Sirturo (bedaquiline) is a new drug approved by the FDA in 2012 for the treatment of multi-drug resistant tuberculosis. It works by inhibiting mycobacterial ATP synthase, which is essential for energy generation in tuberculosis bacteria. Sirturo represents the first new class of tuberculosis drugs approved in over 40 years. It is meant to be used as part of a combination therapy for drug-resistant tuberculosis when alternative treatment options are limited.
This ppt gives you idea about pathophysiology of tuberculosis and the pharmacology of drugs used to treat this infection. And it also give deep introduction of molecular interaction of mycobacteria with body i.e.. immune response by human to this mycobacteria.
it also gives you idea about treatment regimens and strategy for TB. discussed the different types of TB and mechanism of development of resistance by mycobacteria for anti-TB drugs.
complete information of tuberculosis including OLD RNTCP and new RNTCP with the novel drug that is marketed; classification of tuberculosis (MDR XDR TDR). special population and tuberculosis treatment clinical presentation and diagnosis
The following presentation is only for quick reference. I would advise you to read the theoretical aspects of the respective topic and then use this presentation for your last minute revision. I hope it helps you..!!
Mayur D. Chauhan
Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. Tuberculosis generally affects the lungs, but can also affect other parts of the body
This ppt gives you idea about pathophysiology of tuberculosis and the pharmacology of drugs used to treat this infection. And it also give deep introduction of molecular interaction of mycobacteria with body i.e.. immune response by human to this mycobacteria.
it also gives you idea about treatment regimens and strategy for TB. discussed the different types of TB and mechanism of development of resistance by mycobacteria for anti-TB drugs.
complete information of tuberculosis including OLD RNTCP and new RNTCP with the novel drug that is marketed; classification of tuberculosis (MDR XDR TDR). special population and tuberculosis treatment clinical presentation and diagnosis
The following presentation is only for quick reference. I would advise you to read the theoretical aspects of the respective topic and then use this presentation for your last minute revision. I hope it helps you..!!
Mayur D. Chauhan
Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. Tuberculosis generally affects the lungs, but can also affect other parts of the body
This presentation includes introduction, properties, transmission, epidemiology, pathogenesis, mechanism of infection, immunity and hypersensitivity, clinical manifestations, diagnosis, treatment, prevention and control of MYCOBACTERIUM TUBERCULOSIS.
Mycobacterium tuberculosis-importance of TB day,classification of Mycobacterium species,Details on Mycobacterium tuberculosis-morphology,culture,resistance,biochemical reactions,antigenic characters,mode of transmission,pathogenesis,complications,lab diagnosis,treatment,DOTS Strategy and prophylaxis
Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. Over 190 species are recognized in this genus. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis (Mycobacterium tuberculosis) and leprosy (Mycobacterium leprae) in humans.
This presentation includes introduction, properties, transmission, epidemiology, pathogenesis, mechanism of infection, immunity and hypersensitivity, clinical manifestations, diagnosis, treatment, prevention and control of MYCOBACTERIUM TUBERCULOSIS.
Mycobacterium tuberculosis-importance of TB day,classification of Mycobacterium species,Details on Mycobacterium tuberculosis-morphology,culture,resistance,biochemical reactions,antigenic characters,mode of transmission,pathogenesis,complications,lab diagnosis,treatment,DOTS Strategy and prophylaxis
Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. Over 190 species are recognized in this genus. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis (Mycobacterium tuberculosis) and leprosy (Mycobacterium leprae) in humans.
• Tuberculosis (TB) is an infectious disease usually caused by the bacterium Mycobacterium tuberculosis (MTB).
• Tuberculosis generally affects the lungs, but can also affect other parts of the body.
• Most infections do not have symptoms, in which case it is known as latent tuberculosis. About 10% of latent infections progress to active disease, which, if left untreated, kills about half of those infected.
• The classic symptoms of active TB are a chronic cough with blood-containing sputum, fever, night sweats, and weight loss.
