Sulphonamide and Beta lactam Drug

1. HaramayaUniversity
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Dr. Balisa Yusuf

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 Sulfonamides
 Beta lactam
Penicillins, Cephalosporins, Monobactams, Carbapenems
 Tetracycline (Oxytetracyclines, Doxycylines)
 Aminoglycosides (Streptomycion, Gentamicin, Neomycin)
 Macrolides (Erythromycin, Clarithromycin)
 Chloramphenicol
 Fluoroquinolones (Nalidixic acid, Norfloxacin, Ciprofloxacin)
 Miscellaneous Antibacterials
(Polymyxin, Bacitracine, Vancomycine, Novobiocine, Nitrofuran & Nitroimidazol)

3. During/In our study of antimicrobial agents, we will focus on the
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 History and Chemistry
 Spectrum of Antibacterial activity and Resistance
 Mechanism of actions and Classifications
 Pharmacokinetics (ADME)
 Drug interaction
 Toxicity and safety principles
 Primary clinical indications

4. HISTORY:
 The sulphonamides originated from the dye prontosil which was shown in
1935 by Gerhard Domagk to be effective in vivo against haemolytic
streptococcal infection in mice.
 He was awarded the 1939 Nobel Prize of medicine for his discovery.
 First antimicrobial agents effective against bacteria
 Source - Synthetic drugs derived from sulfanilamide
 Prontosil Red (sulfonamide chrysoidine dye) –
 by- Domagk – for – streptococcal infection.
 Broken down in body – into- Sulfanilamide (Active against bacteria)
 Use increased –Overuse- Development– Resistance
 Rarely used (alone) today due to 1/26/2023
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Suphonamides (Sulfonamides)

5. STRUCTURE OF DIFFERENT
SULFA DR
Chemistry
 The sulphonamides are derivatives of P-
aminobenzene sulphonic acid
 Structurally similar to P-aminobenzoic
acid (PABA) an essential member of
Vitamin B complex, and an intermediate
in bacteria synthesis of folic acid
 White crystalline powder, insoluble in water,
soluble in alkaline PH
 Weak organic acids with Pka 4.99 t0 8.56
 Parenteral preparations are alkaline- care
should be taken while administration through IV
route to prevent perivascular damage & shock
 I/m and S/C preparations should be properly
buffered.
 Sulfacetamide- neutral preparation for
ophthalmic use 1/26/2023
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6. Spectrum of Antibacterial activity and
Resistance
 Broad spectrum, primarily bacteriostatic but at higher
concentration bactericidal CDKChx
Antimicrobial activity
Sulphonamides have a broad-spectrum of activity and can inhibit
gram +ve and gram -ve bacteria, Nocardia, Chlamydia trachomatis,
and some protozoa (Coccidia, Neospora, Toxoplasm) & Ricketsiae.
Some enteric bacteria, such as E coli, Klebsiella, Salmonella,
Shigella, and Enterobacter, are also inhibited.
They have limited action against anaerobes (Pyogenic) partially due
to the fact that:
They are readily inactivated in the presence of purulent material
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7.  Bacterial susceptibility
Good susceptibility: Actinomyctes, Bacillus, Brucella, Listeria,
Streptococci, Chlamydia, Cryptosporidium.
Moderate scpty - Staphylococcus and Enterococcus and
some anaerobes.
Resistant: Mycobacteria, Mycoplasma, Rickettsia, Spirochete,
Pseudomonas
 Resistance: occur gradually & may be due to plasmid transfer or random mutation resulting in
 Decrease affinity of the bacterial dihydropterate synthetase for the sulphas,
 Decrease uptake, Adoption of alternate pathway
 Increased PABA synthesis (target amplification) by bacteria.
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8.  Sulfonamide are structural analogs and competitive analogs of PABA.
 PABA is essential for folic acid synthesis of bacteria.
 The folic acids are used for nucleotide (DNA & RNA) synthesis of bacterial cell.
 Sulfonamide blocks a synthesis of folic acid by blocking Dihydropteroic synthase
 Bacteria are unable to take-up folic acid from the environment
 Therefore, must synthesis it from PABA, Pteridine and Glutamate
 The mammalian cells will not be affected by S-amide because they use preformed
folic acid from the diet or from intestinal bacteria.
 So it is non of our business
 Salfonamide are selectively toxic to bacteria.
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Dihydropteridine + PABA
Sulfonamides (PABA analogues)
Sulfomethoxazole (Bacterial)
Sulfadiazine (Bacterial)
Sulfodoxine (Malarial)
Dihydropteroic acid Synthetase
Dihydropteroic acid
Glutamate
Dihydrofolic Acid
Timethoprim (Bacterial) /
Pyrimethamine (Malarial)
Dihydrofolate Reductase
Tetrahydrofolic Acid
Nucleic Bases
Amino Acids
RNA
DNA
Proteins
Folic
Acid
Dihydrofolate
Reductase
(Mammalian)
+ Cotrimoxazole
Cotrimazine
Static
Cidal
Static

