ANTI BIOTICS

(PENICILLINS)
 ANTIBACTERIALS
i. Bacterial Cell-wall synthesis inhibitors e.g.
β-lactam antibiotics.
ii. Bacterial protein synthesis inhibitors. e.g.
Chloramphenicol, aminoglycosides,
tetracyclines, macrolides
Streptogramins,Lincosamides, Fusidic acid,
iii. Folate or Folic acid antagonists, e.g.
sulfonamides.
iv. Bacterial DNA gyrase inhibitors, e.g.
fluoroquinolones, quinolones
v. Antimycobacterial agents e.g.
Anti-tubercular therapy
vi. Miscellaneous antibacterials e.g.
metronidazole, Nitrofurantoin.
 β-lactam Antibiotics

i. Penicillins
ii. Cephalosporins and Cephamycins
iii. Carbapenems (imipenem)
iv. Monobactams (Aztreonam)
V. Glycoproteins (Vancomycin)
 PENICILLINS
Classification
Penicillins can be classified according to their
spectrum of antimicrobial activity. This
grouping is as under:
I-Penicillin G and Congeners:

The close congener of Penicillin G is

penicillin V. These penicillins are highly active
against sensitive strains of gram-positive
cocci but they are readily hydrolysed by
 penicillinase or β-lactamase.
They are not active against gram-negative
bacilli. Penicillin G (Benzylpenicillin) is acid-
labile and destroyed by Gastric HCl.
Penicillin V (Phenoxymethyl penicillin),
another natural penicillin, is acid resistant and
is used for oral administration.
II-Penicillinase-Resistant penicillins:
These are cloxacillin, Flucloxacillin,
Dicloxacillin, Methicillin, nafcillin etc.
 They have less potent antimicrobial activity
against pencillin-G sensitive micro organisms
but they are effective against β-lactamase
producing Staphylococcus aureus and S.
epidermidis.
III- Broad Spectrum Penicillins:
These include amoxicillin, ampicillin
Bacampicillin etc. These exhibit relatively high
antibacterial activity against both gram-positive
and gram-negative (H. influenzae, E.coli and
Proteus mirabilis) bacteria. These are readily
destroyed by β-lactamases
IV Extended Spectrum Penicillins: It is a sub-group of
group III, comprising carbenicillin and ticarcillin, the
antimicrobial activity of these penicillins is extended
to include Pseudomonas, Enterobacter and Proteus
species.
V Other Extended–Spectrum Penicillins:
include mezlocillin and piperacillin, which have
useful antimicrobial activity against Pseudomonas
Klebsiella and certain other gram-negative bacteria.
Reversed Spectrum( Mecillinam):
They are more potent against gram-negative
enteric bacteria than against gram-positive
organisms. They are hydrolysed by β-
lactamase. They can be given I/M or I/V.
Pevmecillinam is a prodrug given orally,
hydrolysed to mecillinam.
β-lactamase Inhibitors
These inhibitors are substrates for β-
lactamases. They are most active against
plasmid encoded β-lactamases (including the
enzymes that hydrolyse ceftazidime and
cefotaxime), but they are inactive at clinically
achieveable concentrations against type-1
chromosomal lactamases induced in gram-
negative bacilli (Enterobacter, Acinectobacter
and Citrobacter) by treatment with second
generation and third generation
cephalosporins.
 The inhibitors are:
i. Clavulanic acid (suicide inhibitor or
irreversible inhibitor)
ii. Sulbactam
iii. Tazobactam
Augmentin = amoxicillin + clavulanic acid
CHEMISTRY:
All the penicillins share the basic structure of
6-aminopenicillanic acid as shown in Figure.
The Basic structure of penicillins consists of a
thiazolidine ring connected to a β-lactam
ring . β-lactam ring carries a secondary amino
group. The side-chain substituents at R
determine the main antibacterial and
pharmacological characteristics of each
particular penicillin. The structural integrity of
6-aminopenicillanic acid nucleus is essential
for the biological activity of the molecule. If the
β-lactam ring is enzymatically cleaved by
bacterial β-lactamase, the resultant product,
penicilloic acid is completely devoid of
antibacterial activity. However, this break down
product carries antigenic determinant of the
penicillin, acts as a sensitizing structure when
