Penicillins

Presented by,
Dr Noor Jahan
Objective
At the end of lecture students will be able to,
 Classify penicillins
 Explain mechanism of penicillin
 Enlist penicillins
 Give indications of penicillins
 Describe mechanism of resistance
 Explain adverse effects and drug interactions

of penicillin
CHEMOTHERAPY
Classification According to Site of Action
 1- Synthesis of bacterial cell wall
 2- Protein synthesis
 3- Nucleic acid metabolism
 4- Permeability of cytoplasmic membrane

cell damage
1- Synthesis of bacterial cell wall:
 a- Cycloserine: Formation of di-d-alanine
 b- Fosfomycin: Formation of N-acetyl
cysteine
 c- Vancomycin , Teicloplanin & Bacitracin:
Elongation of peptidoglycan
 d- β-Lactam antibiotics: last step of cell wall
synthesis. [Transpeptidase
enzyme responsible for cross linking of

the long peptidoglycan]

2- Proteine synthesis through:
 a- Formation of m.RNA [ RNA polymerase] :
eg.: Rifampicin
 b- Binding with 30S ribosomal subunit of

bacteria
eg.:Aminoglycoside , Tetracycline
 c- Binding with 50S ribosomal subunit of

bacteria
eg.:Chloramphenicol , Erythromycin ,
Lincosamides
3- Nucleic acid metabolism:
 a- Folate antagonists:
 - Compete with PABA :eg.: Sulphonamides
 - Dihydrofolate reductase enz.: eg.:
Trimethoprime & Pyrimethamine
 b- DNA:
 -Antiviral & anticancer –Griseofulvine
-Metronidazole & Chloroquine
 -Quinolones [ DNA gyrase enz.]
 c- RNA eg.: Rifampicine [ RNA polymerase
enz.].
4- Permeability of cytoplasmic
membrane cell damage:
 eg.: Amphotericin & Nystatin (antifungal), Daptomycin &
Polymyxin [Colomycin (colistin)].
 Colistin is a polycationic peptide and has

both hydrophilic and lipophilic moieties.
 These cationic regions interact with the bacterial outer

membrane, by displacing magnesium and calcium

bacterial counter ions in the lipopolysaccharide.
 Hydrophobic/hydrophilic regions interact with

the cytoplasmic membrane just like a detergent,

solubilizing the membrane in an aqueous environment.
  It remains one of the last-resort antibiotics for

multidrug-resistant Pseudomonas
aeruginosa, Klebsiella pneumoniae, and Acinetobacter.
Classification According to
Mechanism of Action
 1- Bactericidal: β-lactam antibiotics,
Polymixines, Quinolones, Aminoglycosides ,
Rifampicin

 2- Bacteriostatic: Sulphonamides ,
Chloramphenicol , Tetracyclines

 3- Bcteriostatic & cidal: according to

concentration as: Erythromycin & Isoniazid
Classification According to
Spectrum

 1- Narrow spectrum: Penicillin G ,

Erythromycin, Streptomycin, Sulphonamides

 2- Wide spectrum: Chloramphenicol,

Tetracycline
1-Inhibitors of cell wall synthesis
β-Lactam Antibiotics
 Penicillins
 Cephalosporins
 Monobactams
 Carbapenems
Inhibitors of cell wall
synthesis
Other inhibitors of cell wall
synthesis

 1-Vancomycin (Vancocin)
 2-Teicloplanin
 3-Bacitracin
 4- Fosfomycin
 5-Cycloserine
 Empirical Treatment is a medical treatment
not derived from the scientific method, but
derived from observation, survey or common
use.
 In the medical profession, the term is also used

when treatment is started before a diagnosis is

confirmed (example: antibiotics). The most
common reason is that investigations are
sometimes needed in order to confirm a
diagnosis, which take time, and a delay in
treatment can harm the patient.
 Definitive Treatment
 Any therapy generally accepted as a specific

cure of a disease.
Penicillins

 Penicillins are medicines that kill

bacteria or prevent their growth
β-Lactum
Antibiotics
Discovery
 Alexander
Fleming, who
is credited with
discovering
penicillin in
1928.
  He showed that, if Penicillium rubens were
grown in the appropriate substrate, it would
exude a substance with antibiotic properties,
which he dubbed penicillin.
CLASSIFICATION
 Substituents of the 6-aminopenicillanic acid
moiety determine the essential
pharmacologic and antibacterial properties of
the resulting molecules.
1. Antistaphylococcal Penicillins
(eg, Nafcillin)
 These penicillins are resistant to
staphylococcal-lactamases.
 They are active against staphylococci and

streptococci but not against enterococci,

anaerobic bacteria, and gram-negative cocci
and rods.
2. Extended-Spectrum Penicillins (Ampicillin
and the Antipseudomonal Penicillins)

