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108 Cards in this Set
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Definition of Asthma?
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Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements as mast cells, eosinophils,T-lymphocytes, macrophages, neoutrophils, and epithelial cells play a role. Inflammation will cause the symptoms of wheezing, breathlesness, chest tightnes and cough at night and early morning. These episodes of airflow obstruction will be relieved upon administration of a bronchodilator
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What is the pathophysiology of Asthma
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Asthma precipitatin factors will lead to
1) release of inflammatory mediators (mast cells, macrophages, t-cells and epithelial cells 2)migration and activation of eosinophils 3)airway injury 4)mucous hypersecretion 5)increased smooth muscle reactivity 6)edema 7) increased airway hyper responsiveness to triggers |
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what are respinsoble for the
Histamine and Prostaglandin? |
are responsible for mucus secretion, increased vascular permeability and airways smooth muscle contraction
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What are Leukotriene responsible for?
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responsible for mucus secretion and activate the inflammatory mediators
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what is
Early-phase reaction? |
initiation of specific IGe cells and cause the release of proinflammatory mediators (minutes to hours after exposure)
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what is Late phase-reaction?
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occur 6-9 hour after allergen exposure
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What are the Asthma triggers?
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1)GERD ( improper sphincter constriction)
2)Allergic rhinitis/sinusitis (Ige increases) 3)Allergens ( animal, house, dust mites, outdoor) 4)Emotions ( anxiety, stress) 5)Occupational stimuli ( plastic rubber) 6)Exercise in cold dry climate 7)Infections: respiratory, influenza, pneumonia 8) Drugs/preservatives (nsaids, aceI,beta blockers, ccholinergic. preservatives: bbenzalkonium chloride. |
AA-DIEGO
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What are the signs and symptoms of Asthma?
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Cough at night and early morning
Chest tightness Breatlesness Expiratory Wheezing Dyspnea |
CC-BED
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What are the risk factors for asthma?
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a)Enviromental factors:
Tobacco smoking Socioeconomic status Family size Air pollution Occupational exposure Allergens b)Genetic Predispositon c)Atopy |
PEGA sin P, y la E fatsoa
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What is Atopy?
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Genetically determinant stage of hypersensitivity to environamental allergens
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Inhaled allergen may lead to which types of reactions?
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Early-phase reaction
Late-phase reaction |
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What are the 2 main Mediators involved in pathophysiology of Asthma?
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Histamine and Prostaglandin
Leukotriene |
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How to diagnose Asthma?
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1) Medical History and Physical examination
2)Spirometry (FEV/FVC) 3)Blood gas measurement 4)Peak Expiratory Flow (PEP) |
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When diagnosing Asthma what does Medical history and physical examination includes?
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symptoms of wheezing, SOB, cough, positive family history, cyanosis, prolonged expiration and barrel chest
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Spirometry (FEV/FVC)
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FEV1/FVC if less than 80% indicative of airflow obstruction, FEV1 less than 80% of predicted normal value. FEV1 increases more than 12% and at least 200 ml after using SABA
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Blood gas measurements
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Pa CO2, Pa O2, and PH for severe exacerbations
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What is FVC?
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Is the volume of air resulting from the force expiratory flow test in which a person inspires maxily to his total lung capacity and then exhale as rapidly and completely as possible
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Peak Expiratory Flow (PEF)
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Maximal rate of flow that can be produced during forced expiration
It`s a tool to asses chronic therapy and acute response to bronchodilators It monitors patients in the home and office and done once or twice daily depending on severity Green, yellow and red zone based on PEF accordingly asmathic action plan is taken |
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What are the PEF zones ?
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Green Zone: PEF bt 80-100%
Yellow Zone: PEF bt 50-79% Red Zone: PEF less than 50% |
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What is the Green zone and its asmathic plan?
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If PEF between 80-100% of normal (green zone) : no intervention is required. Patient should continue regular medication
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What is the yellow zone and its asmathic plan?
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If PEF Bbetween 50-79% (yellow zone) : the pt take 3 doses of SABA every 20 min if pt dont improve--- he needs hospitalization
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what is the Red zone and its asmathic plan?
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3)If PEF is less than 50% (red zone) : patient should take SABA and directly visit the ER
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What are the Goals of therapy of asthma?
