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RESPIRATORY DRUGS

dr. SUFI DESRINI M.Sc

http://www.freesfx.co.uk
@ www.iloveppt.org
Learning Objectives

Mucoactiveagents

Cough suppressants
(antitussives)

Bronchodilator

Tuberculosis drugs

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Types of cough

1.Use cough:productive treated by mucoactive agents


(expectorants, mucolytics, etc)

2. Useless cough:dry, non-productive not associated with


sputum and treated by antitussive

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The physiology of mucus and sputum
production in the respiratory system

The main function of the respiratory system ?

Tissues of the respiratory tract are thin and


delicate, and become thinnest at the surfaces
of the aveoli, where gaseous exchange occurs

The body has a number of mechanisms which


protect these tissues and ensure that debris
and bacteria do not reach them.
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The physiology of mucus and sputum production in
the respiratory system

cilia trap large pieces of debris and waft them out of the airways

The reflexes of sneezing and coughing help to expel particles from


the respiratory system and the production of mucus keeps the
tissues moist and helps to trap small particles of foreign matter

Mucus production in the airways is normal. Without it, airways


become dry and malfunction.

This results in the urge to cough and expectorate this mucus as sputum. Sputum
expectoration is not normal and there is always an underlying pathological cause.

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SPUTUM PRODUCTION

Irritation of the respiratory system causes both inflammation of


the air passages and a notable increase in mucus secretion.

A person may become conscious of swallowing the mucus or the inflammation


may trigger a coughing reflex so that they expectorate these secretions as
sputum.

the inflammation of the mucosa is responsible for sputum


production rather than any of the other changes that occur in
diseased lung tissue (Jeffrey Maestrelli et al, 2001).

Expectorated sputum contains lower respiratory tract secretions,


as well as secretions from the nose, mouth and pharynx, and
cellular debris and micro-organisms (Rubin, 2002). In some
disease processes, the sputum changes in nature and colour.

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SPUTUM PRODUCTION

Sputum production is associated with


many lung disease processes and sputum
may become infected, stained with blood
or contain abnormal cells.

Constant coughing to clear the sputum has


an effect on the smooth muscle of the
bronchioles which becomes hypertrophied
(enlarged or overgrown). This in turn
causes more mucus glands to develop.

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Mucoactive agents

Expectorants Mucolytic or
mucoregulators mucokinetics

Interfere with Mucokinetics : Act on


DNA/F-actin network cilia and increase
to regulate secretion mucocilary clearance

Carbocysteine :
antioxidant classic mucolytics
restore the depolymerise mucin
viscoelastic glycoproteins
properties of mucous

peptides mucolytics
:depolymerise DNA
and F-actin polymer
networks
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Classic mucolytics

has significant
The prototype antioxidant
antioxidant
agent : N- and anti-
and anti-
acetyl cysteine inflammatory
inflammatory
(NAC) properties
properties.

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N-acetyl cysteine (NAC)

as an aerosol
dissociates
mucin
disulphide
bonds and can also
NAC decreased
other protect against
airway
disulphide free radical
inflammation
bond crossed damage
linked gel
component to
reduce
viscosity

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NAC decreased airway inflammation

Reducing lysozyme and Inhibiting neutrophils and


lactoferrin concentrations monocytes chemotaxis
in smokers and oxidative
burst responses in vitro

Reducing the activation Inhibiting the adherence


and number of bacteria to ciliated
of neutrophils and epithelial cells in vitro
macrophages

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N-acetyl cysteine (NAC)

There is good evidence of prove that oral


NAC has stabilized disease in idiopathic
pulmonary fibrosis
And may also reduce exacerbation rates in
chronic bronchitis

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N-acetyl cysteine (NAC)

NAC an antidote for hepatotoxicity e.c


acetaminophen overdose

A powerful antioxidant and potential


therapeutic agent in the treatment of cancer,
heart disease, HIV infection, heavy metal
toxicity, and other disease characterized by
oxidative damage

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N-acetyl cysteine (NAC)

Rapidly
Deacetylated
absorbed into
and
various
metabolized in
tissues
the intestines
following an
and liver
oral dose

Peak plasma
Its levels:
metabolites approx.1 hour
incorporated after an oral
into proteins dose.
and peptides Biovailability
only 4-10%
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N-acetyl cysteine (NAC)

NAC can be taken orally, inhalation or


instillation

Side effects :
GIT irritation (oral)
Burning sensation in airways
(inhalation)
Bronchospasm (inhalation)
Sulphorous taste & odor (inhalation)

