Drugs for Chronic Obstructive Drugs for Chronic Obstructive Pulmonary DiseasePulmonary Disease

Chronic obstructive Pulmonary disease

Syndromes•Asthma - acute episodes of reversible

bronchoconstriction cause by underlying

airway inflammation.

• Chronic bronchitis- excessive mucus

production due to hyperplasia and hyper

functioning of mucus secreting goblet cells.

• Emphysema - abnormal and permanent

enlargement of respiratory air spaces of their

walls with fibrosis.

     Number of non-institutionalized adults who currently have asthma: 15.7 million

·        Number of children who currently have asthma: 6.5 million

·        Number of hospital emergency department visits: 1.8 million

·        Number of deaths: 3,780

Asthma statistics

Genetic predisposition

Airway responsiveness

Asthma symptoms

Airway limitation

Enviromental exposure

Airway inflammation

inhaled allergens are ingested by a type of cell known as antigen presenting cells, or APCs. APCs then "present" pieces of the allergen to other immune system . In

asthmatics, IMMUNE CELLS ARE FORMED -(TH2), The resultant TH2 cells activate the humoral immune system which produces antibodies against the inhaled allergen. Later,

when an asthmatic inhales the same allergen, these antibodies "recognize" it and activate a humoral response. Inflammation results: chemicals are produced that cause

the airways to constrict and release more mucus, and the cell-mediated arm of the immune system is activated.

THE FOLLOWING DRUGS ARE KNOWN TO CAUSE THE FOLLOWING DRUGS ARE KNOWN TO CAUSE REACTION AMONG ASTHMATICS:REACTION AMONG ASTHMATICS:

1.1. ASPIRINASPIRIN aspirin sensitivity – 9 to 44%aspirin sensitivity – 9 to 44%2. NSAIDS2. NSAIDS3. ACETAMINOPHEN3. ACETAMINOPHEN 6 – 8% 6 – 8% 4. BETA-BLOCKERS4. BETA-BLOCKERS Can exacerbateCan exacerbate5. ACE – INHIBITORS5. ACE – INHIBITORS Develop coughDevelop cough

Agents Used to treat Agents Used to treat COPDCOPD

I – Bronchodilators

A. Methylxanthines

B.Adrenergic agonists

(Sympathomimetics)

C. Muscarinic antagonist

(Anticholinergics)

II – Mediator Release Inhibitors

A. Cromolyn Sodium (Intal)

B. Corticosteroids

C. IgE BLOCKER

D. Antieukotriene drugs

A. RELIEVERS

1. SHORT ACTING B2 AGONIST

- SALBUTAMOL

- TERBUTALINE

2. ANTICHOLINERGIC

- IPRATROPUIM

-ATROPINE

B. CONTROLLERS (MAINTENANCE)

1. MEDIATOR RELEASE INHIBITORS

- CROMOLYN

- INHALED GLUCOCORTICOIDS

- LEUKOTRIENE MODIFIERS

- MONTELUKAST

-ZILEUTON

5.ORAL

GLUCOCORTICOSTEROIDS

4. LONG ACTING B2 AGONIST

-SALMETEROL

-FORMETEROL

5. SUSTAINED RELEASE THEOPHYLLINE

DRUGS FOR ASTHMA MANAGEMENT

MethylxanthinesMethylxanthinesDegree of Degree of

BronchodilationsBronchodilations

EnprofyllineEnprofylline ++++ ++++

CaffeineCaffeine ++

TheobromineTheobromine ++

TheophyllineTheophylline +++ +++

(Prototype : Theophylline)(Prototype : Theophylline)

MethylxanthinesMethylxanthines

1. Inhibits cAMP phosphodiesterase which leads 1. Inhibits cAMP phosphodiesterase which leads to to cAMP – smooth muscle relaxation cAMP – smooth muscle relaxation bronchodilation.bronchodilation.

xanthinxanthinee

5’ AMP5’ AMP

Cyclic AMP Cyclic AMP phosphodiesterasephosphodiesterase

Cyclic 3’5 AMP Cyclic 3’5 AMP

Mechanism of action

2. Inhibits the re-uptake of catecholamines 2. Inhibits the re-uptake of catecholamines which can elevate cyclic AMP. Theophylline is an which can elevate cyclic AMP. Theophylline is an adenosine receptor antagonist adenosine receptor antagonist