combined with host proteins. Thus it is
considered to be major determinant of penicillin
allergy.
General structure of penicillins
A β-lactam (beta-lactam) ring is a four-
membered lactam. (A lactam is a cyclic amide). It
is named as such because the nitrogen atom is
attached to the β-carbon relative to the carbonyl.
The simplest β-lactam possible is 2-azetidinone.
In chemistry, a lactam is a cyclic amide. The
name is derived from two chemical terms, 
lactone, referring to a cyclic ketone, and
amide, a compound containing a nitrogen
 atom next to a carbonyl group. Lactams are
named according to the size of the cyclic ring
in the lactam: α-lactams, β-lactams, γ-lactams
and δ-lactams contain rings made of three,
four, five or six atoms, respectively.  α-
lactams are also called aziridinones.
Many widely used antibiotic drugs, including the 
penicillins and cephalosporins, owe their activity
to the presence of a  β-lactam structure.
NOMENCLATURE:
Three simplified forms of penicillin
nomenclature have been adopted for general
use. One utilizes the name PENAM for the
unsubstituted bicyclic system, including the
amide carbonyl group, with one of numbering
system i.e. either chemical abstract or USP.
The second, seen more frequently in medical
literature, uses the name penicillanic acid to
describe the ring system with substitutuents
Penam
 that are generally present (i.e. 2,2 dimethyl
and 3-carboxyl). A third form followed trivial
nomenclature to name the entire 6-
carbonylamino penicillanic acid portion of
the molecule as penicillin and then
distinguishes the compounds on the basis of
R group of acyl portion of the molecule.
UNITAGE OF PENICILLINS:
The one international unit of penicillin is the
specific penicillin activity contained in
 0.6 µg sodium penicillin G (mol. wt. = 356.37).
Thus one mg of sodium penicillin G is =1667
units. Whereas 1mg of pure penicillin G
potassium (mol. wt. = 372.48) represents 1595
units. The semi-synthetic penicillins are
prescribed by weight rather than units.
PHARMACOKINETICS:
Following oral administration, the absorption
differs greatly for various penicillins depending
upon their:
i Stability in acid
ii Adsorption onto food particles (protein binding)
In order to avoid the effect of these two factors
on bioavailability, all oral penicillins should be
given at other than meal times (i.e. 1hr before
or 1-2 hrs after meals). After parenteral
administration, most penicillins are absorbed
rapidly and completely. Intravenous route of
administration preferred over I/M because local
irritation and pain follow the intramuscular
injection.
Distribution:
After absorption, penicillins are widely
distributed throughout the body. Therapeutic
concentrations of penicillins are achieved
readily in tissues and body fluids, such as joint
fluid, pleural fluid, pericardial fluid, bile, saliva
and milk. Penicillins cross the placenta and
not blood-brain barrier under normal
conditions.
 Lower concentrations of penicillins are found
in the eye, prostate and the central nervous
system. However, pneumococcal and
meningococcal meningitis can be treated with
systemic penicillins and there is no need of
intrathecal injection of the drug. This is
probable that high levels of penicillins in CSF
in meningitis are achieved due to:
i. Increased permeability of meninges.
ii. Inhibition of normal active transport of
 penicillin out of CSF.
iii. Binding of penicillins to CSF proteins rapidly.
Elimination:
Elimination of most penicillins occurs rapidly
through the kidney. About 10 % of renal
excretion by glomerular filtration and 90% by
tubular secretion. The relatively short plasma
half-life (30-60 min) of penicillins is one of the
major problems in clinical use of drugs.
In renal failure, the half-life of a penicillins can
be prolonged many-fold if the drug is solely
eliminated by kidney, e.g. penicillin G has a
half-life half to 1hr in normal adult but in renal
