| Date post: | 17-Jan-2016 |
| Category: |
Documents |
| Upload: | jeffry-mathews |
| View: | 212 times |
| Download: | 0 times |
Prepared by: Wedad Shubily
Iman AlQarni Iman Al enzy
Hadeel Al otabi
King Saud University Collage of pharmacy Phamacognosy department
Ampicillin
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 intro duction 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 a-carbon of the hydrophobic side chain of benzylpenicillin with either an amino group ampicillin, or carboxyl group carbeni cillin,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 N-acetylmuramic acid (NAM).
-The beta-lactams all work by interfering with the synthesis of the bacterial cell wall by: -1) disruption of mucopeptide syn thesis -2)Penicillin can cause rapid lysis of the bacterial cell by inducing the action of bacterial autolysins (mucopep tide hydrolases). -3) penicillin exposes the cell to osmotic action and water passes from the hypotonic external environment into the interior of the cell.
ampicillinamoxicillinbacampicillin
absorptionOral: 50% nearly complete oral absorption:
more completely absorbed
than ampicillin
DistributionBile, blister, and tissue fluids;
penetration into CSF
occurs with inflamed
meninges only, good only with
inflammation
Protein binding15% to 25%
Half-life elimination
Children and Adults: 1-1.8 hours
61.3 minutes
ExcretionUrine (~90% as unchanged
drug) within 24 hours
Administration
renal
RoutesOral, intravenousOral, intravenous
Bioavailability
40% oral
95% oralThe relative bioavilabilit
y of bacampicilli
n and pivampicilli
n was comparable
where ampicillin was only
2/3 that of the other
Pregnancy categoryA ,B
B
-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 sensi tive 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 penicil linase 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 mi croorganisms; this amidase yields the in active 6-aminopenicillanic acid, but this type of penicillin inactivation does not ap pear 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 pre vent 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 mono cytogenes, and beta-Iactamase negative Haemophilus influenzae.
-Ampicillin should not be used for penicillinase-pro ducing Staphylococcus aureus or beta-Iactamase positive H. influenzae or Moraxella catarrhalis
-Ampicillin is a "drug of choice" for group B strep tococci (S. agalactiae), Proteus mirabilis, and Eiken ella corrodens
-Probenecid and allopurinol increase the serum level of ampicillin and amoxicillin by Inhibiting its elimination .
-chloroquine phosphate , exenatidecombination 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 nameRoute of administration
EpicocillinIM ,IV
OmnipenOral , IV ,IM
PenbritinOral , IM , IV , intraperitoneal , intrapleural , intra-articular , sub-congunctival .
Pentrexyl,Oral
PolycillinOral , IV, IM
StandacillnIV , IM (11)
Thank Thank youyou
