- The patient is experiencing drowsiness and dizziness while taking standard four-drug antimycobacterial therapy including isoniazid, rifampin, pyrazinamide, and ethambutol.
- Rifampin is known to cause adverse effects like headache, dizziness, and gastrointestinal upset.
- The symptoms reported by the patient are consistent with an adverse reaction to rifampin.
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.
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 aminoglycoside class of antibiotics consists of many different agents. In the United States, gentamicin, tobramycin, amikacin, plazomicin, streptomycin, neomycin, and paromomycin are approved by the US Food and Drug Administration (FDA) and are available for clinical use.
Macrolides are a class of drugs used to manage and treat various bacterial infections. Azithromycin, clarithromycin, and erythromycin are commonly used to treat infections like pneumonia, sinusitis, pharyngitis, and tonsillitis. They are also used in uncomplicated skin infections and otitis media in pediatric patients.
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
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
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
The aminoglycoside class of antibiotics consists of many different agents. In the United States, gentamicin, tobramycin, amikacin, plazomicin, streptomycin, neomycin, and paromomycin are approved by the US Food and Drug Administration (FDA) and are available for clinical use.
Macrolides are a class of drugs used to manage and treat various bacterial infections. Azithromycin, clarithromycin, and erythromycin are commonly used to treat infections like pneumonia, sinusitis, pharyngitis, and tonsillitis. They are also used in uncomplicated skin infections and otitis media in pediatric patients.
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
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
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
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
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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
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.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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.
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.
3. Principles of anti Mycobacterial therapy
• Single-drug therapy - high likelihood of developing antimicrobial
resistance
4. The first line
1. Isoniazid
2. Rifampin
3. Pyrazinamide
4. Ethambutol
5. Isoniazid
• Mechanism of action: inhibit
bacterial mycolic acid cell wall
synthesis
• Targets the enzyme acyl
carrier protein reductase
(InhA) and B-ketoacyl-
ACP synthase, essential
for syntesis of mycolic
acid
• Resistance:
• mutations in the INH A gene,
and Kat G
6. Isoniazid
• The pediatric dosage is 10-15 mg/kg/day PO in a single dose not to
exceed 300 mg/day
• M. tuberculosis, Mycobacterium kansasii, and Mycobacterium bovis
• Readily absorbed after oral administration
• Impaired when taken with food
7. • Major adverse events
• hepatotoxicity
• dose-related peripheral neuropathy.
• Pyridoxine can prevent the peripheral neuropathy -25 to 50 mg Vitamin B6
• Minor adverse events:
• rash, worsening of acne, epigastric pain with occasional nausea and vomiting,
decreased vitamin D levels, and dizziness.
8.
9. Rifamycins
• Rifampin, Rifabutin and
Rifapentine
• Macroclide antibiotics -
Streptomyces mediterranei
Mechanism of action:
• inhibit the DNA dependent
RNA polymerase of
mycobacteria
Pyrazinamide
11. Rifamycins
• most gram-positive and gram negative bacteria
• M. tuberculosis, Mycobacterium leprae,
• M. kansasii, and Mycobacterium avium complex.
• 10-15 mg/kg/day PO in a single dose not to exceed 600 mg/day.
• Also used as prophylaxis for individuals exposed to patients with
meningitis
• Meningococci
• Hemophilus influenzae B
12. Adverse effects
• Generally well tolerated
• Transient elevations of liver enzymes; gastrointestinal (GI) upset with
cramps, nausea, vomiting, and anorexia; headache; dizziness; and
immunologically mediated fever and flu-like symptoms.
• turn urine and other secretions (tears, saliva, stool, sputum) orange,
which can stain contact lenses
Pyrazinamide
13. Pyrazinamide
Mechanism of action:
• bacteria-specific enzyme
(pyrazinamidase) converts PZA to
pyrazinoic acid, which leads to low
pH levels not tolerated by M.
tuberculosis.