Membrane Membrane receptorsreceptors

Membrane Membrane receptorsreceptors

Theophylline Theophylline antagonizes antagonizes AdenosineAdenosine

Theophylline Theophylline antagonizes antagonizes AdenosineAdenosine

AdenosineAdenosine(endogenous (endogenous

mediator)mediator)

AdenosineAdenosine(endogenous (endogenous

mediator)mediator)

Pharmacologic Effects:Pharmacologic Effects:A. Respiratory

system1. Rapid relaxation of bronchial sm.

Muscle – bronchodilation

2.Decrease histamine release

3.Stimulate ciliary transport of mucus

4. Improve respiratory performances by

improving contractility of the diaphragm

and by stimulating the medullary

respiratory center.

Pharmacologic Effects:Pharmacologic Effects:B.Effects on other

systems

Caffeine - (+)

1. Heart (+) chronotropic and inotropic effect cardiac stimulation

Theobromine - (++)

Theophylline -

(+++)Enprofylline - (++

++)

Pharmacologic Effects:Pharmacologic Effects:B.Effects on other

systems1. Pulmonary and peripheral vasodilatation ( B.P)

3.Stimulation of gastric acid and pepsinogen release.

2. alertness and cortical arousal medullary stimulation – can cause severe nervousness and seizures.

4. Diuresis

Pharmacokinetics : Prototype drug Pharmacokinetics : Prototype drug TheophyllineTheophylline

• rapidly and completely absorb from GIT

• metabolize in the liver by oxidation and demethylation

• half life – children – 3.5 hrs ; Adult – 8-9 hrsBronchodilator effect is achieve at bld levels of 10-20 mg/ml

(above this is associated with greater toxicity)

* Aminophylline – is a theophylline – ethylene diamine complex

Drug Drug Interactions Interactions

A. Drugs that theophylline effects1. Cimetidine2. Erythromycin , troleandomycin3. Oral contraceptives

B. Drugs that effectiveness of theophylline1. Lithium2. blockers3. Barbiturates4. Beta 5. Phenytoin

HalothaneHalothane - given with theophylline may result - given with theophylline may result to cardiac dysrhythmiasto cardiac dysrhythmias

Adverse EffectsAdverse Effects

1. Vomiting and GI bleeding 2. Cardiac arrhythmais 3. Nervousness , seizures , behavioral problems in children

Clinical Uses1. COPD2.Apnea in pre-term infants

* Initial loading dose – 5mg/kg – by infusion drip over 30 min.* Maintenance- 0.6 to 0.7 mg/kg/h* Pnts with heart or liver disease – 0.3 mg/kg/h

Beta Receptor AgonistBeta Receptor Agonist (Sympathomimetics)(Sympathomimetics)

- relaxes smooth muscle by cAMP as a

result of activation of adenylate cyclase.

cAMP cAMP cAMP cAMP

Activated by Activated by Beta agonistBeta agonist

Activated by Activated by Beta agonistBeta agonist

ATPATPATPATP

Adenylate Adenylate cyclasecyclase

Adenylate Adenylate cyclasecyclase

AgentAgentss 1. Epinephrine- given subcutaneously / 1. Epinephrine- given subcutaneously /

aerosolaerosol2. Ephedrine2. Ephedrine

3. Isoproterenol3. Isoproterenol

4. B4. B22 Selective Selectivea.Metaproterenol (Alupent)a.Metaproterenol (Alupent)b.Terbutaline (Bricanyl)b.Terbutaline (Bricanyl)c.Fenoterol (Berotec)c.Fenoterol (Berotec)d.Pirbuterol d.Pirbuterol e.Procasterol (Meptin)e.Procasterol (Meptin)f.Bambuterol (Bambec)f.Bambuterol (Bambec)g.Salmeterol g.Salmeterol (Serevent) (Serevent)

1. Albuterol1. Albuterol(Ventolin)(Ventolin)

Comparison of Beta – Receptor agonist Comparison of Beta – Receptor agonist on Selectivityon Selectivity

