This presentation describes epidemiology of tuberculosis, classification of anti-tubercular drugs based on the efficacy and priority and the pharmacology of the anti-tubercular drugs.
This presentation describes epidemiology of tuberculosis, classification of anti-tubercular drugs based on the efficacy and priority and the pharmacology of the anti-tubercular drugs.
Antitubercular antibiotics
Tuberculosis is caused by either mycobacterium tuberculosis (in Humans) or by mycobacterium bovis (in animals)
Tuberculosis is a disease of respiratory transmission.
A person gets infected when it comes in contact with the environmental contaminated with viable tubercle Bacilli.
This bacilli are expelled by coughing , sneezing , shouting and singing of a patient with active tuberculosis.
Tubercles are formed in the infected organs during the course of the disease , hence the disease is known as tuberculosis.
Main symptoms are :- cough, tachycardia ,respiratory failure, cynosis (Bluish or greyish colour of the skin, nails, lips or around the eyes.)
The agents or antibiotics which are used to treat tuberculosis these are known as the antitubercular antibiotics.
Drugs includes :-
Rifampicin , streptomycin , cycloserine , capreomycin sulfate and Refabutin
Rifampicine
Orally active bactericidal semi synthetic derivative of Rifamycin B.
This antibiotic is produced by the streptomyces Mediterranei.
It is the first line agent.
Mechanism of Action :-
DNA-dependent-RNA polymerase (DDRP) enzyme is required for the synthesis of RNA.
- Rifampicin binds to Beta subunit of enzyme DDRP and make it inactive.
- so it causes inhibition of bacterial RNA synthesis.
hence there is tuberculocidal effect
SAR
Free OH group is required at C-1, C-8, C-21, and C- 23 .
These group must be in one plane.
Opening of ring will destroy the activity of antibiotic.
Rifampicin is active against both Gram Negative and Gram Positive Bacteria.
resistance is developed when mutation occurs in beta subunit of DDRP.
bacterial resistance develop rapidly if rifampicin taken alone, though the combination with Isoniazid or ethambutol are preferable used.
Adverse effects :
Nausea, Vomiting, headache, erythema, nervousness, emotional disturbances , pulmonary edema, increased cardiac output and cardiac arrythmias
Anti Tubercular Drugs - Mechanism of Action and Adverse effects Thomas Kurian
A brief outline of the mechanism of action and adverse effects of anti tubercular drugs
Only First line and second line drugs are dealt with.First line drugs may be useful for MBBS students and the rest is directed for postgraduate students.
Hope you find it useful.
1. chemotherapy principles and problems JagirPatel3
The objective of chemotherapy is to study and to apply the drugs that have highly selective toxicity to the pathogenic microorganisms in the host body and have no or less toxicity to the host, so as to prevent and cure infective diseases caused by pathogens
TUBERCULOSIS AND ANTI-TUBERCULAR AGENTSN J V S Pavan
This presentation include every data related to TB and anti-TB drugs with neat and understandable picturization and tables..... pharma students are beneficial mostly
Antitubercular antibiotics
Tuberculosis is caused by either mycobacterium tuberculosis (in Humans) or by mycobacterium bovis (in animals)
Tuberculosis is a disease of respiratory transmission.
A person gets infected when it comes in contact with the environmental contaminated with viable tubercle Bacilli.
This bacilli are expelled by coughing , sneezing , shouting and singing of a patient with active tuberculosis.
Tubercles are formed in the infected organs during the course of the disease , hence the disease is known as tuberculosis.
Main symptoms are :- cough, tachycardia ,respiratory failure, cynosis (Bluish or greyish colour of the skin, nails, lips or around the eyes.)
The agents or antibiotics which are used to treat tuberculosis these are known as the antitubercular antibiotics.
Drugs includes :-
Rifampicin , streptomycin , cycloserine , capreomycin sulfate and Refabutin
Rifampicine
Orally active bactericidal semi synthetic derivative of Rifamycin B.
This antibiotic is produced by the streptomyces Mediterranei.
It is the first line agent.
Mechanism of Action :-
DNA-dependent-RNA polymerase (DDRP) enzyme is required for the synthesis of RNA.
- Rifampicin binds to Beta subunit of enzyme DDRP and make it inactive.
- so it causes inhibition of bacterial RNA synthesis.
hence there is tuberculocidal effect
SAR
Free OH group is required at C-1, C-8, C-21, and C- 23 .
These group must be in one plane.
Opening of ring will destroy the activity of antibiotic.
Rifampicin is active against both Gram Negative and Gram Positive Bacteria.
resistance is developed when mutation occurs in beta subunit of DDRP.
bacterial resistance develop rapidly if rifampicin taken alone, though the combination with Isoniazid or ethambutol are preferable used.
