10. Inhibitors of Cell Wall Synthesis

Question 1

What are four inhibitors of cell wall synthesis drugs?

Answer 1

Penicillins

Cephalosporins

Vancomycin

Bacitracin

Question 2

Who discovered penicillin? When?

Answer 2

Alexander Fleming in 1928

Question 3

What was the mold Fleming used to fiht bacteria and agaist which bacteria?

Answer 3

Penicillium notalum was isolated to fight staphylococci

Question 4

What is penicillin’s mechanism of action?

Answer 4

• Bactericidal
• Interferes with last step (transpeptidase) of bacterial cell wall synthesis, causing cell lysis

Question 5

What kind of bacteria is penicillin effective against?

Answer 5

Rapidly growing organisms that synthesize peptidoglycan cell wall

Question 6

Describe the two major steps of peptidoglycan cell wall synthesis

Answer 6

• Synthesis of peptidoglycan in single chains
  
  • occurs in cytoplasmic side of cell membrane
• Polymerization and cross linking of single chain peptidoglycan
  
  • polymerization occurs at cell surface
  • transpeptidase used in this step to polymerize single units

Question 7

What are the components of penicillin’s basic structure?

Answer 7

1. Thiazolidine ring
2. beta-Lactam ring
3. Side chain (R group)
   
   • R group variation results in different penicillins

Question 8

What confers bacterial resistance against penicillin?

Answer 8

• Contain beta-penicillinase or acid that cleaves beta-lactam ring
  
  • hydrolyzes cyclic amide bond of beta-lactam ring
  • usually acquired by transfer of plasmids R
• Decreased permeability to drug
• Altered penicillin binding proteins (PBP)
  
  • PBPs are enzymes involved in forming cross linkages between peptidoglycans

Question 9

What is the antibacterial spectrum of penicillins?

Answer 9

• Natural penicillins
• Extended spectrum penicillins
• Antistaphylococcal penicillins
• Antipseudomonal penicillins

Question 10

What are two examples of natural penicillins?

Answer 10

Penicillin G

Penicillin V

Question 11

What are two examples of extended spectrum penicillins?

Answer 11

Ampicillin

Amoxicillin

Question 12

What are two examples of antipseudomonal spectrum penicillins

Answer 12

Carbenicillin

Ticarcillin

Question 14

What is the function of beta-lactamase inhibitors?

Answer 14

Allows penicillin efficacy in drugs that have developed penicillin resistance via B-lactamase

Question 15

What are two beta-lactamase inhibitors?

Answer 15

Clauvulanic acid (product of Steptomyces clavuligerus)

Sulbactam

Question 16

What is the mechanism of becta-lactamase inhibitors?

Answer 16

Irreversibly binds beta-Lactamase and inactivates them

Question 17

What are 3 formulations of beta-lactamase inhibitors?

Answer 17

Augmentin

Timentin

Unasyn

Question 18

Components of augmentin

Answer 18

amoxicillin + clavulanic acid

Question 19

Components of timentin

Answer 19

ticarillin + clavulanic acid

Question 20

Components of unasyn

Answer 20

ampicillin + sulbactam

Question 21

How do beta-lactamase inhibitors effect the efficacy of penicillins?

Answer 21

Improves efficacy

Question 22

How are penicillins administered?

Answer 22

Oral

IV

IM

Question 23

Which penicillin is absorbed very well?

Answer 23

Amoxicillin

Question 24

Which penicillins are difficult to absorb?

Answer 24

Pen G and Ampicillin bc their absorption are impeded by food

Question 25

Can Pen cross the placenta?

Answer 25

Yes

Question 26

Does Pen hihgly penetrate the bone and CSF?

Answer 26

NO, minimal penetration

Question 27

How does kinetics of IM administration of Pen compare ot kinetics of orally administered Pen?

Answer 27

Reach very high blood levels in comparison to oral

Question 28

Is Pen highly metabolized?

Answer 28

No, minimally

Question 29

How is Pen excreted?

Answer 29

Kidney

Question 30

What drug if taken with Pen can inhibit Pen excretion?

Answer 30

Probenecid inhibits Pen excretion Probenecid treat gouty arthritis

Question 31

What are adverse reactions of Pen?

Answer 31

* Hypersensitivity * Diarrhea * Nephritis * Neurotoxicity * PLT dysfunction * Cation toxicity

Question 32

How does Pen cause hypersensitivity?

Answer 32

* Penicilloic acid isa hapten for immune rxn * Urticaria/angioedema to anaphylaxis * beta-lactam cross reactivity

Question 33

How does Pen cause diarrhea?

Answer 33

disrupt normla flora composition

Question 34

How does cation toxicity arise in Pen use?

Answer 34

* K+ and Na+ levels are augmented bc of disruption of their retention * disruption of Na and K levels result in cardiac side effects

Question 35

What occurs in acute allergic reactions (\< 30mins) to Pen?