• Resistance
• from bacterial pyrazinamidase
alterations.
14. Pyrazinamide
• indicated for the initial treatment phase of active tuberculosis in
combination with other antimycobacterial agents.
• The pediatric dosage is 15-30 mg/kg/day PO in a single dose, not to
exceed 2,000 mg/ day.
15. Adverse Reactions -Pyrazinamide
• GI upset (e.g., nausea, vomiting, poor appetite)
• hepatotoxicity
• elevated serum uric acid levels
• Minor reactions include arthralgias, fatigue, and, rarely, fever.
• Use of PZA in combination with rifampin for short-
16. Ethambutol
• inhibits RNA synthesis needed for cell wall formation
• standard dosages it is bacteriostatic, but at dosages of >25 mg/kg
ethambutol has bactericidal activity
• The mechanism of resistance to ethambutol is unknown,
• develops rapidly when used as a single agent against M. tuberculosis
• 15-20 mg/kg/day PO in a single dose, twice-weekly dosing is with 50
mg/kg PO in a single dose, not to exceed 2,500 mg/day.
17. Adverse effects -Ethambutol
• Optic neuritis
• Visual changes are reversible
• Headache, dizziness, confusion, hyperuicema, Gi upset, peripheral
neuropathy, hepatotoxicity and cytopenias
• Routine monitoring: baseline and periodic visual acuity and color
discrimination testing, CBC, serum uric acid levels, and kidney and
liver function tests.
18.
19. Alternative second line drugs
• Streptomycin
• Cycloserine
• Ethioamide
• Fluoroquinolones
• Macrolides
-less effective and more toxic than first line agents
20. Streptomycin
• Streptomycin, an aminoglycoside antibiotic, was one of the first
effective agents for TB. •
• Its action appears to be greater against extracellular organisms.
21. Fluoroquinolones
• The fluoroquinolones, specifically moxifloxacin and levofloxacin, have
an important place in the treatment of multidrug-resistant
tuberculosis.
22. Macrolides
• The macrolides azithromycin and clarithromycin are included in
regimens for several NTM infections, including MAC.
23. Mycobacterium leprae
• Hansen’s disease (also known as leprosy)
• affect the nerves, skin, eyes, and lining of the nose (nasal mucosa).
• inability to sense touch and pain, which can lead to injuries, like
cuts and burn, if left untreated can cause paralysis in both hands
and feet
24. Dapsone
• structurally related to the sulfonamides and similarly inhibits
dihydropteroate synthetase in the folate synthesis pathway.
• bacteriostatic for M. leprae
• Also used in the treatment of pneumonia caused by Pneumocystis
jirovecii in immunosuppressed patients.
• Pediatric dosage is 1-2 mg/kg/day PO as a single dose, not to exceed
• 100 mg/day for a duration of 3-10 yr.
25. Dapsone Adverse Effects
• Hemolytic anemia
• Pancreatitis
• acute tubular necrosis, acute renal failure, albuminuria
• tinnitus, peripheral neuropathy, photosensitivity,
• and a hypersensitivity syndrome with fever, rash, hepatic
• damage, and malaise.
• CBC weekly during the 1st month of therapy, weekly through 6 mo of
therapy, and then every 6 mo thereafter.
• creatine levels and urinalysis and liver function tests.
26. Clofazimine
• binding to the mycobacterial DNA at guanine sites. generation of
cytotoxic oxygen radicals that are toxic to the bacteria.
• Clofazimine is bactericidal to M. leprae, and it has potentially useful
activity against M. tuberculosis and NTM.
• drug accumulates in tissues, intermittent therapy
• 1 mg/kg/day PO as a single dose (max 100 mg/day in combination
with dapsone rifampin for 2 yr, then as a single agent 1 yr.
27. Clofazimine
• adverse effect is a dosage-related, reversible pink to tan-brown
discoloration of the skin and conjunctiva.
