Brief information about Tuberculosis, drugs used for its treatment including recent advances and drug regimen for patients of different categories of TB suggested by WHO (DOTS therapy) including national and international programes for preventing TB.
The fixed dose combination of trimethoprim and sulfamethoxazole is called cotrimoxazole.
Adverse Drug Reaction, Spectrum, Resistance and Use of Cotrimoxazole.
This PPT covers drug therapy for tuberculosis. It includes classification of antitubercular drugs, chemotherapy for tuberculosis, strategies for addressing resistance and pharmacotherapy of antitubercular drugs
These are antibiotics having a macrocyclic
lactone ring with attached sugars. Erythromycin
is the first member discovered in the 1950s,
Roxithromycin, Clarithromycin and Azithromycin
are the later additions. Antimicrobial spectrum is narrow,
includes mostly gram-positive and a few gramnegative
bacteria, and overlaps considerably with
that of penicillin G. Erythromycin is highly active
against Str. pyogenes and Str. pneumoniae, N.
gonorrhoeae, Clostridia, C. diphtheriae and
Listeria, but penicillin-resistant Staphylococci
and Streptococci are now resistant to erythromycin
also.
All cocci readily develop resistance
to erythromycin, mostly by acquiring the
capacity to pump it out. Resistant Enterobacteriaceae
have been found to produce an erythromycin
esterase. Alteration in the ribosomal binding
site for erythromycin by a plasmid encoded
methylase enzyme is an important mechanism of
resistance in gram-positive bacteria. All the above
types of resistance are plasmid mediated. Change
in the 50S ribosome by chromosomal mutation
reducing macrolide binding a
Sulphonamides Pharmacology For Pharmacy studentsMalay Pandya
This is the PowerPoint presentation of the Antimicrobial drug - SULPHOANMIDE.
Sulphonamide is the first antimicrobial agent
It Can be employed for suppressive therapy of chronic urinary tract infection, streptococcal pharyngitis and gum infection.
Combined with trimethoprim (cotrimoxazole) sulfamethoxazole is used for many bacterial infections.
This will be useful to all Pharmacy Student ...
The current slide include the pharmacology og cephalosporins.
Contents
Introduction to Cephalosporins
Classification of Cephalosporins
Cefazolin
Cephalexin
Cefuroxime
Cefuroxime axetil
Cefotaxime
Cefixime
Cefpodoxime proxetil
Cefepime
Adverse effects of Cephalosporins
Uses of Cephalosporins
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.
The fixed dose combination of trimethoprim and sulfamethoxazole is called cotrimoxazole.
Adverse Drug Reaction, Spectrum, Resistance and Use of Cotrimoxazole.
This PPT covers drug therapy for tuberculosis. It includes classification of antitubercular drugs, chemotherapy for tuberculosis, strategies for addressing resistance and pharmacotherapy of antitubercular drugs
These are antibiotics having a macrocyclic
lactone ring with attached sugars. Erythromycin
is the first member discovered in the 1950s,
Roxithromycin, Clarithromycin and Azithromycin
are the later additions. Antimicrobial spectrum is narrow,
includes mostly gram-positive and a few gramnegative
bacteria, and overlaps considerably with
that of penicillin G. Erythromycin is highly active
against Str. pyogenes and Str. pneumoniae, N.
gonorrhoeae, Clostridia, C. diphtheriae and
Listeria, but penicillin-resistant Staphylococci
and Streptococci are now resistant to erythromycin
also.
All cocci readily develop resistance
to erythromycin, mostly by acquiring the
capacity to pump it out. Resistant Enterobacteriaceae
have been found to produce an erythromycin
esterase. Alteration in the ribosomal binding
site for erythromycin by a plasmid encoded
methylase enzyme is an important mechanism of
resistance in gram-positive bacteria. All the above
types of resistance are plasmid mediated. Change
in the 50S ribosome by chromosomal mutation
reducing macrolide binding a
Sulphonamides Pharmacology For Pharmacy studentsMalay Pandya
This is the PowerPoint presentation of the Antimicrobial drug - SULPHOANMIDE.
