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Drugs Acting on theRespiratory System
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Introduction
The respiratory system is subject tomany disorders that interfere withrespiration and other lung functions,
including Respiratory tract infections Allergic disorders Inflammatory disorders
Conditions that obstruct airflow (e.g.asthma and chronic obstructivepulmonary disease, COPD)
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Introduction (Contd)
Drugs that act on the respiratorysystem include Bronchodilators Corticosteroids Cromoglycates Leukotriene receptor antagonists Antihistamines Cough preparations Nasal decongestants
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Drugs acting on the respiratory system,especially for asthma, can be
administered by inhalation, theadvantages are:
Enhance therapeutic effects
Minimize systemic effects
Rapid relief of acute attacks
Introduction (Contd)
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Asthma is a chronic inflammatory disorder of theairways in which many cells and cellular elements
play a role, in particular, mast cells, eosinophils, Tlymphocytes, macrophages, neutrophils, andepithelial cells. In susceptible individuals, thisinflammation causes recurrent episodes of
wheezing, breathlessness, chest tightness, andcoughing, particularly at night or in the earlymorning. These episodes are usually associatedwith widespread but variable airflow obstructionthat is often reversible either spontaneously or withtreatment. The inflammation also causes anassociated increase in the existing bronchialhyperresponsiveness to a variety of stimuli.
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The condition of a patients asthma may change depending on the
environment, activities, and other factors. When the patient is well,monitoring and treatment are still needed to maintain control.
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There are various types of inhalationdevices:
Metered-dose inhalers (MDIs)Pressurized devices that deliver a measured
dose of drug with each activation
With CFC or non-CFC propellant
Hand-mouth coordination is required
Introduction (Contd)
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Spacers:
Use with MDIs
Increase delivery of drug to the lungs &
decrease deposition of drug on theoropharyngeal mucosa
Especially important for inhaledcorticosteroids
Introduction (Contd)
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Dry-powder inhalers (DPIs)
Include Turbuhalers & Accuhalers
Drugs are in the form of dry, micronizedpowder
No propellant is employed
Breath activated, much easier to use
Introduction (Contd)
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Nebulizers
Small machine to convert a drug solution intomist
Droplets in the mist are much finer than thoseproduced by inhalers
Through face mask or mouth piece heldbetween the teeth
Take several minutes to deliver the sameamount of drug contained in 1 puff from aninhaler
Introduction (Contd)
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Bronchodilators
Drugs used to relieve bronchospasmsassociated with respiratory disorders
Includes: Adrenoceptor agonists
Selective 2-agonists & other adrenoceptoragonists
Antimuscarinic bronchodilators Xanthine derivatives
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Bronchodilators (Contd)
Adrenoceptor agonists
(i) Selective beta2 agonists
Stimulate beta2 receptors in smooth muscleof the lung, promoting bronchodilation, andthereby relieving bronchospasms
They are divided into short-acting & longacting types
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Bronchodilators (Contd)
Drug Formulation Dosage
Adult Child
Salbutamol Oral tablet (C.R) 8 mg twice daily 4 mg twice dailyInhaler (MDI), 100mcg/dose 100-200mcg up to three to
four times dailySame as adult
Syrup, 2mg/5ml 4 mg three to four timesdaily
1-2 mg three to four timesdaily (2 yr)
Terbutaline Oral tablet (S.R) 5-7.5 mg two times daily -
Inhaler 500mg / dose( Turbuhaler)
500 mcg up to four timesdaily
-
Inhaler 250mg / dose (MDI) 250-500mcg up to 3-4 timesdaily
Same as adult
Short-acting -2 agonists
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Bronchodilators (Contd)
Long-acting -2 agonists
Drug Formulation Dosage
Adult Child
Formoterol Inhaler 4.5mcg / dose(Turbuhaer)
4.5-9 mcg once or twicedaily