13. CLASSIFICATION of s-
amide
 Systemic/general
purpose
 Sulfonamide
 Sulfadimidine
 Sulfapyridine
 Sulfadiazine
 Sulfamerazine
 Sulfathiazole
 Sulfamethoxazole
 Gut acting sulfonamides
Succinylsulfathiazole
Sulfaguanidine,
Sulfasalazine- poorly absorbed from the GIT,
useful in enteric infection.
 Topical
Silver sulfadiazine, for burn wounds – prevent
infection effective against pseudomonas
 Ophthalmic: Sulfacetamide
 Highly soluble sulfonamides for UTI
Sulfisoxazole
Sulfasomidine – rapidly absorbed and excreted
through kidney 1/26/2023
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14. CLASSIFICATION
 Potentiated sulfonamides
 Sulfadiazine and Sulfadoxine with Trimethoprim in the ratio of 5:1 Cotrimazine (horse)
 Sulfadoxine in combination with Pyrimethamine = Fansidar (potent A. Maleria)
 Trimethoprim + Sulfamethoxazole= Co-trimoxazole
This is now the major agent used in veterinary medicine (Resistancy)
Sulfonamides + Chlortetracycline act as Growth promoter prevent Clostridial infn
 Triple sulfa
 Sulfamerazine + Sulfapyridine + Sulfadiazine: act additively but excreted individually
 Thus reducing the chance of adverse effect- crystalluria caused due to precipitation of
sulphur crystals
 This can be avoided by urinary alkalinisation and keeping the patient well hydrated
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15. Classification of s-amide based on acting
duration.
Short Acting (4-8hrs)
•Sulfisoxazole
•Sulfadiazine-
•Less protein bound,
•Penetrates BBB- Meningitis
•Acetylated product is less soluble
and cause for crystalluria
Intermediate acting (8-12 hrs)
•Sulfammoxazole
•Sulfamethoxazole –
•Combination with Trimethoprim, FDC ( Cotrimoxazole)
• High fraction is acetylated and may lead to Crystalluria
Long acting (> 12 hrs)
•Sulfadoxine -
•Very high plasma protein binding and slow renal excretion,
•Longest acting,
•Used in malaria, Toxoplasmosis, Pneumocystis,
•In combination with Pyrimethamine they yield fansidar
•Sulfamethoxypyrazine
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16. PHARMCOKINETICS
Absorption
 Rapidly absorbed from GIT, except gut acting sulfas
 Available as bolus, tablets, feed mix, dispersible powder
 I/V- alkaline so slowly administer to prevent shock and perivascular reaction.
 I/M, S/C preparations: suitably buffered
 Intrauterine treatment along with urea increases solubility and inhibits reaction
with protein and neutralizes antagonists to sulfa
Distribution
 Widely distributed in CSF and Synovial fluid, Placenta, Prostate, and Fetus.
 Low concentration in milk-passive diffusion limited use in mastitis
 Exists predominantly in non ionized form in biofluids
 Diffuses through the cell membrane, cellular barriers
 Variable binding to plasma protein (20-90% in serum) varies with spp. &
compounds)
 Protein binding increases the half life 1/26/2023
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17. PHARMCOKINETICS
Metabolism
 It metabolize in the liver and excreted through the kidney.
 Liver –
 Acetylation - less soluble - deposit in renal tubule, pelvis, ureter cause crystalluria.
 Aromatic hydroxylation and Glucoronide conjucation makes more water soluble
Excretion:
 Kidney glomerular filterate, tubular secretion and reabsorption.
 Alkalinisation of urine increases the solubility and elimination.
 Success of sulfonamide therapy depends on
⚫ Presence of sensitive organism
⚫ Adequate concentration in blood and tissue
⚫ Humoral and cellular defense of host
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18. Principles To Be Followed In The Medication of
Sulphonamide
 Start therapy at early stage of infection
 In-effective in chronic cases
 In severe infection administer by IV route
 Administer adequate quantity of drinking water during therapy
 Treatment should not exceed seven days
 Its continued 48 hours after remission to prevent recurrence
for some cases
 If no favorable response within four to five days, discontinue
the therapy
 Immune response of the host should be well maintained
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19. Drug interaction
 PABA antagonizes sulfonamides
 Calcium and antacids inhibits absorption (b/c of its acidic
nature)
 Synergistic with diaminopyrimidines - Trimethiprim,
ormethoprim,
 Sulfonamides + chlortetracycline act as Growth promoter
 Adverse effects
 Crystalluria
 Fixed Drug Reaction,
Hypersensitivity
 Photosensitization,
 Hepatitis
 Contact Dermatitis
 Haemolysis
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20. TOXICITY AND ADVERSE REACTION
 Acetylated derivatives of sulpha deposited in renal tubules, pelvis and
ureter cause renal colic, obstruction of renal tubule and increased BUN
(blood urea nitrogen) level. 6-24mg/dl or 2.1-8.5mmol/l is normal.
 Decreased water consumption and acidic urine precipitate crystal urea
Ensure adequate water intake and administration of sodium bicarbonate.
 Hypersensitivity reaction- skin rashes due to anaphylactic shock- rare
 Doberman breeds seem to be sensitive to the immune reactions (TCP,
HlyA, Arthy)
 Acute toxic effect- rapid I/V excessive dose: Myopathy, Ataxia, Blindness
collapse
 Two hepatotoxic syndromes have been described:
 Acute hepatic necrosis that may be fulminating and a less severe
cholestatic (bile) disorder
 Poultry - decreased egg production and thin shelled eggs 1/26/2023
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21. CLINICAL USES
 Colibacillosis
 Pasteurellosis
 Footrot
 Coccidosis
Poultry - prevention &
treatment of
 Coccidosis
 Infectious coryza
 Pullorum disease
 Fowl typhoid
 The primary indications are to treat:
 Toxoplasmosis (combined with pyrimethamine)
 Pneumocystis carinii and Nocardiosis (combined
with minocycline).
 Chronic colitis in dogs Sulfasalazine besides its
anti-inflammatory properties.
 Its broken to sulfapyridine and 5-amino salicylic
acid in colon (25mg/kg TID for 2-4 wks in dogs)
 Prevention of infection of burn wounds Silver
sulfadiazine is a much less toxic topical su-amide
 Sulphonamides & potentiated sulphonamides
are cheap compared to other antimicrobials
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22. Pharmacokinetics-
•Orally absorbed
•PPB is variable (10-95%)
•Cross Placenta
•Metabolized by Acetylation
•By microsomal acetyl transferase
•Acetylated metabolites inactive but
•Produce Crystalluria
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23. TRIMETHOPRIM
INTRODUCTION
 Weak organic bases, accumulate in acidic urine, milk and ruminal
fluid
 Trimethoprim- poorly soluble in water
 Readily absorbed after oral administration except in ruminants
(herbivores
trapped and undergo microbial degradation.
 30 % to 60% protein bound, widely distributed in tissues including
prostate.
 Partly metabolized in liver and excreted in urine by glomerular
filtration and tubular secretion
 Eg.Trimethoprim, Ormetoprim, Pyrimethamine
 Combination of sulfamethoxazole + trimethoprim (Co- 1/26/2023
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24. Mechanism of action and Resistances
 Inhibits DHFR enzyme – sequential blockade
 Alone bacteriostatic and in combination with sulfa- bactericidal
 Selective toxicity- 50,000 times more active against bacterial DHFR enzyme.
Resistance
 Mutational /plasmid mediated readily develops when used alone.
 High in Enterobacteriaceae
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25. Clinical Indication and Side
Effects
UTI, Enteric infection, Salmonella and Brucellosis
Cattle - Salmonellosis, Diarrhoea pneumonia
Poultry - E.coli
 Side effects
Swelling at injection site
Transient arthritis
Folate deficiency - megaloblastic anemia administration of folic acid.
Keratoconjunctivitis – reduced lacrimal secretion
Idiosyncratic thrombocytopenia.
Salivation in cats.
Generally three days of withdrawal period is needed
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26. BETA-LACTAM ANTIBIOTICS
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This particular group is characterized by its 4-membered, nitrogen-containing beta-lactam
ring at the core of its structure, which is key to the mode of action of this group of AB
They share features of chemistry, MoA, pharmacologic & clinical effect, & immunologic chx
Examples are:
Penicllins:
Natural penicillin : Penicillin G, Penicillin V
Broad spectrum amino penicillin’s: Amoxicillin, Ampicillin, Hetacillin
Penicillinase-resistant penicilllin: Methicillin, Oxacillin, Nafcillin, Cloxacillin, Dicloxacillin
Extended spectrum penicillin: Azlocilin, Carbenicilin, Mezlocilin, Piperacilin, Ticarcilin
Cephalosporins: Cephalothin; Cefamandole, Cefotaxime
Carbapenems: Primaxin
Monobactams: Aztreonam
 History and Chemistry
 Spectrum of ABA & Resistance
 MoA and Classifications
 Pharmacokinetics (ADME)
 Drug interaction Toxicity & safety principles
 Primary clinical indications