failure it many be increased upto 10 hrs. The
problem of short half-life of penicillins can be
tackled either by frequent dosage
administration, or substitution with a slow-
release preparation such as Procain
penicillin.
For those penicillins, whose excretion is
mainly through renal tubular secretion,
administration of probenecid blocks partially
the renal secretion and as a result plasma
level and half-life are increased. Penicillins
can be excreted, to a small extent, in sputum
and milk. The presence of penicillins in the
milk of cows treated for mastitis presents a
problem in human allergy.
Mechanism of Action:
1. Inhibition of Cell Wall Synthesis:
a) Inhibition of Transpeptidation:
The biosynthesis of peptidoglycan involves
about 30 bacterial enzymes. It is completed in
3 stages, first & second stage synthesis
reactions take place in the cytoplasm that mean
inside the cytoplasm membrane. Third stage is
accomplished by transpeptidation and it occurs
outside cytoplasmic membrane. The term
peptidoglycan is derived from peptides and
sugars (glycan) that make up the molecule.
The peptidoglycan layer of cell wall is
composed of glycan chains, which are linear
strands of two alternating aminosugars, N-
acetylglucosamine (G) and N-acetylmuramic
acid (M). To amino sugars are attached short
pentapeptide chains. The exact composition of
side chain varies among species.
The final rigidity of cell wall is imparted by
cross-linking of peptide chains. In cross-
linkage terminal glycine residue of the
pentaglycine bridge is linked to the fourth
residue of the pentapeptide (D-alanine),
releasing the fifth residue (also D-alanine).
The cross linking is accomplished by
transpeptidation reactions catalysed by several
enzymes. Small segments of two polymer chains
and their amino acid side chains are shown in
figure:
These linear polymers must be cross-linked by
transpeptidation of the side chains at the points
indicated by asterisks to achieve the strength
necessary for cell viability.
All penicillins, all cephalosporins, all
monobactams and all carbapenems (beta-
lactam antibiotics) are selective inhibitors of
bacterial cell-wall synthesis. To do so, drugs
bind to bacterial cell receptors called
PENICILLIN-BINDING PROTEINS (PBPs).
The number of PBPs is 3-7 (mol. Wt. 40000 -
120000) in many bacteria.
Different receptors may possess different
affinities for a drug and each PBP may mediate
different function. For example binding of
penicillin to one PBP may result in abnormal
elongation of the bacterial cell while attachment
to another may cause defect of cell wall at the
periphery leading to death of cell. After binding
of beta-lactams to PBPs, the transpeptidation
reaction is inhibited and synthesis of
peptidoglycan is blocked. Then either removal
or inactivation of an inhibitor of autolytic
enzymes (autolysins or murein, hydrolases) in
the cell wall takes place.
This results in activation of lytic enzymes in
microorganisms and leads to death of microbes
if the environment is isotonic. In the hypertonic
environment , the microbes may change into
protoplasts or spheroplasts which are covered
by fragile cell membrane and no cell wall. In
such cells synthesis of proteins and nucleic
acids may continue for some time.
The lack of toxicity of beta-lactams to mammalian
cells must be attributed to the absence of
bacterial type cell wall in the animal cells.
 b)Inhibition of peptidoglycan precursors
synthesis:
Many drugs (such as bacitracin) inhibit different
early steps in the biosynthesis of peptidoglycan
precursors. As the early stages of synthesis
take place inside the cytoplasmic membrane,
these drugs must penetrate the cell membrane
to produce their effect. For example
cycloserine, an analogue of D-alanine, inhibits
incorporation of D-alanine into peptidoglycan by
inhibiting alanine racemase, the enzyme which
converts L-alanine to D-alanine and D-alanyl-D-
alanine ligase.
 L-Aalanine
Cycloserine X Alanine racemase