 These drugs retain the antibacterial spectrum

of penicillin and have improved activity
against gram-negative organisms. Like
penicillin, however, they are relatively
susceptible to hydrolysis by beta-lactamases.
3. Penicillins (eg, Penicillin
G)
 These have greatest activity against gram-
positive organisms, gram-negative cocci, and
non-beta -lactamase-producing anaerobes.
However, they have little activity against
gram-negative rods, and they are susceptible
to hydrolysis by beta-lactamases.
Penicillin Sensitivity Test
 Skin reaction tests involve pricking the skin with
droplets of the allergen
 If there is a reaction to the drop, the skin will swell

and cause a wheal (an enlarged area)

 A positive reaction is noted if the wheal is larger

than the accepted 3 mm criteria

 This test is not considered to be an accurate test for

food allergies
 If the prick test does not show any reactions,

medical professionals may perform a intradermal

test
 Again, this is not another accurate test used for food

allergies
 The RAST (radioallergosorbent test) is a
blood test to determine the level of the IgE
antibody in the system
 A newer blood test, the ImmunoCap has been

used to detect IgE but some medical

personnel chose not to use it because it is
unreliable for skin testing
Before taking penicillin
 Asthma
 Kidney disease
 A bleeding or blood clotting disorder
 A history of diarrhea caused by taking

antibiotics
 A history of any type of allergy.
 Penicillin G
 Penicillin V
 Ampicillin
 Amoxicillin
 Nafcillin
 Oxacillin
 Ticarcillin
 Piperacillin
Structure of Penicillin
Mechanism of Action
 • Penicillins are dipeptide analogs of D-ala-D-
ala.
 • Radiolabelled Penicillin G binds to several

different proteins in the cell wall of bacteria

 • Bactericidal action is primarily due to

inhibition of PBPs 1a & 1b and PBP3 that

function as transpeptidases in the biosynthesis
of the peptidoglycan.
 Bacteria constantly remodel their peptidoglycan cell
walls, simultaneously building and breaking down
portions of the cell wall as they grow and divide
 β-Lactam antibiotics work by inhibiting the
formation of peptidoglycan cross-links in the
bacterial cell wall
 The β-lactam moiety (functional group) of penicillin
binds to the enzyme (DD-transpeptidase) that links
the peptidoglycan molecules in bacteria
 The enzymes that hydrolyze the peptidoglycan
cross-links continue to function, which weakens
the cell wall of the bacterium
Acid Stability
 Pen G is very labile in acid (half-life = 5 min
at pH 2, 37°C) compared to Pen V
(half-life = 5h at pH 1)
 Consequently, Pen V should be used when

oral penicillin is indicated.

PHARMACOKINETIC PROPERTIES OF
THE PENICILLINS
 Penicillin V 60% absorb through the oral route
 60-80% bound to plasma proteins
 All penicillins have short half-lives (0.5-2 h)