Sulphonamide is the first antimicrobial agent
It Can be employed for suppressive therapy of chronic urinary tract infection, streptococcal pharyngitis and gum infection.
Combined with trimethoprim (cotrimoxazole) sulfamethoxazole is used for many bacterial infections.
This will be useful to all Pharmacy Student ...
The current slide include the pharmacology og cephalosporins.
Contents
Introduction to Cephalosporins
Classification of Cephalosporins
Cefazolin
Cephalexin
Cefuroxime
Cefuroxime axetil
Cefotaxime
Cefixime
Cefpodoxime proxetil
Cefepime
Adverse effects of Cephalosporins
Uses of Cephalosporins
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.
Leprosy
Tuberculosis
TYB pharmacy
Pharmacology semester VI notes
Pharmacology VI semester
Pharmacology notes
Third year B pharmacy pharmacology notes
Pharmacology unit 3 notes
Pharmacology VI semester notes
Anti mycobacterial drugs (tuberculosis drugs)Ravish Yadav
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
Tuberculosis is completely curable disease now a days but one should follow the treatment regimens correctly .so for under graduate MBBS students it is clearly explained with animations.Hope you all this will be helpful.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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.
5. Tuberculosis is a chronic
granulomatous inflammatory
reaction of the tissues to the
presence of causative agent,
Mycobacteria.
being characterized by a local
aggregation of large number of
macrophages.
6. Generally caused by Mycobacterium tuberculosis
M. tuberculosis complex (MTBC) includes four other
TB-causing mycobacteria :
i. M. bovis : once was a commom cause but
introduction of pasteurized milk eliminated this as a
health problem
ii. M. africanum : not widespread but is a significant
cause in parts of Africa
iii. M. canetti : is rare and seems to be limited to Africa
iv. M. microti : is also rare and mostly seen in
immunodeficient people
7.
8. KOCH’S DISEASE : TUBERCULOSIS
• Robert Koch (1882) –
M. tuberculosis
1st ifentified and
described on 24
March, 1882 by
Robert Koch.
9. What do you know about
Mycobacterium
Tuberculi…??
11. M. tuberculosis has a tough cell wall that
prevents passage of nutrients into and excreted
from the cell, therefore giving it the
characteristic of slow growth rate.
The cell envelope contains a polypeptide layer, a
peptidoglycan layer, and free lipids.
In addition, there is also a complex structure of
fatty acids such as mycolic acids that appear
glossy.
12.
13. The cell wall also contains lipid complexes
including acyl glycolipids and other complex
such as free lipids and sulfolipids.
There are porins in the membrane to facilitate
transport.
Beneath the cell wall, there are layers of
arabinogalactan and peptidoglycan that lie just
above the plasma membrane.
14. ACID FASTNESS of Mycobacterium tuberculosis is due
to presence of a high molecular weight, hydroxy
acid containing carboxyl groups called Mycolic acid
in the bacterial cell wall or in the semipermiable
membrane around the cell.
[Acid-fast stain of Mycobacterium]
16. FIRST LINE DRUGS:
High antitubercular efficacy as well as low toxicity
Used routinely
E.g.
Isoniazid (H)
Rifampin (R)
Pyrazinamide (Z)
Ethamutol (E)
Streptomycin (S)
17. SECOND LINE DRUGS:
Either low antitubercular efficacy or high toxicity or
both
Used in special cicumstances only
E.g.
Ethionamide (Etm)
Cycloserine (Cys)
ParaAminoSalicylic Acid (PAS)
Thiacetazone (Tzn)
Kanamycin (Kmc)
Amakacin (Am)
Capreomycin (Cpr)
19. ISONIAZID
Isoniazid is the most active drug for the treatment
of tuberculosis.