• The historical term "consumption" came about due to the weight loss. Infection of other organs can cause a wide range of symptoms.
• Tuberculosis is spread through the air when people who have active TB in their lungs cough, spit, speak, or sneeze. People with latent TB do not spread the disease. Active infection occurs more often in people with HIV/AIDS and in those who smoke.
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New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
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This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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
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Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...
Management of multi drug resistant tuberculosis
1. Management of Multi-Drug Resistant
Tuberculosis with SIRTURO(Bedaquiline)
Mrs. Priyanka Namdeo
Assistant Professor
Department of Pharmacology
2. CONTENTS
Introduction of TB
Definitions
Pathophysiology of Tuberculosis
Diagnosis
Management of TB
What is SIRTURO
Mechanism of Action
SIRTURO Treatment
3. INTRODUCTION
(Robert Koch) Discovered of Mycobacterium tuberculosis in 1885.
24th March TB Day
Discovery of staining technique that identified Tuberculosis bacillus
Tuberculosis is called TB is chronic bacterial infection caused by
M. tuberculosis/ M. bovis
It contains unusual cell wall. The cell wall has a high lipid content, resulting high
degree of hydrophobicity and resistance to alcohol, acids, alkalies and some
disinfectants.
4. This organism usually attacks or affects almost any tissue and also affect the
CNS (meningitis), Circulatory System, Genito-urinary system, Bones, joints.
It is characterized by the formation of nodular bodies or tubercles.
Cough lasting > 3 wks and not respond to usual antibiotics, Production of purulent,
sometimes blood- stained sputum, Evening rise of temp.
It is one of the most deadly and common major infectious disease today, more than 2
billion people have been suffering the world’s population
1000 people have been dieing daily in India by TB.
5. Definitions
Multidrug-Resistant Tuberculosis (MDR TB)
Multidrug-resistant TB (MDR TB) is TB that
is resistant
Isoniazid and Rifampicin
These drugs are considered first-line drugs and
are used to treat all persons with TB disease
6. Mode of Transmission
TB spread person to person through the air. Throat cough, laugh, sneeze, even
talk the germs that cause TB may be spread into the air, if another person
breaths in these germs there is a chance that they will be come infected with TB.
Symptoms of TB
Unproductive cough, Difficulty breathing
Feeling tired all time.
Weight loss, loss of appetite, Night time sweating.
Fever, Blood in cough
Fatigue, night sweats, constant tiredness
Transmission of TB
7. Chest x-ray examination reveals
changes like pleural effusion (increase
volume of pleural space), diffuse
infiltrates in lung parenchyma.
Untreated cases may show systemic
secondary amyloidosis ( infiltration of
liver, kidneys, spleen and other tissues
with amyloid.
8. PATHOPHYSIOLOGY
MTBC (M. tuberculosis complex)
M. bovis, M. africanum, M. microti
Rod shaped, aerobic bacterium
mycobacterium tuberculosis
Acid fast bacilli
Cell wall is lipid rich with mycolic
acid which is essential & unique
component
Mycobacterium tuberculosis
9. Pathogenesis of TB
M. Tuberculosis enter the Macrophages
Once inside the macrophage, M Tuberculosis replicate within the
phagosome by blocking fusion of the phagosome and lysosome.
Thus the earliest stage of primary tuberculosis (< 3 weeks ) in the
nonsesitized individual is characterized by proliferation of bacteria in the
pulmonary alveolar macrophage and airspaces, with resulting bacteremia
and seeding of multiple sites.
10. 3
1
2
4
Tubercle bacilli multiply
in the alveoli.
A small number of
tubercle bacilli enter the
bloodstream and spread
throughout the body.
The tubercle bacilli may
reach any part of the body
including areas where TB
disease is more likely to
develop (such as Brain,
larynx, lymph node, lung,
spine, bone, or kidney).