Adverse effects :
Nausea, Vomiting, headache, erythema, nervousness, emotional disturbances , pulmonary edema, increased cardiac output and cardiac arrythmias
Anti Tubercular Drugs - Mechanism of Action and Adverse effects Thomas Kurian
A brief outline of the mechanism of action and adverse effects of anti tubercular drugs
Only First line and second line drugs are dealt with.First line drugs may be useful for MBBS students and the rest is directed for postgraduate students.
Hope you find it useful.
1. chemotherapy principles and problems JagirPatel3
The objective of chemotherapy is to study and to apply the drugs that have highly selective toxicity to the pathogenic microorganisms in the host body and have no or less toxicity to the host, so as to prevent and cure infective diseases caused by pathogens
TUBERCULOSIS AND ANTI-TUBERCULAR AGENTSN J V S Pavan
This presentation include every data related to TB and anti-TB drugs with neat and understandable picturization and tables..... pharma students are beneficial mostly
Remote Sensing and Computational, Evolutionary, Supercomputing, and Intellige...University of Maribor
Slides from talk:
Aleš Zamuda: Remote Sensing and Computational, Evolutionary, Supercomputing, and Intelligent Systems.
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Inter-Society Networking Panel GRSS/MTT-S/CIS Panel Session: Promoting Connection and Cooperation
https://www.etran.rs/2024/en/home-english/
DERIVATION OF MODIFIED BERNOULLI EQUATION WITH VISCOUS EFFECTS AND TERMINAL V...Wasswaderrick3
In this book, we use conservation of energy techniques on a fluid element to derive the Modified Bernoulli equation of flow with viscous or friction effects. We derive the general equation of flow/ velocity and then from this we derive the Pouiselle flow equation, the transition flow equation and the turbulent flow equation. In the situations where there are no viscous effects , the equation reduces to the Bernoulli equation. From experimental results, we are able to include other terms in the Bernoulli equation. We also look at cases where pressure gradients exist. We use the Modified Bernoulli equation to derive equations of flow rate for pipes of different cross sectional areas connected together. We also extend our techniques of energy conservation to a sphere falling in a viscous medium under the effect of gravity. We demonstrate Stokes equation of terminal velocity and turbulent flow equation. We look at a way of calculating the time taken for a body to fall in a viscous medium. We also look at the general equation of terminal velocity.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
Phenomics assisted breeding in crop improvementIshaGoswami9
As the population is increasing and will reach about 9 billion upto 2050. Also due to climate change, it is difficult to meet the food requirement of such a large population. Facing the challenges presented by resource shortages, climate
change, and increasing global population, crop yield and quality need to be improved in a sustainable way over the coming decades. Genetic improvement by breeding is the best way to increase crop productivity. With the rapid progression of functional
genomics, an increasing number of crop genomes have been sequenced and dozens of genes influencing key agronomic traits have been identified. However, current genome sequence information has not been adequately exploited for understanding
the complex characteristics of multiple gene, owing to a lack of crop phenotypic data. Efficient, automatic, and accurate technologies and platforms that can capture phenotypic data that can
be linked to genomics information for crop improvement at all growth stages have become as important as genotyping. Thus,
high-throughput phenotyping has become the major bottleneck restricting crop breeding. Plant phenomics has been defined as the high-throughput, accurate acquisition and analysis of multi-dimensional phenotypes
during crop growing stages at the organism level, including the cell, tissue, organ, individual plant, plot, and field levels. With the rapid development of novel sensors, imaging technology,
and analysis methods, numerous infrastructure platforms have been developed for phenotyping.
Salas, V. (2024) "John of St. Thomas (Poinsot) on the Science of Sacred Theol...Studia Poinsotiana
I Introduction
II Subalternation and Theology
III Theology and Dogmatic Declarations
IV The Mixed Principles of Theology
V Virtual Revelation: The Unity of Theology
VI Theology as a Natural Science
VII Theology’s Certitude
VIII Conclusion
Notes
Bibliography
All the contents are fully attributable to the author, Doctor Victor Salas. Should you wish to get this text republished, get in touch with the author or the editorial committee of the Studia Poinsotiana. Insofar as possible, we will be happy to broker your contact.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
2. Introduction
• Tuberculosis - most important communicable
disease in the world.