In vitro, isoniazid inhibits most tubercle bacilli and is
bactericidal for actively growing tubercle bacilli.
Isoniazid is able to penetrate into phagocytic cells
and thus is active against both extracellular and
intracellular organisms.
20. Mechanism of Action:
Isoniazid inhibits synthesis of mycolic acids, which
are essential components of mycobacterial
cellwalls.
Isoniazid is a prodrug that is activated by KatG, the
mycobacterial catalase-peroxidase enzyme.
The activated form of isoniazid exerts its lethal
effect by forming a covalent complex with an
acylcarrier protein (AcpM) and KasA, a beta-
ketoacyl carrier protein synthetase, which blocks
mycolicacid synthesis.
A gene called inhA which encodes for a fatty acid
synthase enzyme is the target for the drug.
21. Basis of Resistance:
The most common mechanism of resistance is by
mutation of the catalase-peroxidase gene so that
the bacilli do not generate the active metabolite of
the drug.
Resistance may also involve mutation in the target
inh A gene.
Other resistant bacilli lose the active INH
concentrating process.
Combined with other drugs, INH has good
resistance preventing action.
22. Pharmaco Kinetics :
Isoniazid is readily absorbed from the
gastrointestinal tract.
The administration of a 300-mg oral dose (5
mg/kg in children) results in peak plasma
concentrations of 3–5 g/mL within 1–2 hours.
Isoniazid diffuses readily into all body fluids and
tissues.
Acetylated by N-acetyltransferase to N-
acetylisoniazid; it is then biotransformed to
isonicotinic acid and monoacetylhydrazine.
23. Monoacetylhydrazine is associated with
hepatotoxicity via formation of a reactive
intermediate metabolite when N-hydroxylated by the
cytochrome P450 mixed oxidase system.
Fast acetylators 1 hour t½
Slow acetylators 3 hour t½
Isoniazid metabolites and a small amount of
unchanged drug are excreted mainly in the urine.
24. Interactions:
Aluminium Hydroxide inhibits INH absorption.
(by decreasing gastric emptying)
INH inhibits phenytoin, carbamazepine, diazepam
and warfarin metabolism.
(may raise their blood levels)
PAS inhibits INH metabolism and prolongs its half
life.
25. Adverse effects:
• Allergic Reactions :
Fever and skin rashes
Drug-induced systemic lupus erythematosus
• Direct Toxicity :
Isoniazid-induced hepatitis:
The most frequent major toxic effect.
Clinical hepatitis with loss of appetite, nausea,
vomiting, jaundice occurs in 1% of isoniazid
recipients and can be fatal, particularly if the drug is
not discontinued promptly.
26. Peripheral neuropathy: is observed in 10–20% of
patients given higher dosages but is infrequently
seen with the standard 300 mg adult dose.
Neuropathy is due to a relative pyridoxine
deficiency.
Isoniazid promotes excretion of pyridoxine, and this
toxicity is 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.
These may also respond to pyridoxine
27. Miscellaneous: Other reactions include
hematologic abnormalities
provocation of pyridoxin deficiency anemia
Tinnitus
gastrointestinal discomfort
28. RIFAMPIN
Rifampin is a large (MW 823), complex
semisynthetic derivative of rifamycin, an antibiotic
produced by Streptomyces mediterranei.
Susceptible organisms are inhibited by less than
1 g/mL.
29. It readily penetrates most tissues and into
phagocytic cells.
It can kill organisms that are poorly accessible to
many other drugs, such as intracellular organisms
and those sequestered in abscesses and lung
cavities.
30. Mechanism of Action:
Rifampin binds strongly to the subunit of bacterial
DNA-dependent RNA polymerase and thereby
inhibits RNA synthesis.
Basis of Resistance:
Resistance results from one of several possible
point mutations in rpoB, the gene for the beta
subunit of RNA polymerase.
These mutations prevent binding of rifampin to RNA
polymerase.