and must be given 3-4 times per day

 Penetration into CSF is very low when

meninges are not inflamed

 Excrete out through renal route through

tubular secretion and glomerular filtration

 Excretion through glomerular filtration can be

inhibited through probenecid

PENICILLIN SPECTRUM
 1. Strep. pneumoniae, Strep. pyogenes, Group B Strep.,
viridans group Strep., however penicillin-resistant strains
of Strep. pneumoniae are emerging (as high as 60% in
endemic areas). If MIC < 0.1 μg/ml - Pen G or V.
 2. Staphylococcus aureus (non-penicillinase producing
strains)
 3. Enterococcus faecalis, E. faecium (in combination with
aminoglycosides)
 4. Neisseria meningitidis
 5. Treponema pallidum (syphilis)
 6. Listeria monocytogenes
 7. Corynebacterium diphtheriae
 8. Anaerobes - Clostridum perfringens & C. tetani (not C.
difficile), Bacteroides fragilis (non-penicillinase producing
strains), Fusobacterium, Peptostreptococcus
 Staph. aureus
 Strep. pyogenes
 Strep. pneumoniae
 Enterococcus faecalis
 E. coli
 Salmonella typhi
 Neisseria gonorrheae
 N. meningitis
 Haemophilus influenzae
Dosing of Some Commonly Used
Penicillins
 Penicillins 
  Penicillin G (IV): 1–4 mU q4–6h
 Penicillin VK (PO): 0.25–0.5 g qid
 Antistaphylococcal penicillins 
 Cloxacillin, dicloxacillin (PO): 0.25–0.5 g qid
 Nafcillin (IV): 1–2 g q4–6h
 Oxacillin (IV): 1–2 g q4–6h
 Extended-spectrum penicillins 
  Amoxicillin (PO): 0.25–0.5 g tid
 Amoxicillin/potassium clavulanate (PO): 500/125 tid– 875/125 mg 

bid
  Piperacillin (IV): 3–4 g q4–6h
Augmentin
 AUGMENTIN is an oral antibacterial combination consisting
of amoxicillin and the beta-lactamase inhibitor, clavulanate
potassium (the potassium salt of clavulanic acid).
 Augmentin 250, for example, contains 250 mg of
amoxicillin and 125 mg of clavulanic acid. (375mg Tab).
 Film-coated tablet contains amoxicillin trihydrate
equivalent to 500 mg amoxicillin and potassium clavulanate
equivalent to 125 mg of clavulanic acid. (625mg Tab).
 Tablets 875mg amoxicillin plus 125mg potassium
clavulanate (1000mg Tab).
 Suspensions of amoxicillin/clavulanic acid are available for
use in children.
Augmentin Dosage
 Adults and children ≥ 40 kg
 One 250 mg/125 mg dose taken three times

a day. (375mg Tab)

 One 500 mg/125 mg dose taken three times

a day. (625mg Tab)

 Children < 40 kg
 20 mg/5 mg/kg/day to 60 mg/15

mg/kg/day given in three divided doses.

Augmentin uses
 Amoxicillin/clavulanic acid is widely used to treat or
prevent many infections caused by susceptible bacteria,
such as:
 Urinary tract infections
 Respiratory tract infections
 Skin and soft tissue infections
 Sinus infections

 Infections caused by the bacterial flora of the mouth,

such as:
◦ dental infections
◦ infected animal bites
◦ infected human bites (including uncomplicated "clenched-fist" or
"reverse-bite" injuries)
Ampiclox 500mg capsules
 Ampiclox 500mg Capsules is Indicated for the
prophylaxix or treatment of bacterial infections
 It is also appropriate for the treatment of respiratory
tract infections: Bronchitis, pneumonia, empyema, lung
abscess and infections associated with cystic fibrosis.
 Ear, nose and throat infections: Tonsillitis, sinusitis,
pharyngitis, otitis media and quinsy. Pelvic infections:
Septic abortion, salpingitis, puerperpal pyrexia and
caesarian section prophylaxis.
 Urinary tract infections: Cystitis and pyelonephritis.
Skin and soft tissue infections: Abscesses, boils,
carbuncles and post-operative wound infections.
Gastro- intestinal infections, Septicaemia, endocarditis
and orthopaedic infection.
Ampiclox 500mg capsules
 Ingredient
 Each gelatin capsules contains the equivalent

of 250 mg ampicillin and 250 mg cloxacillin.

 Direction
 Adults and children over 10 years: 500mg 1g

(1 to 2 x 500 mg capsules) every 6 hours.