27. Beta Lactam Antibiotics
HISTORY
 In 1928, Alexander Fleming discovered a Penicillin from fungus.
 In 1945, Cephalosporium acremonium was isolated from raw sewage.
 The first cephalosporin,cephalosporin C, was derived from this fungus.
 All other cephalosporins are semisynthetic AB derivatives of cephalosporin C.
 The first cephalosporin was available for clinical use in 1964
 Penicillins & Cephalosporins are still the most commonly used β-lactam AB
 But much progress has been made in the development of new β-lactams recently
 Most notably, these include the β-lactamase inhibitors (e.g., clavulanic acid), the
carbapenems (e.g., imipenem), and the monobactams (e.g., aztreonam).
Sources:
 Penicillin: Penicillum chrysogenum (syn: P. notatum), Aspergillus nidulans
 Cephalosporin: Acremonium chrysogenum (syn: Cephalosporium acremonium),
Paecilomyces persinicus, Streptomyces clavuligerus, Nocardia lactamdurans,
Flavobacterium sp. Lysobacter lactamgenus
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28. Chemical structure and Spectrum of activity
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 Broad-spectrum: Carbapenems, 2nd, 3rd and 4th Generation Cephalosporins.
 Narrow-spectrum: Penicillin, 1st Generation Cephalosporins, Monobactams

29.  All beta-lactams acts by Inhibition of cell wall synthesis.
 Bacterial cell wall is composed of a complex crosslinked polymer, peptidoglycan
(murein, mucopeptide), consisting of polysaccharides and polypeptides.
 The polysaccharide contains alternating amino sugars: N-acetylglucosamine and
N-acetylmuramic acid
 A five-amino-acid peptide is linked to the N-acetylmuramic acid sugar.
 This peptide terminates in D-alanyl-D-alanine (The final peptide bridge).
 The final reaction in bacterial cell wall synthesis is a cross-linking of adjacent
peptidoglycan (murein) strands by a transpeptidation reaction.
 Penicillin-binding proteins-PBPs (bacterial transpeptidases) catalyze the
transpeptidase reaction that removes the terminal alanine to form a crosslink with a
nearby peptide, which gives the cell wall its structural rigidity
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30.  A highly simplified diagram of the cell envelope of a gram-negative bacterium. The outermembrane, a lipid
bilayer, is present in gram-negative but not gram-positive organisms. It is penetrated by porins, proteins that
form channels providing hydrophilic access to the cytoplasmic membrane. The peptidoglycan layer is unique to
bacteria and is much thicker in gram-positive organisms than in gram-negative ones. Together, the outer
membrane and the peptidoglycan layer constitute the cell wall. Penicillin-binding proteins (PBPs) are
membrane proteins that cross-link peptidoglycan. -lactamases, if present, reside in the periplasmic space or on
the outer surface of the cytoplasmic membrane, where they may destroy -lactam antibiotics that penetrate the
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31. Structure of Cell Wall and Possible Site of Entry
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32. Cont…
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33. Betalactam
Antibiotics
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34.  PBPs-a group of enzymes found anchored in the cell membrane, which is involved
in the cross-linking of the bacterial cell wall.
 All of the PBPs are involved with assembly, maintenance, and regulation of
peptidoglycan cell wall synthesis.
 β-Lactam ABs are structural analogs of a terminal D-alanyl-D-alanine substrate so
 They are covalently bound by PBPs at the active site and the resultant acyl enzyme
molecule is stable and inactive.
 The binding of a β-lactam ABs to trans peptidase enzymes will leads to defective cell
walls that osmotically unstable.
 After a β-lactam ABs has attached to the PBP, the transpeptidation reaction is inhibited,
peptidoglycan synthesis is blocked, and the cell dies due to osmotic instability or autolysis.
 Although the exact mechanism responsible for cell death is not completely understood,
autolysins, bacterial enzymes that remodel and break down cell wall, are involved.
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35. Effect on bacteria
 Generally bactericidal
 Examples of applications in Veterinary Medicine
 Ruminants:
 Anthrax, Listeriosis, Leptospirosis, Clostridial and Corynebacterial Infections;
Streptococcal mastitis, Keratoconjunctivitis
 Swine:
Erysipelas, Streptococcal and Clostridial Infections
 Horses:
 Tetanus, Strangles, other Strep and Clostridial infections, Foal pneumonia
 Dogs and cats: Streptococcal and Clostridial infections
 Poultry:
Necrotic enteritis, Ulcerative enteritis, and Intestinal spirochetosis
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36.  Miscellaneous:
 Although ꞵ–lactam AB should theoretically work against all type of bacteria, Isn't the case
This is because different bacteria have varying PBP content and nature
Also, some bacteria have natural structural characteristics which do not favor this MoA
e.g. Gram -Ve have an outer m/b layer which makes PBP more difficult to be reached
 Mechanisms of resistance
 A number of microorganisms have evolved mechanisms to overcome the inhibitory actions
of the β-lactam antibiotics.
 There are four major mechanisms of resistance:
Inactivation of the β-lactam ring (β-lactamase)
Alteration of PBPs (low affinity for β-lactam AB, interspecies homologous recombination events)
Reduction of antibiotic access to PBPs (inability of the agent to penetrate to its site of action)
Elaboration of antibiotic efflux mechanisms (produce xenobiotic efflux pumps to eject AB)
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37. Microbial Resistance
 Three independent factors determine the bacterial resistance
to β-lactam antibiotics. They are
 Production of β-lactamases (in all
gram negative bacteria)
 Permeability of cell wall,
 Sensitivity of the PBP
 β-lactamases are enzymes that inactivate the drugs by hydrolyzing the β-lactam ring
It is the major mechanism of drug resistance.
Different bacteria produce β-lactamases that d/f in physicochemical & functional properti
 Some β-lactamases are specific for penicillins (penicillinases) destroys natural penicillin
Some are specific for cephalosporins (cephalosporinases)
While still others have affinity for both groups
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38. Cont…
There are two mechanisms of β-lactamase production.
Chromosomal and Plasmid
Chromosomally derived β -lactamases are species and genus specific
and can be induced by the presence of any β-lactam compound.
Gram +Ve bacteria generally produce it while gram –Ve produce both
Plasmid-derived β-lactamases can be transferred between bacteria,
increasing the number of bacteria resistant to the antibiotic.
Gram-negative bacteria can produce a cell wall with a modified outer
membrane that is no longer permeable to β -lactam antibiotics.
But it enhance β-lactamases resistance and not by it self
They secrete small amounts of β-lactamases into their periplasmic
space, allowing for optimal location of the enzyme to degrade the β-
lactam upon entry into the organism
Bacteria have an intrinsic resistance to β-lactams because of reduced
sensitivity of the PBP 1/26/2023
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39. HISTORY:
 In 1928, Alexander Flming observed that penicillium mold contaminating petridish
culture of staphylococci colonies was surrounded by a clear zone free of growth
 In 1929 Penicillin discovered in England and in 1942 introduced in UK & England
 Fleming cultured the contaminating mold on a special medium and demonstrated
that the culture broth contained a potent antibacterial substance that was effective
against a variety of gram-positive organisms.
 He named the substance Penicillin.
 In 1940, penicillin was isolated in the form of a brown, impure powder and was the
most powerful chemo-therapeutic agent known at that time.
 In 1954 Penicillin-resistant infections become clinically significant
 The international unit (IU) for penicillin has been identified as the amount of activity
present in 0.6mg of the international pure crystalline standard Na salt of penicillin G
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Penicillin