D-Alanine

Cycloserine X D-alanyl-alanine ligase

D-Ala-D-Ala
c) Inhibition of translocation of peptidoglycan
precursors across the cytoplasmic membrane:
Vancomycin inhibits the enzyme peptidoglycan
synthase responsible for translocation of
precursors across the cytoplasmic membrane
which are subsequently incorporated in the
growing point of pre-existing peptidoglycan.

RESISTANCE TO PENICILLINS
Resistance to penicillins develops because of the
following mechanisms:
Production of β-lactamases

Certain bacteria (staph. aureus,

Haemophilus influenzae and most gram
-ive enteric rods) produce beta-
lactamases which destroy penicillins’
activity by breaking the beta-lactam ring.
There are about 50 such enzymes
produced by different bacteria.
The genetic control of Beta-lactamases
production resides in transmissible
plasmids. β-lactamase-resistant
penicillins (nafcillin, cloxacillin) are active
against beta-lactamase producing
bacteria because the beta-lactam ring of
these drugs is protected by the substituent
groups of the R side chain.
Cloxacillin Nafcillin
One solution to the problem of
susceptibility of penicillins to beta-
lactamases is the concomitant use of
beta-lactamase inhibitors such as
Clavulanic acid, Sulbactam and
Tazobactam.
II REDUCTION IN THE PERMEABILITY OF
OUTER MEMBRANE

Reduction in the permeability of outer

membrane causes a decreased
ability of the drug to penetrate to the
target site. This occurs in gram-
negative bacteria because they
possess the outer membrane.
III OCCURANCE OF MODIFIED
PENCILLIN-BINDING SITES

Sometimes, penicillin binding sites

are lacking or are altered due to
mutation in certain bacteria and as a
result of it resistance develops.
IV LACK OF AUTOLYTIC ENZYMES

Autolytic enzymes in the cell wall of certain

bacteria are not activated by penicillins
and these bacteria (certain staph.
streptococci) become resistant to drugs.
Such bacteria can be inhibited but not
killed.
V LACK OF ACTIVITY OF CELL
WALL

The organisms which are metabolically

inactive or lack cell-wall will not be susceptible
to penicillins and other cell-wall synthesis
inhibitors, as they do not synthesize
peptidoglycan.
VI. Some organisms (staphlococci) may
be resistant even to the action of β-
lactamase resistant pencillin (methicillin).
The mechanism of this type of tolerance
seems to be the deficiency or
inaccessibility of PBP receptors. This
mode of resistance is independent of
beta-lactamase production.
 PENICILLIN G (Benzylpenicillin)