Same as adult
Inhaler 9mcg / dose(Turbuhaer)
Salmeterol Inhaler 25mcg / dose(MDI)
50-100 mcg twice daily Same as adult
50 mcg / dose (Accuhaler) 50 mcg twice Same as adult
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Bronchodilators (Contd)
Adverse effects
Tachycardia andpalpitations
Headache
Tremor
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Bronchodilators (Contd)
(ii) Other adrenoceptor agonists
Less suitable & less safe for use asbronchodilators because they are more likely
to cause arrhythmias & other side effects
Ephedrine
Adults: 15-60 mg tid po
Child: 7.5-30 mg tid po
Adrenaline (epinephrine) injection is used inthe emergency treatment of acute allergicand anaphylactic reactions
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Bronchodilators (Contd)
Nursing Alerts
When 2 or more puffs are needed, inform the patientthat at least 1 minute should be allowed between puffs
Inform the patient that salmeterol and formoterol, andoral -2 agonists should be taken on a fixed schedule,not on a prn basis
Instruct the patient to report chest pain and changes inheart rhythm or rate, because -2 agonists can cause
cardiac stimulationContact physician if symptoms such as nervousness,
insomnia, restlessness and tremor become severe
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Bronchodilators (Contd)
Antimuscarinic bronchodilators Blocks the action of acetylcholine in
bronchial smooth muscle, this reducesintracellular GMP, a bronchoconstrictivesubstance
Used for maintenance therapy of
bronchoconstriction associated withchronic bronchitis & emphysema
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Bronchodilators (Contd)
Drug Formulation Dosage
Adult Child
Ipratropium Inhaler 20 mcg / dose(MDI)
20-80 mcg three to fourtimes a day
20-40 mcg three to fourtimes a day (6yrs)
Tiotropium Inhaler 18 mcg /dose 18 mcg daily Not recommended inchildren and adolescents
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Adverse effects:
Dry mouth
Nausea Constipation
Headache
Bronchodilators (Contd)
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Bronchodilators (Contd)
Xanthine Derivatives
Main xanthine used clinically istheophylline
Theophylline is a bronchodilator whichrelaxes smooth muscle of the bronchi, it isused for reversible airway obstruction
One proposed mechanism of action is that
it acts by inhibiting phosphodiesterase,thereby increasing cAMP, leading tobronchodialtion
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Bronchodilators (Contd)Drug Formulation Dosage
Adult Child
Theophylline Tablet 200 / 300 mg(S.R.)
200 300 mg twice daily 10 mg / kg ((2yrs) twicedaily
Capsule 50 / 100 mg
(Slow release)
7-12 mg/ kg / day in two divided
doses
10-16 mg / kg / day in two
divided doses (916yrs)
13-20 mg / kg / day in twodivided doses (30 months 8yrs)
Syrup 80 mg / 15 ml 25 ml q6h 1 ml / kg (Max 25 ml) q6h(2yrs)
Aminophylline Injection 25 mg / ml
10 ml
500 mcg / kg / hr IV infusion,adjust when necessary
1 mg / kg /hr (6 months 9years)
800 mcg / kg /hr (10 16 yrs)
IV infusion, adjust whennecessary
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Bronchodilators (Contd)
Adverse effects:
Toxicity is related to theophyline levels(usually 5-15 g/ml)
20-25 g/ml : Nausea, vomiting, diarrhea,insomnia, restlessness
>30 g/ml : Serious adverse effects includingdysrhythmias, convulsions, cardiovascular
collapse which may result in death
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Bronchodilators (Contd)
Nursing alerts:
Plasma theophylline levels should be monitoredto keep it in the therapeutic range, usually 5-15
g/ml. Dosage should be adjusted to keeptheophylline levels below 20 g/ml
If patients miss a dose, the following dose shouldnot be doubled
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Nursing alerts (Contd):
Instruct the patient that sustained-release
formulations should be swallowed intactCaution patients in consuming caffeine
containing-beverages and other sources ofcaffeine. Caffeine can intensify the adverseeffects and decrease the metabolism of
theophylline
Bronchodilators (Contd)
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Corticosteroids
Used for prophylaxis of chronic asthma
Suppressing inflammation
Decrease synthesis & release of inflammatory
mediators
Decrease infiltration & activity of inflammatory cells
Decrease edema of the airway mucosa