40. 40
 The essential penicillin molecule contains a fused ring system:
the β-lactam and thiazolidine.
 The physical and chemical properties, especially solubilities, of penicillins are
related to the structure of the acyl side chain and the cations used to form salts.
 Aqueous solutions of the alkaline Na salts of sulfonamides
inactivate penicillin
The antimicrobial activity of penicillin resides in a β-lactam rings
 Penicillin is incompatible with heavy metal ions, oxidizing agents, and strong
concentrations of alcohol
 Hydrolysis is the main cause of penicillin
degradation and can take place in the syringe
when penicillin is mixed with another drug.
 Some penicillins are rapidly hydrolyzed by
gastric acid, making them un-suitable for oral
administration.
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Chemistry

41. The penicillins are a large group of bactericidal compounds.
They can be subdivided and classified by their chemical structure and
spectrum of Activities
The structure common to all penicillins is a β-lactam ring fused
with a thiazolidine nucleus.
Splitting of the ring by either acid hydrolysis or β-lactamases
results in the formation of penicilloic acid, a product without AB actṉ
Addition of various side chains (R) to its basic molecule creates
classes of compounds with the same mechanism of action as penicillin
but with different chemical and biological properties.
The parent substance of this group is penicillin G (benzylpenicillin)
obtained from Penicillium notatum
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42. Broken by Betalactamase enzyme
Broken by Amidase enzyme
Active material
Raw material for other
penicillin
Inactive
Responsible for
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43. Active material
Raw material for other
penicillin
Inactive (Major Determinant)
Responsible for
hypersensitivity
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44. Penicillin
Beta Lactamase inhibitor (Claulanic acid and Sulbactam)
Suicide Inhibitors
Monobactam
Carbapenem
Cephalosporins
Beta Lactamase 1/26/2023
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46. Classification and Microbial Susceptibility
The clinically available penicillins encompass several distinct classes of
compounds with varying spectrums of activity:
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47. Classification and Microbial Susceptibility
The clinically available penicillins can be classified in to:
 Natural penicillins: Penicillin G and its close congener Penicillin V
active against:
Sensitive strains of gram positive cocci
Many Streptococci spp. and non-penicillinase-producing Staphylococci spp.
Some gram-positive and gram-negative bacilli, including Corynebacterium,
Listeria monocytogenes, Pasteurella multocida, and Haemophilus influenzae.
Anaerobic bacteria: Fusobacterium, Streptococcus & some spp of Clostridium.
But they are readily hydrolyzed by penicillinase, so ineffective to most S. aureus
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 Procaine penicillin G is the 1rst choice of drugs for anthrax and closterdial D+ like
black leg (high dose). Active against many Strepto & non-PP Staphylo & most Gram +ve
 But, high doses IM may result in nervous excitement particularly in horses and this is most
likely to occur when the procaine has dissociated from the penicillin
 It should not be administered IV, b/c can adversely affect cardiac conduction systems
The phenoxy-methyl group imparts more acid stability.
Procaine, K+ , Na+ salt, not for herbivores (bloat)

48.  Broad spectrum amino penicillin’s: Amoxicillin, Ampicillin, Hetacillin
 Active against the microbes that are susceptible to natural penicillins.
 They are also active against some Enterobacteriaceae, including strains of E. coli,
Proteus mirabilis and Salmonella.
 But inactive against Pseudomonas, Bacteroides fragilis, and PP-Staphyloc spp.
 Half-life is 1-1 ½ hrs
 These agents have now been replaced in general practice by penicillin
& β-lactamase inhibitors
 Amoxicillin differs from ampicillin by the addition of the parahydroxy groups
 It has greater resistance to gastric acid and is more completely absorbed than
ampicillin.
 Ampicillin is used in combination with cloxicillin as an intramammary
formulation to treat bovine mastitis.
 Such formulations are colored brilliant blue to ensure the milk is discarded
 Hetacillin is prepared by a reaction of ampicillin with acetone then back conv’t
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49.  Penicillinase-resistant pen: Clo, Dicloxacillin, Oxacillin, Nafcillin, Methicillin
 Have a ring structure attached to the carbonyl carbon of amid side chain
 Substituents on the ring protect the lactam ring from β- lactamases.
 Have less potent A-microbial activity against microorganism that are
sensitive to penicillin G
 But they are the agents of first choice for treatment of penicillinase-
producing Staphylococcus spp which are resistant to natural
penicillins and the aminopenicillins.
 Have some activity to other gram +Ve & gram -Ve bacteria & spirochetes.
 Methicillin Na is water-soluble producing therapeutic concentratṉ in
CNS
 Oxacillin, Cloxacillin, Dicloxacillin, and Nafacillin resist acid hydrolysis
and can be administered orally.
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50.  Extended-spectrum Penicillins (Azlocilin, Carbenicilin, Mezlocilin,
Piperacilin, Ticarcilin, Ampicillin Amoxicillin, Antipseudomonal Penicillins)
Have either carboxylic acid group or basic group at the α position which gives this drug a
wider spectrums of activities than the other three groups.
Antimicrobial activity is extended to include gram-negative microorganisms.
Frequently these drugs are administered with a b-lactamase inhibitor such as Clavulanate or
Sulbactam to prevent hydrolysis by broad-spectrum β-lactamases
Have high activity against gram -ve aerobic & anaerobic bacteria of all of a penicillin groups
Means it works in 4 quadrant Amoxycillin-clavulanate/ ticarcilin-clavulanate
Remember as the spectrum of activity widen the MIC of these agent usually increase
The drugs are active against many strains of Enterobacteriaceae & some Pseudomonas strn
Carbenicillin & ticarcillin are active against some strains of E. coli, Proteus & Salmonella.
Mezlocillin and Piperacillin are active against some strains of Enterobacter, Citrobacter,
Klebsiella, and Serratia.
Generally more active against Bacteroides fragilis than any other penicillins avail
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Pharmacokinetic Parameters of Selected Penicillins

