Opath 1 - Block 2 - Chiu - Cell Wall Synthesis Inhibitors

Front 1

Cell wall synthesis inhibitors

Back 1

penicillins
cephalosporins
vancomycin
bacitracin

Front 2

Penicillins - discovery

Back 2

- Alexander Flemming
- Staphylococcus was lysed by contamination with mold

Front 3

Mechanism of action

Back 3

- bactericidal
- Interferes with last step (transpeptidase) of bacterial cell wall synthesis, causing cell lysis
- Only effective against rapidly growing organisms that synthesize a peptidoglycan cell wall

Front 4

Peptidoglycan synthesis

Back 4

- Initial synthesis at
cytoplasmic side
of cell membrane
- Polymerization at cell surface

Front 5

Penicillin structure

Back 5

Basic structure consists of a thiazolidine ring connected to a b-lactam ring, to which is attached a side chain (R group)

Front 6

R group in penicillins

Back 6

- the R group determines the drug's stability and affects its antibacterial specture

Front 7

Groups of penicillins

Back 7

- natural penicillins - penicillin G, penicillin V
- extended spectrum penicillins - ampicillin, amoxicillin (most common)

Front 8

Penicillin - bacterial resistance

Back 8

- B-lactamase - hydrolyzes the cyclic amide bond of B-lactam ring. usually acquired by transfer of plasmids "R."
- Decreased permeability to the drug
- Altered binding proteins

Front 9

B-lactamase inhibitors

Back 9

- Clavulanic acid - binds B-lactamases and inactivates them

Front 10

Formulations of B-lacatamse inhibitors

Back 10

- AUGMENTIN: amoxicillin + clavulanic acid
- TIMENTIN: ticarcillin + clavulanic acid
- UNASYN: ampicillin + sulbactam

Front 11

Penicillin - pharmacology

Back 11

- Administration - oral, IV, IM
- Absorption - Amoxicillin most completely absorbed. Ampicillin and Pen G absorption impeded by food in stomach.
- Distribution - All cross placenta. Minimal penetration into bone and CSF.
- Metabolism - minimal
- Excretion - kidney. Adjust dose if pt's renal system is compromised. Probenecid inhibits penicillin excretion.

Front 12

Penicillin - adverse reactoins

Back 12

hypersensitivity
diarrhea
nephritis
neurotoxicity
platelet dysfunction
cation toxicity

Front 13

Pencillin - allergic reactions

Back 13

- Acute (<30 min) - urticaria, angioedema, bronchoconstriction, shock
- Accelerated (30 min-48 hours) - urticaria, pruritis, wheezing, mild laryngeal edema, local inflammatory rxns
- Delayed (>2 days) - skin rash, furred tongue, stomatitis

Front 14

Penicillin - tx of allergic reactions (mild and severe)

Back 14

- Mild: Benadryl 25-50 mg IV/IM/PO
- Severe: Epinephrine 0.03-0.05 mg
- Skin tests: benzylpenicilloyl-polylysine

Front 15

Penicillin - therapeutic uses in dentistry

Back 15

- Penicillin V - most frequent use for dental infections
- Amoxicillin - superior pharmacokinetics. Used for perio infections with gram +/- aeronic/anaeronic microorganisms.
- Penicillin G - parenteral. For severe infections only.

Front 16

Penicillins - summary of pharmacokinetics

Back 16

- A: oral and parenteral
- D: variable. no CNS entry except with meningitis.
- M: not extensively metabolized
- E: filtration and excretion. short half life (1-2 hr)

Front 17

Cephalosporins

Back 17

- B-lactam antibiotics
- Related to penicillins structurally and functionally-have a dihydrothiazine ring rather than a thiazolidine ring
- More resistant to b-lactamases

Front 18

Semi synthetic cephalosporins

Back 18

synthesized by addition of different chemical groups at R1 and R2

Front 19

Cephalosporins - with increased generation, you get...

Back 19

- increased gram negative bacterial susceptibility
- increased b-lactamase resistance
- decreased efficacy against gram +

Front 20

Which generation of cephalosporins gets into the CSF?

Back 20

3rd generation

Front 21

Cephalosporins - therapeutic uses in dentistry

Back 21

- good activity against many orofacial pathogens, but LIMITED ACTIVITY AGAINST ORAL ANAEROBES
- odontogenic infections - orally active first or second gen
- bacterial endocarditis prophylaxis - cephalexin, cefazolin

Front 22

Cephalosporins - adverse effects

Back 22

- Allergy- 15% cross sensitivity with Pen allergy
- Disulfiram-like effect: Cefamandole, cefoperazone when ingested with alcohol block second step in oxidation and RESULTING IN ALDEHYDE ACCUMULATION
- bleeding
- renal, hepatic dysfunction

Front 23

Cephalosporins summary - pharmakokinetics

Back 23

- A: oral and parenteral
- D: wide. 3rds penetrate CSF.
- M: not extensively metabolized
- E: renal filtration. some 3rds are excreted through bile.
- T: relatively nontoxic.

Front 24

Cephalosporin hypersensitivity

Back 24

- proximal renal tubular necrosis
- disulfaram-like toxicity