ADMINISTRATION:
ORAL
Approximately one-third of orally administered
dose is absorbed from GIT. Acidic pH 2 of
gartric juice readily destroys penicillin G.
 A decrease in gastric HCl production with
age accounts for better absorption of the
antibiotic in old age people. Following oral
administration, peak plasma
concentrations are achieved within 30-60
min. Despite the convenience of oral
route, penicillin G is rarely used orally in
clinical practice.
 PARTENTERAL
Following I/M administration, the peak
plasma concentration are achieved
within 15-30 min. The half-life of the
drug is 30 min. Probenecid, given
concurrently, can increase the half-life by
preventing renal tubular secretion of the
drug but it is rarely used for this purpose.
For avoiding too frequent administration of
penicillin G, two repository preparations of
the drug are employed. These are
penicillin G procaine and penicillin G
benzathine. These preparations release
penicillin G slowly from the site of injection
and produce low but persistent levels of
the drug in the blood.
 DISTRIBUTION
Penicillin G is distributed widely
throughout the body but with varying
concentrations in different fluids and
tissues. The drug appears in significant
amount in liver, bile, kidney, semen, joint
fluid, lymph and intestine.
About 60% of the drug is
reversibly bound to albumin in
plasma.
Probenecid increases plasma levels
and produces a significant decrease
in apparent volume of distribution.
 CEREBROSPINAL FLUID
Penicillin G does not readily enter CSF
when the meninges are normal. However,
it penetrates readily when meninges are
acutely inflammed and concentration
reaches 5% of the value in plasma. Even
such low concentration is therapeutically
effective against sensitive microbes.
Penicillin and other organic acid are
transported from CSF into blood
stream by an active transport
mechanism.
Probenecid elevates the CSF levels
of penicillin G by competitively
inhibiting this transport system. In
uremia, the accumulated organic
acids in CSF compete with penicillin
for secretion into blood stream and
occasionally may raise the brain
concentration of the drug to toxic level
that can produce convulsions.
 EXCRETION
Under normal conditions, penicillin G is
quickly eliminated from the body mainly by
kidneys and in a small part in bile and
other routes. The half-life of the drug is 30
min. Ten percent of the urinary excretion
occurs through glomerular filtration and
90% by tubular secretion.
Renal clearance values in neonates
and infants are significantly lower as
compared to the values in adult
because of incomplete development
of renal function.
Thus dose should be carefully suggested
for neonates and infants. When renal
function is impaired, 7-10% of the drug
may be inactivated each hour by liver.
Anuria (failure
( of the kidneys to produce
urine) may raise the half-life of the drug
upto about 10 hours. Thus dose of the
drug should be adjusted carefully during
dialysis and the period of recovery of renal
function.
If, in addition to renal failure, hepatic
insufficiency also exists, the half-life
of the drug will be prolonged even
further.
 THERAPEUTIC USES OF
PENICILLIN G (Benzylpenicillin)
Pneumococcal Infections:
Penicillin G remains the drug of
choice for the management of
infection caused by sensitive strains
of Streptococcus pneumoniae (Gram
positive, diplococci or short chain).
The most common diseases
produced by the organism are
meningitis (Pneumococcal
meningitidis) and pnenmonia
(Pneumococcal pneumoniae).
STREPTOCOCCAL INFECTIONS
Penicillin G is effective in treating
Streptococcal pharangitis,
pnenmonia, arthritis and endocarditis
when caused by Streptococcus
pyogenes (Gram positive cocci).
 The drug is also used to treat infectious
endocarditis caused by viridans streptococci
(Strep. sanguis, Strep. mutans (Gram
positive), the most common cause of
infectious endocarditis. Penicillin G is used
in combination with aminoglycosides, for
synergistic effect, to treat enterococcal
endocarditis.
INFECTIONS WITH ANAEROBES

Many anaerobic infections are caused by

mixtures of microorganisms. The majority
of these is sensitive to penicillin G with the
exception of Bacteroides fragilis.
STAPHYLOCOCCAL INFECTIONS

The vast majority of staphylococcal infections

are produced by microorgranisms which
produce beta-lactamase enzyme.
Thus these infections cannot be treated with
penicillin G and need penicillinase-resistant
penicillins like nafcillin, methillin etc.
 MENINGOCOCCAL INFECTION

Penicillin G remains the drug of choice for

meningococcal disease (Neisseria
meningitidis (meningococcus, gram-
negative diplococci). Some penicillin-
resistant strains have been found in some
parts of the world but they are infrequent.
 GONOCOCCAL INFECTIONS
Neisseria gonorrheae (gonococcus, Gram-
negative) cocci have become resistant to
penicillin G and gonococcal infections in such
cases are treated with other penicillins or
cephalosporins (ceftriaxone, third generation).
Penicillin G should be used in established
sensitive strain of gonococcus.
 SYPHILIS
Syphilis is caused by Treponema pallidum
(spirochete). Penicillin G is highly
effective in primary, secondary and latent
syphilis of less than one year duration. It
is also effective in infants with congenital
syphilis discovered at the time of birth or
during postnatal period.
 ACTINOMYCOSIS

For the treatment of all forms of

actinomycosis, (Actinomyces israelii;
actinomycetes are true bacteria,
some are gram-positive and some are
also acid fast), penicillin G is an agent
of choice.
 DIPHTHERIA

Diphtheria is caused by Corynebacterium

diphtheriae (Non-spore-forming gram
positive rod club shaped) and its clinical
findings include thick grey adherent
membrane over the tonsils and throat
and fever, sore throat and cervical
adenopathy.
 Adenopathy: Large or swollen lymph
nodes. Lymph nodes can become
enlarged as a result of inflammatory
diseases, infection, or cancer.
No pencillin or other antibiotic is said
to alter the incidence and
complications of diphtheria; only
specific antitoxin is the effective
treatment. Penicillin-G is claimed to
eliminate the carrier state.
 ANTHRAX