52. Pharmacokinetic property
Most penicillin's are rapidly absorbed when injected in aqueous suspension by
the IM or SC route. IM injection is the most common route of administration
Maximum blood concentrations result in 15-30 minutes.
It is necessary to orally administer 5 times the amount of penicillin G
necessary for IM injections to produce comparable blood concentrations,
because of inactivation by the gastric acid and enteric bacteria.
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The oral absorption characteristics are dependent upon its classes
Penicillin G is the only available oral penicillin that is substantially affected by gastric pH
and can be completely inactivated at PH’s of less than 2.
The other orally available penicillins are resistant to acid degradation but bioavailability
can be decreased by the presence of food.
Perhaps by adsorption of the antibiotic onto food particles

53. Absorption of penicillin occurs during the first few hours after
intramammary infusion.
Blood concentrations are consistently higher when penicillin is
infused in infected quarters than when infused in to normal quarters.
Serum plays a significant role in transfer of it from treated quarter to
untreated quarter.
There is systemic absorption of sodium benzyl penicillin and procaine benzyl
penicillin administered intrauterine to horses and cattle, respectively
Penicillins are generally distributed widely throughout the body.
Significant amounts appear in the liver, bile, kidney, semen, joint
fluid (synovial), lymph, and intestine.
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54. Bieng polar they rely on renal elimination and have very short half-
lives requiring frequent dosing & very high conc. are attained in urine
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The oil vehicle prolong a duration of therapeutic blood concentrations
Na or K penicillin suspended in an inert oil prolongs absorption of
penicillin from the site of injection for ~18hrs.
ↈProcaine penicillin G is a buffered aqueous suspension available
for IM injection, with prolonged absorption.
Incorporation of the poorly soluble procaine penicillin in oil
prolongs absorption for 24hrs or more hours.
Addition of 2% aluminum monostearate to a suspension of penicillin
in oil markedly slows absorption of PP by producing a gel with HDWR
ↈBenzathine penicillin G is a repository salt of penicillin and the
absorption of this compound may be prolonged for 7 or more days

55. Most penicillins are rapidly excreted largely unchanged by the
kidneys into the urine via glomerular filtration and tubular secretion.
But in small part in the bile and by other routes.
Approximately 60-90% IM dose of penicillin G in aqu solṉ eliminated
in the urine (10%GF & 90%TS) largely within the first hrs of injection
The remainder is metabolized to penicilloic acids no phar-cal activity
Clearance values are considerably lower in neonates & young subject
because of incomplete development of renal function.
Penicillin will diffuse across the placenta, into the fetal circulation.
Penicillins do not penetrate the CNS to any great extent
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56. Cont…
 High concentrations are generally reached in kidneys, liver & lung.
Tissue residues of penicillin in slaughtered animals are considered a
public health hazard b/c of potential hypersensitivity rxn in people.
Penicillins and their metabolites are excreted in the urine within 1hr
of IM injection of Na or K penicillin in aquas solution
Penicillin is also eliminated in milk at 1/5th of serum concentration
thus milk from cows treated systemically or intramammary with
penicillin must be discarded.
It can affect cheese making/production process
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57. Toxicity/Adverse reaction
Penicillins are very safe drugs, with relative few adverse effect reported
Hypersensitivity rxn are by far the most common adverse effects noted
with the penicillins, and these agents probably are a common cause of
Acute allergic reactions which are the most common effects in people
manifestations of allergy to penicillins include:
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 Maculopapular Rash
 Urticarial Rash (red & itchy)
 Fever
 Bronchospasm (constriction)
 Vasculitis
 Exfoliative dermatitis (spreading)
 Anaphylaxis
 In Sensitized Animals there can be
 Acute Anaphylaxis & Collapse
 Hypersalivation, Shaking, Vomiting
 Urticaria, Fever,
 Eosinophilia, Agranulocytosis,
 Neutropenia, Thrombocytopenia, Leukopenia,
 Anemia
 Lymphadenopathy

58. Therapeutic Indication
Penicillins are useful for treating β-haemolytic streptococci infections such as
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 Post castration wounds in horses
Equine Strangles (pathogen Streptococcus equi var equi)
Clostridial diseases (Chuv and Novi)
Listeriosis
Anaerobic conditions such as abscesses, pyothorax and foot rot.
 Penicillins should not be used in hind gut fermenters animals
e.g. guinea pigs, rabbits, chinchillas, hamsters.
 As it results in the production of iota toxin by Clostridium spiroforme
leading to:
 Enteritis
 Enterotoxaemia and
 Death.

59. Contraindications with Therapeutic Indication
The incidence of non-allergic ampicillin eruptions is 40 to 100% in patients with:
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 concomitant Epstein-Barr virus (mononucleosis), & Cytomegalovirus
 Acute lymphocytic leukemia
 Lymphoma and Reticulosarco
 Super infections (Ampicillin), Nephrotoxicity (Methicillin causing nephritis)
 Increase in Prothrombin time leading to bleeding
 Jarisch -Herxheimer Reaction-
 Common in secondary syphilis,
 Release of Spirochetal lytic products (Heat stable proteins, endotoxins)
 Characterized by fever, myalgia, exacerbation of lesions,
 Usually occurs within 2 hours of first dose
 Also in Borelliosis, Leptospirosis, and Brucelosis
 Adolf Jarisch an Austrian and Karl Herxheimer a German dermatologist