Beta Beta 11

Beta Beta 22

RemarksRemarks

- highly potent - highly potent - orally active- orally active- safe- safe- less cardiac - less cardiac - - stimulationstimulation

++++++++++

2.2.TerbutalineTerbutaline(Bricanyl)(Bricanyl)

- more side - more side - effects than - effects than -- albuterolalbuterol

++++++++

3. Procaterol3. Procaterol (Meptin) (Meptin)

- more potent, - more potent, - more effective - more effective -- than albuterolthan albuterol

++++++++++

4. Fenoterol4. Fenoterol (Berotec) (Berotec)

Comparison of Beta – Receptor agonist Comparison of Beta – Receptor agonist on Selectivityon Selectivity

Beta Beta 11

Beta Beta 22

RemarksRemarks

- - more selective more selective - for lung tissue 2x - for lung tissue 2x - potent than - potent than - albuterol by - albuterol by aerosol aerosol -long acting -long acting

++++++++++

5. Pirbuterol5. Pirbuterol (Exirel) (Exirel)

- - improve cardiac improve cardiac performances performances

- more selective on - more selective on

lung tissuelung tissue

++++++++++

6.Epirephrine6.Epirephrine

-rapid onset more rapid onset more cardiac side cardiac side effects effects activity +++activity +++

++++++++

++++++++

Comparison of Beta – Receptor agonist Comparison of Beta – Receptor agonist on Selectivityon Selectivity

Beta Beta 11

Beta Beta 22

RemarksRemarks

7.Isoproterenol7.Isoproterenol - - cardiac side cardiac side effects effects

++++++++

++++++++

8.Metaproterenol 8.Metaproterenol // Alupent Alupent

-less effective -less effective than albuterolthan albuterol

++++

++++

Long acting beta – receptor agonist , are analogs of albuterol and are long acting(12 hrs) , more affinity to the beta 2 receptor , has slow onset of action .

1. salmeterol

2. formeterol

Adverse Adverse EffectsEffects

1. Cardiac effects – arrhythmias 2.CNS effect – stimulation3.Skeletal muscle tremor

Anticholinergics:Anticholinergics:

Mech. of Action – competitively inhibit the effects of acetylcholine at muscarinic receptors

- block the contraction of airway sm. muscle-block in secretion of mucus in response to vagal activity.- Very effective in achieving bronchodilation in patients with hyperreactive airway disease due to vagal stimulation.

Ipratropium bromide (AtroventIpratropium bromide (Atrovent))

- is a quarternary ammonium deriv of

atropine that is given by aerosol. It does

not cross Bld-Brain barrier and is poorly

absorb from GIT , thus minimizing Anti-

cholinergic side effects.

- useful in chronic bronchitis , emphysema

and in pnts who cannot tolerate Beta

receptors agonist.

Combivent – combination of albuterol + ipratropium bromide

Mediator Release InhibitorsMediator Release Inhibitors : : (MRI)(MRI)

• Cromolyn Na (Intal) – Mech. of action – it

stabilizes Mast cell membranes and prevent

release of mediators in response to various

stimuli.

• It inhibits both early and late Phase rxn to

antigen exposure.

• It inhibit release of histamine & leukotriene Dose – 20 mg inhaled 4x a day

ANTILEUKOTRIENE DRUGS

1. ZAFIRLUEKAST , MONTELEUKAST 1. ZAFIRLUEKAST , MONTELEUKAST (singulair)(singulair)

-are selective reversible inhibitor of the cysteinyl -are selective reversible inhibitor of the cysteinyl leukotriene 1 receptor ,thereby blocking the effects of leukotriene 1 receptor ,thereby blocking the effects of cysteinyl leukotrienescysteinyl leukotrienesdose : ADULT -10mgs , children -5 mgs Once a day at 6 pmdose : ADULT -10mgs , children -5 mgs Once a day at 6 pm

2. ZILEUTON- is a selective and specific inhibitor of 5 2. ZILEUTON- is a selective and specific inhibitor of 5 lipoxygenase ,preventing the formation of LTB4 and the lipoxygenase ,preventing the formation of LTB4 and the cysteinyl leukotrienecysteinyl leukotriene