Anthrax is caused by Bacillus

anthracis (gram positive, spore-
forming rod). Penicillin G is drug of
choice for all clinical forms of anthrax.
However some resistant strains of B.
anthracis have been recovered from
human infections.
 CLOSTRIDIAL INFECTIONS
Clostridia are responsible for four groups
of infections
i- Wound infection, of which closteridial
myonecrosis (gas gangrene) is most
serious (caused by C. perfringens, C.
novyi and C. septicum).
ii Tetanus (C. tetani)
iii Botulism (C. botulinum)
iv Pseudomonas colitis (C.
difficile).
Penicillin G is drug of choice for gas
gangrene. For C. tetanus,
administration of tetanus immune
globulin may be indicated. Penicillin
G is given to eradicate vegetative
forms of bacteria that may persist.
 RAT BITE FEVER

Two microorganisms, Spirillum minor

and Streptobacillus moniliformis, are
responsible for this infection and both
are sensitive to penicillin G.
 LISTERIA INFECTIONS
Listeria monocytogenes (Gram positive
rod) causes meningitis and sepsis in new
borns and immunosuppressed adults.
Penicillin G or ampicillin with or without
gentamycin are regarded as drug of
choice for listeria infections.
 ERYSIPELOID

It is a skin infection that usually

occurs on the hands of meat and fish
handlers. It is caused by
Erysipelothrix rhusiopathiae, a gram
positive rod. The uncomplicated
infection responds well to penicillin G.
 Dose of penicillin G
Only one third of the orally administered dose is
absorbed from GIT. Gastric pH at 2 rapidly
destroys penicillin G. Mostly penicillin G is
given by I/M or I/V. Penicillin G is not used
orally in clinical practice. The dose and
dosage regimen depend upon the severity and
type of infection; most of the infections respond
to daily doses of penicillin G, 0.6-10 million
units (0.36-6g).
 UNTOWARD REACTIONS TO
PENICILLINS
One of the remarkable features of
penicillins is their relative freedom
from direct toxic effects. The main
unwanted effects of penicillins are the
hypersensitivity reactions.
 ALLERGY
Hypersensitivity reactions may occur with
any dosage from of penicillin. Allergy to
one penicillin exposes the patient to a
greater risk of reaction if another is given.
Allergic reactions may occur even in the
absence of a previous exposure to the
drug for medical purposes.
This may be caused by unrecognized
previous exposure to penicillin in the
food of animal origin. The severity of
allergic reaction is variable.
In certain cases it is so mild that it disappears
even during the continued use of the drug.
Sometimes it vanishes with the discontinuation
of drug use . In certain instances, the
manifestations of reaction last for 1-2 weeks or
even longer after stoppage of therapy. In rare
case it may be exceptionally dangerous and
many prove fatal.
The major antigenic determinant of
penicillin hypersensitivity is the metabolic
product, penicilloic acid, which after
binding with proteins serves as hapten to
cause the immune reaction. Even intact
molecules of penicillins can serve as
minor determinants. Allergic reactions
may occur as:
 Acute Anaphylactic Shock
This is the most important immediate
danger connected with the use of
penicillins. It may occur at any age. Its
occurrence is very rare i.e. in 0.004%-
0.04% of recipients. About 0.001% of
patients treated with these drugs are
reported to die from anaphylactic shock .
Anaphylactic shock most often follows
the injection of penicillin, although it
has been observed to occur after oral
administration of the drug.
Even it has resulted from intradermal
injection of small quantity of drug for
hypersensitivity testing. The most serious
clinical manifestations are sudden severe
hypotension and rapid death. In other
cases, bronchoconstriction, abdominal
pain, nausea, vomiting, extreme
weakness, fall in B.P. diarrhea and
purpuric skin eruption have
characterized the anaphylactic shock.
Immediate treatment of anaphylactic
shock is absolutely essential. (i.e.
Adrenaline + Anti histamine +
corticosteroid)
 Serum Sickness

