

Penicillins are ________, thus it works well in intracellular concentrations than those found in extracellular fluids.

polar

____________ and ____________ penicillins are formulated to **delay absorption**, resulting in **prolonged blood and tissue concentrations**

Benzathine and procaine

# T or F Penicillin is also excreted into sputum and breast milk to levels 3–15% of those in the serum

T

Penicillin is rapidly excreted by the _______

kidneys (majority)

The normal half-life of penicillin G is approximately ____________ but, in **renal failure**, may be as long as **10 hours**

30 minutes

# T or F **Ampicillin** and the **extended-spectrum penicillins** are secreted **more slowly** than penicillin G and have half-lives of **1 hour**

T

# Give the ROA Penicillins: Penicillin G

Intravenous (IV)

# Give the ROA Penicillins: Penicillin V

Oral Administration (PO)

# Give the ROA Antistaphylococcal penicillins: Cloxacillin, dicloxacillin

Oral Administration (PO)

# Give the ROA Antistaphylococcal penicillins: Nafcillin

Intravenous (IV)

# Give the ROA Antistaphylococcal penicillins: Oxacillin

Intravenous (IV)

# Give the ROA Extended-spectrum penicillins: Amoxicillin

Oral Administration (PO)

# Give the ROA Extended-spectrum penicillins: Amoxicillin/potassium clavulanate

Oral Administration (PO)

# Give the ROA Extended-spectrum penicillins: Piperacillin/tazobactam

Intravenous (IV)

Nafcillin is primarily cleared by ____________ excretion

biliary excretion