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,Biological sources,History,Sturctures,SAR,Mechanism of action,Spectrum of activity,Important structural units and the three acidity constants in the tetracycline molucule,amphoteric nature,epimerisation, chelation with metals,toxicity and uses.
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,Biological sources,History,Sturctures,SAR,Mechanism of action,Spectrum of activity,Important structural units and the three acidity constants in the tetracycline molucule,amphoteric nature,epimerisation, chelation with metals,toxicity and uses.
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 antibiotics chloramphenicol, anaerobic,soil bacteria. Description includes Physicochemical Properties,Mechanism of action-50S ribosome ,Inhibits Bacterial protein synthesis,Resistance,Interactions,Indications of chloramphenicol-Pyogenic meningitis.
Anaerobic infections.
Intraocular infections.
Enteric fever
Drug of choice in some conditions.
Urinary tract infections
Topically In conjunctivitis & external ear Infections. Snehal chakorkar
The fixed dose combination of trimethoprim and sulfamethoxazole is called cotrimoxazole.
Adverse Drug Reaction, Spectrum, Resistance and Use of Cotrimoxazole.
Phsicochemical properties according to pci syllubus.
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties : Physical property of drug is responsible for its action
2)Chemical Properties :The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
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 antibiotics chloramphenicol, anaerobic,soil bacteria. Description includes Physicochemical Properties,Mechanism of action-50S ribosome ,Inhibits Bacterial protein synthesis,Resistance,Interactions,Indications of chloramphenicol-Pyogenic meningitis.
Anaerobic infections.
Intraocular infections.
Enteric fever
Drug of choice in some conditions.
Urinary tract infections
Topically In conjunctivitis & external ear Infections. Snehal chakorkar
The fixed dose combination of trimethoprim and sulfamethoxazole is called cotrimoxazole.
Adverse Drug Reaction, Spectrum, Resistance and Use of Cotrimoxazole.
Phsicochemical properties according to pci syllubus.
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties : Physical property of drug is responsible for its action
2)Chemical Properties :The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Tetracyclines and Chloramphenicol (Broad-Spectrum Antibiotics).pptxsapnabohra2
TYB pharmacy
Pharmacology VI semester
Pharmacology notes
Tetracycline and chloramphenicol notes ppt
broad spectrum antibiotics
Third year B pharmacy pharmacology notes
Pharmacology unit 3 notes
Pharmacology VI semester notes
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
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).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
1. Dr. N. S. MEENA
DEPARTMENT OF VETERINARY PHARMACOLOGY AND
TOXICOLOGY
Post Graduate Institute of Veterinary Education and Research (PGIVER)
(Rajasthan University of Veterinary and Animal Sciences)
N.H. 11, Agra Road, Jamdoli campus, Jaipur – 302031
2. • Tetracyclines are a group of broad-spectrum antibiotics having
a nucleus of four cyclic rings. They are either obtained naturally
from soil actinomycetes or prepared semi-synthetically. They
have similar antimicrobial features, but differ somewhat from
one another in terms of their antimicrobial spectra and
pharmacokinetics.
• The general usefulness of tetracyclines has declined with the
onset of bacterial resistance, but still they remain the
treatment of choice for some specific infections.
TETRACYCLINES
3. History
• Tetracycline antibiotics were produced by systemic screening of
soil microorganisms. The first member of the group was
chlortetracycline derived from soil actinomycete Streptomyces
aureofaciens introduced in 1948. This was followed by
oxytetracycline.
• Removal of chlorine atom from chlortetracycline produced
semi-synthetic tetracycline introduced in 1952.
• Further discovery led to other semi-synthetic tetracyclines like
metacycline, doxycycline and rolitetracycline. Doxycycline and
minocycline are relatively newer tetracyclines with high lipid
solubility and longer duration of action.
• In 2005, tigecycline, the first member of a new subgroup of
tetracyclines named glycylcyclines, was introduced to treat
infections which are resistant to other antimicrobials including
conventional tetracyclines.
4. Chemistry and Properties
• Tetracyclines are close congeners of polycyclic
naphthacenecarboxamide. They are a family of four ringed
amphoteric compounds which differ by specific substitutions at
different points on the rings. As a group, tetracyclines are acidic
and hygroscopic compounds, which in aqueous solution form
salts with both acids and bases.
5. • Tetracyclines are generally classified according to their duration
of action.