• Other adverse effects include a dry, itchy skin rash, headache,
dizziness, abdominal pain, diarrhea, vomiting, peripheral neuropathy,
and elevated hepatic transaminases.
• Routine laboratory monitoring includes periodic liver function
28. A 13 y/o male came in for consult for his >3 month history of productive cough,
and weight loss. He is currently taking Carbamazepine for seizures. Two weeks ago,
he had a positive tuberculosis skin test (PPD test), and a chest radiograph showed
evidence of right upper lobe infection. He was started on standard four-drug
antimycobacterial therapy. He has come to the clinic complaining of “drowsiness
and dizziness.” Which of the following antimycobacterial drugs is likely to have
caused this patient’s symptoms?
A. Ethambutol
B. Isoniazid.
C. Pyrazinamide.
D. Rifampin.
E. Streptomycin
29. • Which of the following is correct regarding clofazimine in the
treatment of leprosy?
A. Clofazimine should not be used in patients with a deficiency in
glucose-6-phosphate dehydrogenase (G6PD).
B. Peripheral neuropathy is one of the most common adverse effects
seen with the drug.
C. Clofazimine may cause skin discoloration over time.
D. The risk of erythema nodosum leprosum is increased in patients
given clofazimine
30. • A 10-year-old male has returned to the clinic for his 1-month check-
up after starting treatment for tuberculosis. He is receiving isoniazid,
rifampin, pyrazinamide, and ethambutol. He states he feels fine, but
now is having difficulty distinguishing the green and red crayons .
Which of the following drugs may be causing his decline in vision?
A. Isoniazid.
B. Rifampin.
C. Pyrazinamide.
D. Ethambutol.
Editor's Notes
Good afternoon, Dr. De Castro, Dr. Cantimbuhan, fellow residents, interns and clerks.
For our Infectious Diseases Hour for today, I will be discussing about Antimycobacterials
What is a Mycobacteria?
A hallmark of all mycobacteria is its acid fastness—the capacity to form stable mycolate complex with arylmethane dyes (crystal violet, carbolfuchsin, auramine,and rhodamine).
They resist decoloration with ethanol and hydrochloric or other acids
There are more than 200 mycobacterium species but Mycobacterium tuberculosis ccauses tuberculosis and is a very important pathogen of humans especially in the Philippines
Mycobacterium leprae causes leprosy.
Mycobacterium avium-intracellulare ( M avium complex,
or MAC) and other nontuberculous (NTM) mycobacteria, the opportunistic pathogens in other immunocompromised persons
The treatment of mycobacterial infection and disease can be challenging. Patients require therapy with multiple agents, the offending pathogens commonly exhibit complex drug resistance patterns, and patients often have underlying conditions that affect drug choice and monitoring.
Single-drug therapy of Mycobacterium tuberculosis and nontuberculous mycobacteria is not recommended because of the high likelihood of developing antimicrobial resistance
needed for the last step of the mycolic acid biosynthesis
pathway of cell wall production
Isoniazid enters bacilli by passive diffusion. The drug is not directly toxic to the bacillus but must be activated to its toxic form within the bacillus by KatG, a multifunctional catalase-peroxidase. The activated drug forms adducts with bacillar NAD+ and NADP+ that inhibit essential steps in mycolic acid synthesis (cell wall) and nucleic acid synthesis (Figure 56–3). Other products of KatG activation of INH include superoxide, H2O2, alkyl hydroperoxides, and the NO radical, which may also contribute to the mycobactericidal effects of INH.
Its antibacterial actibity involeves targeting
The primary target of INH involves the INH A gene, which encodes the enoyl ACP (acyl carrier, protein) reductase needed for the last step of the mycolic acid biosynthesis
pathway of cell wall production.