Oral dose : 600-1.500 mg daily in 3


divided doses

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N-acetyl cysteine (NAC)

NAC inhibits
cytotoxicity of
NAC might
Warning and the cancer
reduce thc
chemotherapy
Contraindicati drug cisplatin
action of
ons: doxorubicine
(Roller et al.,
antineoplastic
1998; Miyajima
et al., 1999)

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Other Mucolytics (Classic )
Erdosteine and fudosteine :

Erdosteine :
an antioxidant with mucolytic properties and
also reduces bacterial adhesiveness

A small randomized controlled trial showed


fewer exacerbations, reduced hospitalization
time and improved quality of life in patients
with COPD that were treated with erdosteine
when compared with placebo

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Other Mucolytics (Classic )

Fudosteine is a cysteine with greater bio-


availability than NAC.
It reduces hypersecretion by down regulation of
mucin gene expression

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Peptide Mucolytic

Dornase alpha :

proteolytic enzyme that cleaves DNA polymers


and is used in the long term of mucous
hypersecretion in cystic fibrosis (CF)
Pulmozyme
(dornase alfa) Inhalation Solution
These agents need to be evaluated further in
clinical trial

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PULMOZYME

is a sterile, clear, colorless, highly purified


solution in single-use ampules.

Each ampule delivers 2.5 mL of the solution


to the nebulizer bowl.

Each mL of aqueous solution contains 1 mg


dornase alfa, calcium chloride dihydrate
(0.15 mg) and sodium chloride (8.77 mg).

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Current Recommendations for Clinical
Use of Mucolytic Drugs

Even though there is abundance of mucoactive drugs which


are available only a few are recommended for use in
respiratory hypersecretory disease.

Hypertonic Saline :

Aerosol using hypertonic saline (saline, urea, or ascorbic


acid) has been thought to induce ciliary motility,
proteolysis and mucous liquefaction
The metanalysis : nebulized HS improved mucociliary
clearance in CF but was less efective than DNAase
An effective tool for the generation of sputum for
diagnostic and research purposes

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Current Recommendations for Clinical
Use of Mucolytic Drugs

Guaifenesin (Glyceryl Guaiacolate)


May help to reduce bronchial sputum surface tension
Mainly for symtomatic treatment of cough producing small
quantities of thick viscous secretion
Has not been shown to be useful in randomized clinical
trials

Ion Channel Modifiers

Trycylic nucleotides (uridine triphosphate and adenosisne


triphosphate) regulate ion transport through P2Y2
purinergic receptors that increase intracellular calcium
Nebulized uridine triphosphate enhances mucociliary
clearance in healthy subjects

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GG
Mekanisme kerjanya
GG memiliki aktivitas sebagai ekspektoran dengan
meningkatkan volume dan mengurangi kekentalan
sputum yang terdapat di trakhea dan bronki. Dapat
meningkatkan reflek batuk dan memudahkan untuk
membuang sputum.
Akan tetapi bukti objektif masih sedikit.
Dose : Oral 200400 mg/4 hours, max dose
2400 mg/d
adult : 3 x12 tab

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Mucokinetics

These agents act on cilia and increase


mucociliary clearance
Mucokinetic medication includes
bronchodilators, tricyclic nucleotides and
ambroxol
Surfactants also promote cough clearance
of mucous by decreasing the surface
adhesion between mucous and airway
epithelium

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Mucokinetics
salmeterol could restore secretory
functions in CF airway sub-mucosal
glands serous cells

Bronchodilators

2 adrenergic agonists can enhance


mucociliary clearance in patients
with airway

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Mucokinetics

to stimulate surfactant and mucous


secretion, promoting normalization of
mucous viscosity in viscid secretions.

Ambroxol

A recent systematic review towards evidence


of generalized benefit using ambroxol for a
range of parameters including secretolytic
activity (promoting mucous clearance), anti
inflammatory and anti oxidant activity and
exerts local anesthetic effect
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AMBROXOL

Dosis:
Dewasa: sehari 3 kali 1 tablet.
Anak-anak 5 - 12 tahun : sehari 3
kali 1/2 tablet.
Anak-anak 2 - 5 tahun : sehari 3
kali 7,5 mg
Anak-anak di bawah 2 tahun :
sehari 2 kali 7,5 mg

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Mucoactive drugs and their potential
mechanisms of action