Decrease airway mucus production
Increase the number of bronchial beta2receptors & their responsiveness to beta2agonists
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Corticosteroids (Contd)
Drug Formulation Dosage
Adult Child
Beclomethasone Inhaler 50 mcg / dose
(MDI)
200 mcg twice daily /100mcg three to fourstimes daily
Up to 800 mcg daily
50 100 mcg two to fourtimes daily
Inhaler 250 mcg / dose
(MDI)
500 mcg twice daily / 250mcg four times daily
Not recommended
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Corticosteroids (Contd)Drug (Contd) Formulation Dosage
Adult Child
Budesonide Inhaler 50 mcg / dose(MDI)
200 mcg twice daily
Up to 1.6 mg daily
50 400 mcg twicedaily
Up to 800 mcg daily
Inhaler 200mcg / dose(MDI)
Inhaler 100 mcg / dose(Turbuhaler)
200-800 mcg once dailyin evening
Up to 1.6 mg daily intwo divided doses
200-800 mcg daily intwo divided doses /200-400 mcg oncedaily in evening
(
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Corticosteroids (Contd)Drug (Contd) Formulation Dosage
Adult Child
Fluticasone Inhaler 25mcg / dose (MDI) 100 1000 mcgtwice daily
50-100 mcg twice daily(4-16 yrs)
Inhaler 50 mcg / dose (MDI)
Inhaler 125 mcg / dose (MDI)
Inhaler 250 mcg / dose (MDI)
Inhaler 50 mcg / dose (Accuhaler)
Inhaler 100 mcg / dose (Accuhaler)
Inhaler 250 mcg / dose (Accuhaler)
Acute attacks of asthma should be treated with short coursesof oral corticosteroids, starting with a high dose for a few days
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Corticosteroids (Contd)
Adverse effects
Inhaled corticosteroids:
Candidiasis of the mouth or throatHoarseness
Can slow growth in children
Adrenal suppression may occur in long-term,high dose therapy
Increases the risk of cataracts
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Corticosteroids (Contd)
Nursing alerts
Rinse mouth with water without swallowing
after administration to reduce the risk ofcandidiasis
If taking bronchodilators by inhalation, usebronchodilators several minutes before the
corticosteroid to enhance application of thecorticosteroid into the bronchial tract
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Combination Products
May be appropriate for patients stabilised onindividual components in the same proportion
Muscarinic antagonist+2 agonist
Combivent (20mcg Ipratropium & 100mcgsalbutamol /dose, MDI)
Corticosteroid+2 agonist
Symbicort (160mcg Budesonide+4.5mcg
Formoterol / dose, Turbuhaler)
Seretide (Salmeterol+Fluticasone: MDi in Lite,Medium, Forte preparation & Accuhaler)
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Cromoglycates
Stabilise mast cells & prevent therelease of bronchoconstrictive &
inflammatory substances when mastcells are confronted with allergens &other stimuli
Only for prophylaxis of acute asthma
attacks
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Cromoglycates (Contd)
Drug Formulation Dosage
Adult Child
Cromoglycate Na Inhaler (1 mg
& 5mg/dose)
10 mg four times daily, may be
increased to six to eight timesdaily
Same as adult
Nebulisersolution 10 mg/ ml 2 ml
20 mg four times daily, may beincreased six times daily
Same as adult
Nedocromil
Sodium
Inhaler 2 mg /
dose (MDI)
4 mg two to four times daily Sames as adult (>6
yrs)
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Cromoglycates (Contd)
Adverse effects Nursing Alerts
Transient Bronchospasm A selective 2 agonist such as
salbutamol or terbutaline maybe inhaled a few minutesbeforehand
Others: coughing, throat irritation
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Nursing Alerts (Contd)
Cromoglycates are for long-term
prophylaxis, patients should administer ona regular schedule & the full therapeuticeffects may take several weeks to develop
They are contraindicated in patients who
are hypersensitive to the drugs
Cromoglycates (Contd)
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Leukotriene receptor
antagonists Act by suppressing the effects of
leukotrienes, compounds that promote
bronchoconstriction as well aseosinophil infiltration, mucus productions,& airway edema
Help to prevent acute asthma attacks
induced by allergens & other stimuli Indicated for long-term treatment of
asthma
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Dosage:
Montelukast (5 & 10 mg tablets)
Adult: 10 mg daily at bedtimeChild:
(2-5yrs) 4 mg daily at bedtime
(6-14yrs) 5 mg daily at bedtime
Leukotriene receptor