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1) Prevent chronic symptoms
2) Maintain normal pulmonary function 3) Maintain normal activity levels 4) Prevent recurrent exacerbation of ashtma 5) Minimize the need for ER visits and hospitalization 6)Provide optimal pharmacotherapy with minimal or no adverse effects 7) Meet patients and families expectations ans satisfaction with care. |
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What are the major components of Long term therapy in asthma?
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1) Initial and periodic assesment and monitoring
2) Control of risk factors (smoking, allergy) that leads to asthma severity 3) Pharmacologic therapy against inflammation and bronchospasm 4) Education for follow-up, and use of inhalers. |
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Non-pharmacological therapy in asthma
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1) Avoid Allergens
2)Control of Tobacco smoke 3) Dust mite control |
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Pharmacological management in asthma
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Controller medications
Reliever medications |
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Controller medications
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-ICS
-LABA -Leukotriene Modifiers -Methylxanthines -Cromolyn |
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Reliever medications
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-SABA
-Anticholinergics -Methylxanthines -Systemic CS |
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Aerosol therapy for asthma
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1)Advantage: site-specific : enhancing therapeutic benefits and better absorption ( less SE)
2) Rapid onset of action due to the small size of delivered particles that deposit in the airways 3)Specific agents as formoterol, salmeterol, and ipratropium are only effective by inhalation |
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examples of aerosol therapy for asthma
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nebulizers
MDI (meter dose inhaler) DPI (dry powder inhaler) |
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MDI
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1) A pressurized canister with a metering valve and mouth piece where the canister contains the active drug, low-vapor pressure propellants as CFC (chlorfluorcarbon) or HFA (hydrofluoroalkane), cosolvents, and or surfarctants
Active drug is either in solution or suspension ( shake the canister before use) 3)Spacers are used with MDI to decrease oropharyngeal deposition, enhance lung delivery, evaporate propellant prior to inhalation, and obviate the need for good hand-lung coordination. It permits greater number of drug particles to have respirable drop size. |
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Indications for spacers
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1) Adults with poor coordination when using a metered dose inhaler
2)Children of all ages and children under 4 years can use MDI and a small volume spacer and a facemask 3)During an acute attack where administration of a reliever medication with a MDI and spacer is alternative to the use of nebulizer |
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Proper use of MDIs
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1) Take off the cap and shake the inhaler
2) Breathe out all the way 3) Hold the inhaler either infront of your mouth or put the inhaler in your mouth. 4) Start breathing slowly through your mouth 5)Hold the breath for 5-10 seconds 6) Wait at least 1 minute between puffs 7) Rinse the mouth if steroids was used. |
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Breath-Activated MDI Autohaler
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1) Reduced the need for hand-lung coordination for proper activation
2) Dont allow the use of a spacer device Limitation: If inadequate respiration the done wont be expelled from the MDI because its breath-activated ( requires rapid inhalation to active) |
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Example of breath activated autohaler (MDI)
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Maxair Autohaler ( Pirbuterol)
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DPI
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1) Advantages: breath-activated and require minimal hand-lung coordination
2) Powders are directly inhaled into the lungs |
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DPI Medication
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tiotropium, steroids, beta-agonists, and cromolyn
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DPI available in
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Diskus, turbuhaler, rotahaler, and aerolizer.
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Proper use of DPI
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1) Open the device: slide back thumb key
2) Activate the inhaler: push thumb grip back to click 3)Hold the inhaler level, parallel to the floor. Do not tilt or blow into the inhaler device, may cause spilling of powder 4) Exhale to the end of a normal breath away from the inhaler device 5) Inhale slowly and deeply where inhaling too fast may deposit powder on tongue and throat not into the lungs 6) Hold your breath for 10 seconds allowing time for particles to travel into lungs before exhalling. |
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Proper use of turbuhaler
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1) Unscrew the plastic cover and lift off
2) Load the medication by twisting the colored on the bottom as fas as it goes ( it turns one way only) Then twist the knob back in the opposite direction until you hear a clik 2) Turn head away from the turbuhaler and breather out 3) Put the mouthpiece in your mouth and close your teeth and lips around it 4) Take one fast deep full breath in through your mouth to suck the medication into the lungs 5) Remove turbuhaler from the mouth, close your lips and hold your breath for 10 seconds |
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Nebulizers
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Available in jet nebulizer and ultrasonic nebulizer
Atrovent and combivent |
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Jet nebulizer
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Jet nebulizers produce an aerosol from liquid solution or suspension placed in a cup. A tube connected to a stream of compressed air or oxygen flows up making drug solution up. Not suitable for LABA
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Which nebulizer is not suitable for LABA?