Adverse effects :Adverse effects :1.1. Elevation of hepatic enzymes Elevation of hepatic enzymes zileuton and zafirlukast are inhibitors of cytochrome P450zileuton and zafirlukast are inhibitors of cytochrome P450 both drugs increases levels of warfarinboth drugs increases levels of warfarin2. Headache and dyspepsia 2. Headache and dyspepsia 3 . Eosinophilic vasculitis ( CHURG- STRAUSS SYNDROME )3 . Eosinophilic vasculitis ( CHURG- STRAUSS SYNDROME )

(SEE FIG 27.6 pg 319 LIPPINCOT )

CorticosteroidsCorticosteroids

MECHANISM OF ACTION:MECHANISM OF ACTION: -REDUCE THE SYNTHESIS OF ARACHIDONIC ACID BY -REDUCE THE SYNTHESIS OF ARACHIDONIC ACID BY

PHOSPHOLIPASE A2 AND INHIBIT THE EXPERSSION OFPHOSPHOLIPASE A2 AND INHIBIT THE EXPERSSION OF CYCLOOXEGENASE 2 ( COX 2)CYCLOOXEGENASE 2 ( COX 2)

- no direct effect on airway - no direct effect on airway -decreases the number and activity of inflammatory cells .-decreases the number and activity of inflammatory cells . Inhaled corticosteroids Inhaled corticosteroids 1.1. BudesonideBudesonide 3. flunisolide 3. flunisolide 2.2. Fluticasone Fluticasone 4. beclomethasone4. beclomethasone

SIDE EFFECTS : CANDIDIASIS ; SORE THROAT SIDE EFFECTS : CANDIDIASIS ; SORE THROAT

Systemic corticosteroidSystemic corticosteroid - prednisone - prednisone -methylprednisone -methylprednisone

Action of steroids on lungs Action of steroids on lungs 1. reduces hyperresposiveness of airways to a 1. reduces hyperresposiveness of airways to a

variety of bronchoconstrictor stimuli ( such as variety of bronchoconstrictor stimuli ( such as allergens , cold air , and exercise ) allergens , cold air , and exercise )

2 . Reverses mucosal edema 2 . Reverses mucosal edema 3. decreases the permeability of capillaries 3. decreases the permeability of capillaries 4. inhibit the release of leukotrienes 4. inhibit the release of leukotrienes

Advantages of using inhaled steroids Advantages of using inhaled steroids 1.1. Better asthma control ( fewer symptoms and Better asthma control ( fewer symptoms and

flare –ups )flare –ups )2.2. Decrease use of beta agonist and systemic Decrease use of beta agonist and systemic

steroids steroids 3.3. Improve lung function Improve lung function 4.4. Reduce the need for hospitalizationReduce the need for hospitalization

Monoclonal antibodies

OMALIZUMAB - - IS A RECOMBINANT DNA – IS A RECOMBINANT DNA – DERIVED MONOCLONAL ANTIBODIES THAT DERIVED MONOCLONAL ANTIBODIES THAT SELECTIVELY BINDS TO HUMAN IgE .SELECTIVELY BINDS TO HUMAN IgE .

- REDUCES BINDING OF IgE TO RECEPTORS IN - REDUCES BINDING OF IgE TO RECEPTORS IN MAST CELLS AND BASOPHILS MAST CELLS AND BASOPHILS

- GIVEN PARENTERALY TWICE WEEKLY - GIVEN PARENTERALY TWICE WEEKLY

EXPOSURE TO ANTIGEN

ANTIGEN AND IgE on MAST CELLS

MEDIATORS

( LEUKOTRIENES , CYTOKINES,etc )