I. Short-acting tetracyclines (t1/2 = <8 hours)
e.g. oxytetracycline, tetracycline and chlortetracycline,
II. Intermediate acting tetracyclines (t1/2 = 8-16 hours)
e.g. demeclocycline and metacycline.
III. Long-acting tetracyclines (t1/2 = >16 hours)
e.g. doxycycline, minocycline and tigecycline.
Classification
6. Mechanism of Action
• Tetracyclines inhibit bacterial protein synthesis and are primarily
bacteriostatic.
• The action of tetracyclines can be divided Into two processes-
– Passage of tetracyclines into bacterial cell
– Interaction of tetracyclines with bacterial ribosomes.
7. • Passage of tetracyclines into bacterial cell:
• Tetracyclines enter gram-negative bacteria by two transport
mechanism- in part by a passive process and in part by an
active process. The first is passive diffusion through the
hydrophilic channels formed by the porin proteins in outer
cell membrane. The more lipid soluble membrane (e.
doxycyline and minocycline) pass directly through the lipid
bilayer by passive diffusion
• The second mechanism involves an energy dependent active
transport system that pump all tetracyclines across
cytoplasmic membrane although passage of tetracycline in to
gram-positive bacteria is less well understood it requires an
energy dependent carrier transport mechanism.
8. • Interaction of tetracyclines with bacterial ribosomes:
• Once the tetracyclines gain access to bacterial cell, they bind
to the 30S ribosomal subunit. They prevent binding/ access
of aminoacyl t-RNA to the acceptor (A) site on the m-RNA-
ribosom complex. This prevents addition of amino acid to
growing peptide chain resulting in inhibition of protein
synthesis .
9. • Tetracyclines are highly effective against multiplying
microorganisms and are more active at pH 6-6.5.
• Effects of tetracyclines are mostly reversible as the bacterial
protein synthesis is restored when the drug is removed.
Although the tetracyclines are primarily bacteriostatic, at high
concentrations (e.g. in urine) they tend to become bactericidal
because at high concentrations they appear to affect the
functional integrity of bacterial cell membranes as well.
Moreover, the mammalian protein synthesising apparatus is
less sensitive to tetracyclines.
10. Fig. 1: Bacterial protein synthesis and the site of action of antibiotics
11. Pharmakinetics
• Absorption: The oral absorption of tetracyclines is variable
with older drugs (e.g. chlortetracycline) being less
bioavailable and newer lipid soluble tetracyclines (e.g.
minocycline and (loxycycline) being 100% bioavailable.
Absorption of tetracyclines From GI tract is decreased in
presence of polyvalent cations (e.g. Ca++ Mg++ and Fe+++)
which are present in food, and milk and milk products.
• All tetracyclines produce varying degree of tissue irritation
on parenteral administration, especially chlortetracycline.
'Therefore for parenteral administration, buffered solutions
are prepared. Procaine is added to tetracyclines solution for
IM administration in case of small animals.
12. Distribution
• Tetracyclines bind to plasma proteins to varying degrees and
are widely distributed in most tissues including kidneys, liver,
lungs, bile and bones. However, with exception of lipid soluble
members (e.g. doxycycline and minocycline), tetracyclines do
not penetrate the brain and CSF.
• Tetracyclines are stored in the reticuloendothelial cells of liver,
spleen and bone marrow. They are also incorporated into
forming bone and enamel and dentine of unerupted teeth
possibly because of their binding action with Ca++.
Tetracyclines cross the placenta and enter foetal circulation
and amniotic fluid.
13. Biotransformation and excretion:
• With exception of lipid soluble tetracyclines, the tetracycline
antibiotics are not metabolised to a significant extent in the
body. Most tetracyclines are excreted in urine (60%) via
glomerular filtration pathway and in faeces (40%) via biliary
excretion. Tetracyclines undergo enterohepatic circulation,
which may affect their duration of action.
14. Side Effects/Adverse Effects
• The tetracyclines have a relatively low toxicity at normal
dosage levels. However, a number of side effects have been
associated with tetracyclines. Side effects may be worsened
in animals with renal disease due to decreased elimination
of the drug.
15. Gastrointestinal upsets
• All tetracyclines produce GI irritation to varying degree in
some patients, particularly after oral administration. Anorexia,
abdominal pain, diarrhoea, nausea and vomiting in small
animals may occur.
• Superinfection by non-susceptible pathogens such as fungi,
yeast and resistant bacteria is a possibility, which if occurs may
lead to disturbances in the intestinal function with candidiasis,
enterocolitis or pseudomembranous colitis.
