Tetracyclines slide contains full information about uses, adverse effect, marketed preparation, precaution, route of drug administration, antimicrobial spectrum, mechanism of action, pharmacokineticks and pharmacodynamics of tetracyclines. This slide is very helpful for pharmacy and pharmacology student for the study about tetracyclines.
Broad Spectrum Antibiotic:Tetracycline,four cyclic rings,Physicochemical Properties,Classification-According to source and Based on Duration of action ,Mechanism of action-30S ribosomes ,Inhibit protein synthesis,Antimicrobial spectrum
Resistance
Adverse effects
Precautions,Uses by snehal chakorkar
Tetracyclines slide contains full information about uses, adverse effect, marketed preparation, precaution, route of drug administration, antimicrobial spectrum, mechanism of action, pharmacokineticks and pharmacodynamics of tetracyclines. This slide is very helpful for pharmacy and pharmacology student for the study about tetracyclines.
Broad Spectrum Antibiotic:Tetracycline,four cyclic rings,Physicochemical Properties,Classification-According to source and Based on Duration of action ,Mechanism of action-30S ribosomes ,Inhibit protein synthesis,Antimicrobial spectrum
Resistance
Adverse effects
Precautions,Uses by snehal chakorkar
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H1-antihistamines are used to treat allergy symptoms. Within this group are two generations called the first generation and second generation antihistamines. H2-antihistamines are used to treat gastrointestinal conditions.
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Antiprotozoal agents is a class of pharmaceuticals used in treatment of protozoan infection. Protozoans have little in common with each other and so agents effective against one pathogen may not be effective against another
H1-antihistamines are used to treat allergy symptoms. Within this group are two generations called the first generation and second generation antihistamines. H2-antihistamines are used to treat gastrointestinal conditions.
The H2 receptor antagonists are reversible competitive blockers of histamine at the H2 receptors, particularly those in the gastric parietal cells, where they inhibit acid secretion. They are highly selective, do not affect the H1 receptors, and are not anticholinergic agents.
The key difference between H1 and H2 receptors is that the H1 receptor couples with Gq/11 stimulating phospholipase C while the H2 receptor interacts with Gs to activate adenylyl cyclase. Histamine is an organic nitrogenous compound that involves local immune responses.
Anthelmintics | B.Pharm 3rd year 2nd Sem | Medicinal Chemistry-III | History, Classification, Structures & Synthesis of anthelmintics, Synthesis of Diethylcarbamazine citrate, Synthesis of Mebendazole
AMINOGLYCOSIDE-INTRODUCTION,HISTORY, MECHANISM OF ACTION, CHEMISTRY, RESISTANCE TO ANTIBIOTICS, CLASSIFICATION ,PHARMACOKINETIC, ADVERSE EFFECT, THERAPEUTIC USE
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RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
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Antibiotics inhibiting protein synthesis 2 aminoglycosides 03 05-2018
1. Antibiotics inhibiting protein synthesis:
Aminoglycosides
Dr Ravi Kant Agrawal, MVSc, PhD
Senior Scientist (Veterinary Microbiology)
Food Microbiology Laboratory
Division of Livestock Products Technology
ICAR-Indian Veterinary Research Institute
Izatnagar 243122 (UP) India
2. Steps in Protein synthesis
STEP 1:
• Transcription of mRNA from a DNA in the nucleus.
• Synthesis of the various other types of RNA using
the appropriate DNA.
• Migration of RNAs from the nucleus into the
cytoplasm.
• Prior to the beginning of the protein synthesis, all of
the component parts are assembled in the
ribosome.
3. Steps in Protein synthesis
STEP 2: Initiation:
• In the cytoplasm, protein synthesis is actually initiated
by the AUG codon on mRNA.
• The AUG codon signals both the interaction of the
ribosome with m-RNA and also the tRNA with the
anticodons (UAC).
• The tRNA which initiates the protein synthesis has N-
formyl-methionine attached.
• The next step is for a second tRNA to approach the
mRNA
• The final process is to start growing peptide chain by
having amine of 2nd
AA to bond to the carboxyl acid
group of methinone (met) in order to elongate the
peptide
4. Steps in Protein synthesis
STEP 3: Elongation:
• Elongation of the peptide begins as various
tRNA's read the next codon.
• Role of Peptidyl transferase
5. Steps in Protein synthesis
Step 4: Termination:
• When the stop signal on mRNA is reached, the protein
synthesis is terminated. The last amino acid is
hydrolyzed from its t-RNA.
• The peptide chain leaves the ribosome.
• The ribosome is now ready to repeat the synthesis
several more times.
• http://pharmaxchange.info/press/2011/05/mechanism-of-tran
6.
7. Sites at which antibiotics acts
• 30 s ribosomal Unit:
Aminoglycosides
Tetracyclins
• 50s ribosomal Unit
Chloramphenicol
Macrolides
Streptogamidins
Oxazolidinones
8. Aminoglycosides: History
• Most aminoglycosides are naturally occurring
substances produced by actinomycetes of either the
genus Streptomyces or Micromonospora.