• Mycobacteria are intrinsically resistant to most
antibiotics
– Grows more slowly than other bacteria – antibiotics
active against rapidly growing cells
– lipid-rich mycobacterial cell wall is impermeable to
many agents
– It grows inside macrophage – poorly penetrated by
drugs
– Excellent ability to develop resistance – Multiple Drug
Resistant (MDR)
3. Introduction
• Combinations of two or more drugs
– to overcome these obstacles
– to prevent emergence of resistance during the
course of therapy
• The response of mycobacterial infections to
chemotherapy is slow - treatment must be
administered for months to years, depending
on which drugs are used
4. Classification
• According to clinical utility the anti TB drugs
can be divided into 2 groups
– First Line : high antitubercular efficacy as well as
low toxicity – routinely used
• Isoniazid (H) , Rifampin (R), Pyrazinamide (Z),
Ethambutol (E), Streptomycin (S) - HRZES
– Second Line : low antitubercular efficacy or high
toxicity
• Paraminosalicylic Acid, Cycloserine, Kanamycin,
Amikacin, Ciprofloxacin, Olfloxacin, Clarithromycin,
Azithromycin
6. ISONIAZID
• Isonicotinic acid hydrazide
• Most active drug for the treatment
of tuberculosis
• freely soluble in water
• bactericidal for actively growing
tubercle bacilli
• less effective against atypical
mycobacterial
species
• penetrates into macrophages and is
active against
both extracellular and intracellular
organisms
7. Mechanism of Action &
Basis of Resistance
• inhibits synthesis of mycolic acids - essential
components of mycobacterial cell walls
• Higly selective for mycobacterium
• Resistance
– Its prodrug – activated by enzyme catalase-peroxidase
– Mutation causes inhibition of this enzyme
– No cross resistance occurs with other antitubercular
drug
– Always given in combination
8. Pharmacokinetics
• Readily absorbed from the gastrointestinal tract -
diffuses readily into all body fluids and tissues.
• acetylation by liver N -acetyltransferase, is
genetically determined
• half-lives :1 hour(fast acetylators) and 3 hours
(slow acetylators)
• Excreted, mainly in the urine - need not be
adjusted in renal failure
• Contraindicated - severe preexisting hepatic
insufficiency
9. Clinical Uses
• Typical dosage of isoniazid is 5 mg/kg/d – 10
mg/kg/d (sever infection) or 15 mg/kg dose –
twice weekly
• Adult dose : 300 mg oral dose O.D.
• Pyridoxine, 25–50 mg/d - predisposing to
neuropathy, an adverse effect of isoniazid
• Can also be given parenterally in the same dosage
• Latent tuberculosis : 300 mg/d (5 mg/kg/d)
or 900 mg twice weekly for 9 months
10. Adverse Reactions
• Depends on dosage and duration of administration
• Immunologic Reactions
– Fever and skin rashes are occasionally seen.
– Drug-induced systemic lupus erythematosus has been
reported.
• Direct Toxicity
– Clinical hepatitis with loss of appetite, nausea, vomiting,
jaundice – promptly discontinued
– The risk of hepatitis is greater in individuals
• Alcohol dependence
• Possibly during pregnancy and the postpartum period
11. Adverse Reactions : Direct
• Peripheral neuropathy is observed in 10–20% - occur in
slow acetylators and patients with predisposing
conditions
– malnutrition,
– alcoholism,
– diabetes,
– AIDS, and uremia
• Relative pyridoxine deficiency - promotes excretion of
pyridoxine
• readily reversed by administration of pyridoxine in a
dosage as low as 10 mg/d
• Central nervous system toxicity : less common, includes
memory loss, psychosis, and seizures.
12. RIFAMPIN
• Semisynthetic derivative of rifamycin -produced
by Streptomyces mediterranei
• Active in vitro against gram-positive and gram-
negative cocci, some enteric bacteria,
mycobacteria, and chlamydiae.
• Resistant mutants - approximately 1 in 106
organisms
• Rapidly selected out if rifampin is used as a single
drug – must be used in combination
• no cross-resistance to other classes of
antimicrobial drugs
13. Mechanism of Action & Resistance
• Binds to the bacterial DNA-dependent RNA
polymerase - inhibits RNA synthesis
• Bactericidal for mycobacteria
• Readily penetrates most tissues and penetrates into
phagocytic cells
• Can kill organisms that are poorly accessible to many
other drugs
– Intracellular organisms
– sequestered in abscesses and lung cavities
• Resistance: mutations result in reduced binding of
rifampin to RNA polymerase
14. Pharmacokinetics
• Well absorbed after oral administration and
excreted mainly through the liver into bile
• Enterohepatic recirculation - bulk excreted as a
deacylated metabolite in feces and a small
amount excreted in the urine
• Dosage adjustment for renal or hepatic
insufficiency is not necessary.
