Download Ampicillin is a

King Saud University
Collage of pharmacy
Phamacognosy department
Ampicillin
Prepared by:
Wedad Shubily
Iman AlQarni
Iman Al enzy
Hadeel Al otabi
Supervised by:
Dr. Qadria AL-Deab
Dr. Areej Altaweel
-Antibiotics
are specific chemical substances derived from or
produced by living organisms that are capable of
inhibiting the life processes of other organisms.
- Penicillins are a group of closely related
antibiotics used to treat a wide variety of
bacterial infections occurring in the body.
In 1928 Alexander Fleming, working in Almroth Wright's department,he noted that some colonies of
staphylococci were lysed when the medium was
contaminated by a mould Iater classified as Penicillium
notatum, He isolated the mould, showed that the
culture fluid beneath it had antibacterial properties
and that it was non-toxic to mice when injected even in
the undiluted state.
- Many Research efforts in the field of penicillin modification
during the 1950s concentrated on solving three problems
1-stabilizing the molecules against the action of staphylococcal
peniciIlinases was solved by Compounds such as methicillin,
oxacillin, and nafcillin were the successful products of these
research efforts
2-expand the spectrum of the penicillins to include inhibition of
gram-negative bacteria was solved by derivatives such as
ampicillin and carbenicillin resulted from these efforts.
3- chemical stability and enhanced adsorption was solved by the
development of acid-stable and orally adsorbable penicillin
derivatives like penicillin V and oral ampicillin.
- Ampicillin has antibacterial spectrum included strains
of Escherichia coli, Proteus mirabilis, and H.
influenzae, also, to the gram positive cocci.
ampicillin and its esters were inactive against Klehsiella, indole-positive Proteus, Serratia, and
Pseudomonas and was destroyed by the B-lactamase of
S. aureus.
- Ampicillin became widely used in pediatrics, primarily because of its excellent in vitro activity against H.
influenzae, N. meningitidis, and S. pneumoniae.
1-Natural Penicillins (Penicillin G, Procaine, Penicillin G, Penicillin V,
Benzathine)
-They are effective against gram-positive strains of streptococci,
staphylococci, and
some gram-negative bacteria such as meningococcus.
2- Penicillinase-Resistant Penicillins (Cloxacillin, Dicloxacillin,
Methicillin, Nafcillin, Oxacillin).
-They are a more narrow spectrum of activity than the natural
penicillins.
3-Broad - spectrum penicillin " Aminopenicillins"
-The aminopenicillins were the first penicillins discovered to be active
against gram-negative bacteria
-they are acid-resistant so administered orally.
- these agents are susceptible to inactivation by beta-lactamase
4-Extended Spectrum Penicillins
- include both alpha-carboxypenicillins (carbenicillin and
ticarcillin) and acylaminopenicillins (piperacillin,
azlocillin, and mezlocillin).
- These agents have similar spectrums of activity as the aminopenicillins but with additional activity against
Pseudomonas aeruginosa.
- they are susceptible to inactivation by beta-lactamase-
- An intact B-lactam / thiazolidine
fused ring system was believed to
be essential for antibiotic activity.
- The parent compound,
phenylpenicillin was less active
than benzylpenicillin but the
introduction of substituents in
the ortho-position in the ring
brought in a measure of steric
hindrance around the amide
bond and this greatly reduced
the affinity for the active site of
staphylococcal-lactamases.
Examples, methicillin
- simple substitution on the acarbon of the hydrophobic side
chain of benzylpenicillin with either
an amino group ampicillin, or
carboxyl group carbenicillin,can .
penetration into Gram-negative
bacteria
The walls of bacteria are made of a complex polymeric material called peptidoglycan.
It contains both amino acids and amino sugars.- The amino sugars are of two kinds N-acetylglucosamine (NAG) and Nacetylmuramic acid (NAM).
-The beta-lactams all work by interfering with the
synthesis of the bacterial cell wall by:
-1) disruption of mucopeptide synthesis
-2)Penicillin can cause rapid lysis of the bacterial cell
by inducing the action of bacterial autolysins
(mucopeptide hydrolases).