antagonists (Contd)
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Adverse effects:
GI disturbances
Hypersensitivity reactions Restlessness & headache
Upper respiratory tract infection
Manufacturer advises to avoid these drugs
in pregnancy & breast-feeding unlessessential
Leukotriene receptor
antagonists (Contd)
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Management of Chronic Asthma foradults & schoolchildren above 5yrs
Step 1: Occasional relief short-acting
beta2 agonist
Step 2: Add regular preventer therapy
Standard-dose inhaled corticosteroid
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Management of Chronic Asthma foradults & schoolchildren above 5yrs
(Contd)
Step 3: Add long-acting inhaled beta2 agonist;
dose of inhaled corticosteroid may also be increased
Step 4: Add high dose of inhaled corticosteroids
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Management of Chronic Asthma foradults & schoolchildren above 5yrs
(Contd)
Step 5: Add regular oral corticosteroid
E.g. prednisolone
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Stepping down:
Review treatment every 3 months
If symptoms controlled, may initiatestepwise reduction
Lowest possible dose oral corticosteroid
Gradual reduction of dose of inhaledcorticosteroid to the lowest dose whichcontrols asthma
Management of Chronic Asthma foradults & schoolchildren above 5yrs
(Contd)
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Antihistamines
H1 receptor antagonists
Inhibit smooth muscle constriction in bloodvessels & respiratory & GI tracts
Decrease capillary permeability
Decrease salivation & tear formation
Used for variety of allergic disorders to
prevent or reverse target organinflammation
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All antihistamines are of potential valuein the treatment of nasal allergies,
particularly seasonal allergic rhinitis (hayfever)
Reduce rhinorrhoea & sneezing but areusually less effective for nasal
congestion Are also used topically in the eye, in the
nose, & on the skin
Antihistamines (Contd)
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First-generation H1 receptor antagonists
Non-selective/sedating
Bind to both central & peripheral H1receptors
Usually cause CNS depression(drowsiness, sedation) but may causeCNS stimulation (anxiety, agitation),
especially in children Also have substantial anticholinergic
effects
Antihistamines (Contd)
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Antihistamines (Contd)
Drug Dosage
Adult Child
Chorpheniramine(4 mg tablet,2mg/ml Elixir &
expectorant)
4 mg q4-6hr, max: 24 mgdaily
1-2yrs: 1 mg twice daily
2-12yrs: 1- 2 mg q4-6h, Max:12 mg daily
Hydroxyzine (25mg tablet)
25 mg at night; 25mg three tofour times daily whennecessary
6 months-6yrs: 5-15 mg daily; 50 mgdaily in divided dose if needed
>6yrs: 15-25 mg daily; 50-100 mg daily individed dose if needed
Diphendramine (10mg/5ml Elixir)
25-50 mg q4-6h 6.25-25 mg q4-8 hr ( >1 yr)
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Antihistamines (Contd)
Drug (Contd) Dosage
Adult Child
Promethazine (10 &
25 mg tablets,5mg/5ml Elixir)
25 mg at night; 25 mg twice daily
if needed
2-10yrs: 5-25 mg daily in 1 to 2
divided dose
Azatadine (1 mgtablet)
1 mg twice daily 1-12 yrs: 0.25-1 mg twice daily
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Antihistamines (Contd)
Adverse effects:
Sedation
Dry mouth
Blurred vision
GI disturbances
Headache
Urinary retention Hydroxyzine is not recommended for
pregnancy & breast-feeding
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Second-generation H1 receptor antagonists
Selective/non-sedating
Cause less CNS depression because they areselective for peripheral H1 receptors & do notcross blood-brain barrier
Longer-acting compared to first-generation
antihistamines
Antihistamines (Contd)
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Antihistamines (Contd)
Drug Dosage
Adult Child
Acrivastine(Semprex)
8 mg three times daily Not recommended
Cetirizine(Zyrtec)
10 mg daily 5 mg daily / 2.5 mg twice daily (2-6 yrs)
Desloratadine(Aerius)
5 mg daily 1.25 mg daily (2-5 yrs)
2.5 mg daily (6-11yrs)
Fexofenadine(Telfast)
120-180 mg daily Not recommended
Loratadine(Clarityne)
10 mg daily` 5 mg daily (2-5 yrs)
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Antihistamines (Contd)
Adverse effects:
May cause slight sedation
