2.CW inhibit P1

Gram (+ve) Physical properties

peptidoglycan layer is much thicker in grampositive than in gram-negative

Penicillin-binding proteins (PBPs) are membrane proteins that cross-link peptidoglycan.

TRUE/FALSE

True

Cell wall inhibitors work on actively proliferating microorganisms (no effect on bacteria that are not growing and dividing)

True/false

True

Characteristic of Penicillin?

widely effective and least toxic

Note: Penicillins

Penicillins are only effective against rapidly growing organisms that synthesize a peptidoglycan cell wall

(inactive against mycobacteria, protozoa, fungi, and viruses).

MOA of penicillin(2)

1.Inhibit PBP

2.Production of autolysins

MOA of penicillin for inhibit PBP?detailed

1. Bacterial cell wall consists of strands of repeating (NAG) and (NAM) subunits. The NAM subunits have short peptide chains (used in cross-linking).

2. The penicillin binding protein (PBP) forms a crosslink

3. The PBP dissociates from the wall once the cross-link has been formed.

4. Penicillin is added to the system. It enters the active site of the PBP and reacts with the serine group.

5. The beta-lactam ring of penicillin covalently linked to the PBP and permanently blocks the active site.

Thus blocking cross linking of peptidoglycan

MOA of penicillin for production of autolysins?

Autolysins are produced by bacteria to remodel the bacterial cell wall. In the presence of penicillin, the cell wall degradation by autolysins proceeds

in short MOA of penicillin?

inhibition of cell wall synthesis and destruction of existing cell wall by autolysins

Is penicillin time dependent and bactericidal?

YES

How to obtain Natural Penicillins

Obtained from fermetation of fungus penicillium chrysogenum)

Properties of Penicillin V

Poor oral absorption

More acid stable than Penicillin G

Natural Penicillin cover what bacteria?

Syphilis

Gonorrhea

Streptococcal Pneumonia

Example pf Antistaphylococcal penicillin(beta-lactamase resistant penicillin)

Methicillin

Methicilin is toxic (interstitial nephritis),not clinically used anymore

True

Example of extended spectrum penicillins

Amoxicillin and Ampicillin

Amoxicillin prevents bacterial endocarditis during dental surgery

True

Extended spectrum penicillin always pair with ?

Beta lactamase inhibitor eg. clavulanic acid /sulbactam

Coverage of Ampicillin

Extended spectrums penicillins are more effective toward gram (-VE)

True

Extended spectrum penicillin is use to treat

respiratory infections

MRSA can be treated by?

vancomycin

Coverage of Antipseudomonal penicillins (ticarcillin and piperacillin)

not towards Kblesiella

What cause resistance toward penicillin groups?

inactivation of antibiotic by beta-lactamase(major)

modification of PBPs

impaired penetration of drug to target PBPs

efflux

Pharmacokinetics of Penicillins

Absorption?

incompletely oral absorption.

However, amoxicillin is almost completely absorbed

Penicillins should be given on empty stomach (1-2 hours before or after meal). Why?

because food and stomach acids delay absorption, reducing the amount of medicine that enters your bloodstream

Pharmacokinetics of Penicillins

Distribution

Well-distributed

• Cross placental barrier, but none-teratogenic.

• Low penetration into bone and cerebrospinal fluid (Unless the sites are inflamed which will ↑ drug penetration).

• Penicillin is not effective for prostate infection

Pharmacokinetics of Penicillins

Metabolism

insignificant metabolism(unchanged drug)

But Nafcillin and oxacillin are primarily metabolized in the liver

Pharmacokinetics of Penicillins

Excretion

Glomerular filtration and active tubular secretion.

penicillins are also excreted in breast milk.

What do you have to do for patients with impaired renal function?

Dose Adjustments

Avoid Nephrotoxic Drugs

Dietary Management

Dose adjustment is not required for Nafcillin and oxacillin in patients with impaired renal function are exceptions. Why?

they are primarily eliminated via the hepatobiliary (liver) system rather than the kidneys

Probenecid (used to prevent gout attacks by helping the body eliminate excess uric acid)

inhibits the secretion of penicillins by competing for active tubular secretion via the organic acid transporter So?

Toxic la). Note: Penicillin itself is actually remarkable non-toxic

Adverse effect of Penicillin

1.Hypersensitivity-angioedema,anaphylaxis

2.Diarrhoea-disruption of normal balance intestinal flora(Clostridium difficile)

3.Nephritis

4.Neurotoxicity-seizure if injected intrathecally

-cause GABAergic inhibition(reduce the electrical activity of neurons in the brain)

5.Hematologic toxicity(Cytopenia)-decrease in bone marrow and blood cell