-3) penicillin exposes the cell to osmotic action and
water passes from the hypotonic external environment
into the interior of the cell.
ampicillin
amoxicillin
bacampicillin
nearly complete oral more completely
absorbed than
absorption:
ampicillin
absorption
Oral: 50%
Distribution
Bile, blister, and
tissue
fluids;
penetration
into
CSF
occurs
with
inflamed
meninges only,
good only with
inflammation
Protein binding
15% to 25%
Half-life
elimination
Children and Adults: 61.3 minutes
1-1.8 hours
Excretion
Urine (~90% as
unchanged
drug) within 24 renal
hours
Administration
Routes
Oral, intravenous
Bioavailability
Oral, intravenous
95% oral
40% oral
Pregnancy
category
B
A ,B
The
relative
bioavilability
of
bacampicilli
n
and
pivampicillin
was
comparable
where
ampicillin
was only 2/3
that of the
other
-Resistance to antibiotics may result through spontaneous or
induced genetic mutation.
Bacterial cells can acquire genetic material from other bacterial cells through the processes of transformation, transduction, and
conjugation.
-Some modes of resistance that can be noted include:
1. Enzymatic inactivation of the antibiotic;
2. Altered permeability of the pathogen to the antibiotic
3. Development of altered, less sensitive enzymes or of
alternate metabolic pathways in the pathogen
- The ,B-lactamase inactivation of penicillins and cephalosporins is
by far the best documented mechanism leading to antibiotic
resistance
- The significance of penicillinase was recognized at an early date
in antibiotic therapy, and the semisynthetic penicillins are a direct
result of efforts to avoid the specificity of this enzyme.
-A penicillin amidase also occurs in some microorganisms; this
amidase yields the inactive 6-aminopenicillanic acid, but this type
of penicillin inactivation does not appear to contribute
significantly as a means of pathogenic resistance in any actual
therapeutic problem.
-Amoxicillin is only available for oral use
. It used for the following:
a. Acute otitis media for which amoxicillin is the
initial agent of choice
b. Acute sinusitis and exacerbations of chronic
bronchitis
c. Susceptible pathogens in UTI.
d. Completion of therapy in which intravenqus(IV)
ampicillin was initially used.
e. Because it is very well absorbed, it is used in oral
prophylactic antibiotic regimens to prevent
endocarditis after dental manipulations.
- Ampicillin prodrug is Broad - spectrum penicillin used against gram +ve and gram –ve bacteria
- ampicillin is more active against enterococci, Listeria monocytogenes, and beta-Iactamase negative Haemophilus influenzae .
- Ampicillin should not be used for penicillinase-producing
Staphylococcus aureus or beta-Iactamasepositive H. influenzae or
Moraxella catarrhalis
- Ampicillin is a "drug of choice" for group B streptococci (S.
agalactiae), Proteus mirabilis, and Eikenella corrodens
- Probenecid and allopurinol increase the serum level of ampicillin
and amoxicillin by Inhibiting its elimination.
- chloroquine phosphate , exenatide
combination may decrease orall ampicillin level by decrease
absorption
- methotrexate
lead to increase the methotrexate so, increase the risk of toxicity –"
by decrease renal excretion "
- warfarin
increase the risk of bleeding by possibly altered vit-k production by
gut flora
-acetaminophen/ tramadol / bupropion/ sodium phosphate /
tiagabine / tramadol
increase the risk of seizures
-allopurinol
increase the risk of rash by increase level of ampicillin
-Also these drugs might decrease the activity of concurrently
administered oral contraceptives
-An allergic reaction may cause
*shortness of breath
* swelling of your lips, face, or tongue
*rashor fainting
*severe watery diarrhea and abdominal cramps
*or unusual bleeding or bruising.
-Other, less serious side effects may be more likely to
occur.as
*mild nausea
* vomiting,
*white patches on the tongue (thrush/yeast infection)
itching or discharge of the vagina (vaginal yeast infection•
*or black, "hairy" tongue or sore mouth or tongue.
•
*and in very high doses, seizures have been reported.
Preparation & trade name:
trade name
Route of administration
Epicocillin
IM ,IV
Omnipen
Oral , IV ,IM
Penbritin
Oral , IM , IV , intraperitoneal ,
intrapleural , intra-articular , subcongunctival .
Pentrexyl,
Oral
Polycillin
Oral , IV, IM
Standacilln
IV , IM (11)
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