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Jet nebulizer
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Ultrasonic nebulizer
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Produce an aerosol by generating sound waves. It's ineffective for nebulizing micronized suspension. Suitable for SABA and cromolyn solution.
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Which nebulizer is suitable for SABA and cromolyn solution
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Ultrasonic nebulizer
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Pharmacotherapy. What are the medications used to treat asthma?
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1.- Corticosteroids
2.- Long acting Beta Agonists 3.- Leukotriene Modifiers 4.- Mast Cell Stabilizers 3.- Theophylline 6.- Omalizumab |
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Corticosteroids
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Reduce inflammation by minimizing bronchial hyperresponsivenes and alleviating symptoms, reducing the frequency of exacerbations and hospitalizations, improving health status, and decreasing risk of death from asthma.
.- Most potent and effective long term control for asthma |
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Inhaled Corticosteroids
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ICS reduce the need for oral CS.
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Oral CS
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Oral Cs are indicated for short term 3-10 days "burst" to have a quick control of inadequately controlled persistent asthma
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ICS vs SCS
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ICS have high topical potency and low systemic effects
Systemic CS have different potency and its equipotent on mcg basis |
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Local side effects of corticosteroids
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1)Oropharyngeal Candidiasis
2)Dysphonia 3)Cough So rinse mouth after each use |
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Systemic Side effects of corticosteroids
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1)Adrenal supression
2)Osteoporosis 3)Cataract 4)Growth supression 5)Skin thinning 6)Easy bruising 7)Electrolytes imbalance: hyperglycemia 8) Moon face |
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Corticosteroids used
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Beclomethason Dipropionate (Clenil, Becloforte)
Budesonide ( Pulmicort) Fluticasone (Flixotide) Flunisolide Mometasone Triamcinolone Acetonide (Azmacort) |
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Costicosteroids dose
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1-2 inhalations q 12 hours
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Combination of ICS and LABA
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Fluticasone + Salmeterol (Advair diskus as U.S.) and Seretide Diskus at lebanon.
500/50, 250/50 and 100/50 Dose: 1 inhaler q 12 hours 2) Budesonide + Formeterol turbuhaler ( Symbicort) |
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Beclomethasone Dipropionate
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Dosage form: MDI (CFC, HFA)
Approved age: Adults, children more than 5 years |
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Budesonide
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Dosage form: DPI, Nebulizer
Approved Age: Adults, children more than 6 years Children 12 months- 8 years Budesonide is the only CS that is available as nebulizer |
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Flunisolide
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Dosage form: MDI (CFC)
Adults, Children more than 6 years |
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Fluticasone
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Dosage forms: DPI, MDI (CFC, HFA)
Approved age: Adults, children more than 4 years of age |
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Mometasone
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Dosage form: DPI
Approved Age: Adults, Children more than 12 years |
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Triamcinolone Acetonide
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Dosage Form: MDI (CFC)
Adults, Children more than 6 years |
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Long Acting Beta Agonists (LABA)
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1)Bronchodilation by relaxing smooth muscles
2)Long term prevention of symptoms especially nocturnal symptoms 3) Not to be used in avute exacerbations 4)Tolerance development occurs after chronic therapy 5)Synergistic symptom control occurs after addition to ICS Salemeterol: Servent Diskus for age more than 4 y Formoterol : Foradil Aerosol. for age more than 5 y 6) Symtpoms exacerbations occur at night and early morning so we can refer to LABA because it provides long duration |
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Formoterol
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Full agonist it has faster onset of action than salmeterol
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LABA can be given for exercises tha need long duration
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Salmeterol given 30 min b4 exercise
Formoterol give 5-15 min before exercise |
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Side effects of LABA
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1) Tachychardia, Tachyphilaxis
2) Skeletal muscle tremors 3) Hypokalemia, Hyperglycemia 4) Prolongation of QT interval 5) Anxiety, dizziness 6) Nausea, vomiting 7) Aggravate glaucoma 8) Rebound bronchoconstriction |
TSH-PANAR
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Leukotriene Modifiers
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1.-Leukotriene receptor antagonist