• Distributed widely in body fluids and tissues.
• Relatively highly protein bound
15. Clinical Uses
• 10 mg/kg/d O.D. for 6 months in combination
with isoniazid or other antituberculous drugs to
patient.
• Some atypical mycobacterial infections and in
leprosy
• 600 mg twice daily for 2 days can eliminate
meningococcal carriage
• 20 mg/kg/d for 4 days - prophylaxis in contacts of
children with Haemophilus influenzae type b
disease
• Serious staphylococcal infections - osteomyelitis
and prosthetic valve endocarditis
16. Adverse Reactions
• harmless orange color to urine, sweat, and
tears
• Occasional adverse effects include
– rashes, thrombocytopenia, and nephritis
– cholestatic jaundice and occasionally hepatitis
– light-chain proteinuria
– flu-like syndrome characterized by fever, chills,
myalgias, anemia, and thrombocytopenia
17. Adverse Reactions
• Induces most cytochrome P450 isoform -
elimination of numerous other drugs
• Methadone,
• Anticoagulants,
• Cyclosporine,
• Some anticonvulsants,
• Protease inhibitors,
• some nonnucleoside reverse transcriptase inhibitors
• contraceptives,
• And a host of others
18. ETHAMBUTOL
• Synthetic, water-soluble, heat-stable
compound - dispensed as the dihydrochloride
salt
• Bacteriostatic
• Additionally it slows the rate of sputum
conversion
• Development of resistance
• Given in the combination with RHZ
19. Mechanism of action
• Inhibits mycobacterial arabinosyl transferases
an essential component of the mycobacterial
cell wall.
• Resistance : Due to alteration in target gene
• No cross resistance with other drug
• Resistance to ethambutol emerges rapidly
when the drug is used alone - combination
with other antituberculous drugs
20. Pharmacokinetics
• well absorbed from the gut
• 20% of the drug is excreted in feces and 50%
in urine in unchanged form
• crosses the blood-brain barrier only when the
meninges are inflamed
• Temporarily stored in RBC
• T ½ - 4 hrs
• Caution taken for renal failure patient
21. Clinical Use
• Ethambutol hydrochloride - 15–25 mg/kg/d
O.D
• higher dose is recommended for treatment of
tuberculous meningitis
• 50 mg/kg when a twice-weekly dosing
schedule
22. Adverse Reactions
• Retrobulbar neuritis - 25 mg/kg/d continued
for several months.
– loss of visual acuity and red-green color blindness.
– 15 mg/kg/d or less, visual disturbances are
very rare
• Contraindicated in children too young to
permit assessment of visual acuity and red
green color discrimination
23. PYRAZINAMIDE
• Relative of nicotinamide
• Stable and slightly soluble
in water but week drug
• Inactive at neutral pH, but
at pH 5.5 it inhibits tubercle
bacilli
• Taken up by macrophages
and exerts its activity
• Highly effective during the
first 2 month of therapy
24. Mechanism of Action
• Pyrazinamide is converted to pyrazinoic acid
(active form) - by mycobacterial
pyrazinamidase.
• Disrupts mycobacterial cell membrane
metabolism and transport functions
• Resistance
– impaired uptake of pyrazinamide
– mutations of enzyme causing conversion of
pyrazinamide to its active form
25. Pharmacokinetis
• well absorbed from the gastrointestinal tract
• widely distributed in body tissues, including
inflamed meninges
• half-life is 8–11 hours
• Metabolized by the liver
• Metabolites are renally
• no cross-resistance
26. Clinical Use
• Used as front line drug for tuberculosis with
rifampin and isoniazid
• Normal Dose: 40–50 mg/kg thrice weekly or
twice-weekly treatment regimens for 6
months
• Hemodialysis patients & creatinine clearance
less than 30 mL/min : 25–35 mg/kg three
times weekly (not daily)
27. Adverse Effect
• Hepatotoxicity : (in1–5% of patients) –
less common in Indian population
• Nausea, vomiting, drug fever, and
hyperuricemia.