Mucoactive drugs Potential mechanism of action


Expectorants: Increases secretion volume and/or
Hypertonic saline hydration
Guaifenesin Stimulates secretion and reduces
mucus viscosity
Mucoregulators: Metabolism of mucus producing
Carbocysteine cells, antioxidant and antiinflammatory
Anticholinergic agents effects, modulates mucus production.
Glucocorticoids
Decreases secretion volume
Macrolide antibiotics
Reduces airway inflammation and
mucin secretion.
Reduces airway inflammation and
mucin secretion

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Carbosystein:
Nama dagang di Indonesia: Rhinathiol
Bentuk sediaan:
Capsul 375 mg
Adult syr 250 mg/5 mL
Infants syr 100 mg/mL
Dosis : awal 3x2 caps per hari, dan
bila gejala membaik menjadi 4 x 1
caps perhari
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Mucoactive drugs and their potential
mechanisms of action
Mucoactive drugs Potential mechanism of action
Mucolytics: Breaks disulphide bonds linking
N-Acetylcysteine mucin polymers
N-Acystelyn Antioxidant and anti-inflammatory
Erdosteine
effects.
Dornase alfa
Increases chloride secretion and
Gelsolin
Thymosin 4 breaks disulphide bonds
Dextran Modulates mucus production and
Heparin increases mucociliary transport
Hydrolyses the DNA in mucus and
reduces viscosity in the lungs
Severs actin filament cross-links
Severs actin filament cross-links
Breaks hydrogen bonds and
increases secretion hydration
Breaks both hydrogen and ionic
bonds
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Mucoactive drugs and their potential
mechanisms of action

Mucoactive drugs Potential mechanism of action

Mucokinetics:- Improves cough clearance by


Bronchodilators increasing expiratory flow
Surfactants Decreases sputum/mucus
Ambroxol adhesiveness
Stimulates surfactant production and
inhibits neuronal sodium channels

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BRONCHODILATOR

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INTRODUCTION

Make breathing easier by relaxing the muscles in the


lungs and widening the bronchi

Some bronchodilators help clear mucus from the


lungs and reduce inflammation

The way in which they widen or dilate the airways

beta-agonists
Anticholinergic
Phosphodiesterase (PDE)inhibitors : Theophylline

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INDICATION

Asthma

Bronchiectasis

Chronic obstructive pulmonary disease (COPD) :


breathlessness, cough, sputum production

Reliev worsening symptoms short actingnot the


best way to control day-to-day symptoms

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BETA-AGONISTS

Mainly affect the muscles around the airways

Types according to how long they work short-


acting and long-acting drugs

Short-acting :

Work quickly (3-5 minutes)


A reliever medications
can also to reduce symptoms is caused by spesific situation
such as exercise, going out in the cold air
Usually inhaled by a MDI or in liquid form from a nebulizer
device

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SHORT-ACTING
Albuterol/salbutamol
Bambuterol
Fenoterol
Isoetherine
Isoproterenol
Levalbuterol
Metaproterenol
Terbutaline
Tornalate
Pirbuterol

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LONG-ACTING
Formoterol
Salmeterol

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EPINEPHRINE

An effective, rapid-acting bronchodilator when injected sc


(0,4 mL of 1:1000 solution) or inhaled as a microaerosol
from a pressurized canister (320 mcg per puff).

Maximal bronchodilation is achieved 15 minutes after


inhalation and lasts 60-90 minutes

Stimulates alpha and beta-1 as well as beta-2


receptostachycardia, arrhytmias and worsening of angina
pectoris

Its use in asthma has been displaced by other beta2


selective agents

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ISOPROTERENOL

A potent bronchodilator
Inhalation : 80-120 mcg maximal
bronchodilation within 5 minutes
Duration of action : 60-90 minutes
United Kingdom, 1960 an increase in the
asthma mortality use of high dose oh inhaled
isoproterenol
Now rarely used for asthma

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BETA-2 SELECTIVE DRUGS

Particularly albuterol the most widely used


sympathomimetics for treatment of the
bronchoconstriction of asthma at present

Differ structurally from epinephrine in having a


larger substitution on the amino group and inthe
position of hydroxyl groups on the aromatic ring