2.-Long term control and prevention of symptoms in mild persistent asthma for patients more than 12 months of age 3)Less effective than ICS and can be added to low dose ICS for better control in mild persistent asthma |
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Montelukast
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Leukotriene Modifier
Singulair for age more than 1 years of age Available in 4 chewable tablets where 4 mg as granules/packet and as 10 mg tablet. Dose: 1 tablet po daily in the evening to achieve control with the time where maximal airway narrowing occurs. Granules can be mixed with applesauce, carrots, rice and administer within 15 minutes |
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Zafirlukast
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Leukotriene Modifier
Zafirlukast : Accolate for age more than 5 years. Available in 10 and 20mg tablets Dose: 1 tablet po q 12 hours take at least 1 hour before or 2 hours after meals becaue bioavailability decreases after food. Caution: inhibits metabolism of warfarin and increases PT |
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Zilueton
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Leukotriene Modifier
a 5-lipooxygenase inhibitor, inhibit leukotriene synthesis was withdrawn from U.S. market in 2003 due to case reports of reversible hepatitis and hyperbillirrubinemia |
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Side Effects of Leukotriene Modifiers
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1) Headache
2) Abdominal pain 3) Nausea 4) Influenza 5) Diarrhea |
HANID
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Mast Cell stabilizers
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Anti/inflammatory blocks early and late reactions to allergen. Stabilize mast cell membranes and inhibit activation and release of mediators from eosinophils and epithelial cells
2) Not effective in acute settings because therapeutic response occurs after 2 weeks 3) Preventive treatment prior to exposure to exercise or known allergen 4) Long/term prevention of symptoms, may modify inflammation. 5) Less effective than ICS and can be used as a trial before starting ICS in children |
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Mast Cell stabilizer
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Less effective than beta agonist in exercise induced asthma
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Sodium Cromoglycate
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Mast cell stabilizer
Intal available as nebulizer for children older than 2 years and as MDI for children older than 5 years. Dose: starts with Qid dosing, then tid |
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Nedocromil
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Mast Cell Stabilizer
Tilade Available in MDI for children older than 5 years |
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Mast Cell stabilizers: Side EFfects
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1) Unpleasant taste after inhalation
2)Cough 3)wheezing It is extremely safe |
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Theophylline
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1)Methylxanthine class, bronchodilator effect from phosphodiesterase inhibition and mild anti-inflammatory activity
2)Long term control and prevention of symptoms specially nocturnal asthma. Alternative in combination with ICS to ICS and LABA 3) Narrow therapeutic window with range from 5-15 mcg/ml and monitor peak rather than trough for efficacy and safety. Serum concentration at steady state wich is reached in 48 hours |
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Theophylline Dosage Forms
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Oral (tablet, capsules as IR, SR)
Liquids (solution, elixir syrup) IV REctal suppositories |
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Why shouldnt theophylline be given in acute settings?
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Theophylline shouldnt be given en acute settings because it doesnt provide additional benefits over SABA and produces adverse effects.
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Theophylline: Side effects
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Side effects are concentration dependant:
5-25 mcg/ml: GI upset, nausea, vomiting, abdominal pain, nervousness, headache, insomnia, agitation, dizziness, muscle cramp and tremor 25-35 mcg/ml: tachychardia and occasional PVC more than 35 mcg/ml: Ventricular tachycardia, frequent PVC, seizure, hyperglycemia, hyperkalemia, hypotension, and death |
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Theophylline: Dose
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dose: 12-14 mg/kg/day. maximum 300mg/day for children up to 15 years of age
adult dose: 300 mg/day |
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Theophylline: Elimination
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Elimination mainly via hepatic metabolism CYP 1A2, 3A3, 2E1
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Factors that affect theophylline metabolism
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high protein diet: Increase metabolism
High carbohydrate diet: Decrease metabolism Cor pulmonale, CHF Hypoxia: decrease metabolism Age: younger than 6 months, and elderly: increase metabolism Smoking: increase metabolism Phenobarbital, Phenytoin, Rifampin: Increase metabolism Cimetidine, erythromycin, quinolones: Decrease metabolism |
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Omalizumab
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Xolair
Recombinant humanized monoclonal anti-IgE antibody indicated in allergic asthma and other igE-related allergic ilnesses |
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When is Omalizumab useful?