– occurs uniformly – drug therapy should be not
stopped
• Contraindicated in liver disease patient
28. Streptomycin
• Part of aminoglycosides antibiotic
• First clinically useful antitubercular drug, but
less effective than INH or rifampin
• Acts only on extracellular bacilli – poor
penetration into cells
• Doesn’t cross the BBB, but penetrates
tubercular cavities
29. Mechanism of action
• Irreversible inhibitors of protein synthesis,
• Bactericidal
• Inside the cell, aminoglycosides bind to specific
30S-subunit ribosomal proteins and inhibits
protein synthesis
• Resistance
– Inactivation by adenylylation, acetylation, or
phosphorylation
– impaired entry into the cell
– receptor protein on the 30S ribosomal subunit -
deleted or altered as a result of a mutation
30. Pharmacokinetics
• absorbed very poorly from the intact
gastrointestinal tract
• intramuscular injection or usually
administered intravenously as a 30- to 60-
minute infusion
• Normal half-life - 2–3 hours, but in renal
failure patient it reduces to 24-48 hrs
31. Clinical Use
• Treatment of infections resistant to other drugs
• Adults: 20–40 mg/kg/d daily for several weeks
– Followed by 1–1.5 g two or three times weekly for
several months
• Other drugs are always given in combination to
prevent emergence of resistance
• Nontuberculosis species of mycobacteria other
than Mycobacterium avium complex (MAC)
and Mycobacterium kansasii are resistant
• Dose is reduced to half in hemodialysis patient
32. Adverse Reactions
• Ototoxic and nephrotoxic
• Vertigo and hearing loss - common adverse
effects and may be permanent
• Dose-related, and the risk is increased in the
elderly
• Therapy should be limited - no more than 6
months whenever possible
34. Second Line Drugs
• This drugs are considered only when
– resistance to first-line agents
– failure of clinical response to conventional therapy;
– Serious treatment-limiting adverse drug reactions
• Expert guidance to deal with the toxic effects is
required
• Ex: Paraminosalicylic Acid, Cycloserine,
Kanamycin, Amikacin, Ciprofloxacin, Olfloxacin,
Clarithromycin, Azithromycin
35. Para-aminosalicyclic Acid
– structural analogue of paminobenzoic acid (PABA)
–highly specific for M. tuberculosis - not effective
against other mycobacterium species
–Combined with isoniazid - an alternative substrate
and block hepatic acetylation of isoniazid- increasing
free isoniazid levels.
– limited to the treatment of MDR tuberculosis
–Discouraged its use : primary resistance, poor
compliance due to GI intolerance, and lupus like
reactions
36. Ethionamide
• Chemically related to isoniazid
• Blocks the synthesis of mycolic acids
• Poorly water soluble and available only in oral
form.
• Dosage of 15 mg/kg/d - initial dose of 250 mg
once daily, which is increased in 250-mg
increments to the recommended dosage
• Intense gastric irritation and neurologic
symptoms as well as hepatotoxic
37. Capreomycin
• peptide protein synthesis inhibitor antibiotic
obtained from Streptomyces capreolus
• Daily injection of 15 mg/kg/d intramuscularly
• treatment of drug-resistant tuberculosis
• Strains of M tuberculosis that are resistant to
streptomycin or amikacin - susceptible to
capreomycin.
• Nephrotoxic and ototoxic - Tinnitus, deafness,
and vestibular disturbances occur
• local pain, and sterile abscesses may occur
38. Cycloserine
• inhibitor of cell wall synthesis
• 0.5–1 g/d in two divided oral doses
• Cleared renally - Dose is reduced to half in
case of renal dysfunction
• peripheral neuropathy and central nervous
system dysfunction, including depression and
psychotic reactions.
• Pyridoxine, 150 mg/d given in addition to it
39. Kanamycin & Amikacin
• Treatment of tuberculosis suspected or known to be
caused by streptomycin-resistant or multidrug-
resistant strains
• Kanamycin is more toxic comparatively – absolute
• Prevalence of amikacin-resistant strains is low (< 5%)
• Also active against atypical mycobacteria.
• 15 mg/kg intravenous infusion
• No cross-resistance between streptomycin and
amikacin but it occurs with kanamycin
• used in combination with at least one and preferably
two or three other drugs
40. Fluoroquinolones
• In addition to their activity against many
gram-positive and gram-negative bacteria
inhibit strains of M. tuberculosis
• Also active against atypical mycobacteria
• Standard dosage
– Ciprofloxacin: 750 mg orally twice a day
– Levofloxacin: 500–750 mg once a day
– Moxifloxacin: 400 mg once a day
41. Revised National Tuberculosis Control
Programme (RNTCP 1997) Guidelines-
India
TB
category
Type of TB Initial phase Continuation
Phase
Total
duration
I New, untreated TB 2H3R3Z3E3 4H3R3 6
II Smear positive failure,
relapse and interrupted
treatment cases
2H3R3Z3E3S3-
1H3R3Z3E3
5H3R3E3 8
III Less severe form extra-
pulmonary TB – smear
negative
2H3R3Z3 4H3R3 6
* Numeral before a phase is duration in months
# Sub-script numbers – does per week
Followed Under DOTS - Directly Observed Treatment