EARLY RESPONSE

BRONCHOCONSTICTIONLATE RESPONSE

INFLAMMATION

ACUTE SYMPTOMS BRONCHIAL HYREPREACTIVITY

AVOIDANCE

CROMOLYN, STEROIDS ZILEUTON

STEROIDS , CROMOLYN,

LEUKOTRIENE

ANTAGONIST BRONCHODILATORS

phrasesphrases

wheezeswheezes

CyanosisCyanosis

More than 45 More than 45 mmHgmmHg

breathless

mild moderate severeRespiratory arrest

Walking, can lie down

talking ,prefers sitting

At rest , hunched forward

talksentences

words

alertness agitated agitated agitated

Use of accessory muscle

none usually

usuallyParadoxical breathing

Moderate ,end expiratory loud loud absent

paO2 Normal Less than 60mmHg

More than 60 mm Hg

paCO2 less than 45 mm Hg

Less than 45 mmHg

More than 45 mm Hg

Severity of asthma exacerbations

More than More than once a week once a week Daily

Nighttime Nighttime symptomsymptom

More than 2x a month

Less than Less than once a week once a week

More than More than once a week once a week

intermittentmild moderate

severe

Exacerbationbrief

Affects daily activity and sleep

Limits activity/ sleep

Daytime symptom

night

Once a week

Daily

Less than 2x a month

PEFR MORE THAN 80%

MORE THAN 80% 60- 80 % LESS

THAN 60%

CLASSIFICATION OF ASTHMA BASED ON SEVERITY

Clinical (Mngt) PharmacologyClinical (Mngt) PharmacologyHome or OPD Mngt of Asthma

A. Mild asthma ( attacks less than 2 per week) – inhaled Beta agonist (e.g albuteral) on an “as needed basis”

1. Acute attacks Inhaled short Beta agonist 3- 4x2.

B. M ILD PERSISTENCE (more than two attacks per week)

Long term control inhaled antiflammatory – Cromolyn or inhaled Corticosteroid – 200 – 400 mcg/day.

May use a combination of inhaled long actging beta 2 agonist + corticosteroid . SERETIDE 250 DISKUS ONCE A DAY

Seretide 250 diskus –contains salmeterol xinafoate Seretide 250 diskus –contains salmeterol xinafoate 50mcgs and fluticasone propionate 250mcgs50mcgs and fluticasone propionate 250mcgs

C. Moderate persistence ( daily attacks , PF =60- 80 % of C. Moderate persistence ( daily attacks , PF =60- 80 % of normal )normal )

1. acute attacks – short acting beta2 agonist 1. acute attacks – short acting beta2 agonist

2. long term control 2. long term control

medium dose corticosteroid 400-800mcgs /day+ long acting medium dose corticosteroid 400-800mcgs /day+ long acting beta2 agonist combination OR beta2 agonist combination OR

Seretide 250 diskus twice a day Seretide 250 diskus twice a day

D. SEVERE PERSISTENCE ( CONTIUOUS ATTACK AND PF of less D. SEVERE PERSISTENCE ( CONTIUOUS ATTACK AND PF of less than 60% of normal )than 60% of normal )

1. acute attacks – short acting beta 2 agonist 1. acute attacks – short acting beta 2 agonist

2. long term control 2. long term control

high dose corticosteroid 800mcg to 1,600 mcg per day high dose corticosteroid 800mcg to 1,600 mcg per day

+ long acting beta2 agonist combination + long acting beta2 agonist combination

Seretide 500 diskus –contains salmeterol xinafoate 50mcgs Seretide 500 diskus –contains salmeterol xinafoate 50mcgs

and fluticasone propionate 500mcgsand fluticasone propionate 500mcgs

3. sustained release theophylline 3. sustained release theophylline

Theophylline should be reserved for patients in whom symptoms remain poorly controlled despite combination treatment.

• If above regimen is not enough to control symptoms – add an oral conticosteroid – PREDNISONE 40-50 mgs /day for 5 days - Or methylprednisolone 16 mgs every other day

Hopitalized patients if :

1. No improvement within 2-6 hrs after corticosteroid treatment

2. High risk patient (hospitalization within one year)

3. Exacerbation is severe

4. There is further deterioration despite all medications

Treatment of STABLE COPD Treatment of STABLE COPD

MILD COPDMILD COPD - SHORT ACTING BRONCHODILATORSHORT ACTING BRONCHODILATOR

MODERATE COPDMODERATE COPD --REGULAR USE OF MORE THAN ONE BRONCHODILATOR REGULAR USE OF MORE THAN ONE BRONCHODILATOR - INHALED GLUCOCORTICOSTEROIDS- INHALED GLUCOCORTICOSTEROIDS

