Beta-Lactam Antibiotics
Penicillins & Cephalosporins
Dr V Karthik
Department of Pharmacology
CDSIMER
Beta-Lactam Antibiotics
Penicillins & Cephalosporins
CONTENT
-INTRODUCTION
-GENERAL CONSIDERATION OF ANTIMICROBIALS
-CLASSIFICATION OF BETA LACTAMS
-PENCILLIN & CEPHALOSPORINS
HISTORY
CLASSIFICATION
INDIVIDUAL DRUGS
PHARMACOKINETICS
PHARMACODYNAMICS
USES
ADVERSE EFFECTS
Penicillins and Cephalosporin
INTRODUCTION
Antimicrobials agents (AMAs) • Design to inhibit/kill the infecting microorganism
( Bacteria, Fungi, Viruses) without affecting the host.
• Synthetic as well as naturally obtained.
Antibiotics –
• Substance produced by microorganism (Natural).
• Suppress the growth or kill the other organisms
at low concentrations.
Mechanism of action
Penicillins and Cephalosporins
Penicillins and Cephalosporins
β-Lactam antibiotics – β-lactam ring
-- Interfere with the synthesis of bacterial cell wall
-- Most widely produced and used.
β lactams include
• Penicillins
• Cephalosporins
• Carbapenems
• Monobactams
Penicillins & Cephalosporins
PENICILLINS
• First described by Fleming in 1929
• Isolated by Florey and Chain
• In 1940 from Penicillium notatum
• First clinical application(Streptococcal
septicemia) in 1941
Benzathine PnG
Procain Pn G
Penicillins & Cephalosporins
CLASSIFICATION
1.Acid-resistant alternative to penicillin G
Phenoxymethyl penicillin (Penicillin V).
2. Penicillinase-resistant penicillins
Methicillin, Cloxacillin, Dicloxacillin.
3. Extended spectrum penicillins
(a) Aminopenicillins: Ampicillin, Bacampicillin, Amoxicillin
(b) Carboxypenicillins: Carbenicillin
(c) Ureidopenicillins: Piperacillin, Mezlocillin
• β-lactamase inhibitors Clavulanic acid, Sulbactam, Tazobactam
Penicillins and Cephalosporins
MECHANISM OF ACTION
GRAM POSITIVE
GRAM NEGATIVE
• Interference with cell wall synthesis (Inhibit the transpeptidase) .
Penicillins and Cephalosporins
Penicillin G
• Prototype penicillin
• Narrow spectrum, primarily gram-positive
• P/K- Acid labile, less than 1/3rd of oral dose absorbed,
peak plasma level within 30min , 60% plasma protein bound
Little metabolized because of rapid excretion
t1/2 30min.
Therapeutic Uses
Penicillins and Cephalosporins
Uses
Pneumococcal.Pneumonia
(Respiratory infection)
Spectrum
Gram +ve cocci
Streptococcus pneumoniae
Streptococcus pyrogens
Streptococcus viridans
Gram +ve bacilli
Baciluus antracis
C.diptheria
Gonorrhaea(UTI, Menengitis)
Gram –ve cocci
N.Gonorrhoeae
N.menengitidis
Syphilis
T .pallidam
Tetanus
C .tetani
Prophylactic
Rheumatic fever
Sub acute bacterial endicarditis
Others
Diptheria
Penicillins and Cephalosporins
Adverse effects
• Hyper sensitivity reaction (6-amino pencillanic acid )
10%,Swelling of lips, tongue, peri-orbital area,
dermatitis,rashes.
TESTING: Scratch test, Intradermal test (2-10U)
• Diarrhea
• Nephritis –interstitial nephritis
• Neurotoxc –seizures
Penicillins and Cephalosporins
Penicillin V
• It differs from PnG only in that it is acid stable
• Oral absorption is better; peak blood level is reached in 1 hour and
plasma t½ is 30–60 min
Penicillins and Cephalosporins
2. Penicillinase-Resistant Penicillins :
Methicillin- prototype drug, followed by oxacillin, nafcillin,
cloxacillin and dicloxacillin
METHICILLIN
• Highly penicillinase resistant but not acid resistant—must be injected
• MRSA have emerged in many areas-The drug of choice for thesevancomycin/linezolid, ciprofloxacin can also be use
Penicillins and Cephalosporins
3.Extended spectrum Penicillins
(a)Aminopenicillins (Ampicillin, Amoxicillin, Bacampicillin).