Some antihistamines may interact withantifungal, e.g. ketoconazole; antibiotics,e.g. erythromycin; prokinetic drug--cisapride or grapefruit juice, leading topotentially serious ECG changes e.g.Terfenadine
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Cough preparations
There are three classes of coughpreparations:
Antitussives Expectorants
Mucolytics
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Antitussives
Drugs that suppress cough
Some act within the CNS, some actperipherally
Indicated in dry, hacking, nonproductivecough that interfere with rest & sleep
Cough preparations (Contd)
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Cough preparations (Contd)
Drug Dosage
Codeine phosphate 25mg/5ml syrup 15-30 mg three to four times daily
Pholcodine 5mg/5ml Elixir 5-10 mg three to four times daily
Dextromethorphan 10mg/5ml in PromethazineCompound Linctus
10-30 mg q4-8h
Diphenhydramine 10 mg/ 5ml 25 mg q4h, Max:150 mg daily
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Adverse effects:
Drowsiness
Respiratory depression (for opioid
antitussives)
Constipation (for opioid antitussives)
Preparations containing codeine or similaranalgesics are not generally recommendedin children & should be avoided altogetherin those under 1 year of age
Cough preparations (Contd)
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Nursing Alerts:
Observe for excessive suppression of thecough reflex (inability to cough effectivelywhen secretions are present). This is apotentially serious adverse effect becauseretained secretions may lead to lungscollapse, pneumonia, hypoxia, hypercarbia,
and respiratory failure
Cough preparations (Contd)
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Expectorants
Render the cough more productive bystimulating the flow of respiratory tractsecretions
Guaifenesin is most commonly used
Available alone & as an ingredient in many
combination cough & cold remedies
Cough preparations (Contd)
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Dosage
Guaifenesin
100-400 mg q4h po
Ammonia & Ipecacuaha Mixture
10-20 ml three to four times daily po
Cough preparations (Contd)
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Mucolytics
Reacts directly with mucus to make it morewatery. This should help make the coughmore productive
Cough preparations (Contd)
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Dosage
Acetylcysteine 100 mg two to four times daily
200 mg two to three times daily 600 mg once daily
Bromhexine 8-16 mg three times daily po
Carbocisteine 750 mg three times daily, then 1.5 g daily in
divided doses
Cough preparations (Contd)
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Sympathomimetics are used to reducenasal congestion
Stimulate alpha1-adrenergic receptors onnasal blood vessels, which causesvasoconstriction & hence shrinkage ofswollen membranes
Nasal Decongestants
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Topical administration:
Response is rapid & intense
Oral administration: Response are delayed, moderate &
prolonged
Nasal Decongestants (Contd)
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Nasal Decongestants (Contd)Drug Formulation Dosage
Adult Child
Oxymetazoline Nasal Drops 0.025% 20 ml - 2-3 drops q12h (2-5 yrs)
Nasal Spray 0.05% 15 ml 2-3 sprays q12h Same as adults forchildren >6 yrs
Phenylephrine Nasal Drops 0.5% 10 ml Several drops q2-4h -
Xylometazoline Nasal Drops 0.05% / 0.1% 2-3 drops q8-10h (0.1%) 2-3 drops q8-10h (2-12yrs) (0.05%)
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Nasal Decongestants (Contd)
Adverse effects:
Rebound congestion develops with topicalagents when used for more than a few days
CNS stimulation (such as restlessness,irritability, anxiety and insomnia) occurs withoral sympathomimetics
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Adverse effects (Contd):
Sympathomimetics can causevasoconstriction by stimulating -1adrenergic receptors. More common withoral agents
Sympathomimetics cause CNS stimulation,and can produce effects similar toamphetamine. Hence, these drugs aresubject to abuse
Nasal Decongestants (Contd)
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Nasal Decongestants (Contd)
Nursing alerts:
Overuse of topical nasal decongestantscan cause rebound congestion, meaning
that the congestion can be worse with theuse of drug. To minimise this, drugtherapy should be discontinued gradually.