Resistance to INH occurs following
mutations in the INH A gene or in other genes encoding
enzymes that activate INH, such as kat G
INH resistance has been associated with deletions or mutations
in the catalase-peroxidase gene (katG); these isolates become
catalase negative or have decreased catalase activity. INH
resistance has also been associated with alterations in the inhA
gene, which encodes an enzyme that functions in mycolic
acid synthesis.
INH is associated with mutation or deletion of katG, overexpression of the genes for inhA (confers low-level resistance to INH and some cross-resistance to ethionamide) Because TB cavities may contain as many as 107-109 microorganisms, preexistent resistance can be expected in pulmonary TB cavities of untreated patients. T
hese spontaneous mutants will be selected and amplified by monotherapy.
Thus, 2 or more agents are usually used.
KatG gene– activates pro drug
producing mutants incapable of prodrug activation
The pediatric dosage is 10-15 mg/
kg/day PO in a single dose not to exceed 300 mg/day. The adult dosage
is 5 mg/kg/day PO in a single dose not to exceed 300 mg/day
INH is indicated for the treatment of
INH needs to be taken 1 hr before or 2 hr after meals because
food decreases absorption.
Mycobacterium kansasii is a slow-growing, non-tuberculosis mycobacterium (NTM) that, like other mycobacterial species, tends to cause six clinical patterns of infection: pulmonary disease, skin and soft tissue disease, musculoskeletal infections including monoarticular septic arthritis and tenosynovitis, disseminated .
Major adverse events include hepatotoxicity in 1% of children and
approximately 3% of adults (increasing with age) and dose-related
peripheral neuropathy. Pyridoxine can prevent the peripheral neuropathy
and is indicated for breastfeeding infants and their mothers,
children and youth on milk- or meat-deficient diets, pregnant adolescents,
and symptomatic HIV-infected children. Minor adverse events
include rash, worsening of acne, epigastric pain with occasional nausea
and vomiting, decreased vitamin D levels, and dizziness. The liquid
formulation of INH contains sorbitol, which often causes diarrhea and
stomach upset
Routine baseline liver function testing or monthly monitoring is only
indicated for persons with underlying hepatic disease or on concomitant
hepatotoxic drugs, including other antimycobacterial agents, acetaminophen,
and alcohol.
Hepatitis is the most serious adverse effect associated with isoniazid incidence increases with age, and those who are alcoholic
Peripheral neuropathy , manifesting as paresthesia of the hands and feet, this can be avoided with Vitamin B6 supplementation of 25 to 50 mg per day of pyridoxine
Because Isoniazid inhibits the metabolism of carbamazepine and phenytoin, isoniazid can potentiate the adverse effects of thi sdrugs, for example nystagmus and ataxia
are a class of macrolide antibiotics developed from Streptomyces mediterranei
The rifamycins inhibit the DNA-dependent RNA polymerase of mycobacteria, resulting in decreased RNA synthesis. They are generally bactericidal at treatment doses, but they may be bacteriostatic at lower doses.
. Rifampin enters bacilli in a concentration-dependent manner, achieving steady-state concentrations within 15 min. The drug binds to the β subunit of DNA-dependent RNA polymerase (rpoB) to form a stable drug–enzyme complex, suppressing chain formation in RNA synthesis.
Alteration of target protein structure, prevents drug recognition
The prevalence of rifampin-resistant isolates is due to altered rpoB. Mutations in genes involved in DNA repair mechanisms will impair the repair of multiple genes, which may lead to hyper-mutable
Antibiotics, endogenous oxidative and metabolic stressors lead to DNA damage, which induces dnaE2. The induction is associated with error-prone DNA repair and leads to higher rates of rifampin resistance.
Because resistant strains rapidly emerges from monotherapy, it is never given as a single agent in treatment of active tb
Rifampin inhibits the growth of most gram-positive bacteria as well as many gram-negative microorganisms.
Rifampin is active against M. tuberculosis, Mycobacterium leprae,
M. kansasii, and Mycobacterium avium complex. Rifampin is an integral
drug in standard combination treatment of active M. tuberculosis
disease and can be used as an alternative to INH in the treatment of
latent tuberculosis infection in children who cannot tolerate INH.