• The oral administration of tetracyclines may lead to fatal
diarrhoea in horses and indigestion due to deleterious effect
on rumen microbes in ruminants.
16. Effect on bones/teeth
• Tetracyclines are deposited in growing teeth and bones due
to their chelating properties with calcium. They form
tetracycline-calcium orthophosphate complex, which inhibits
calcification (e.g. hypoplastic dental enamel) and results in
permanent discolouration (first yellowish then brownish) of
the teeth.
• The stained and hypoplastic teeth are more prone to various
degenerations. High concentrations of tetracyclines can
interfere with the calcium deposition in bones and delay
fracture healing. Given during pregnancy or in neonates,
tetracyclines may cause temporary suppression of bone
growth.
17. • Hepatotoxicity:
Tetracyclines in excessive doses can produce fatty
infiltration of liver. Hepatotoxicity with jaundice due to
large doses of tetracyclines has been reported in pregnant
women and in some animals.
• Nephrotoxicity:
Tetracyclines are potentially nephrotoxic, particularly in
renal insufficiency. They may impair urinary concentrating
ability in patients even with normal renal function.
The administration of expired tetracycline products may
lead to b acute tubular nephrosis in animals. The
inhibition of mammalian protein synthesis has catabolic
effect resulting in increase in the blood urea nitrogen
(BUN).
18. • Hypersensitivity reactions:
Hypersensitivity reactions are not common with tetracyclines.
Rarely, they may produce skin rashes, urticaria, pruritus and
exfoliattve dermatitis. Angioedema and anaphylaxis are
extremely rare. Compelete cross-sensitisation is exhibited by
tetracyclines. Minocycline may be more likely to cause allergic
drug reactions.
• Cardiovascular effects:
The rapid intravenous administration of tetracyclines may
result in hypotension, collapse and sudden death in animals.
This has been related to rapid chelation of blood calcium,
although a depressant effect by propylene glycol carrier itself
may also be involved. Pre-treatment with calcium
borogluconate and slow rate of IV infusion prevent these
unwanted effects.
19. • Other effects:
• Tetracyclines cause irritation on parenteral administration.
Swelling, necrosis and yellow discolouration usually occur at
injection site.
• The tetracyclines inhibit WBC chemotaxis and phagocytosis
at injection sites, particularly when present in high
concentrations.
• Tetracyclines may prolong blood coagulation either directly
by chelating calcium or indirectly by depressing prothrombin
synthesis due to depression of vitamin K by bacterial flora.
• Other adverse effects caused by tetracyclines include drug
fever in cats, photoallergic dermatitis in humans and
antianabolic effect in many species.
20. Clinical Uses
• Although tetracyclines are broad-spectrum antibiotics, they
should be employed only for those infections for which a
more selective and less toxic AMA is not available. Clinical
use of tetracyclines has very much declined due to
availability of fluoroquinolones and other efficacious AMAs.
21. 1.Empirical therapy
• Tetracyclines are often employed when the nature and
sensitivity of the infecting organism cannot be reasonably
guessed, but they are not dependable for empirical
treatment of serious/life-threatening infections.
• They may also be used for initial treatment of mixed
infections, although a combination of β-lactam and an
aminoglycoside antibiotic or a third generation
cephalosporin or a fluoroquinolone are now preferred.
22. 2. Tetracyclines are the first choice drugs:
despite development of resistance by many organisms in:
(a) Venereal diseases:
• Chlamydial nonspecific urethritis/endocervicitis:
7 day doxycycline treatment is as effective as azithromycin
single dose.
• Lymphogranuloma venereum: resolves in 2–3 weeks.
• Granuloma inguinale: due to Calymm. granulomatis: a
tetracycline administered for 3 weeks is the most effective
treatment.
24. 4. Other situations in which tetracyclines may be used are:
(a) Urinary tract infections:
(b) Community-acquired pneumonia, when a more selective
antibiotic cannot be used.
(c) Amoebiasis:.
(d) As adjuvant to quinine or sulfadoxinepyrimethamine for
chloroquine-resistant P. falciparum malaria .
(e) Acne vulgaris:
(f) Chronic obstructive lung disease:
25. Contraindications and Precautions
• Tetracyclines are contraindicated in hepatic insufficiency,
renal diseases and in patients those are hypersensitive to
them.
• Oral administration of tetracyclines to ruminants and horses
is not recommended because they inhibit the normal
bacterial fermentation of plant fibres. They should not be
used in the last 2-3 months of gestation in pregnant animals
and up to 4 weeks in neonates.