31. Human RNA polymerase does not bind rifampin and
is not inhibited by it
Administration of rifampin as a single drug produces
highly resistant organisms.
There is no cross-resistance to other classes of
antimicrobial drugs but there is cross
resistance to other rifamycin derivatives.
e.g.rifabutin.
32. Pharmaco Kinetics:
Rifampin is well absorbed after oral administration
and excreted mainly through the liver into bile.
It then undergoes enterohepatic recirculation, with
the bulk excreted as a deacylated metabolite in
feces and a small amount in the urine.
Rifampin is distributed widely in body fluids and
tissues.
Rifampin is relatively highly protein-bound but
adequate cerebrospinal fluid concentrations are
achieved only in the presence of meningeal
inflammation.
33. Interactions:
It is a microsomal enzyme inducer-increases several
CYP450 isoenzymes, including CYP3A4, CYP2D6,
CYP1A2 and CYP2C subfamily.
It thus enhances its own metabolism as well as that
of many drugs including warfarin, oral
contraceptives, corticosteroids, sulfonylureas,
digitoxins, steroids, HIV protease inhibitors, NNRTIs,
theophylline, metoprolol, fluconazole, ketoconazole
etc.
34. Adverse Effects:
Rifampin imparts a harmless orange color to urine,
sweat, tears, and contact lenses (soft lenses may be
permanently stained).
Occasional adverse effects include rashes,
thrombocytopenia, and nephritis.
It may cause jaundice and occasionally hepatitis.
Rifampin commonly causes light chain proteinuria.
If administered less often than twice weekly,
rifampin causes a flu-like syndrome characterized by
fever, chills, myalgias, anemia, thrombocytopenia
and sometimes is associated with acute tubular
necrosis.
35. ETHAMBUTOL
Ethambutol is a synthetic, water-soluble, heat-
stable compound.
Susceptible strains of M tuberculosis and other
mycobacteria are inhibited in vitro by ethambutol
1–5 mcg/mL.
It is selectively tuberculostatic.
Fast multiplying bacteria are more susceptible.
Addition to the triple drug regimen of RHZ it has
been found to hasten the rate of sputum conversion
& to prevent development of resistance.
36. Mechanism of Action:
Ethambutol is an inhibitor of mycobacterial
arabinosyl transferases, which are encoded by the
embCAB operon.
Arabinosyl transferases are involved in the
polymerization reaction of arabinoglycan, an
essential component of the mycobacterial cell wall.
37. Basis of Resistance:
Resistance to ethambutol is due to mutations
resulting in overexpression of emb gene products or
within the embB structural gene.
No cross resistance with any other antitubercular
drug has been noted.
38. Pharmaco Kinetics:
• Ethambutol is well absorbed from the gut.
Following ingestion of 25 mg/kg, a blood level peak
of 2–5 mcg/ml is reached in 2–4 hours.
• About 20% of the drug is excreted in feces and 50%
in urine in unchanged form.
• Ethambutol accumulates in renal failure, and the
dose should be reduced by half if creatinine
clearance is less than 10 ml/min.
• Ethambutol crosses the blood-brain barrier only if
the meninges are inflamed.
39. Adverse Effects:
Hypersensitivity to ethambutol is rare.
The most common serious adverse event is
retrobulbar neuritis causing loss of visual acuity and
red-green color blindness (dose-related side effect).
Ethambutol is relatively contraindicated in children
too young to permit assessment of visual acuity and
red-green color discrimination.
40. PYRAZINAMIDE
Pyrazinamide (PZA) is relative to nicotinamide,
stable, slightly soluble in water, and quite
inexpensive.
At neutral pH, it is inactive in vitro, but at pH 5.5 it
inhibits tubercle bacilli and some other
mycobacteria.
Drug is taken up by macrophages and exerts its
activity against intracellular organisms residing
within this acidic environment.
