Cell Wall Inhibitors (penicillin )

Question 1

What are cell wall inhibitors ?

Answer 1

1)Penicillins
2) Cephalosporins
.
.
.
.

Question 2

Penicillin Structure :

Answer 2

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

Question 3

The importance of The side chain :

Answer 3

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

Question 4

MOA of penicillins :

Answer 4

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

Question 5

What is transpeptidation ?

Answer 5

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

Question 6

MOA of penicillins ( detailed )

Answer 6

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

Question 7

What are the consequences of transpeptidation inhibition ?

Answer 7

1) weak bacterial cell wall
2) bacterial cell lysis

Question 8

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

Answer 8

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

Question 9

Why are penicillins effective against rapidly growing bacteria ?

Answer 9

Because it requires active cell wall Synthesis to apply its mechanism

Question 10

What are Natural Penicillins ?

Answer 10

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 )

Question 11

Antibacterial spectrum and clinical spectrum of natural penicillins :

Answer 11

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

Question 12

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

Answer 12

Semi-Synthetic penicillins / amoxicillin and ampicillin

Question 13

Anti-bacterial spectrum of extended-spectrum penicillins :

Answer 13

Extended to include gram-negative bacilli

Question 14

Clinical spectrum of Ampicillin :

Answer 14

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

Question 15

Clinical Spectrum of amoxicillin :

Answer 15

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

Question 16

Extended-Spectrum penicillins usually combine with :

Answer 16

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

Question 17

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

Answer 17

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

Question 18

What are anti-staphylococcal penicillins ?

Answer 18

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

Question 19

About Methicillin :

Answer 19

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

Question 20

Anti-bacterial spectrum of staphylococcal penicillins :

Answer 20

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

Question 21

What is the antipseudomonal penicillin ?

Answer 21

Piperacillin

Question 22

Common combination of piperacillin :

Answer 22

Piperacillin and tozabactam

Question 23

Anti-bacterial Spectrum of antipseudomonal penicillin :

Answer 23

Effective against gram-negative bacilli but not klebsiella

Question 24

MOR of penicillins :

Answer 24

1) intrinsic Resistance
2) Acquired Resistance

Question 25

Intrinsic resistance is in : 2cases

Answer 25

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

Question 26

Acquired resistance of penicillins is represented by :

Answer 26

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

Question 27

Explanation of decreased membrane permeability of penicillins :

Answer 27

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

Question 28

Altered PBPs:

Answer 28

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

Question 29

What is the B-lactamase activity ?

Answer 29

Hydrolyse the cyclic amide bond of the B-lactam ring

Question 30

How the B-lactamase acquired ?

Answer 30

Via Plasmids

Question 31

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

Answer 31

Extracellularly

Question 32

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

Answer 32

Periplasmic

Question 33

How to solve the B-lactamase resistance :

Answer 33

By giving B-lactamase inhibitors beside the penicillin

Question 34

About B-lactamase inhibitors :

Answer 34

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

Question 35

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

Answer 35

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

Question 36

Routes of administration of penicillins:

Answer 36

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

Question 37

Penicillins that are taken IV/IM only :

Answer 37

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

Question 38

Penicillins that are taken Orally only :

Answer 38

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

Question 39

Penicillins that are taken in depot forms :

Answer 39

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

Question 40

Absorption of penicillins:

Answer 40

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

Question 41

Distribution of penicillins :

Answer 41

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

Question 42

Penicillins and pregnancy :

Answer 42

Penicillins can cross the placenta but with no teratogenic effect.

Question 43

Metabolism of penicillins:

Answer 43

Usually insignificant metabolism

Question 44

Exceptions of penicillin metabolism :

Answer 44

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

Question 45

What are the routes of elemination of penicillins :

Answer 45

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

Question 46

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

Answer 46

Probenecid

Question 47

Adverse effects of penicillins :

Answer 47

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

Question 48

Penicillins and hypersensitivity:

Answer 48

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

Question 49

Penicillins as a toxic agent :

Answer 49

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

Question 50

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

Answer 50

Extended-Spectrum agents / intestinal flora imbalances