The
pediatric dosage of rifampin is 10-15 mg/kg/day PO in a single dose,
not to exceed 600 mg/day.
The most common adverse reaction include, nausea, vomiting, rash and flu like syndrome
Hepatitis, should be used cautiously in older patients, alcoholics and those with chronic liver disease
Increase incidence of hepatic dysfunction when rifampin is co administedre w/ isoniazid
Rifampin can be associated with adverse events such as transient
elevations of liver enzymes; gastrointestinal (GI) upset with cramps,
nausea, vomiting, and anorexia; headache; dizziness; and immunologically
mediated fever and flu-like symptoms.
All rifamycins can turn urine and other secretions (tears, saliva,
stool, sputum) orange, which can stain contact lenses. Patients and
families should be warned about this common but otherwise innocuous
adverse effect.
Rifamycins induce the hepatic cytochrome P450 isoenzyme system
and are associated with the increased metabolism and decreased
level of several drugs when administered concomitantly. These drugs
include digoxin, corticosteroids such as prednisone and dexamethasone,
dapsone, fluconazole, phenytoin, oral contraceptives, warfarin,
and many antiretroviral agents
A bacteria-specific enzyme (pyrazinamidase) converts PZA
to pyrazinoic acid, which leads to low pH levels not tolerated by
M. tuberculosis. Resistance is poorly understood but can arise from
bacterial pyrazinamidase alterations.
PZA is indicated for the initial treatment
Adverse events include GI upset (e.g., nausea, vomiting, poor appetite)
in approximately 4% of children, dosage-dependent hepatotoxicity,
and elevated serum uric acid levels that can precipitate gout in
susceptible adults. Approximately 10% of pediatric patients have elevated
uric acid levels but with no associated clinical sequelae. Minor
reactions include arthralgias, fatigue, and, rarely, fever.
Use of PZA in combination with rifampin for short-
Ethambutol
Ethambutol is a synthetic form of ethylenedi-imino-di-1-butanol dihydrochloride
that inhibits RNA synthesis needed for cell wall formation.
At standard dosages it is bacteriostatic, but at dosages of >25 mg/kg
ethambutol has bactericidal activity. The mechanism of resistance to
ethambutol is unknown, but resistance develops rapidly when ethambutol
is used as a single agent against M. tuberculosis.
Ethambutol is indicated for the treatment of infections caused by
M. tuberculosis, M. kansasii, M. bovis, and M. avium complex. Ethambutol
should only be used as part of a combination treatment regimen
for M. tuberculosis. Daily dosing is 15-20 mg/kg PO in a single dose,
not to exceed 2,500 mg/day. Twice-weekly dosing is with 50 mg/kg PO
in a single dose, not to exceed 2,500 mg/day. Dosage adjustment is
needed in renal insufficiency. Ethambutol is available in 100 and
400 mg tablets.
The major adverse effect with ethambutol is optic neuritis, and thus
ethambutol should generally be reserved for children old enough to
have visual acuity and color discrimination reliably monitored. Visual
changes are usually dosage dependent and reversible. Other adverse
events include headache, dizziness, confusion, hyperuricemia, GI
upset, peripheral neuropathy, hepatotoxicity, and cytopenias, especially
neutropenia and thrombocytopenia.
Routine laboratory monitoring includes baseline and periodic visual
acuity and color discrimination testing, CBC, serum uric acid levels
major adverse effect with ethambutol is optic neuritis,
Which results in diminished visual acuity and lnability to discriminate red and green
Higher risk of ON for patient w/ renal impairment
and thus
ethambutol should generally be reserved for children old enough to
have visual acuity and color discrimination reliably monitored. Visual
changes are usually dosage dependent and reversible. Other adverse
events include headache, dizziness, confusion, hyperuricemia (uric acid excretion is decreased by ethambutol, GI
upset, peripheral neuropathy, hepatotoxicity, and cytopenias, especially
neutropenia and thrombocytopenia.