41. Mechanism of Action:
Pyrazinamide is converted to pyrazinoic acid, the
active form of the drug, by mycobacterial
pyrazinamidase, which is encoded by pncA.
It inhibits mycolic acid synthesis (same as INH but
by interacting with a different fatty acid synthase
encoding gene).
42. Base of Resistance:
Resistance is due to mutations in pncA that
impair conversion of pyrazinamide to its active
form.
Impaired uptake of pyrazinamide may also
contribute to resistance.
43. Pharmaco Kinetics:
Pyrazinoic acid is hydroxylated by xanthine oxidase
to 5-hydroxypyrazinoic acid
Serum concentrations of 30–50 mcg/ml at 1–2
hours after oral administration are achieved with
dosages of 25 mg/kg/d.
Pyrazinamide is well absorbed from the
gastrointestinal tract and widely distributed in body
tissues, including inflamed meninges.
The half-life is 8–11 hours.
44. Adverse Effects:
Major are:
hepatotoxicity (in 1–5% of patients)
nausea
Vomiting
drug fever
Hyperuricemia
The latter occurs uniformly and is not a reason to
halt therapy.
Hyperuricemia may provoke acute gouty arthritis.
46. STREPTOMYCIN
It is a bactericidal Aminoglycoside antibiotic drug.
IT was 1st clinically useful antiTB drug.
It is less effective than INH or Rifampin as it acts
only on extracellular bacilli (poor penitration into
cell).
It penetrates tubercular cavities but does not cross
the CSF & has poor action in acidic medium.
47. Mechanism of Action:
It transport through the bacterial cell wall and
cytoplasmic membrane (through porin channels)
and bind to ribosomes resulting in inhibition of
protein synthesis.
Base of Resistance:
Resistance is due to a point mutation in either the
rpsL gene encoding the S12 ribosomal protein gene
or rrs, encoding 16S ribosomal rRNA, that alters the
ribosomal binding site.
48. Adverse Effects:
Streptomycin is ototoxic and nephrotoxic.
Vertigo and hearing loss are the most common side
effects and may be permanent.
Toxicity is dose-related and the risk is increased in
the elderly.
As with all aminoglycosides, the dose must be
adjusted according to renal function.
Toxicity can be reduced by limiting therapy to no
more than 6months whenever possible.
49. ETHIONAMIDE:
Ethionamide is chemically related to isoniazid and
also blocks the synthesis of mycolic acids.
It is poorly water soluble and available only in oral
form.
It is metabolized by the liver.
Most tubercle bacilli are inhibited in vitro by
ethionamide.
although effective in the treatment of tuberculosis,
is poorly tolerated because of the intense gastric
irritation and neurologic symptoms that commonly
occur.
Ethionamide is also hepatotoxic.
50. CYCLOSERINE:
It is an antibiotic obtained from S. orchidaceus, and
is a chemical analogue of D-alanine.
Inhibits bacterial cell wall synthesis by inactivating
the enzymes which recemize L-alanine and link two
D-alanine residues.
It is tuberculostatic.
Cycloserine is absorbed orally, diffuses all over.
CSF concentration is equal to that in plasma.
About 1/3rd of a dose is metabolized, the rest is
excreted unchanged by kidney.
51. The CNS toxicity of the drug is high:
Sleepiness
Headache
tremor and psychosis (convulsions may be)
prevented by pyridoxine 100 mg/day.
o It is rarely used (only in resistant cases)
52. PARAAMINO SALICYLIC ACID
(PAS)
It is related to sulfonamides:
chemically as well as in mechanism of action.
It is not active against other bacteria: selectivity
may be due to difference in the affinity of folate
synthase of TB and other bacteria for PAS.
PAS is tuberculostatic and one of the least active
drugs.
It does not add to the efficacy of more active drugs
that are given with it; only delays development of
resistance.
53. Resistance to PAS is slow to develop.
PAS is absorbed completely by the oral route and
distributed all over except in CSF.
