Intro To Antimicrobials/ Beta Lactams

Front 1

What are the 5 Mechanisms of Action of ANTIMICROBIALS?

Back 1

1. Inhibition of protein synthesis
-tendency to be bacteriostatic
-Act at the site of BAC ribosome
2. Inhibition of nucleic acid synthesis
-DNA & RNA
3. Disruption of cell walls
4. Disruption of cell membranes
5. Interfere with metabolic pathways

Front 2

ANTIBIOTIC

Back 2

- substance produced by a micro-organism that kills or inhibits other micro-organisms

Front 3

ANTIBACTERIAL

Back 3

- these are synthetic agents which have activity against bacteria( sulpha & F quinolones )

Front 4

ANTIMICROBIAL

Back 4

- any substance, natural, semi synthetic or synthetic that kills or inhibits growth of a micro-organism without damaging the host

Front 5

Name the 3 types of Antimicrobial Resistance

Back 5

1. Inherent resistance
2. Chromosomal mediated resistance
3. Transferable drug resistance
- conjugation
- transduction
- transformation

Front 6

What is INHERENT Antimicrobial Resistance?

Back 6

- Mycoplasma resistance to B-lactams
- Anaerobic organisms resistant to aminoglycosides
- Aerobic organisms resistance to nitromidazoles

Front 7

What is CHROMOSOMAL Antimicrobial Resistance?

Back 7

- This type of resistance develops slowly and often requires multiple steps
- 1 in 10 million BAC cells give rise to a daughter cell with a mutation

Front 8

What is TRANSFERABLE Antimicrobial Resistance?

Back 8

- Mainly associated with plasmids

Front 9

What is MIC?

Back 9

- Minimal inhibitory concentration
- Highest dilution at which there is NO GROWTH after incubation
-quantitative value that defines susceptibility and is used to determine DRUG DOSE

Front 10

POST ANTIBIOTIC EFFECT= TIME DEPENDENT

Back 10

-efficacy.....time that the serum concentration of the antimicrobial remains about the MIC
- don't want to miss dose!!! NO post anti-b under MIC
EX:
B-lactams & Tetracyclines

Front 11

POST ANTIBIOTIC EFFECT = DOSE DEPENDENT

Back 11

- efficacys.....peak serum concentration
- min dosing frequencies
- post antibiotic effect!!
- High peak vs MIC
EX:
aminoglycosides and the F quinolones

Front 12

What are the Beta-Lactams?

Back 12

- Narrow spec penicillins
- Broad spec penicillins
- Antipsuedomonal penicillins
- CEPHALOSPORINS
-1st, 2nd, 3rd, 4th GENs

*Monobactams
*Carbapenems

Front 13

WHAT IS THE MECH OF ACTION FOR PENICILLINS?

Back 13

-inhibit transpeptidase enz. (target for pens & cephs)
- Prevent BAC cell wall formation
- Disrupt crosslinking in cell wall
- lysis cell wall in growing cells
- BACTERICIDAL

Front 14

Penicillin activity depends on..........

Back 14

- Pen binding proteins
- Ability to penetrate LPS of Gram (-) BAC mem
- Resistance to B lactamase
- Amount of Peptidoglycan in cell wall

Front 15

What is B- Lactamase?

Back 15

- ENZ produced by certain BAC which can CLEAVE the Beta lactam ring structure
- Staphs! (+) good at producing this enz
- (-) e. coli, salmonella

Front 16

What are the Pharmacokinetics of Penicillins?

Back 16

-Acids pKa 2.7
-Low Vd (.2-.3L/kg) ECF!
- short t 1/2 = .5-1.2 hrs
- Does not get into CSF, and acqueous humour
- mostly ionized at plasma pH
- penetration enhanced by inflam
-DOES NOT GET INSIDE CELLS

Front 17

HOW ARE PENICILLINS EXCRETED?

Back 17

- Renal- Glom filtration & tubular ex. high levels!
- good for UTI's
- slow kill rate, not much post ABS effect

Front 18

WHAT ARE THE GROUPS OF PENICILLINS?

Back 18

- NARROW SPEC
- BROAD SPEC
- ANTIPSUEDOMONAL

Front 19

WHAT ARE THE NARROW SPEC PENICILLINS?

Back 19

- PEN-G
gram +, acid LABILE ( no oral ), B lac susceptible

- PEN-V
gram +, acid STABILE (oral), B Lac susceptible

- Cloxacillin, nafcillin
gram +, ACID & B lac stabile

Front 20

Name some limitations of PEN-G?