The use of topical agents is limited to no
more than 3 to 5 days
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Nasal Decongestants (Contd)
Nursing alerts (Contd):
The patients blood pressure and pulse
should be assessed before a decongestantis administered
Inform the patient that nasal burning andstinging may occur with topicaldecongestants
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Intranasal Corticosteroids
Intranasal Corticosteroids
Most effective for treatment of seasonaland perennial rhinitis
Have inflammatory actions and canprevent or suppress all major symptoms ofallergic rhinitis including congestion,rhinorrhea, sneezing, nasal itching anderythema
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Intranasal Corticosteroids (Contd)
Drug Formulation Dosage
Adult Child
Beclomethasone
Dipropionate
Nasal Spray 50 mcg /
dose
1 spray in each nostril
four times dailyMax. 10 sprays / day
4-6 sprays / day
Nasal Spray 50 mcgdose (Aqueous)
2 applications intoeach nostril twice tofour times daily
Max. 400 mcg daily
Same as adult (>6 yrs)
Not recommended inchildren
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Intranasal Corticosteroids (Contd)
Drug (Contd) Formulation Dosage
Adult Child
Budesonide Nasal Spray 50 mcg /dose (Aqueous)
1-2 sprays into eachnostril twice daily; after2-3days: 1 spray intoeach nostril twice daily
Not recommended forage 12 yrs or below
Turbuhaler 100mcg /dose
400 mcg in the morninggiven as 2 applications
into each nostril; thenreduce to the smallestamount necessary
-
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Intranasal Corticosteroids (Contd)
Drug (Contd) Formulation Dosage
Adult Child
Fluticasone Nasal Spray 50 mcg/ dose (Aqueous)
2 sprays into eachnostril in the morning
Max: 8 sprays/day
1 spray into eachnostril in the morning(4-11yrs)
Max: 4 sprays/day
Mometasone Nasal Spray 50 mcg/ dose
2 sprays in eachnostril once daily;1spray in each nostrilas maintenance
Max: 8 sprays/day
1 spray in eachnostril once daily
(3-11yrs)
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Adverse effects:
Mild
Most common effects are drying of nasalmucosa & sensations of burning or itching
Intranasal Corticosteroids (Contd)
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Chronic Obstructive PulmonaryDisease (COPD)
Umbrella term for various conditionscharacterized by limitation of airflow that is notfully reversible
Chronic airflow limitation caused by a mixture ofsmall airway disease and parenchymaldestruction
Airflow limitation is often progressive
Associated with an abnormal inflammatory
response of lungs to noxious substances PREVENTABLE and TREATABLE disease
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Relationship between COPD andemphysema/chronic bronchitis
Emphysema
Destruction of the gas exchanging surfaces of the lung(alveoli)
Pathological term that describes only one of several
structural abnormalities present in patients with COPD Chronic bronchitis
Presence of cough and sputum production for at least 3months in each of two consecutive years
Remains a clinically and epidemiologically useful term,but does not reflect the major impact of airflow limitationon morbidity and mortality in COPD patients
The emphasis on these conditions are not included in thedefinition of COPD in current relevant clinical guidelines
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Mechanisms of COPD
Ref: Global Initiative for Chronic Obstructive Lung Disease (GOLD), National Heart, Lung, and Blood Institute (U.S.) - FederalGovernment Agency [U.S.] World Health Organization - International Agency. 2001 (revised 2006).
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Risk factors
Genes Exposure to particles
Tobacco smoke
Occupational dusts, organic and inorganic
Indoor air pollution from heating and cooking with biomass in
poorly vented dwellings Outdoor air pollution
Lung Growth and Development Oxidative stress Gender (appears to be related to cigarette use?) Respiratory infections
Socioeconomic status Nutrition Comorbidities (e.g. asthma)
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GOLD report COPD StagingSystem
Stage /Severity
PostbronchodilatorFEV1/ FVC and FEV1 pred.
Characteristics
Stage I:Mild
FEV1/FVC < 0.70
FEV1 80% predicted
chronic cough and sputum production may bepresent, but not always
Stage II:Moderate
FEV1/FVC < 0.70
50% FEV1 < 80% predicted
shortness of breath typically developing onexertion and cough and sputum production
sometimes also presentStage III:Severe
FEV1/FVC < 0.70
30% FEV1 < 50% predicted
greater shortness of breath, reduced exercisecapacity, fatigue, repeated exacerbations thatalmost always have an impact on patients quality
of life
Stage IV:Very
severe
FEV1/FVC < 0.70
FEV1 < 30% predicted or FEV1