SEVERE COPDSEVERE COPD

-REGULAR USE OF MORE THAN ONE BRONCHODILATOR -REGULAR USE OF MORE THAN ONE BRONCHODILATOR INHALED GLUCOCORTICOSTEROIDS INHALED GLUCOCORTICOSTEROIDS -ANTIBIOTICS-ANTIBIOTICS-LONG TERM OXYGEN THERAPY-LONG TERM OXYGEN THERAPY

Other drugs for COPD

Alpha1 – proteinase inhibitors (Prolastine) –

use to treat emphysema caused by a

deficiency in alpha1 – proteinase a peptide

that inhibits elastase, in patients with the deficiency, elastase destroys lung parenchyma.Other Agents affecting the Respiratory

Tract Drugs Used to treat Rhinitis

1. Antihistaminics (Hi- receptors antagonist)

a. chlorpheniramine

b. diphenhydraminec.loratidine

secretion and parasympathetic activity

Drugs Used to treat Rhinitis (alpha) receptor agonist

A. Nasal aerosols 1.Epinephrine 2.Oxymetazoline 3.Phenylephrine

Constrictdilated arterials in nasal mucosa

3. Topical corticosteroids1 .Beclomethasone (Beconase)2. Fluticasone (Flixotide)3. Flunisolide (Nasalide)

4. Cromolyn Na

B. Administered orally 1.Phenylpropanolamine 2.Pseudoephedrine

3.Xylometazoline 4.Phenylephrine

EXPECTORANTSEXPECTORANTSA.A. VAGAL STIMULANTSVAGAL STIMULANTS

1.1. GLYCERYL GUIACOLATEGLYCERYL GUIACOLATE

2.2. SALT SOLUTIONSSALT SOLUTIONS

B. DIRECT STIMULANTSB. DIRECT STIMULANTS

1. POTASSIUM IODIDE1. POTASSIUM IODIDE

SATURATED SOLUTION (KISS)SATURATED SOLUTION (KISS)

2. BROMHEXINE2. BROMHEXINE

3. CARBOCISTEINE3. CARBOCISTEINE

4. AMBROXOL4. AMBROXOL

ANTITUSIVESANTITUSIVES

I. I. NARCOTIC ANTITUSSIVESNARCOTIC ANTITUSSIVES• HEROIN / MORPHINEHEROIN / MORPHINE• CODEINECODEINE

II. NON-NARCOTIC ANTITUSSIVESII. NON-NARCOTIC ANTITUSSIVES

A. MORPHINAN DERIVATIVES A. MORPHINAN DERIVATIVES

DEXTROMETHORPHANDEXTROMETHORPHAN

B. BENZYLISOQUINOLINESB. BENZYLISOQUINOLINES

NOSCAPINE/ NORCEINENOSCAPINE/ NORCEINE

HYDRASTINE / HOMARYLAMINEHYDRASTINE / HOMARYLAMINE

ANTITUSIVESANTITUSIVES

II. NON-NARCOTIC ANTITUSSIVESII. NON-NARCOTIC ANTITUSSIVESC. DIPHENYLAKYLAMINESC. DIPHENYLAKYLAMINES

CHLOPHENDIANOLCHLOPHENDIANOLLEVOPROPXYPHENELEVOPROPXYPHENE

D. PHENYLCYCLOPENTALKYLAMINESD. PHENYLCYCLOPENTALKYLAMINESCARAMIPHENCARAMIPHENCARBETAPENTANECARBETAPENTANE

E. MISCELLANEOUSE. MISCELLANEOUSBENZONATATEBENZONATATECLOBUTINOLCLOBUTINOLDIBUNATESDIBUNATES

CODEINECODEINE- PHENATHRENE DERIVATIVE OPIATE AGONISTPHENATHRENE DERIVATIVE OPIATE AGONIST- PPC: 1 TO 2 HOURS; DURATION: 4 HRSPPC: 1 TO 2 HOURS; DURATION: 4 HRS

ACTION:ACTION: DIRECT EFFECT ON THE CENTERDIRECT EFFECT ON THE CENTER DRYING EFFECTDRYING EFFECT DECREASE VISCOSITYDECREASE VISCOSITY ANALGESIC & SEDATIVE EFFECTANALGESIC & SEDATIVE EFFECT