About 50% PAS is acetylated; competes with
acetylation of INH (prolongs its t½).
PAS formulations interfere with absorption of
rifampin.
It is excreted rapidly by glomerular filtration and
tubular secretion
t½ is short (1 hour)
54. Patient acceptability of PAS is poor because of:
Frequent anorexia
Nausea
epigastric pain
Other adverse effects are:
Rashes
Fever
malaise
goiter
liver dysfunction
55. THIACETAZONE
Thiacetazone is a tuberculostatic, low efficacy drug.
does not add to the therapeutic effect of H, S or E
but delays resistance to these drugs.
Orally active
Primarily excreted unchanged in urine with a t½ of
12 hr.
It is a reserve anti-TB drug, sometimes added to INH
in alternative regimens.
56. The major adverse effects are:
hepatitis
Exfoliative dermatitis
Stevens-Johnson syndrome
bone marrow depression (rarely)
The common side effects are:
anorexia
abdominal discomfort
loose motions
minor rashes.
A mild anaemia persists till Tzn is given.
57. KANAMYCIN, AMIKACIN, CAPREOMYCIN :
All three are more toxic antibiotics used as reserve
drugs in rare cases not responding to the usual
therapy.
Any one of these is used at a time in combination
with the commonly employed drugs to which
resistance has not developed.
Because all exhibit similar oto- and nephrotoxicity,
they are not combined among themselves or with
streptomycin.
58. Capreomycin, inaddition, can induce electrolyte
abnormalities.
All act by inhibiting protein synthesis.
None is effective orally; none penetrates meninges.
All are excreted unchanged by the kidney.
59. FLUOROQUINOLONES:
These are an important addition to the drugs
available for tuberculosis,especially for strains that
are resistant to first-line agents.
Resistance, which may result from any one of
several single point mutations in the gyrase A
subunit, develops rapidly if a fluoroquinolone is
used as a single agent; thus, the drug must be used
in combination with two or more other active
agents.
60. They penetrate cells and kill mycobacteria lodged in
macrophages as well.
Because of their good tolerability, ciprofloxacin and
ofloxacin are being increasingly included in
combination regimens against MDR tuberculosis
and MAC infection in HIV patients.
They are also being used to supplement ethambutol
+ streptomycin in cases when H, R, Z have been
stopped due to hepatotoxicity.
61. MACROLIDE ANTIBIOTICS:
Clarithromycin & Azithromycin, these macrolide
antibiotics are most active against nontubercular
mycobacteria including MAC, M. fortuitum, M.
Kansasii and M. marinum.
Clarithromycin has been used to a greater extent
because its MIC values are lower, but azithromycin
may be equally efficacious due to its higher tissue
and intracellular levels.
In AIDS patients, life-long therapy is required—may
cause ototoxicity.
65. MDR-TB:
Resistance to both H and R and may
be any number of other anti-TB
drugs.
For H resistance:
RZE given for 12 months is recommended.
For H + R resistance:
ZE + S/Kmc/Am/Cpr + Cipro/ofl ± Etm could be
used.
67. XDR-TB:
Resistant to at least 4 most effective cidal
drugs, i.e. H, R, a FQ, one of
Kmc/Am/Cpr with or without any
number of other drugs.
68. RECENT APPROACHES:
DOTS (Directly Observed Treatment
Short course)
RNTCP (Revised National Tuberculosis
Control Program)
National strategic plan TB India (2012-
17)
Modification of drug regimen
70. The DOTS strategy ensures that infectious TB
patients are diagnosed and treated effectively till
cure, by ensuring availability of the full course of
drugs and a system for monitoring patient
compliance to the treatment.
The DOTS strategy is cost-effective and is today the
international standard for TB control programmes.
71. DOTS is a systematic strategy
which has five components:
Political and administrative commitment
Good quality diagnosis
Good quality drugs
Supervised treatment to ensure the right treatment
Systemic monitoring and accountability
72. SHORT COURSE CHEMOTHERAPY (SCC)
These are regimens of 6–9 month duration which
have been found highly efficacious.