Back 20

unstable in gastric acid

B- lac susceptible

Inactive against (-) BAC

Front 21

How do we administer narrow spec PENS?

Back 21

PEN G
-salts that vary in solubility & duration of action
- Na salt- IV 4 hrs

PEN Procaine
- slightly soluble, up to 24hrs

Benzathine benzylpenicillin
- less soluble, lower levels over a longer period, slow release from inj site

Front 22

What are the B lac resistant pens?

Back 22

- Methicillin
- Cloxacillin

Front 23

WHAT ARE THE BROAD SPEC PENS?

Back 23

- AMINOPENICILLINS
- AMOXI
- AMPI

- ANTI-PSUEDOMONALS
- CARBENICILLIN
- TICARCILLIN

Front 24

WHAT ARE THE AMINOPENICILLINS USED FOR?

Back 24

- (+) & (-), ACID STABILE, B-LAC SUSCEPTIBLE

- AMOXI is more orally bioavailable than AMPI
- May be used with Clavulanate and Clavulanic acid for broader spec (-)

Front 25

HOW DO WE GIVE AMINOPENICILLINS?

Back 25

- Na salts
- Trihydrate salts main form for both oral and inj *

Front 26

WHAT ARE ANTIPSUEDOMONAL PENS?

Back 26

- Dicarboxylic acid derivatives
- TICARCILLIN
- synergistic with aminoglycosides (gentamycin)
- sensitive to B lac of P. aueruginosa and gastric acid

- Ureidopenicillins
- PIPERACILLIN

Front 27

B LAC INHIBITORS

Back 27

- bind irreversibly to B lac enzs
- synergise B lac ABS
- weak antibacterials
- EX:
- CLAVULANIC ACID , TAZOBACTAM, & SULBACTAM are suicide inhibitors

Front 28

ARE PENICILLINS SAFE? WHY/ WHY NOT?

Back 28

YES! VERY SAFE

OCCASIONAL ANALPHYLAXIS

**** CAUSES FATAL CLOSTRIDIAL COLITIS IN SMALL FURRIES- messes up gut flora

Front 29

What are cephalosporins? How are they organized?

Back 29

They belong to the B lactams, group of antimicrobials

They are organized into generations based on their activity

They are resistant to B lac ENZ's

Front 30

Cephalosporin 1st GEN uses

Back 30

- good for (+), including penicillinase producing BAC and anaerobes
- moderate vs (-)
- oral admin most common
EX:
CEPHALEXIN

Front 31

Cephalosporin 2nd GEN uses

Back 31

- similar to 1st
- BETTER vs e. coli, Klebsiella, Proteus
EX:
Cefuroxime ( not licensed Vet product )

Front 32

Cephalosporin 3rd GEN uses

Back 32

- EXCELLENT vs. enterobacteriaceae ( e. coli ), fair vs Pseudomonas
EX:
Ceftiofur, does not cross into milk, Zero withdrawal

Front 33

Cephalosporin 4th GEN use

Back 33

- Broad spec (-)
- Not destroyed by B- Lac producing Klebsiella or Psuedomonas
- injectable
- licensed for FOOD ANIMAL
EX:
Cefquinome

Front 34

What is the MECH of ACTION for Cephalosporins?

Back 34

- same as Pens
- Bactericidal antibiotics
-Time-dependant antimicrobials

Front 35

What are the Pharmacokinetics of the Cephalosporins?

Back 35

- Distribution similar to PENs ( low Vd, ECF )
- High concentrations in urine & bile
- admin every 6-8 hrs
- NO POST ABS effect
- excluded from prostate, CSF, aqueous except later generations
- Renal excretion
- some cephalosporins de-acetylated in liver

Front 36

Name some Cephalosporins used in Vet Med

Back 36

- Companion Animals
- Cephalexin- 1st GEN, oral, inj
- Cefovecin (Convenia(TM))- 3rd GEN, Parenteral ONLY, every 14 days, LONG acting, great for cats that want to eat your face
- Food Animals
-Ceftiofur- 3rd GEN
- Cefquinome- 4th GEN (-)

Front 37

What are the Carbapenems & Monobactams?

Back 37

- Antimicrobials developed to deal with B-lac producing (-) organisms
- NOT LICENSED !!
- Use sparingly, as last resort

***** Carbapenem
- Imipenem- given with cilastatin to inhibit renal hydrolysis
- Cilastatin prevents the imipenam metab to potential toxic compound

***** Monobactam
- Aztreonam