ADVERSE EFFECT:ADVERSE EFFECT: NAUSEA & VOMITINGNAUSEA & VOMITING CONSTIPATIONCONSTIPATION DIZZINESSDIZZINESS PRURITUSPRURITUS TOLERANCE & PHYSICAL DEPENDENCETOLERANCE & PHYSICAL DEPENDENCE

DEXTROMETHORPHANDEXTROMETHORPHAN

- METHYL ETHER OR DEXTROROTATORY FORM OF METHYL ETHER OR DEXTROROTATORY FORM OF LEVORPHANOLLEVORPHANOL

- PPC: 15 – 30 MINS; DURATION: 6 - 8 HRSPPC: 15 – 30 MINS; DURATION: 6 - 8 HRS- USEFUL FOR CHRONIC NON-PRODUCTIVE COUGHUSEFUL FOR CHRONIC NON-PRODUCTIVE COUGH

SIDE EFFECTS:SIDE EFFECTS:

* NAUSEA* NAUSEA * DRYING EFFECT* DRYING EFFECT

* DIZZINESS* DIZZINESS

DRUG INTERACTIONS:DRUG INTERACTIONS:

* PENICILLIN* PENICILLIN *TETRACYCLINES*TETRACYCLINES

*SALICYLATES*SALICYLATES * PHENOBARBITAL* PHENOBARBITAL

* KISS* KISS

BROMHEXINEBROMHEXINE- SYSTEMICALLY ACTIVE MUCOLYTIC AGENT- SYSTEMICALLY ACTIVE MUCOLYTIC AGENT

ACTION:ACTION: Depolymerization of MucopolysaccharideDepolymerization of Mucopolysaccharide Direct Effect on Bronchial GlandsDirect Effect on Bronchial Glands Liberation of Lysosomal Enzymes producing cells Liberation of Lysosomal Enzymes producing cells

which digest mucopolysaccharide fiberswhich digest mucopolysaccharide fibers

INDICATIONS:INDICATIONS: ALL forms of TRACHEOBRONCHITISALL forms of TRACHEOBRONCHITIS Emphysema with BronchitisEmphysema with Bronchitis PneumoconiosisPneumoconiosis Chronic Inflammatory Pulmonary ConditionsChronic Inflammatory Pulmonary Conditions Bronchitis with BronchospasmBronchitis with Bronchospasm AsthmaAsthma

BROMHEXINEBROMHEXINE

SIDE EFFECT:SIDE EFFECT:

EPIGASTRIC DISTRESSEPIGASTRIC DISTRESS

DRUG INTERACTIONS: DRUG INTERACTIONS:

INCREASE ANTIBIOTIC INCREASE ANTIBIOTIC CONCENTRATIONCONCENTRATION

AMBROXOLAMBROXOL- MUCOKINETIC & SECRETOLYTIC- MUCOKINETIC & SECRETOLYTIC

ACTION:ACTION: INCREASE RESP. TRACT SECRETIONSINCREASE RESP. TRACT SECRETIONSENHANCE PULM. SURFACTANT ENHANCE PULM. SURFACTANT

PRODUCTIONPRODUCTIONSTIMULATES CILIA ACTIVITYSTIMULATES CILIA ACTIVITY

IMPROVED MUCUS FLOW & TRANSPORTIMPROVED MUCUS FLOW & TRANSPORT

(CILIARY CLEARANCE FACILITATES (CILIARY CLEARANCE FACILITATES EXPECTORATION)EXPECTORATION)

AMBROXOLAMBROXOLUSE:USE: SECRETOLYTIC THERAPHY IN ACUTE SECRETOLYTIC THERAPHY IN ACUTE

& CHRONIC BRONCHO-PULMONARY & CHRONIC BRONCHO-PULMONARY DISEASES ASSTD WITH ABNORMAL DISEASES ASSTD WITH ABNORMAL SECRETIONS & IMPAIRED MUCUS SECRETIONS & IMPAIRED MUCUS TRANSPORT.TRANSPORT.

SIDE EFFECT:SIDE EFFECT: NAUSEA & VOMITINGNAUSEA & VOMITINGRASHESRASHESCAN INCREASE ANTIBIOTIC CONC.CAN INCREASE ANTIBIOTIC CONC.

