Beta Lactam Flashcards
In Gram + bacteria what is the main barrier for drugs?
Bacterial membrane
Main barrier for drugs in Gram -?
Outer membrane
Where do beta-lactamases go in Gram +?
Extracellular
Where do beta-lactamases go in Gram -?
Periplasmic space
Does gram + or gram - have the thicker peptidoglycan?
Gram +
How many membranes does Gram + have?
G-?
1
2
Besides thickness, what is a difference in structure between G+ and G- peptidoglycan?
G- has meso-diaminopimelic acid residue (DAP) while Gram + has L-lysine residue (COOH of DAP replaced by H)
Which bond is Lysozyme sensitive?
Beta (1,4)
How is peptidoglycan linked in Gram -?
Bridge between DAP residue and terminal D-Ala on different strands
How is peptidoglycan linked in Gram +?
Bridge L-Lys and terminal D-Ala
How many amino acids make up the crosslink?
5
Mechanism behind B-lactam antibiotics?
Inhibition of transpeptidases that glue peptidoglycan together.
With transpeptidase inhibited what kills the cell?
Osmotic stress resulting in cell lysis and cell death
What is responsible for reactivity of B-lactam system?
Highly strained four membered ring
What is normal bond angle?
120
What is compressed bond angle of B-Lactam?
90
Why do bacterial transpeptidases not catalyze reactions with host cell proteins?
Bacteria have unnatural D-Ala amino acids not recognized in host
What will cause resistance to Beta lactams?
Decreased cellular uptake of drug
Mutation of penicillin binding proteins
Efflux pump that pumps drug out
Beta-lactamases do what to neutralize beta lactams?
Hydrolyze
What is the spectrum of allergies for beta lactam antibiotics?
Drug rash to anaphylactic shock
What do beta-lactams act as to elicit allergic reaction?
Haptens
If someone is allergic to one penicillin can they be given another?
No
How do you test for an allergy to beta-lactam?
Topical flare
Wheal test
Under acidic conditions, main degradation products of Pen G are?
Benzylpenicillenic acid
Benzylpenillic Acid
Benzylpenicilloic acid
Do penicillin hydrolysis products have any antibiotic activity?
No
Is hydrolysis of beta-lactam reversible?
No
Which penicillin is more stable in the stomach?
Penicillin V due to electronegativity from extra Oxygen
What does the increased electronegativity reduce in beta lactam hydrolysis?
Nucelophilicity
Ideal pH for penicillins to be stored?
6-6.8
What catalyzes penicillin degredation reactions?
Heavy metal ions
Penicillins with more lipophilic side chains are more what?
Highly protein bound
Protein binding does what?
Reduces bioavailability
Protects from degradation
How does protein binding effect half lives of penicillin?
It doesnt
Why does protein binding not effect half life of penicillin?
Dissociation rate from protein is fast
Renal excretion rate is rate-limiting
Most lipophillic penicillin?
Cloxacillin
What rapidly excretes penicillins?
Kidneys or biliary routes
What does most of the work in renal excretion?
10% glomerular filtration
90% tubular secretion
Kidney disease/failure will cause what?
Prolonging of pencillin half life
Is penicillin an anion or cation?
Anion
What are the two mechanisms of tubular secretion for?
1 for cations and 1 for anions
Why will penicillin treatment combined with probenecid cause an increase in half life?
Penicillin will be in competetion with probenecid for tubular secretion via anion mechanism
Antimicrobial spectrum for Pen G?
Gram + cocci,
Neisseria gonorrhoeae
Haemophilus influenzae
Most effective route of Pen G administration?
Parenteral
Why is methicillin beta lactamase resistant?
Steric hindrance protects it from nucelophilic attack
Why must methicillin be injected?
Stomach pH makes its half life go to about 5 minutes
Antimicrobial spectrum for methicillin?
Narrow, mainly for staph aureus
Why is methacillin resistant staph aureus resistant to methicillin?
Mutation in penicillin binding protein
Name of the penicillin binding protein that methicillin resistance gene codes for?
PBP2
Difference between Cephapirin and penicillin
Six membered sulfur containing ring fused to beta lactam instead of five membered ring
What inactives the Cephapirin?
Host esterases via acetate in 3-postion
Difference between penicillin and imipenem?
Sulfur in thiazolidine ring replaced by methylene group
What is the result of the ring change between penicillin and Imipenem?
Reactivity increased in Imipenem due to greater ring strain
What does imipenem do to beta lactamases?
Inhibits them
What hydrolyzes imipenem?
renal dehydropeptodase-1
How do you stop the hydrolyzing of imipenem?
Co-administer with dehydropeptidase-1 inhibitor cilastatin
Combination with larger spectrum than anything else in U.S?
Imipenem with cilastatin (G+ and G-)
How is imipenem-cilastatin administered?
Parenterally
Antibiotic spectrum of Aztreonam?
G-