• This group, led by ampicillin, has an amino substitution in the side
chain
AMPICILLIN
• Active against all organisms sensitive to PnG
• In addition, many gram-negative bacilli, e.g. H. influenzae, E. coli,
Proteus,Salmonella Shigella and Helicobacter pylori are inhibited
Penicillins and Cephalosporins
3.Extended spectrum Penicillins
a)Aminopenicillins (Ampicillin, Amoxicillin, Bacampicillin).
PHARMACOKINETICS
• Ampicillin is not degraded by gastric acid; Food interferes with
absorption
• Partly excreted in bile and reabsorbed
• Primary channel of excretion is kidney. plasma t½ is 1 hr
Penicillins and Cephalosporins
3.Extended spectrum Penicillins
USES
• Urinary tract infections
• Respiratory tract infections
• Meningitis
• Gonorrhoea
• Subacute bacterial endocarditis
ADVERSE EFFECTS
• Diarrhoea
• Rashes
Penicillins and Cephalosporins
3.Extended spectrum Penicillins
AMOXYCILLIN
It is similar to AMPICILLIN except
• Oral absorption is better; food does not interfere with absorption;
• higher and more sustained blood levels are produced.
• Incidence of diarrhoea is lower.
• Less active against Shigella and H.influenzae.
• More active against penicillin resistant Strep. pneumoniae
Penicillins and Cephalosporins
(b)Carboxypenicillins
• Carbenicillin- Pseudomonas aeruginosa and indole positive Proteus
which are not inhibited by PnG or aminopenicillins
• t½ 1 hr
Penicillins and Cephalosporins
(c)Ureidopenicillins
• Piperacillin antipseudomonal penicillin is about 8 times more active
than carbenicillin
• Klebsiella, many Enterobacteriaceae and some Bacteroides
Penicillins and Cephalosporins
BETA LACTAMASE INHIBITORS
Clavulinic acid, sulbactum, tazobactum
• Obtained from Streptomyces clavuligerus
• Has rapid oral absorption and bioavailability of 60% , t½ -1 hr
• Addition of clavulanic acid re-establishes the activity of amoxicillin
against β-lactamase producing resistant Staph. Aureus, H. influenzae,
Salmonella and Shigella
USES:
• Skin and soft tissue infections, intra abdominal and gynaecological sepsis,
urinary, biliary and respiratory tract infections
Penicillins and Cephalosporins
CEPHALOSPORINS
• Fungus Cephalosporium
• Chemically related to penicillins;
• Nucleus consists of a β-lactam ring fused to a dihydrothiazine ring,
Cephalosporins
MECHANISM OF ACTION
• Inhibition of bacterial cell wall synthesis
• Bind to different proteins than those which bind Penicillins
Cephalosporins
Cephalosporins
FIRST GENERATION (Cefaczolin.Cefadroxil,cefalexine)
Cefazolin
• PnG sensitive organisms, i.e. Streptococci (pyogenes as well as
viridans), gonococci, meningococci etc
• Preferred parenteral first generation cephalosporin, especially for
surgical prophylaxis
Cephalosporins
SECOND GENERATION
CEPHALOSPORINS(Cefuroxime,cefotoxime,cefoclore cefprozil)
• Developed subsequent to the first generation compounds
• More active against gram-negative organisms, with some active
against anaerobes as well, but none inhibits P. aeruginosa
Cephalosporins
THIRD GENERATION(Cefotaxime Cefatriaxone, cefixime,
cephadoxime, cefdinir,ceftanat,cefoperazone)
Cefotaxime
• Aerobic gram-negative as well as some gram positive bacteria,
• Indications- meningitis caused by gram-negative bacilli (attains
relatively high CSF levels), life-threatening resistant/hospital-acquired
infections, septicaemias
• Immunocompromised patients
• Typhoid fever
Cephalosporins
THIRD GENERATION(Cefotaxime Cefatriaxone, cefixime,
cephadoxime, cefdinir,ceftanat,cefoperazone)
Ceftriaxone
• Longer duration of action (t½ 8 hr), permitting once, or at the most
twice daily dosing
• Penetration into CSF is good
USES
bacterial meningitis (especially in children)
multi resistant typhoid fever
complicated urinary tract infections
abdominal sepsis
septicaemias
Cephalosporins
ADVERSE EFFECTS
• Pain
• Nephrotoxicity
• Bleeding
• Diarrhoea
• Hypersensitivity reactions
Cephalosporins
Uses
• Respiratory infections
• Urinary tract infections
• Soft tissue infections
• Meningitis
• Typhoid
• Septicemia
• Gonorrhoea
THANK YOU