Routine laboratory monitoring includes baseline and periodic visual
acuity and color discrimination testing, CBC, serum uric acid levels,
and kidney and liver function tests.
Hansen’s disease (also known as leprosy) is an infection caused by bacteria called Mycobacterium leprae. These bacteria grow very slowly and it may take up to 20 years to develop signs of the infection.
The disease can affect the nerves, skin, eyes, and lining of the nose (nasal mucosa). The bacteria attack the nerves, which can become swollen under the skin. This can cause the affected areas to lose the ability to sense touch and pain, which can lead to injuries, like cuts and burns. Usually, the affected skin changes color and either becomes:
lighter or darker, often dry or flaky, with loss of feeling, or
reddish due to inflammation of the skin.
If left untreated, the nerve damage can result in paralysis of hands and feet. In very advanced cases, the person may have multiple injuries due to lack of sensation, and eventually the body may reabsorb the affected digits over time, resulting in the apparent loss of toes and fingers. Corneal ulcers and blindness can also occur if facial nerves are affected. Other signs of advanced Hansen’s disease may include loss of eyebrows and saddle-nose deformity resulting from damage to the nasal septum.
Dapsone [DAP-sone] is structurally related to the sulfonamides and similarly inhibits dihydropteroate synthetase needed for the bacterial synthesis of folic acid. in the folate synthesis pathway. It is bacteriostatic for M. leprae, and resistant strains may be encountered for microorganism w/ alteration of PABA binding site. Dapsone also is used in the treatment of pneumonia caused by Pneumocystis jirovecii in immunosuppressed patients.
Dapsone is used in the treatment of M. leprae in combination with
other antileprosy agents (rifampin, clofazimine, ethionamide). The
pediatric dosage is 1-2 mg/kg/day PO as a single dose, not to exceed
100 mg/day for a duration of 3-10 yr.
adverse events, including dosage related
hemolytic anemia, especially in patients with glucose-6-
phosphate dehydrogenase deficiency, pancreatitis, renal complications
(acute tubular necrosis, acute renal failure, albuminuria), increased
liver enzymes, psychosis, tinnitus, peripheral neuropathy, photosensitivity,
and a hypersensitivity syndrome with fever, rash, hepatic
damage, and malaise. A lepra reaction may occur with treatment,
which is a nontoxic, paradoxical worsening of lepromatous leprosy
with the initiation of therapy. This hypersensitivity reaction is not an
indication to discontinue therapy. Dapsone should be used with
caution in patients with glucose-6-phosphate dehydrogenase deficiency
or taking other folic acid antagonists. Dapsone levels can
decrease with concomitant rifampin and can increase with concomitant
clotrimazole.
Routine laboratory monitoring includes CBC weekly during the 1st
mo of therapy, weekly through 6 mo of therapy, and then every 6 mo
thereafter. Other periodic assessments include kidney function with
creatine levels and urinalysis and liver function tests.
binding to the mycobacterial DNA at guanine sites. It has a slow
bactericidal activity against M. lepra
Patients typically develop a pink to brownish-black discoloration of the skin and should be informed of this in advance. Eosinophilic and other forms of enteritis, sometimes requiring surgery, have been reported. Clofazimine has some anti-inflammatory and anti-immune activities. Thus, erythema nodosum leprosum may not develop in patients treated with this drug
Because Isoniazid inhibits the metabolism of carbamazepine and phenytoin, isoniazid can potentiate the adverse effects of thi sdrugs, for example nystagmus and ataxia
C: adverse effect is a dosage-related, reversible pink to tan-brown discoloration of the skin and conjunctiva.
Clofazimine has some anti-inflammatory and anti-immune activities. Thus, erythema nodosum leprosum may not develop in patients treated with this drug