Effective after inhaled or oral administration and


have a long duration of action

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BETA-2-SELECTIVE DRUGS

Albuterol, terbutaline, metaproterenol, and pirbuterol


are available s metered-dose inhalers

Given by inhalation bronchodilation equivalent to


that produced by isoproterenol

Maximal bronchodilation : 15-30 minutes

Duration of action : 3-4 hours

Can be diluted in saline for administration from a


hand-held nebulizer

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BETA-2-SELECTIVE DRUGS

Albuterol and terbutaline also available in tablet form

Usual regimen : 1 tablet 2-3 times daily

Adverse effects : tremor, nervousness and weakness

Only terbutaline is available for SC injection (0,25 mg)


for severe asthma requiring emergency treatment when
aerosol therapy is not available or has been effective

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BETA-2-SELECTIVE DRUGS

A new generation : salmeterol and


formoterol long-acting

Potent selective beta-2 agonists

Duration of action : 12 hours or more

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BETA-2-SELECTIVE DRUGS

Toxicities:

Possible cardiac arrhytmyas


hypoxemia acutely
Tachyphylaxis
When taken an as needed basis for relieve symptoms safe
and effective

Chronic treatment increase risk of adverse effect :

For some individuals carrying a specific genetic variant for


the beta receptor
Patients homozygous for arginine at the B-16 locus of the
beta receptor (16% in the Caucasian population and more
commonly in african americans)

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METHYLXANTHINE DRUGS

Methylxantine : THEOPHYLLINE, theobromine, caffeine

A theophylline preparation commonly used for therapeutic purpose


: aminophylline ( a theophylline ethlenediamine complex)

Inhibit several members of PDE enzyme family

PDE hydrolyze cyclic nucleotides inhibition results in higher


concentrations of intracellular cyclic AMP (cAMP) and cGMP

cAMP is responsible for a myriad of cellular functions stimulation


of cardiac function, relaxation of smooth musclea and reduction in
the immune and inflammatory activity of specific cells
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METHYLXANTHINE DRUGS
Theophylline should be used only where methods to measure
theophylline blood levels are available

Is metabolized by liver

Improves long-term control of asthma when added to inhaled


corticosteroids

Inexpensive

Orally :prompt-release : 3-4 mg/kg every 6 hours

The dosage may be increased at intervals of 2-3 days until


therapeutic plasma concentration are achieved (10-20 mg/L)
or until adverse effects develop

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ANTIMUSCARINIC AGENTS

Muscarinic antagonists competitively inhibit the effect of


acethylcoline at muscarinic receptor

Effective bronchodilators

Protype : atropine

Derivate of atropine : ipratropium bromide inhalation can be


delivered in high doses because it is poorly absorbed into the
circulation and does not readily enter the central nervous system

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TUBERCULOSIS DRUGS

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INTRODUCTORY

The history of What was considered


tuberculosis (TB) until then as a disease
Tuberculosis (TB)
changed dramatically to be treated in
remains one of the
after the introduction sanatoria turned into
leading public health
of the first drugs with a malady that could
problems worldwide.
anti-mycobacterial be managed with
activity. antibiotics.

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BIG PROBLEM

However, not long after the first


antibiotic was introduced in 1944, drug
resistance emerged, mainly due to the
use of streptomycin as monotherapy

With the discovery of several other


drugs with anti-TB activity, multidrug
therapy became fundamental for the
control of the disease by promoting the
cure of the patients and interrupting the
chain of transmission

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The chemotherapy of tuberculosis started with
the introduction of streptomycin in 1946

By 1955, the combination of streptomycin, p-


aminosalicylic acid and isoniazid was adopted
as a standard treatment by the western world.

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TB TREATMENT
The aims of TB treatment are:
To cure the patient and restore quality of life
and productivity;
To prevent relapse of TB;
To reduce the transmission of TB to others;
To prevent the development and transmission
of drug resistant TB.

("Treatment of Tuberculosis guidelines", WHO, Geneva, 2011, 29 www.who.int/tb/en/)

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RCOMMENDED DOSES OF FIRST LINE
ANTI-TB DRUGS FOR ADULTS
Drug Daily 3 times per week

Dose & range Maximum (mg) Dose & range Daily maximum
(mg/kg BW) (mg/kg BW) (mg)

Isoniazid 5 (4-6) 300 10 (8-12) 900

Rifampicin 10(8-12) 600 10 (8-12) 600

Pyrazinamide 25 (20-30) - 35 (30-40) -

Ethambutol 15 (15-20) - 30 (25-35) -

Streptomycin 15 (12-18) 15 (12-18) 1000

Patients aged over 60 years may not be able to tolerate more than 500750 mg daily, so
some guidelines recommend reduction of the dose to 10 mg/kg per day in patients in this
age group (2). Patients weighing less than 50 kg may not tolerate doses above 500750
mg daily (WHO Model Formulary 2008, www.who.int/selection_medicines/list/en/)