Within 2 to 8 weeks,
special immune cells
called Macrophages
ingest and surround
the tubercle bacilli
The cells form a
barrier shell, called
a Granuloma, that
keeps the bacilli
contained and under
control (LTBI).
If the immune system
cannot keep the tubercle
bacilli under control, the
bacilli begin to multiply
rapidly (TB disease).
This process can occur
in different areas in the
body, such as the lungs,
kidneys, brain, or bone
12. DIAGNOSIS
Conventional Methods- Microscopy examination, Chest X-rays,
Culturing using Lowenstein- Jensen medium
Immunological Methods- ELISA
Tuberculin skin test (TST) or blood tests
Interferon Gamma Determination
Novel Diagnostic Methods-
Automated BACTEC MGIT
Multiplex PCR
AMTD
13. MANAGEMENT OF TB
TB involves screening those at high risk, early detection and treatment of cases and
vaccination with the bacillus Calmette- Guerin vaccine. Those at high risk
include household, workplace, and social contacts of people with active TB. Type of
T. B. Pulmonary Tuberculosis Extra pulmonary Tuberculosis.
Anti-tubercular drugs are the agents which are used to treatment of tuberculosis.
In 1938, Sulphanilamide was discovered and was found to possess bacteriostatic
action.
Later Dapsone was developed, Although dapsone was effective it was not
considered for clinical use because it associated with toxicity.
14. Streptomycin, PASA, Isoniazid, Ethambutol, Rifampicin
The discovery of Rifampicin was a major break through in the treatment of Tuberculosis.
This is because combination of Isoniazid, Ethambutol and Rifampicin required
Comparatively less time for producing effective results than the individual drugs Used alone.
The Three drugs have acquired prime importance in the treatment of tuberculosis.
Drug-resistant TB disease can develop in two different ways, called
HIV infection is the greatest for the development of TB disease in persons with
LTBI, due to a weakened immune system.
15. First line drugs: kill active
bacteria, important in the
early stages of infection.
Second line drugs: hinder
bacterial growth.
- Strengthen treatment
- Less efficient and
generally more toxic than
first line drugs.
16. Antitubercular drugs are also classified on the basis of Chemical
moiety as:-
1. Salicylic acid derivatives: Para amino salicylic acid
2.Pyridine derivatives: Isoniazid (Isonicotinic acid hydrazine) ,Ethionamide,
Prothionamide
3. Pyrazine derivatives: Pyrazinamide
4. Ethylene diaminobutanol derivatives: Ethambutol
5. Antibiotics: Streptomycin, Refampin (Refampicin), Kanamcin
6. Miscellaneous drugs: Fluoroquinolones: Ofloxacin ,Ciprofloxacin, Macrolides,
Clarithromycin, Azithromycin
17. ISONIAZID-
Isoniazid, is an antibiotic used as a first-line agent for the prevention and treatment of both
latent and active tuberculosis.
It is effective against mycobacteria, particularly Mycobacterium tuberculosis.
Mechanism ofAction-
Isoniazid is a prodrug and must be activated by a bacterial catalase-peroxidase enzyme in
Mycobacterium tuberculosis called KatG
Appears to penetrate host cells readily and diffuses across the cell membrane.
Reported to inhibit multiple essential cellular pathways including synthesis of nucleic acids,
phospholipids & NAD metabolism
Primary pathway responsible for the killing activity is inhibition of mycolic acid synthesis by
inhibiting NADH dependent enoyl-ACP reductase, which is encoded by inhA.
18.