The dose of first line anti-TB drugs has been
standardized on body weight basis and is applicable
to both adults and children.
74. All regimens have:
Initial intensive phase:
lasting for 2–3 months aimed to rapidly kill
the TB bacilli, bring about sputum conversion
and afford symptomatic relief.
This is followed by
Continuation phase:
Lasting for 4–6 months during which the remaining
bacilli are eliminated so that relapse does not occur.
76. Treatment regimen followed in India
under the RNTCP (1997) :
TB Category Initiation
Phase
Continuation
Phase
I 2H₃R₃Z₃E₃ 4H₃R₃
II 2H3R3Z3E3S3
+ 1H₃R₃Z₃E₃
5H3R3E3
III 2H3R3Z3 4H3R3
77. RNTCP (1997) :
To control TB, National Tuberculosis Control
Programme (NTCP) has been in operation in the
country since 1962.
This could not achieve the desired results.
Therefore, it was reviewed by an expert committee
in 1992 and based on its recommendations,
Revised National TB Control Programme (RNTCP),
which is an application of WHO-recommended
strategy of DOTS, was launched in the country on
26 March 1997.
78. The objectives of RNTCP
are:
1. To achieve and maintain a cure rate of at least 85%
among newly detected infectious TB cases
2. Achieve and maintain detection of at least 70% of
such cases in the population
79. NATIONAL STRATEGIC PLAN
12th Five Year Plan of Government of India.
Proposed strategies:
1. Case finding and diagnostics
2. Patient friendly treatment services
3. Scale-up of Programmatic Management of Drug
Resistance –TB
4. Scale -up of Joint TB-HIV Collaborative Activities
5. Control TB
80. Modifiaction of Drug Regimen:
There are currently at least ten compounds in
various stages of clinical development for TB.
Four of these are existing drugs that are either
being redeveloped or repurposed for the
treatment of TB and there are six new chemical
compounds that are being specifically
developed as TB drugs.
81. Phase 1 Phase 2 Phase 3
Existing drugs
redeveloped
Or
repurposed for
TB
1)Rifa
pentine
2)Linezoli
d
1)Gati
floxacin
2)Moxi
Floxacin
New drugs
developed
specifically for
TB
1) SQ-
109
2)PNU-
100480
1) PA-
824
2)AZD58
47
1)Delamani
d(OPC-
67683)
82. SIRTURO ( Bedaquiline)
In December 2012 the FDA gave approval for the drug
to be used as part of combination therapy to treat
adults with multi drug resistant (MDR) TB, when no
other alternatives are available.
Diaryl quinolone drug.
Bedaquiline inhibits enzyme needed by M. tuberculosis
to replicate & spread throughout body. This mechanism
is unlike that of all other quinolone antibiotics, whose
target is DNA gyrase.
83. Drug Interactions:
Bedaquiline should not be co-administered with
other drugs that are strong inducers or inhibitors
of CYP3A4, the hepatic enzyme responsible for
oxidative metabolism of the drug.
Co-administration with rifampin, a strong
CYP3A4 inducer, results in a 52% decrease in the
AUC of the drug. This reduces the exposure of
the body to the drug and decreases the
antibacterial effect.
Co-administration with ketoconazole, a strong
CYP3A4 inhibitor, results in a 22% increase in the
AUC, and potentially an increase in the rate of
adverse effects experienced
84. Adverse Effects:
The most common are:
nausea
joint and chest pain
Headache
arrhythmias as it may induce long QT syndrome
. Tuberculosis most commonly affects the lungs (pulmonary TB). Patients with active pulmonary TB usually have a cough, an abnormal chest x-ray, and are infectious. TB can also occur outside of the lungs (extrapulmonary), most commonly in the central nervous, lymphatic, or genitourinary systems, or in the bones and joints