This reaction usually appears after 7-12

days treatment with penicillin, it may be
delayed as well. Serum sickness caused
by penicillins may persist for a week or
longer. It varies from mild fever, rash and
leukopenia to severe arthralgia
or arthritis, purpura, lymphadenopathy,
angioneurortic edema (marked by swelling
and itching of areas of skin), mental
changes, myocarditis, generalized edema,
albuminuria and hematuria. Serum
sickness is mediated by IgG antibodies.
OTHER SENSITIVTY REACTIONS

Angioedema with marked swelling of lips,

tongue, face and periorbital tissues,
frequently accompanied by asthmatic
breathing has been observed following
topical, oral or systemic administration of
penicillins.
Skin rashes of all types have been
observed as well. Contact dermatitis
is observed occasionally in
pharmacists, nurses and physicians
handling penicillin solutions.
During corticosteroid therapy, the patients
known to be allergic to penicillin can
tolerate the drug. However,
desensitization with gradually increasing
doses is not recommended. The
individuals hypersensitive to penicillin can
be treated with alternative drugs.
 NEUROTOXICITY
All penicillins being irritant to CNS can
greatly enhance the excitability of neurons
and can provoke seizures if given in large
doses. Thus patients should not be given
more than 20,000 units of penicillin
interathecally on any one day but, at
present, there is little indication for
intrathecal administration.
 DIARRHOEA
Penicillins, given orally in large doses, may
cause irritation of GIT leading to nausea,
vomiting and diarrhea. This occurs more
commonly with broad-spectrum penicillins
(ampicillin, amoxycillin) than other penicillins.
Oral penicillin therapy may cause disruption of
normal flora of intestine and may be
accompanied by overgrowth of
staphylococci, Pseudomonas, Proteus or
yeasts which may occasionally cause
super infection (enteritis). Superinfection
in other organ systems of the body may be
caused by penicillins as occurs with an
antibiotic therapy.
 NEPHRITIS
Interstitial nephritis may rarely be produced
by the penicillins. Methicillin has more
potential than nafcillin to cause acute
interstitial nephritis.
 CATION TOXICITY
Most penicillins are dispensed as sodium or
potassium salt of free acid. Toxicities may be
caused, in patients with renal failure and
cardiac problems, by the large quantities of
sodium or potassium that accompany the
penicillin. For example excess of sodium may
result in hypokalemia. Such problems can be
overcome by using more potent drugs that
permit lower doses of antibiotics and
accompanying cations.
 HEMOSTATIC DEFECTS
Penicillins may induce hemostatic defects
leading to a bleeding tendency. This
side-effect involves decreased platelet
agglutination. Anti-pseudomonal
penicillins (Carbenicillin and Ticarillin) are
known to cause this effect. It is generally
a concern when patients predisposed to
haemorrhage or receiving anticoagulants
are treated with penicillins.
 BLOOD DYSCRASIAS
Eosinophilia is an occasional
accompaniment of other allergic reactions
to penicillins. At times, it may be the sole
abnormality and levels of eosinophils may
reach 10% to 20% or even more of the
total circulating white blood cells.
 SPECTRUM
Narrow Spectrum:
Antibiotics are those agents which are
active against only a single or limited
group of microorganisms e.g. isoniazid is
active against mycobacterium tuberculosis
Extended Spectrum Antibiotics:
These are effective against gram + ive
organism and also against a significant
number of gram negative bacteria e.g.
Ampicillin.
 Broad-Spectrum-Antibiotics

Those agents which are effective against a

wide variety of microbial species. The use
of such drug may lead to a drastic
alteration in normal flora of the body and
precipitate a superinfection e.g. Candida
albicans. Growth is inhibited by normal
flora but due to alteration in normal flora
this organism can cause infection.
United States Adopted Names are unique nonproprietary names assigned
to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council,
which is co-sponsored by the American Medical Association (AMA), the United States
Pharmacopeial Convention (USP), and the American Pharmacists Association (APhA)