• 1944: First member Streptomycin discovered by
Waksman from Streptomyces griseus.
• 1949: Discovery of Neomycin Streptomyces fradiae.
• 1957: Discovery of Kanamycin Streptomyces
kanamycetius
• 1963: Gentamicin discovered from Micromonospora
purpurea.
9. Structure
• Features of aminoglycosides include
amino sugars bound by glycosidic
linkages to a relatively conserved six-
membered ring that itself contains amino
group substituents (Aminosugars).
• Complex heterocyclic compound
• Aminocyclitol group+ one/more Amino
Sugars group
• Depending on Aminocyclitol ring mainly
two types
• Aminocyclitol is Streptidine
(Streptomycin, Dihydrostreptomycin)
• Aminocyclitol is Deoxystreptamine
Neomycin derivative: Neomycin,
Fremycetin
Kanamycin derivative: Kanamycin,
Amikacin, Tobramycin
Gentamicin derivative: Gentamicin,
Netilmicin, Sisomicin, Spectinomicin
10. Pharmacological Properties
• Poor absorption by oral route
• I/M or I/V route recommended
• Do not cross BBB
• Only extracellular distribution- Extensively distributed in
extracellular fluid
• Polar and water soluble
• Do not enter cell due to polar nature
• Limited biotransformation- Not significantly metabolized
• Excreted unchanged in urine via glomerular filtration
• Half life 2-4 hrs
• Low protein binding
• Used mainly as Sulphate salt
• More active in alkaline pH
• Ototoxicity and Nephrotoxicity
• Narrow margin of safety
• Rapid development of antibacterial resistance
12. Mechanism of Action
• Aminoglycosides bind to the 30S subunit of the
bacterial ribosome, thereby inhibiting bacterial protein
synthesis (translation):
1. Interfere with formation of initiation complex of peptide
formation
2. Binds to Ribosome and alter its shape in such a way
that there is misreading of mRNA causing
incorporation of incorrect AA.
3. Causes breakup of polysomes into nonfunctional
monosomes
4. Interfere with attachment of tRNA to mRNA-Ribosome
complex protein
• Requires oxygen uptake, therefore ineffective
against anaerobes.
• Bactericidal
• http://pharmaxchange.info/press/2011/05/mechanism-of-ac
13.
14. Antimicrobial Spectrum:
1. Gram (-) Aerobic Bacilli
2. Beta-lactamase producers:
Staph. aureus
N. gonorrhea
3. Mycobacteria
Clinical Uses:
Severe gram (-) rod infections
Mycobacterial infections
15. Bacterial resistance to aminoglycosides occurs via one of
three mechanisms that prevent the normal binding of the
antibiotic to its ribosomal target:
1. Efflux pumps prevent accumulation of the
aminoglycoside in the cytosol of the bacterium.
2. Production of Enzymes Aminoglycosyl acetyl
transferase, Aminoglycosyl nucleotidyl transferase,
Aminoglycosyl phosphotransferase that adenylate or
phosphorylate hydroxyl group on aminoglycoside
molecules or acetylate exposed aminosugars thus modify
Aminoglycoside prevents binding to the ribosome.
3. Mutations within the ribosome prevent aminoglycoside
binding.
Resistance
16. Toxicity
• All members are Nephrotoxic and Ototoxic but vary in
ability to cause this adverse effect.
• Ototoxicity (esp. with loop diuretics):
• Auditory damage – Neomycin, Kanamycin
and Amikacin
• Vestibular Damage – Streptomycin,
Gentamicin; Tobramicin and Gentamicin less likely to
cause vestibular toxicity.
• Nephrotoxicity (esp. with cephalosporins)
Neomycin, Tobramycin, Gentamicin - most
nephrotoxic
• NM Blockade: It causes NM blockade by interfering with
acetyl choline release from motor nerve by blocking Ca+
+ ion
19. Streptomycin
• Oldest aminoglycoside
• Narrow spectrum
• Used with penicillin
• Rapid drug resistance: Ribosomal resistance to this agent develops
readily, limiting its role as a single agent
• Mainly used as a second line agent for treatment of tuberculosis
• Given at 0.5-1 g/d (7.5-15 mg/kg/day for children) IM or IV
• Should be used only in combination with other agents to
prevent emergence of resistance
• In plague, tularemia and sometimes brucellosis, 1 g/d (15
mg/kg/day for children) IM or IV + oral tetracycline +Penicillin
• Effective for enterococcal endocarditis and 2 week therapy of
viridans streptococcal endocarditis
• Can cause fever, skin rashes and other allergic reactions, pain at
injection site
• Vestibular dysfunction – most serious toxic
effect
• If given during pregnancy, can cause deafness in the newborn
20. Neomycin
• Streptomyces fradiae
• Broad spectrum
• Complex of A (Neamine), B (Framycetin), C (Neomycin)
• Neomycin B most commonly used
• Used for oral and topical application
• Effective against many Gram negative and Gram positive
bacteria
• Not active against Pseudomonas aeruginosa
21. Kanamycin
• Streptomyces kanamycetius
• Broad spectrum
• Kanamycin A,B,C
• Kanamycin A is major component
• Active against aerobic gram negative bacteria
• Used for Topical application and oral route for enteric
infection
• Paromomycin is also a member of this group and all have
similar properties.