26. • Tetracycline preparations should never be used beyond their
expiry date because they cause damage to the proximal
renal tubule due to the formation of a degradation product,
anhydro-4-epitetracycline causing `Fanconi syndrome'.
• In Fanconi syndrome glucose, amino acids, uric acid,
phosphate and bicarbonate are passed into the urine,
instead of being reabsorbed.
27. • Tetracyclines should never be administered with food, milk
and milk products because they bind with food particles and
also easily with magnesium, aluminium, iron and calcium in
food and milk products thereby forming insoluble
complexes, which reduce the absorption ability of
tetracyclin. Therefor oral tetracyclines are generally given at
least 1-2 hours before or after food and milk or any cation
containing product.
• Partial exceptions to these rules occur for doxycycline and
minocycline, which may be taken with food (though not iron,
antacids, or calcium supplements).
• Tetracyclines should not be given intrathecally.
28. AMPHENICOLS
• Amphenicols are a group of broad spectrum bacteriostatic
drugs which function by blocking protien synthesis of
suceptible bacteria.
• These drugs are structurally related and belong to the class
of antibiotics with a phenylpropanoid structure.
• Amphenicols includes chloramphenicol the parent compund
and its congeners thiamphenicol, florfenicol and
azidamfenicols.
29. CHLORAMPHENICOL
• Chloramphenicol was initially obtained from Streptomyces
venezuelae in 1947. It was soon synthesized chemically and the
commercial product now is all synthetic.
• It is a yellowish white crystalline solid, aqueous solution is quite
stable, stands boiling, but needs protection from light.
• It has a nitrobenzene substitution, which is probably
responsible for the antibacterial activity and its intensely bitter
taste.
30. Mechanism of action Chloramphenicol
• Inhibits bacterial protein synthesis by interferring with
‘transfer’ of the elongating peptide chain to the newly
attached aminoacyl-tRNA at the ribosome-mRNA complex.
• It specifically attaches to the 50S ribosome and thus may
hinder the access of aminoacyl-tRNA to the acceptor site for
amino acid incorporation.
• Probably by acting as a peptide analogue, it prevents
formation of peptide bonds.
• At high doses, it can inhibit mammalian mitochondrial
protein synthesis as well. Bone marrow cells are especially
susceptible.
31. Fig. 1: Bacterial protein synthesis and the site of action of antibiotics
32. Antimicrobial spectrum
• Chloramphenicol is primarily bacteriostatic, though high
concentrations have been shown to exert bacteriocidal
effect on some bacteria. It is a broad-spectrum antibiotic,
active against nearly the same range of organisms (gram-
positive and negative bacteria, rickettsiae, mycoplasma) as
tetracyclines
33. Adverse effects
1. Bone marrow depression of all drugs, chloramphenicol is the
most important cause of aplastic anaemia, agranulocytosis,
thrombocytopenia or pancytopenia. Two forms are
recognized:
(a) Non-dose related idiosyncratic reaction: This is rare (1 in
40,000), unpredictable, but serious, often fatal, probably has
a genetic basis and is more common after repeated courses.
Aplastic anaemia is the most common manifestation.
Apparently, a longer latent period of onset of marrow
aplasia is associated with higher mortality. Many victims,
even if they survive, develop leukaemias later.
34. (b) Dose and duration of therapy related myelosuppression: a
direct toxic effect, predictable and probably due to inhibition
of mitochondrial enzyme synthesis. This is often reversible
without long-term sequelae. Liver and kidney disease
predisposes to such toxicity.
35. 2. Hypersensitivity reactions Rashes, fever, atrophicglossitis,
angioedema are infrequent.
3. Irritative effects Nausea, vomiting, diarrhoea, pain on
injection.
4. Superinfections These are similar to tetracyclines, but less
common.
36. 5. Gray baby syndrome
• It occurred when high doses (100 mg/kg) were given
prophylactically to neonates, especially premature. The baby
stopped feeding, vomited, became hypotonic and
hypothermic, abdomen distended, respiration became
irregular; an ashen gray cyanosis developed in many,
followed by cardiovascular collapse and death. Blood lactic
acid was raised. It occurs because of inability of the newborn
to adequately metabolize and excrete chloramphenicol.
• At higher concentration, chloramphenicol blocks electron
transport in the liver, myocardium and skeletal muscle,
resulting in the above symptoms. It should be avoided in
neonates, and even if given, dose should be 25 mg/kg/day.