CARBOCISTEINECARBOCISTEINE(S-CARBOXYMETHYLCYSTEINE)(S-CARBOXYMETHYLCYSTEINE)

- MUCOREGULATOR IN RESP. TRACT MUCOREGULATOR IN RESP. TRACT DISORDERS CHARS BY EXCESSIVE OR DISORDERS CHARS BY EXCESSIVE OR VISCOUS MUCUSVISCOUS MUCUS

- ACT BY REGULATING AND ACT BY REGULATING AND NORMALIZING THE VISCOSITY OF NORMALIZING THE VISCOSITY OF SECRETION FROM THE MUCUS CELLS SECRETION FROM THE MUCUS CELLS OF RESP. TRACTOF RESP. TRACT

- STIMULATES THE LESS VISCOUC STIMULATES THE LESS VISCOUC SIALOGLYCOPEPTIDES AND SIALOGLYCOPEPTIDES AND SULFOGLYCOPEPTIDESSULFOGLYCOPEPTIDES

CARBOCISTEINECARBOCISTEINE

- STIMULATES THE LESS VISCOUS NEUTRAL STIMULATES THE LESS VISCOUS NEUTRAL GLUCOPEPTIDES DUE TO ACTIVATION OF GLUCOPEPTIDES DUE TO ACTIVATION OF SIALYLTRANSFERASE OR INHIBITON OF SIALYLTRANSFERASE OR INHIBITON OF NEURAMIDASENEURAMIDASE

- DECREASE THE SIZE AND NUMBER OF DECREASE THE SIZE AND NUMBER OF MUCUS PRODUCING CELLS.MUCUS PRODUCING CELLS.

SIDE EFFECTSIDE EFFECT::

GIT BLEEDING, NAUSEA, DIARRHEA, RASH, GIT BLEEDING, NAUSEA, DIARRHEA, RASH, DIZZINESS, HEADACHE, PALPITATIONSDIZZINESS, HEADACHE, PALPITATIONS

MUCOLYTIC AGENTSMUCOLYTIC AGENTSACETYLCYSTEINE: (MUCOMYST)ACETYLCYSTEINE: (MUCOMYST) REDUCES THE THICKNESS & STICKINESS OF REDUCES THE THICKNESS & STICKINESS OF

PURULENT & NONPURULENT PULMONARY PURULENT & NONPURULENT PULMONARY SECRETIONSSECRETIONS

BREAKS DISULFIDE LINDAGES OR BONDS OF BREAKS DISULFIDE LINDAGES OR BONDS OF MUCOPROTEIN MOLECULES OF RESP. MUCOPROTEIN MOLECULES OF RESP. SECRETIONS INTO SMALLER, MORE SOLUBLE SECRETIONS INTO SMALLER, MORE SOLUBLE & LESS VISCOUS STRANDS& LESS VISCOUS STRANDS

ANTIDOTE FOR PARACETAMOL POISONING ANTIDOTE FOR PARACETAMOL POISONING

MUCOLYTIC AGENTSMUCOLYTIC AGENTSACETYLCYSTEINE (con’t..)ACETYLCYSTEINE (con’t..) BRONCHOPULMONARY DSES.BRONCHOPULMONARY DSES.

i.e. CYSTIC FIBROSISi.e. CYSTIC FIBROSIS DXs AID IN BRONCHIAL STUDIESDXs AID IN BRONCHIAL STUDIES

(bronchospirometry/ bronchograms)(bronchospirometry/ bronchograms)GIVEN: GIVEN:

INHALATION/ INSTILLATIONINHALATION/ INSTILLATIONADVERSE EFFECTS:ADVERSE EFFECTS:

Hemoptysis, resp. irritation & difficultyHemoptysis, resp. irritation & difficultyN & V, inc temp, throat irritationN & V, inc temp, throat irritation

Clinical case scenario

Two year ago , a 31 year old female came to your clinic complaining of paroxysmal cough accommpanied by chest tightness and shortness of breath . This occur when her family moved into a new house 4 weeks PTC. This happened 2-3 x per week and affected her sleep .