60. Jarisch Herxheimer Reaction
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61. Drug Interactions
 Antagonism With Tetracyclines, Chloramphenicol, Erythromycin-
 Synergism. Penicillin with Aminoglycosides-
 Inactivate each other Penicillin & Aminoglycosides or Penicillin &
hydrocortisone in same syringe
 High incidence of non-urticarial maculopapular rashes Ampicillin with
Allopurinol
 Prolongs action of penicillin by decreasing tubular secrṉ Penicillin with
Probenecid
 In vitro studies have demonstrated that penicillins can have synergistic activity
against certain bacteria when used with aminoglycosides or cephalosporins.
 Use of bacteriostatic antibiotics (e.g., chloramphenicol, erythromycin,
tetracyclines) with penicillins is generally not recommended, particularly in
acute infections where the organism is proliferating rapidly.
 Because the antibacterial action is highest during periods of greatest
bacterial multiplication
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62. Hypersensitivity testing
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63. Uses
 General , Plus
 Rheumatic fever
 Streptococcal viridans
 Gonorrhea
 Syphilis-
 Procaine penicillin for 12 days or
 Benzathine Penicillin
 Leptospirosis (Weil’s Disease)
 Actinomycosis, Listriosis, Lyme Disease, Anthrax, Rat bite fever, Erysipeloid,
Gingivostomatitis
 Diphtheria
 Tetanus
 Gas gangrene (Clostridium pefringens (welchii)
 Prophylaxis-
 Rheumatic fever
 Agranulocytosis
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64. For Dogs:
 Penicillin G potassium: 20,000 Units/kg IV, IM, SQ q4h or 40,000 IU/kg PO on an empty stomach q6h
 Penicillin G procaine: 20,000 Units/kg IM, SQ q12-24h Dose =
𝑾𝒊𝒆𝒈𝒕 𝒙 𝑫𝒐𝒔𝒆
𝑪𝒐𝒏𝒄𝒆𝒏𝒕𝒓𝒂𝒕𝒊𝒐𝒏
 Penicillin G benzathine: 50,000 IU/kg IM q5 days
 For adjunctive therapy of septicemia: Penicillin G sodium/potassium: 25,000 IU/kg IV q6h.
 Too rapid IV infusions may cause neurologic signs; hypersensitivity may also occur.
Cats:
For susceptible infections:
 Penicillin G potassium: 20,000 Units/kg IV, IM, SQ q4h or 40,000 IU/kg PO on an empty stomach q6h
 Penicillin G procaine: 20,000 Units/kg IM, SQ q12-24h
 Penicillin G benzathine: 50,000 IU/kg IM q5 days
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Doses  Q6h= Every 6 hours

65. Dosage
calculation
 How do you convert IU/kg in to ml/kg ?
 formulas for dosage calculation
Dose =
𝑊𝑖𝑒𝑔𝑡 𝑥 𝐷𝑜𝑠𝑒
𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛
The drug procaine penicillin is powder
form, so it is diluted with distilled water
 One vial procaine penicillin is diluted
with 10 ml distilled water
 The concentration of Pn is 300,000
IU/ml.
 The dose is 20,000-45,000 IU/kg
E.g. how much ml of pn is required for
300 kg of ox for one injection
 Total dose=
𝑊𝑖𝑒𝑔𝑡 𝑥 𝐷𝑜𝑠𝑒
𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛

300𝑘𝑔 𝑥 20,000 𝐼𝑢/𝑘𝑔
300,000 𝐼𝑈/𝑚𝑙

6,000,000 𝐼𝑈
300,000 𝐼𝑈/𝑚𝑙
20ml
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66. 1/26/2023 Dr. Balisa Yusuf

67. Broad spectrum, bactericidal antibiotics chemically related to penicillins
The nucleus consists of a β –lactam ring fused to a dihydrothiazine
Semisynthetic antibiotics derived from products of various
microorganisms, including Cephalosporium and Streptomyces.
⚫ Good ability to penetrate bacterial cell walls also activity against PBP.
⚫ Originally introduced for the treatment of penicillinase resistant Staphylococci infṉ
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Cephalosporins
 All true cephalosporins are derived from cephalosporin C which is produced from
Cephalosporium acremonium
 Presently >20 differnt cephalosporin drugs are available for human & veterinary use
Isolation of the active nucleus of cephalosporin C, 7-aminocephalosporanic
acid= dihydrothiazine β-lactam ring system, & with the addition of side chain
The 7- aminocephalosporanic acid molecule also provides more sites
for manipulation in the production of semi-synthetic drugs

68. Chemistry and Structure of Cephalosporin
 They have a 7-aminocephalosporanic
acid (active nucleus) composed of a
dihydrothiazine ring fused to a β-
lactam ring (common to all).
 As with the penicillins, the cephalosporin β-
lactam ring is the chemical group
associated with antibacterial activity.
 Relatively stable in dilute acid and
highly resistant to penicillinase
regardless of the nature of their side
chains & their affinity for the enzyme
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69. N
O
H
H
H
N
O
S
CO2H
O
C
Me
O
H2N
CO2H
7
H
6
1
2
3
4
5
8
7-Aminoadipic side chain
Structure of Cephalosporin C
b-Lactam
ring
Dihydrothiazine
ring
N
O
H
H
H2N S
CO2H
O
C
Me
O
7-Aminocephalosporinic acid (7-ACA)
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70. N
O
H
H
H
N
O
S
CO2H
O
C
Me
O
H2N
CO2H
7
H
6
1
2
3
4
5
8
Properties of Cephalosporin C
 Advantages
 Non toxic
 Lower risk of allergic reactions compared to penicillins
 More stable to acid conditions and to b-lactamases
 Ratio of activity vs Gram -ve and Gram +ve bacteria is better
 Disadvantages
 Polar due to the side chain - difficult to isolate and purify
 Low potency - limited to the treatment of urinary tract infections
where it is concentrated in the urine
 Not absorbed orally
Conclusion
• Useful as a lead compound
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71. Classification of Cephalosporin
 The cephalosporins are classified into generations according to their
antibacterial spectrum and stability to β-lactamases.
The first-generation cephalosporins: have good activity against gram
+ve bacteria (streptococci), S. aureus, and a few gram-negative bacilli.
 Generally lower activity than comparable penicillins but Better range of activity
 Best activity is against Gram-positive cocci & Useful against some Gram -ve infecṉ
 Useful against S. aureus and strepto infṉ when penicillins have to be avoided
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 Poorly absorbed across the gut wall (except for 3-methyl substituted cephalospo)
 Most are administered by injection (PO Absorption is poor in horses and ruminants)
 More than half of the drug is bound to plasma P Excreted by kidneys unmetabolzd
 Good for staph and strep skin and soft tissue infections
 Resistance has appeared amongst Gram -ve bacteria (presence of more effective
b-lactamases)

72. The second-generation cephalosporins:
 First b-lactam to be isolated from a bacterial sourcea (culture of Strep. clavuligerus)
 Absorption and excretion same as first generation.
 Resistant to esterases due to the urethane group
 Wide spectrum of activity being Useful against organisms that have gained resistance to penicillin
 Good for treating respiratory tract infections, intra-abdominal infections, pelvic inflammatory
disease, diabetic foot ulcers
 Used clinically against respiratory infections Reserved for life threatening G -ve infecṉ
 Not active against P. aeruginosa and have greater stability against:
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 β-lactamase inactivation and possess a broader spectrum of activity
to include gram +ve cocci, gram -ve organisms & anaerobes.
 Among the second-generation cephalosporins, the Cephamycins
 Cefoxitin [Mefoxin] Cefotetan [Cefotan]
 Cefmetazole [Zefazone]) have the most activity against Bacteroides fragilis.
 Cefuroxine: Cross BBB, dry cow therapy; Ceftiofur: –Shipping fever (Pasteurella)