22. Used for bowel preparation for elective surgery.
There is complete cross-resistance between kanamycin
and neomycin.
Not significantly absorbed from the GIT; excretion of any
absorbed drug is mainly through GF into the urine.
Too toxic for parenteral use, now limited to topical and oral
use.
Solutions 1-5 mg/ml – used on infected surfaces or
injected into joints, pleural cavity, tissue spaces or
abscess cavities where infection is present (15
mg/kg/day).
23. Ointments (Neomycin-Polymyxin-Bacitracin
combination) applied to infected skin lesions or in the
nares for suppression of staphylococci.
In preparation for elective bowel surgery, 1 g of Neomycin
given orally q 6-8 hours + 1 g of erythromycin base.
Paromomycin, 1 g q 6 hours orally for 2 weeks; effective in
intestinal amoebiasis.
Sudden absorption of postoperatively instilled kanamycin
from the peritoneal cavity (3-5 g) has resulted in curare-
like neuromuscular blockade and respiratory arrest
(Calcium gluconate and neostigmine can act as
antidotes).
Prolonged application to skin and eyes-severe allergic
reactions.
24. Gentamicin
• Extended spectrum aminoglycoside
• Microspora purpurea (micin)
• Gentamicin C1,1a, 2
• Active against Gram negative, Gram positive bacteria
• Also active agaisnt Pseudomonas aeruginosa, Klebsiella
• Most commonly used Aminoglycoside
• Used for urinary tract infection, GI infection, soft
tissues, Metritis, Mastitis.
• Also given as intramammary and intrauterine route
25. Employed mainly in severe infections (sepsis and
pneumonia) caused by gram (-) bacteria in
combination with a cephalosporin or a penicillin.
may be life saving
given at 5-6 mg/kg/day IV in three equal doses + Penicillin
G for bactericidal activity in endocarditis due to viridans
streptococci or enterococci and in combination with
Nafcillin in selected cases of staphylococcal endocarditis
Serum concentrations and renal function should be
monitored if administered for more than a few days or if
renal function is changing (eg. Sepsis; often complicated
by acute renal failure)
26. Gentamicin sulfate 0.1% -0.3% cream, ointment – for the
treatment of infected burns, wounds, or skin lesions and
the prevention of intravenous catheter infections
Topical gentamicin is partly inactivated by purulent
exudates
Ten milligrams can be injected sub-conjunctivally for
treatment of ocular infections.
Nephrotoxicity is reversible and usually mild
Irreversible ototoxicity manifested as vestibular
dysfunction
hypersensitivity reactions are uncommon
27. Amikacin
• Semisynthetic derivative of kanamycin
• Acetylated derivative of Kanamycin A
• Wide spectrum
• E. coli, Proteus, Pseudomonas, Salmonella,
Enterobacter, Mycoplasma, Staphylococcus
• Amikacin is resistant to many Aminoglycoside
inactivating enzymes
• For tuberculosis; given at 7.5 – 15 mg/kg/d as a once
daily or 2- 3x weekly
• Serum concentrations should be monitored
• Nephrotoxic and ototoxic
28. Antimicrobial spectrum and pharmacokinetic properties
virtually identical to gentamicin
Given at 5-6 mg/kg IM or IV into three equal
amounts q 8 hours
Blood levels should be monitored in renal
insufficiency
Slightly more active against Pseudomonas but not E.
faecium
Ototoxic and nephrotoxic
TOBRAMYCIN
29. Shares many characteristics with gentamicin and
tobramycin.
Dosage and the routes of administration are the same,
completely therapeutically interchangeable with
gentamicin or tobramycin and has similar
toxicities.
NETILMICIN
30. It is in aminocyclitol class, closely related to the aminoglycosides,
produced by the bacterium Streptomyces spectabilis.
Binds at the 30 S subunit and inhibits protein synthesis.
(bacteriostatic)
Dispensed as the dihydrochloride pentahydrate for IM
injection (Trobicin)
Used almost solely as an alternative treatment for
gonorrhea in patients who are allergic to penicillin
or whose gonococci are resistant to other drugs
Single dose of 2 g ( 40 mg/kg )
SPECTINOMYCIN
31. Thanks
Acknowledgement: All the material/presentations available
online on the subject are duly acknowledged.
Disclaimer: The author bear no responsibility with regard to the
source and authenticity of the content.