19. PHARMACOKINETICS
Absorption
Rapid and complete, rate can be slowed with food
Peak Plasma Time: 1-2 hr Distribution
Distribution
All body tissues and fluid including to CSF, Crosses placenta, enters breast milk
Protein bound: 10-15%
Metabolism
Hepatic ( fast, slow acetylators)
Elimination
Half life elimination: slow acetylators 2-5 hr, may be prolonged with hepatic or severe renal
impairment
Excretion: Urine (75-95%), feces
20. Contraindications
Previous INH hepatic injury or reaction, acute liver damage
Hypersensitivity
Cautions
Alcohol or illicit injectable drug use, severe renal impairment, chronic liver damage
Drug Interactions
INH can increase CBZ concentrations and cause CBZ toxicity. This interaction occurs more often
with INH doses at >/=200 mg/day
INH and ethionamide may cause a temporary increase in serum concentrations of INH.
, decrease the absorption of INH by a reducing gastric emptying.Administration of
antacids is recommended.
INH may inhibit valproic acid hepatic metabolism. Elevated valproic acid concentrations and
hepatotoxicity.
21. RIFAMPICIN
Rifampin is a semisynthetic derivative of rifamycin, an antibiotic produced by
Streptomyces mediterranei
It is active against gram positive and gram negative cocci, some enteric bacteria mycobacteria
and chlamydia
Mechanism of Action
Rifampin binds to the β subunit of bacterial DNA–dependent RNA polymerase, the direct
blocking of Elomgating RNA and thereby inhibits RNA synthesis. Resistance results from any
one of several possible point mutations in repoB, the gene for the β subunit of RNA
polymerase.
22. Absorption
Orally well absorbed, food may delay absorption
Peak plasma time: 2-4 hr Distribution
Distribution
Highly lipophilic, crosses blood-brain barrier well with or without inflammation
Protein bound: 80%
Metabolism
Metabolized by liver, undergoes enterohepatic recirculation
Elimination
Half-life: 3-4 hr (prolonged in hepatic impairment), in end-stage renal disease.
Excretion
Feces (60-65%) and urine (~30%) as unchanged drug
PHARMACOKINETICS
23. Contraindications and Cautions
Hypersensitivity to rifamycins
Administration of bacterial vaccines
Contraindicated in patients receiving ritonavir-boosted saquinavir, because of increased risk of severe
hepatocellular toxicity
Precautions
May decrease the effectiveness of oral contraceptive pills (OCPs)
Discontinue therapy if patient develops any signs of hepatocellular damage, including
hyperbilirubinemia
Drug Interactions
Drugs that induce hepatic microsomal enzymes, particularly those drugs that increase CYP2C9 or
CYP2C19 metabolism, can accelerate phenytoin clearance, reduce the plasma concentrations and also
possibly the efficacy of phenobarbital.
24. SIRTURO
Sirturo (bedaquiline) has been approved by the FDA on Dec 2012, as part of
combination therapy for adults with multi-drug resistant tuberculosis. This is the
first TB medication to be approved, the FDA informed.
25. What is sirturo?
Also known Bidaquiline or TMC207
Is an diarylquinoline anti-tuberculosis drug.
It was described for the first time in 2004 at the
Interscience Conference on Antimicrobial Agents
and Chemotherapy (ICAAC).
Sirturo is used in combination with other
tuberculosis medicines in adults and children (aged
at least 5 years and weighing at least 15 kg).
Sirturo is the first medicine specifically designed for
treating Multi-drug-resistant tuberculosis
26. By inhibiting mycobacterial
adenosine 5-triphosphate
(ATP) synthase
Inhibiting the proton pump of
M. tuberculosis and
therefore interfering with the
rotation properties of the
transmembrane disk, leading
to ATP depletion.
MACHANISM OF
ACTION
27. SIRTURO TREAETMENT
SIRTURO was administered as 400 mg once daily for the first two weeks and
200 mg three times per week for the following 22 weeks
The FDA looked at two Phase 2 clinical trials to determine Sirturos safety and
efficacy. In the first trial, patients were randomly selected to be treated with Sirturo
along side other TB medications.
In the second trial patients received Sirturo plus other TB medications.
In both studies, the aim was to determine how long it took for the patients sputum to
be free of M. tuberculosis.