73. The extended spectrum, or third-generation cephalosporins:
 Possess a high degree of in vitro potency and β-lactamase stability
 Broader spectrum of action against many common gram -ve bacteria & anaerobes
 While retaining good activity against streptococci.
 Aminothiazole ring enhances its penetration across the outer membrane of Gram
-ve bacteria while increasing its affinity for the transpeptidase enzyme
 Variable activity against Gram +ve cocci and also vs. P. aeruginosa
 Lack activity vs MRSA. Generally reserved for troublesome infections
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 The agents with the greatest activity against P. aeruginosa are
Cefepime
Cefoperazone
Ceftazidime.
 Ceftazidime Injectable cephalosporin
 Excellent activity vs. P. aeruginosa and other Gram -ve bacteria
Can cross the blood brain barrier thus Used to treat meningitis

74. Third Generation Cephalosporins
 Ceftaxime, ceftriaxzone,
cefoperazone, cefpodoxime
 Broad spectrum killers
 Drugs of choice for serious
infections
 No effect against Listeria and
beta-lactamase producing
pneumococci
 Cefpodoxime given orally, others
parentally
 Most excreted by kidney
 Therapeutic uses
Bacterial meningitis (2 exceptions)
Lyme disease
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75. The fourth-generation cephalosporin: Cefepime
 Same antimicrobial spectrum as third generation but resists more ꞵ-lactamase
 Given parentally
 Excellent penetration into CSF
 Good for nosocomial infections
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 Enhanced ability to cross the outer
membrane of Gram negative bacteria
 Good affinity for the transpeptidase enzyme
 Low affinity for some b-lactamases
 Active vs. Gram +ve cocci and a broad array
of Gram -ve bacteria
 Active vs. P. aeruginosa
1st generation
2nd generation
3rd generation
4th generation
G+
increasing
ß-lactamase
stability
G-

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77. Generation Oral Parenteral
First -Cephalexin
-cephradine
-cefadril
-Cephalotine
-Cephaprine
-Cephazolin
-Cephaloridine
-Cephalonium
Second -Cefachlor
-Cefuroxime
-Cefaxetil
-Cefamandole
-Cefoxitine
-cefuroxime
-Ceftiofur
Third -Cefixime
-cefdinir
-Ceftriaxon
-cefotaxime
-cefoperazone
-ceftazidime
-cefsulodine
Forth -Cefepime
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78.  Similar to Penicillin Bind to PBP inhibit action of trans peptidase
 Bind to several enzymes (Carboxypeptidases, Transpeptidases, Endopeptidases)
within the bacterial cytoplasmic m/b that are involved with cell wall synthesis.
 Time dependent, need frequent administration, effective in rapidly growing organsm
 Like other beta-lactam antibiotics, cephalosporins are generally considered to be
more effective against actively growing bacteria.
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Mechanism of Action
Antibacterial spectrum
They possess generally excellent coverage against most gram-positive pathogens
and variable to poor coverage against most gram negative pathogens.
They are usually active against ꞵ-hemolytic strepto & ꞵ-lactamase producing
staphyloc: but not against methicillin (oxacillin) resistant Staphylococci
Most enterococci are resistant except E-coli and salmonella which are susceptibl
Mycobacteria are resistant

79.  There are reported spp variation in the oral bioavailability of some cephalosporins
(can be administered intramuscularly or intravenously)
 Cephalosporins are widely distributed to most tissues and fluids, including bone,
pleural fluid, pericardial fluid and synovial fluid.
 Higher levels are found in inflamed bones than in normal bone.
 Very high levels are found in the urine, but they penetrate poorly into prostatic
tissue and aqueous humor.
 Bile levels can reach therapeutic concentrations with several of the agents as long as
biliary obstruction is not present.
 Cephalosporins cross the placenta and fetal serum concentrations can be 10%
or more of those found in maternal serum.
 Cephalosporins enter milk in low concentrations.
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Pharmacokinetics

80. Cephalosporins and their metabolites (if any) are excreted
primarily by the kidneys, via tubular secretion and/or glomerular
filtration.
Some cephalosporins (e.g., cefotaxime, cefazolin, and
cephapirin) are partially metabolized by the liver to desacetyl
compounds that may have some antibacterial activity.
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 Good bioavailability after parenteral administration.
 Oral –food interferes bioavailability –Cefaclor, Cephradine
 Poor BBB penetration excpt Cefotaxime, Ceftriaxone, Cefepine, Cefuroxime
 Excretion –Urine
 The mechanisms of resistance to cephalosporin is similar with that of penicillin

81. Clinical Indications
Limited in Veterinary practice because of the cost
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 Cefazolin –Surgical Prophylaxis
 Cefalexin –Dermatitis
 Ceftiofur–Shipping fever, Uriniary tract infection
 Ceftriaxone, Cefataxime –Meningitis
 Cefoperazone, Cefsulodine, Ceftazidime –Pseudomonal infection

82. Toxicity/Adverse reaction
Contraindications/Precautions in patients who are documented
hypersensitive to other beta-lactam antibiotics
e.g., penicillins, cefamycins, carbapenems
Adverse Effects: Adverse effects with the cephalosporins are usually not
serious and have a relatively low frequency of occurrence.
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 Hypersensitivity rxn
 Pain at the injection site
when administered by IM
 GI effects when given PO
 Anorexia
 Vomiting
 Diarrhea
 High doses/very prolonged use has been associated Ŵ
 Neurotoxicity
 Neutropenia
 Agranulocytosis
 Thrombocytopenia
 Hepatitis
 interstitial nephritis
 Tubular necrosis

83. Drug Interactions:
Can have synergistic/ additive activity against certain bacteria
when used Ŵ aminoglycosides, penicillins/ chloramphenicol
Probenecid competitively blocks the tubular secretion of
most cephalosporins, thereby increasing serum levels and
serum half-lives.
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 Generally non-toxic
 Cephaloridine –Nephrotoxicity
 I/M –Painful, Repeated I/V –Phlebitis
 Nausea, Vomiting, Diarrhea – Occasionally
 Superinfection
 Hypersensitivity –Acute Penicillin allergy –Cross reactions may occur

84. Toxicity/Contraindications of
Cephalosporins
• Hypersensitivity reactions (uncommon)
essentially same as for penicillins
• Cross-reaction between 2 classes
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Beta lactamase inhibitors
They irreversibly bind to the beta lactamase enzyme and thus allowing the active β-lactam
antibiotic to kill the organisms
 It itself is a beta-lactam compound produced by Streptomyces clavuligerus, but
has negligible antibacterial activity.
 During the process of inhibiting the beta-lactamase it gets inactivated, hence the
process is called Suicidal inhibition.
 It has good affinity for the
Majority of plasmid mediated beta lactamases
All chromosomally mediated penicillinase
But little affinity for chromosomal mediated cephalosporinases.
 Amoxicillin and ticarcillin are combined with Clavulanic acid in the ratio of 4:1
and 15:1, respectively and the combinations are bactericidal
Clavulanic acid

