Beta- Lactams Antibiotics( part -I)- (A)Pencillins
Pencillins: Pencillin was the first antibiotic to be used clinically in 1941. Penicillins are a group of antibiotics originally obtained from pencillium notatum principally P. chrysogenum and P. rubens. Most penicillins in clinical use are chemically synthesized from naturally-produced penicillins. A number of natural penicillins have been discovered, but only two purified compounds are in clinical use: penicillin G (intravenous use) and penicillin V (given by mouth). Penicillins were among the first medications to be effective against many bacterial infections caused by staphylococci and streptococci. They are members of the β-lactam antibiotics.They are still widely used today for different bacterial infections, though many types of bacteria have developed resistance following extensive use.
Mechanism of action:
The penicillins as well as other β-lactam antibiotics are bactericidal drugs. They kill susceptible bacterial by inhibiting the synthesis of the bacterial peptidoglycan cell wall. The peptidoglycan provides the cell with rigid stability due to its highly cross-linked structure and its synthesis has 3 stages. The first and second stages take place in the cytoplasm. The final stage occurs outside the cell to complete the cross-link, when new subunits are added to the growing peptidoglycan. Rapid cell wall synthesis occurs organisms are actively multiplying, Beta-lactam antibiotics are more lethal in this phase. The peptidoglycan cell wall is unique to bacteria. In gram positive bacteria, the cell wall is almost made up of peptidoglycan, which is >50 layers thick and cross linked , so it may be regarded as as single giant mucopeptide molecule. In gram negative bacteria it consists of alternating layers of lipoproteins and peptidoglycan with 1-2 molecule thick with little cross linking.
Pencillin G: It is narrow spectrum antibiotic, active against gram positive bacteria ad few others. It is also known as benzylpencillin. It is a natural penicillin antibiotic that is administered intravenously or intramuscularly due to poor oral absorption. Penicillin G may also be used in some cases as prophylaxis against susceptible organisms. Natural penicillins are considered the drug of choice for many infections caused by anaerobic organism such as Streptococcus pneumoniae, groups A, B, C and G streptococci and non-penicillinase producing staphylococcus. The natural penicillins may also be used as first or second line agents against susceptible gram positive aerobic bacilli such as Bacillus anthracis, Corynebacterium diphtheriae, and Erysipelothrix rhusiopathiae. Natural penicillins have limited activity against gram negative organisms; however, they may be used in some cases to treat infections caused by Neisseria meningitidis and Pasteurella. They are not generally used to treat anaerobic infections. Resistance patterns, susceptibility and treatment guidelines vary across regions.
Pencillinase: It is a narrow spectrum Beta-lactamse which opens the Beta- lactam ring and inactivates PnG. Majority of organisms such as Staphylococci, some strains of gonococci, B. subtulis, .coli, H. influenzae and few other bacteria producing pencillinase.
Mechanism of action:
The bactericidal activity of penicillin G results from the inhibition of cell wall synthesis and is mediated through penicillin G binding to penicillin binding proteins (PBPs). Penicillin G is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, penicillin G inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that penicillin G interferes with an autolysin inhibitor.
Pharmacokinetics: Rapidly absorbed following both intramuscular and subcutaneous injection. PnG is acid- labile destroyed by gastric acid. Less than 1/3rd of an oral dose is absorbed in the active form. Distribution is extracellularly, distributed mostly in body fluids , but poor permeability in CSF and in serous cavities. About 60%plasma protein bound. It is little metabolized due to rapid excretion. About 16-30% of an intramuscular dose is metabolized to penicilloic acid, an inactive metabolite. Rapid excretion about 10% is excreted through glomerular filtration and the rest by tubular secretion. The plasma t1/2 is of 30min. Tubular secretion of PnG is blocked by probenecid- higher and longer plamsa concentrations are achieved.
- Local irritancy and direct toxicity: Nausea on oral ingestion, pain at i.m site, thrombophlebitis of injected vein. Toxicity to the brain- mental confusions, muscular twitchings, convulsions and coma. Bleeding can occur due to the interference with platelet function.
- Hypersensitivity: Rashes, itching urticaria, wheezing, fever, angioneurotic edema, serum sickness, exfoliative dermatitis are less common. anaphylaxis are rare. angioedema, bronchospasm.
- Superinfections: These are rare with PnG because of its narrow spectrum, though bowel, respiratory, cutaneous microflora does undergo changes.
- Jarisch-Herxheimer reaction: Pencillin injected in syphilitic agent may produce shivering, fever, myalgia, vascular collapse.
Uses : Pencillin G is a drug of choice for sveral infections
- Streptococcal infections: Pharyngitis, otitis media, scarlet fever
- Pneumococcal infections: PnG is not used now for pneumococcal infections because many strains have become pencillin resistant. PnG 3-6 MU i.v every 6 hrs is the drug of choice if organism is sensitive.
- Meningococcal infections: Meningitis can be treated with higher doses.
- Gonorrhoea : Treatment of ophthalmia neonatorum due to sensitive N. gonorrhoea consist of salin irrigation+ so. PnG.
- Syphilis: PnG is a drug of choice.
- Diphtheria: Procaine pencillin 1-2MU daily for 10 days.
- Tetanus and gas gangrene: PnG 6-12 MU/day is used to kill the causative organism
- PnG is the drug of choice for rare infections like anthrax, actinomycosis, trench mouth, rat bite fever .
- Rheumatic fever, bacterial endocarditis.
- Pencillin is a drug of choice for orofacial infections
Cell-wall Biosynthesis is Inhibited by Antibiotics by Inhibiting the Biosynthesis of Which of the Following?
Which of the Following Antibiotic Functions as Cell Wall Inhibitors:
Benzylpenicillin is the Chemical Name for Which of the Following Penicillin?
a) Penicillin V
b) Penicillin G
c) Penicillin F
What is the Typical Drug of Choice for Most Orofacial Infection:
- Which drug is bind to penicillin binding proteins (PBPs) during inhibition of cell wall synthesis.
d) Pencillin G
6. The Penicillins act by :
a). inhibition of protien synthesis
b). interfering with bacterial cell wall synthesis.
c). inhibition of neuclic acid synthesis
d). phagocytic action.
7. The most important side-effect of the Penicillins is
a). gastrointestinal disturbances.
c). hypersensitivity reactions
8. Regarding the pharmacokinetics of the penicillin
a). Penicillin are 40 to 80 % bound by serum proteins
b). Absorption is enhanced by coadministration of antacids
c. Penicillin cross the blood brain barrier easily
d. Penicillin is rapidly excreted by the glomerular filtration and tubular secretion.
9. Tubular secretion of penicillin is blocked by
d). None of them
10. Antibiotics are used to treat infections by
c) All the microorganisms
d) None of the above
11. What is meant by antibiotic resistance?
a). It means the bacteria have developed antibiotic resistance
b). It means our body has become resistant to the antibiotic
c). Both (a) and (b)
d). None of the above
12. What are the uses of penicillin G
a). Gas gangrene
b). Stretptococcal infections
d). All of above
13. Which enzyme opens the Beta- lactam ring and inactivates PnG
a). Beta- lactamase
14. Penicillin belongs to which spectrum of antibiotics
a). Broad spectrum
b). Narrow spectrum
15. Action of Beta-lactam antibiotics
- “K.D,Tripathi”, Beta-lactams penicillins, page no- 694-699, 6th edition nov 2007.
- “Dawn Merton Boothe”, Department of anatomy, physiology and pharmacology, nov 2015.