Drugs for Chronic Obstructive Drugs for Chronic Obstructive Pulmonary Disease Pulmonary 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.
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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:
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
- 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
-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 .
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.
-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
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
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
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
ACTION:ACTION: DIRECT EFFECT ON THE CENTERDIRECT EFFECT ON THE CENTER DRYING EFFECTDRYING EFFECT DECREASE VISCOSITYDECREASE VISCOSITY ANALGESIC & SEDATIVE EFFECTANALGESIC & SEDATIVE EFFECT
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
- 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.
MUCOLYTIC AGENTSMUCOLYTIC AGENTSACETYLCYSTEINE: (MUCOMYST)ACETYLCYSTEINE: (MUCOMYST) REDUCES THE THICKNESS & STICKINESS OF REDUCES THE THICKNESS & STICKINESS OF
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
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 .