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New patients with pulmonary TB

New patients are defined as those who have no history


of prior TB treatment or who received less than 1
month of anti-TB drugs (regardless of whether their
smear or culture results are positive or not)

New patients with pulmonary TB should receive a


regimen containing 6 months of rifampicin:
2HRZE/4HR

WHO no longer recommends omission of ethambutol during the intensive phase of treatment for
patients with non-cavitary, smear-negative PTB or EPTB who are known to be HIV-negative. In
tuberculous meningitis, ethambutol should be replaced by streptomycin.
H = isoniazid, R= rifampicin, Z = pyrazinamide, E= ethambutol, S = streptomycin
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Dosing frequency for new TB
patients
Dosing frequency Comment

Daily Daily optimal


Daily 3 x per week Acceptable alternative
for any new TB patient
receiving directly
observed th/
3 x per week 3 x per week Acceptable alternative
provided that the patient
is receiving directly
observed therapy and is
not living with HIV or
living in an HIV-
prevalent setting

Note: Daily (rather than three times weekly) intensive-phase dosing may help to prevent
acquired drug resistance in TB patients starting treatment with isoniazid resistance
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Second-line agents
Amikacin (15 mg/kg/d)

Aminosalisalicylic acid (8-12 g/d)

Capreomycin (15 mg/kg/d)

Ciprofloxacin (1500 mg/d,divided)

Clofazimine (200 mg/d)

Cycloserine (500-1000 mg/d, divided)

Ethionamide (500-750 mg/d)

Levofloxacin (500 mg/d)

Rifabutin ( 300 mg/d2 )

Rifapentine (600 mg once or twice weekly)

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ISONIAZID

The most active drug for TB caused by susceptible strains

It is small (MW 137)

The structural similarly to pyridoxine

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ISONIAZID

INH inhibits synthesis of mycolic acids

Mycolic acids are essential components of mycobacterial cell walls

INH is a prodrug activated by KatG (the mycobacterial catalase


peroxidase)

The activated form forms a covalent complex with an acyl


carrier protein (AcpM) and KasA, a beta-ketoacyl carrier protein
synthetase blocks mycolic acid synthesis and kills the cell

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ISONIAZID

INH is readily absorbed from the GI tract

A 300-mg oral dose (5 mg/kg in children) achieves peak


plasma concentration of 3-5 mcg/mL within 1-2 hours

Diffuses readily into all body fluids and tissues

Metabolism is genetically determined acetylation by liver


N-acetyltransferase

The average plasma concentration in rapid acetylators is


about one third to one half of that in slow acetylators, and
average T1/2 are less than 1 hour and 3 hours, respectively

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ISONIAZID

INH metabolites and a small amount of unchanged drug are


excreted, mainly the urine

The typical dosage : 5 mg/kg/d

A typical adult dose is 300 mg once daily

If serious infection or alabsorption is a problem up to 10


mg/kg/d

A 15 mg/kg dose or 900 mg a twice-weekly dosing regimen


in combination with a second antiTB agent ( eq rifampin 600
mg)

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ISONIAZID

For latent TB : 300 mg/d (5 mg/kg/d) or 900 mg


twice weekly for 9 months

Adverse reaction:

Fever and rashes


Direct toxicity : INH-induced hepatitis
Peripheral neuropathy slow acetylators and pt with
predisposing conditions : malnutrition, alcoholism, diabetes,
AIDS, and uremia
Central nervous syst rare :memory loss, psychosis, seizures
Reduce metabolism of phenytoin blood level
Tinnitus, hematologic abn, GI discomfort

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RIFAMPIN

A semisynthetic derivate of rifamycin

It is active in vitro against gram + and gram _ cocci, some


enteric bacteria, mycobacteria and chlamydia

Binds to the beta subunit of bacterial DNA-dependent RNA


polymerase and thereby inhibits RNA synthesis

Well absorbed after oral administration

Excreted mainly through the liver into bile enterohepatic


recirculation deacylated metabolite in feces (major) and a
small amount in the urine
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RIFAMPIN

Dosage : 600 mg/d (10 mg/kg/d)