86. Clavulanic acid- Amoxicillin (Augmentin)
 Excellent susceptibility of gram +ve bact including ꞵ-lactamase producing S. aureus.
 Some gram -ve bacteria and strains resistant to amoxicillin are also susceptible
 Eneterobacteriaceae and most anaerobes are susceptible.
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 Clinical application in Cattle, sheep and goat
 Lower respiratory tract infection
 Anaerobic soft tissue infections
 Neonatal diarrhea caused by E.coli and Salmonella.
 Clinical mastitis in cattle both parenetral and intramammary
 Pasteurellosis in sheep
 Swine: Neonatal diarrhea caused by E.coli
Clavulanic acid- Ticarcillin (Timentin)
 It has greater activity against Enterobacter and Pseudomonas aeruginosa and
 To the majority of ticarcillin resistant organisms. 1/26/2023
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87. Sulbactam (Penicillic acid sulfone)
 It is a synthetic derivative of 6-amino penicillanic acid.
 It has no antibacterial activity by itself but irreversibly binds to ꞵ-lactamases.
 The affinity of sulbactam is lower compared to clavulanic acid.
 It is combined with ampicillin because of similar pharmacokinetic properties and
also with cefoperazone.
Sulbactam – Ampicillin (Unasyn)
 Antibacterial activity is broader but lower than clavulanic acid-amoxicillin combṉ
(Augmentin)
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Tazobactam
 Its activity is broader than clavulanic acid and sulbactam.
 It resist hydrolysis by some beta lactamases.
 It is combined with piperacillin in a ratio of 8:1 (Piperacillin:Tazobactam) Zosyn
 and has enhanced activity against pseudomonas.
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88. Carbapenems
 Carbapenems are a potent class of β-lactams which attack a wide range of PBPs
 have low toxicity, and are much more resistant to β-lactamases than the penicillins or
cephalosporins.
 Carbapenems includes Imipenem, Meropenem, Panipenem and Thienamycin
 Carbapenems are derivatives of Streptomyces spp.
 They are highly active against a wide variety of gram positive and gram negative
bacteria are resistant to many beta lactamases
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Thienamycin,
 Thienamycin, discovered by Merck in the late 1970’s
 It is one of the most broad spectrum antibiotics ever discovered.
 It uses import porins unavailable to other β-lactams to enter Gram (-) bacteria.
 Due to its highly unstable nature this drug and its derivatives are created through
synthesis, not bacterial fermentation.
 Due to its rapid degradation by renal peptidase it is administered with an
inhibitor called cilastatin under the name Primaxin
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89.  Thienamycin was slightly modified and marked as Imipenem.
 Imipenems: Are active against almost all important aerobes and anaerobes
 Imipenem may cause seizures or sever allergic reactions.
 Other modifications of Thienamycin have produced superior carbapenems called
Meropenem and Ertapenem, which are not as easily degraded by renal peptidase
and do not have the side effects of Imipenem.
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Monobactams
 Aztreonam and Carumonam belong to Monobactams
 The only clinically useful monobactam is aztreonam.
 While it resembles the other β-lactam antibiotics and targets the PBP of bacteria
 It is highly effective in treating Gram (-) bacteria and
Lower respiratory tract, skin, intra-abdominal infections
Urinary tract infections
gynecologic infections and septicemia
 And is resistant to many β-lactamases 1/26/2023
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90. Aminopenicillins:
ampicillin-sulbactam = Unasyn
amoxicillin-clavulante = Augmentin
Extended-Spectrum Penicillins
piperacillin-tazobactam = Zosyn
ticarcillin-clavulanate = Timentin
Others
Thienamycin-cilastatin = Primaxin 1/26/2023
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91. SULFONAMIDES
Mode of
action:
Inhibition of other metabolic processes. Sulfonamides interfere with folic acid synthesis
by preventing addition of para-aminobenzoic acid (PABA) into the folic acid molecule
through competing for the enzyme dihydropteroate synthetase.
Example: Sulfadiazine, sulfamethoxazole, sulfadoxine
Spectrum of
act
Effect on
bacte
Broad-spectrum; affects Gram-positive and many Gram-negative bacteria, toxoplasma
and protozoal agents
Bacteriostatic
Examples of
applications in
Veterinary
Medicine:
Colibacillosis, Pasteurellosis, Footrot, Coccidosis, Infectious coryza, Pullorum disease, Fowl
typhoid
The primary indications are to treat:
Toxoplasmosis (combined with pyrimethamine) Pneumocystis carinii and Nocardiosis (combined
with minocycline).
Chronic colitis in dogs Sulfasalazine besides its anti-inflammatory properties.
Prevention of infection of burn wounds Silver sulfadiazine is a much less toxic topical su-amide
Sulphonamides & potentiated sulphonamides are cheap compared to other antimicrobials
DIAMINOPYRIMIDINES (TRIMETHOPRIM)
Mode of
action:
Inhibition of other metabolic processes. Trimethoprim interferes with the folic acid
pathway by binding the enzyme dihydrofolate reductase.
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92. BETA LACTAM ANTIBIOTICS
Mode of
action:
Inhibition of cell wall synthesis. This particular group is characterized by its four-membered,
nitrogen-containing beta-lactam ring at the core of its structure, which is key to the mode of action
of this group of antibiotics. Beta lactam antibiotics target the penicillin-binding proteins or PBPs - a
group of enzymes found anchored in the cell membrane, which is involved in the cross-linking of
the bacterial cell wall. The beta-lactam ring portion of this group of antibiotics binds to these
different PBPs, rendering them unable to perform their role in cell wall synthesis. This then leads to
death of the bacterial cell due to osmotic instability or autolysis.
Examples: Penicllins: Natural: penicillin G, penicillin V; Penicillinase-resistant penicilllin: methicillin; oxacillin,
nafcillin; Extended spectrum penicillin: ampicillin, amoxicillin, carbenicillin. Cephalosporins:
cephalothin; cefamandole, cefotaxime
Carbapenems: primaxin. Monobactams: aztreonam
Source: Penicillin: Penicillum chrysogenum (syn: P. notatum), Aspergillus nidulans
Cephalosporin: Acremonium chrysogenum (syn: Cephalosporium acremonium), Paecilomyces
persinicus, Streptomyces clavuligerus, Nocardia lactamdurans, Flavobacterium sp. Lysobacter
lactamgenus
Spectrum of
activity
Effects
Broad-spectrum: carbapenems, 2nd, 3rd and 4th generation cephalosporins
Narrow-spectrum: penicillin, 1st generation cephalosporins, monobactams
Generally bactericidal
Examples of
applications
in Veterinary
Ruminants: Anthrax, listeriosis, leptospirosis, clostridial & corynebacterial infectṉ; streptocl mastitis,
keratoconjunctivitis
Swine: erysipelas, streptococcal and clostridial infections
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