Answer 35

* Urticaria * Angioedema * Bronchoconstriction * Shock

Question 36

What occurs in accelerated (30 mins - 48 hrs) allergic reactions from Pen?

Answer 36

Urticaria Pruritis Wheezing Mild laryngeal edema Local inflammatory rxns

Question 37

What occurs in delayed (\< 2 days) allergic rxns to Pen?

Answer 37

Skin Rash Oral glossitis Furred tongue Black and brown tongue Cheilosis Severe stomatitis with loss of buccal mucosa

Question 38

Tx for mild allergic rxn to Pen

Answer 38

Benadryl 25-50 mg IV/IM/PO

Question 39

Tx for severe allergic rxn to Pen

Answer 39

Epinephrine .03-.05 mg

Question 40

How to determine if pt has allergy to Pen?

Answer 40

Skin test with benzylpenicilloyl-polylysine

Question 41

What is the dental use of Pen V?

Answer 41

Most frequently used for infection of dental origin

Question 42

What is the dental use of amoxicillin?

Answer 42

Superior pharmacokinetics Periodontal infectoin associated with Gram + or Gram - aerobic and anaerobic microorganisms

Question 43

What is the dental use of Pen G (parenteral)?

Answer 43

Reserved for severe infections

Question 44

**_Pharmacokinetics of Pen:_** ## Footnote A: ? D: ? M: ? E: ?

Answer 44

A: Oral and parenteral D: Variable; No CNS entry except with meningitis M: Minimal E: Filtratation and excretion: short half life (1-2 hrs)

Question 45

How was Cephalosporins discovered?

Answer 45

Cephalosporium acremonium was first isolated in 1948 from sea near sewer outlet off Sardinian coast

Question 46

How does Cephalosporin structure compare to Pen?

Answer 46

Very similar in structure and function but have a dihydrothiazine ring instead of a thiazdolidine ring

Question 47

How does Cephalosporin resistance to beta-lactamase compare to Pen?

Answer 47

More resistant to beta-lactamase but still susceptible

Question 48

How are semi-synthetic cephalosporins synthesized?

Answer 48

Synthesized by adding different chemical groups at R1 and R2 to make different varieties of cephalosporins

Question 49

How have subsequent generations of cephalosporin changed in comparison to previous generations?

Answer 49

Subsequent generations has increased Gram - bacterial susceptibility, increased beta-lactamase resistance and decreased efficacy against Gram +

Question 50

What are the 3 categories of cephalosporins antibacterial spectrum?

Answer 50

1st generation 2nd genertaion 3rd genertaion

Question 51

What are the two first genertaion cephalosporins drug and their use?

Answer 51

Cefazolin Cephalexin Used for endocarditis

Question 52

What are two 2nd genertaion cephalosporin drugs?

Answer 52

Cefaclor Cefoxitin

Question 53

What is a 3rd genertaion cephalosporin drug and its use?

Answer 53

Ceftriaxone Used for endocarditis

Question 54

How has the CNS penetration trend changed with each subsequent cephalosporin generation?

Answer 54

Increased CNS penetration

Question 55

How is cefazolin administered?

Answer 55

Parenteral

Question 56

How is Cephalexin administered?

Answer 56

Oral

Question 57

how od cephalosporins distribute in the body?

Answer 57

Distribute well thorug body fluids Only 3rd generation Cephalosporins distribute well into the CSF

Question 58

How are cephalosporins excreted?

Answer 58

Renal elimination

Question 59

Which cephalosporins are not excreted renally? How are they elminated?

Answer 59

Cefoperazone & Ceftriaxone Exreted through bile and feces

Question 60

What is the limitation in the dental use of Cephalosporins?

Answer 60

Good activity against many orofacial pathogen but limited agfainst oral anaerobes

Question 61

What cephalosporins drugs are used against odontogenic infections? Administration?

Answer 61

Orally active first or second generation Cephalosporins

Question 62

Which Cephalosporin drugs are used for bacterial endocarditis prophylaxis?

Answer 62

Cephalexin Cefazolin

Question 63

What are the adverse effects of Cephalosporins?

Answer 63

Allergy Disulfram-like effect Bleeding Renal, hepatic dysfunction

Question 64

What is the rate of allergy cross sensitivity b/t cephalosporins and Pen?

Answer 64

15%

Question 65

What is cephalosporins disulfram like effect?

Answer 65

When taken with alcohol, will cause **aldehyde accumulation** Results in respiratory difficulty, nausea and HTN

Question 66

Why do Cephalosporins cause bleeding?

Answer 66

Anti-Vit K effect

Question 67

**_Cephalosporins Pharmacokinetics Summary_** * A: ? * D: ? * M: ? * E: ? * T: ?

Answer 67

* A: Oral and parenteral * D: Wide; 3rd gen penetrates into CSF * M: Not extnesively * E: Renal filtration; 3rd gen by bile/feces * T: Relatively non-toxic (like Pens); * Hypersensitivity leads to proximal renal tubular necrosis * Disulfram like toxicity