Dosage can vary depending on the nature and
severity of infection.
Amoxil
 Amoxicillin is indicated for the treatment of bacterial 
infections caused by amoxicillin-sensitive gram-
positive and gram-negative pathogens. 
 This could include infections of the upper respiratory 

tract, including infections of the ears, nose and throat: 
Acute otitis media, acute sinusitis and bacterial 
pharyngitis; Infections of the lower respiratory tract: 
Acute exacerbation of chronic bronchitis, community-
acquired pneumonia; Infections of the lower urinary 
tract: Cystitis; Prophylaxis of endocarditis in patients at 
risk i.e. surgery in the oral cavity or upper airways.
Amoxil
 In haemolytic streptococcal infections the duration of therapy should 
be 6-10 days in order to achieve eradication of the organism.
 Adult dosage (including elderly patients):  Standard dosage: The 

usual dosage covers a range from 750 mg to 3g amoxicillin daily in 
divided doses. In some areas 1500 mg amoxicillin daily in divided 
doses are recommended as the upper usual dose. Special dosage
recommendation: Acute exacerbation of chronic bronchitis in 
adults: 2 x 1 g per day.
 Children's dosage (under 40 kg):  The daily dosage for children is 

40 - 90 mg/kg/day in two to three divided doses (not exceeding 3 
g/day) depending on the indication, the severity of the disease and 
the susceptibility of the pathogen. Children weighing more than 40
kg should be given the usual adult dosage.
Difference of Penicillin and
Amoxicillin
 Amoxicillin does not have to be taken as long as
penicillin. It does the job in a shorter period of
time.
 A study published June 2007 in the journal

"Thorax" compared amoxicillin and penicillin for

treatment of strep throat. The study authors
concluded, "The efficacy and safety of amoxicillin
50 mg/kg/day twice daily for 6 days were not
statistically different from those of penicillin 45
mg/kg/d three times a day--for 10 days in the
treatment of GAS tonsillopharyngitis."
USES FOR PENICILLIN G AND
PENICILLIN V
 1. Streptocococcal Infections - Pen G is the
most potent compound of all the penicillins
and cephalosporins for susceptible Gram +
bacteria. Pen V is normally used for oral
administration (more acid stable)
 a. Strep throat & scarlet fever - Strep.

pyogenes is generally sensitive

 b. Streptococcal skin and soft tissue

infections (Erysipelas & cellulitis) caused by

Strep pyogenes
 c. Pneumonia & Meningitis due to Strep.
pneumoniae
 Strep. pneumoniae
 d. Endocarditis due to Strep. viridans &
Enterococcus sp.
 • Enterococcal endocarditis (Pen G in combination
with Aminoglycosides)
 • Group B Strep., Viridans group Streptococci -
usually sensitive to Pen G alone
 e. Anaerobic streptococcal infections &
Peptostreptococcus
 2. Gram positive rods - Clostridia
(anaerobic infections) & Bacillus sp.
 a. Tetanus
 b. Gas gangrene
 c. Anthrax
 3. Meningococcal Infections – Neisseria
(Gram – cocci)
 • Meningitis due to N. meningitidis - usually

sensitive to high dose Pen G

 • Meningococcemia – overwhelming sepsis
 4. Syphilis
 • Primary syphilis –single dose of Benzathine

Penicillin G as Treponema pallidum is

exquisitely sensitive to low concentrations.
 • Secondary syphilis – Procaine Pen G
 • Neurosyphilis - high dose Pen G

(continuous infusion)
 5. Prophylaxis for scarlet fever - recent
local epidemics of scarlet fever
 Streptococci have occurred in U.S.
 Benzathine Pen G
Penicillins Advantages:
 Bactericidal against sensitive strains
 Relatively nontoxic
 Have excellent tissue penetration
 Efficacious in the treatment of infections
 Relatively inexpensive in comparison with

other antibiotics
 Newer penicillins are resistant to stomach

acid, such as penicillin V, or have a broader

spectrum, such as ampicillin and amoxicillin
 Penicillin is produced by Penicillium
chrysogenum
 Alteration of the culture medium by feeding
 precursors, phenylacetic acid for Penicillin G or

phenoxyacetic acid for Penicillin V is used for

large scale production
 Other penicillins are produced semi-

synthetically
Penicillins Disadvantages:
 Acid lability - most of these drugs are destroyed
by gastric acid
 Short duaration of action - because of this short
half-life, the penicillins must be administered at
short intervals, usually every 4 hours
 Lack of activity against most Gram-negative
organisms
 Drug hypersensivity - about 10% of population
has allergy
 Many patients experience GI upset
 Painful if given intramuscularly
Thank you