Cell Wall Inhibitors (penicillin ) Flashcards by Salam Almasri

What are cell wall inhibitors ?

1)Penicillins
2) Cephalosporins
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Penicillin Structure :

R substituent ( Side Chain ) attached to 6-Aminopenicillinic acid residue

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The importance of The side chain :

1) affects the antibacterial spectrum of penicillins
2) Stability to Stomach Acid
3) Cross-hypersensitivity
4) Susceptibility to bacterial degradative enzymes

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MOA of penicillins :

Inhibition of the last step of bacterial cell wall Synthesis
WHICH IS the process of transpeptidation

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What is transpeptidation ?

The cross-linking of adjacent peptidoglycan strands during bacterial cell wall synthesis.

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MOA of penicillins ( detailed )

Since penicillins resemble the terminal portion of the peptidoglyacan strand , they compete and bind to penicillin-binding proteins ( catalyse the transpeptidase and facilitate the cross-linking of the cell wall )

يعني ما بصير عنّا cross linking لل peptidoglycan فا بيطلع عنّا weak cell wall

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What are the consequences of transpeptidation inhibition ?

1) weak bacterial cell wall
2) bacterial cell lysis

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Penicillins are …………….. & …………………. & ……………….

1) bactericidal
2) Time-dependant
3) effective against rapidly growing bacteria

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Why are penicillins effective against rapidly growing bacteria ?

Because it requires active cell wall Synthesis to apply its mechanism

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What are Natural Penicillins ?

Penicillin G , Penicillin V ( Oral form of penicillin G because it has more stability to gastric acidity and it is only available in the oral form )

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Antibacterial spectrum and clinical spectrum of natural penicillins :

1) Gas Gangrene caused by Clostridium Perfringens
2) Syphilis caused by treponema pallidum
3) Gonorrhea
4) Pneumococcal pneumonia ( بس بالnorth America )

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Extended-spectrum Penicillin : ( other name and what are they )

Semi-Synthetic penicillins / amoxicillin and ampicillin

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Anti-bacterial spectrum of extended-spectrum penicillins :

Extended to include gram-negative bacilli

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Clinical spectrum of Ampicillin :

1)Gram-positive bacillus L.monocytogenes
2) Enterococci
3) Respiratory infections

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Clinical Spectrum of amoxicillin :

1) Ear , nose and throat infections
2) Dental Prophylaxis

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Extended-Spectrum penicillins usually combine with :

B-lactamase inhibitors ( لأنه فيهم B-lactam ring فا بترتبط بال B-lactamase inhibitors وال anti-biotic بياخد مفعوله )

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Example on the combination of B-lactamase inhibitors and extended-bacterial spectrum penicillins

MSSA is resistant against amoxicillin and ampicillin if it is given without B-lactamase inhibitors

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What are anti-staphylococcal penicillins ?

MOND
1) Methicillin
2) Oxacillin
3) Nafcillin
4) doxacillin

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About Methicillin :

It is not used clinically because it cause nephrotoxicity
It is used in labs just to determine MSSA and MRSA

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Anti-bacterial spectrum of staphylococcal penicillins :

effective against penicillinase- producing Staphylococci ( MSSA)
minimal activity against gram- negative

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What is the antipseudomonal penicillin ?

Piperacillin

Common combination of piperacillin :

Piperacillin and tozabactam

Anti-bacterial Spectrum of antipseudomonal penicillin :

Effective against gram-negative bacilli but not klebsiella

MOR of penicillins :

1) intrinsic Resistance
2) Acquired Resistance

Intrinsic resistance is in : 2cases

1) Microorganism that lack peptidoglycan cell wall as M.pneumonia 2) Microorganism that has impermeable cell wall

Acquired resistance of penicillins is represented by :

1) deceasing membrane permeability 2) B-lactamase activity 3) altered PBPs

Explanation of decreased membrane permeability of penicillins :

1) Reduced Permeability , P.aeruginosa ( by lacking porin channels ) 2) Efflux pump , klebsiella pneumonia

Altered PBPs:

Gene mutations—> Structural alteration to decrease affinity to B-lactams —> MRSA resistance to most B-lactams.

What is the B-lactamase activity ?

Hydrolyse the cyclic amide bond of the B-lactam ring

How the B-lactamase acquired ?

Via Plasmids

Gram-positive bacteria secrete B-lactamase ……………

Extracellularly

Gram-negative bacteria secrete B-lactamase ……………

Periplasmic

How to solve the B-lactamase resistance :

By giving B-lactamase inhibitors beside the penicillin

About B-lactamase inhibitors :

- they have no antibacterial activity -they contain B-lactam ring -acts as a substrate for B-lactamase instead of the anti-biotic

Examples on the combination of B-lactamases inhibitors and antibiotics :

1)Amoxicillin is given with clavulonic acid 2) Sulbactam and tazobactam

Routes of administration of penicillins:

1) IV & IM only 2) Orally only 3) Depot form

Penicillins that are taken IV/IM only :

1) Nafcillin 2) Oxacillin 3) Ampicillin & sulbactam 4) Piperacillin & tazobactam

Penicillins that are taken Orally only :

1) amoxicillin 2) Amoxicillin + clavulanic acid 3) dicloxacillin 4) Penicillin V

Penicillins that are taken in depot forms :

1) Benzathine penicillin G ( IM ) 2) Procaine penicillin G

Absorption of penicillins:

Most of them are incompletely absorbed after oral administration They must be taken on empty stomach , because as gastric emptying time increases , the drug is destroyed by gastric acidity

Distribution of penicillins :

They distribute in the body fluids but insufficient penetration to bone or CSF unless inflamed.

Penicillins and pregnancy :

Penicillins can cross the placenta but with no teratogenic effect.

Metabolism of penicillins:

Usually insignificant metabolism

Exceptions of penicillin metabolism :

In renal impairment: Metabolism of penicillin G In the liver : metabolism of Nafcillin and Oxacillin

What are the routes of elemination of penicillins :

1) Tubular Secretory System 2) Glomerular Filtration 3) Liver 4) breast milk

…………… is an inhibitor in the renal tubular secretion of penicillin :

Probenecid

Adverse effects of penicillins :

1) Hypersensitivity 2) Nephrotoxicity 3) Neurotoxicity 4) Hematological toxicities 5) diarrhoea

Penicillins and hypersensitivity:

1) ( Simple Skin Rash —> Angioedema —> anaphylaxis )in 5%-10% of patients have this allergy which must be inquired for 2) Cross-allergy

Penicillins as a toxic agent :

1) Nephrotoxicity : as in Methicillin 2) Neurotoxicity : if penicillin injected intrathecally 3) Hematological toxicities : decreased coagulation & Cytopenia

Diarrhoea caused by …………………………. Of penicillins and due to ……………….. :

Extended-Spectrum agents / intestinal flora imbalances