Must be administered with INH or other antiTB drugs to patient


with active TB to prevent emergence of drug-resistant
mycobacteria

600 mg daily or a twice weekly effective in combination with


other agents

600 mg daily for 4 months as a single drugalternative to INH


prophylaxis for patient with latent TBC only who are unable to
take INH or who have had exposure to a case of active TB
caused by an INH-resistant, rifampin-susceptible strain.
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RIFAMPIN
Orange color to urine, sweat, tears,
and contact lenses
Rashes, thrombocytopenia, and
nephritis (occasional)
Cholestatic jaundice
Hepatitis
Light-chain proteinuria
If administrated < 2 weekly flu-like
Adverse syndromefever,chills, myalgia,
anemia, thrombocytopenia and acute
Reactions: tubular necrosis
Induce CYP450 isoforms(CYP 1A2, 2C9,
2C19, 2D6,3A4) INCREASES
elimination numerous other drugs:
methadone, cyclosporine, protease
inhibitors, contraceptives, some
anticonvulsants significantly lower
serum levels

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ETHAMBUTOL
A synthetic, water-soluble, heat-soluble compound, the dextro-
isomer

Susceptible mycobacterium TB inhibited by ethambutol 1-5


mcg/mL.

Inhibits mycobacterial arabinosyl transferases which are encoded


by the embCAB operon
Arabynosil transferases involved in polymerization reaction of
arabinoglycan (an essential component of the mycobacterial cell
wall)

Well absorbed from the gut

After ingestion of 25 mg/kg a blood level peak : 2-5 mcg/mL is


reached in 2-4 hours
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ETHAMBUTOL

20% Excreted in feces and 50% in urine in


unchanged form

Accumulates in renal failure

If creatinine clearance < 10 mL/min Dose should be


reduced by half

Crosses the blood-brain barrier only when the


meninges are inflamed

Always given in combination with other antiTB drugs

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ETHAMBUTOL

15-25 mg/kg, Adverse


single daily reactions :
dose, in
combination
with INH or Hypersensitivity is rare
rifampin

Most common :
TB meningitis retrobulbar neuritis loss
the higher visual acuity and red-
dose green blindness dose-
related at dosages : 25
mg/kg/d continued for
several months

Contra indicated in
children

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PIRAZYNAMIDE (PZA)

A relative of nicotinamide, stable, and slightly soluble in water

Inactive at neutral pH

At pH 5,5 inhibits tubercle bacilli and some other


mycobacteria at concentration 20 mcg/mL
PZA is taken up by macrophages and exerts its activity
against mycobacteria residing within the acidic environment of
lysosomes
Converted to pyrazinoic acid by mycobacterial pyrazinamidase
which encoded by pncA

The drug target and mechanism : unknown

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PZA

Dosage 25 mg/kd/d achieves serum concentration 30-50


mcg/mL at 1-2 hours after oral administration

Well absorbed from the GI tract

Widely distributed in body tissues, incl inflamed meninges

T12 : 8- 11 hours

The parent compound is metabolized by the liver

The metabolites are renally cleared in hemodyalisis pt or the


creatinine clearence < 30 mL/mg/kg 25-35 mg/kg 3 x weekly

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PZA

An important front-line drug used in conjuction with lNH and


rifampin in short course regimen as asterilizing agent active
against residual intracellular organism that may relapse

Adverse Effects:

Hepatotoxicity (in 1-5% pt)


Nausea
Vomiting
Drug fever
Hyperuricemia acute gouty arthritis

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STREPTOMYCIN

Streptomycin is bactericidal in action.

It inhibits protein synthesis by combining irreversibly with the


30S subunit of the70S ribosomes, found normally in
prokaryotes.

It therefore changes its shape so that it inhibits protein


synthesis by causing a misreading of messenger RNA
information.

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STREPTOMYCIN

Mainly used as a second-line agent for treatment TB

Daily therapy: 15 mg/kg IM qDay; no more than 1 g/day


Twice weekly therapy: 25-30 mg/kg IM 2 times/week; no more
than 1.5 g/day

IM well absorbed IM or IV

Only in combination with other agents to prevent resistance

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STREPTOMYCIN

Protein Bound: 34%

Half-life elimination: newborns: 4-10 hr; adults:


2-4.7 hr, prolonged with renal impairment

Peak Plasma Time: within 1 hr

Excretion: urine (90% as unchanged drug);


feces, saliva, sweat, & tears (<1%)

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STREPTOMYCIN

Adverse Effects:
Fever, skin rashes, and other allergic
manifestations
Pain at the injection site
Disturbance of vestibular function-
vertigo and loss of balance
Vestibular toxicity irreversible
During pregnancy deafness in the
newborn
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Thank You