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Useful in moderate-severe persistent asthma with a positive skin test or inadequately controlled asthma with ICS
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Omalizumab dosage forms
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Available in SC form. and it is given every 2-4 weeks interval
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Omalizumab: Side effects
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1)Injection site reactions
2)Viral infections 3)URTI 4)headache 5)sinusitis 6)Pharyngitis |
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Exercise induced Asthma (EIA)
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1) Diagnosed by a reduction in FEV1 by more than 15% of the baseline after 6-8 minute treadmill or bycicle test
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Factors that trigger EIA
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Breathing cool or dry air
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Factors that decrease risk of EIA
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1) intermittent exercise
2) breathing warm humid air 3) premedication prior to any exercise |
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Treatment of Exercise induced asthma (EIA)
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1) inhaled SABA is the drug of choice for prophylaxis.
2) in case of prolonged periods of exercise, LABA is the drug of choice |
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EIA: SABA
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in case of exercise for less than 3 hours pretreatment with albuterol 5-15 minutes before exercise is recommended
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EIA: LABA
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In case of prolonged periods of exercise: LABA: Formoterol administer 15 minutes before exercise, whereas salmeterol administer at least 30 minutes before exercise
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Acute Asthma Exacerbations
Symptoms |
1) Dyspnea, expiratory wheezes and cough
2) Hyperinflated chest, hypoxemia 3) Ohter signs: vital signs and incread pulse and RR |
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Acute Astham Exacerbations: Risk factors
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1) Previous history of asthma exacerbations (hospitalization, intubation, seizures)
2) Presence of complicating ilnesses (cardiac, diabetes) and use of more than 2 canisters/month 3) Current intake of oral CS or recent withdrawal from oral CS |
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Principles Goals of Therpay in Acute Asthma
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1) Correction of hypoxemia
2) Rapid reversal of airflow obstruction 3) Reduction in the recurrence of airflow obstruction 4)Development of a written action plan in case of further exacerbations |
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Outcome Measures in Acute Asthma
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1) Improvement in FEV1 at 30 minutes after SABA
2) Maintenance in O2 saturation above 90% |
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Pharmacological Therapy in Asthma Exacerbations
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1) Oxygen therapy to treat hypoxemia an maintain oxygen stauration more than 90%
2) Short acting beta agonist (SABA) 3) Anticholinergics 4) Corticosteroids (systemic) 5) Ohters (Theophylline, magnesium) |
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SABA
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1) first choice for the treatment of acute asthma FEV1 improvement is the primary outcome after administration
2) Inhaled route provides greater bronchodilation with fewer systemic side effects than oral or parenteral form 3) Administration of the first dose of SABA by nebulizer is prefered in adults and children due to intensive therapy and then MDI and spacers |
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SABA: dosing schedule
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dosing schedule is done q 20 minutes. If the nebulizer is given: adult dose: 2.5mg q 20 min then 2.5 - 10 mg q 1-4 hrs as needed or 10-15 mg/ hr continously
If MDI is given: Adult dose: 4-8 puffs q 30 min up to 4 hrs then q 1-4 hrs as needed |
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Which one is the prefered SABA?
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All B2 agonists are potent in equimolar doses. No advantage of one to another but the preferred is albuterol due to its higher selectivity
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Levalbuterol
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Levalbuterol the R-albuterol isomer is available as nebulizer further studies are needed
Levalbuterol is given at 1/2 dose of albuterol because its 2x as potent as albuterol |
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System B2 agonists in Acute asthma
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Systemic B2 aqonists ( Epinephrine, Tertbutaline) are needed in case of severe exacerbations and are given as SC q 20 min for 3 doses
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Anticholinergics
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1) Competitive inhibitors of muscarinic receptros, only reverse cholinergic-mediated bronchoconstriction
2) Not a first line of therapy usually used in combination with SABA if PEF less than 30 after saba administration |
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Ipratropium
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Anticholinergic
Ipratropium is quaternary amine, poorly absorbed and produces minimal Side effects Dose of ipratropium: MDI 4-8 puffs as needed |
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Anticholinergic Side effects
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1) Blurred vision
2) Urinary retention 3) Constipation 4) Headache 5) Tachychardia |
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Acute Asthma Exacerbations: Corticosteroids
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1) Most effective anti-inflammatory drugs for asthma
advantages of CS: 1) increases the number of B2 receptors and improve the receptor responsiveness to B2 stimulation 2) Reduces mucous production and hypersecretion 3) Prevents and reverses airway remodeling 4) Reduces bronchial hyperresponsivenessS |
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Acute Asthma Exacerbations: Systemic Oral CS
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Systemic oral CS is indicated if there isn't immediate response to SABA. Oral CS is used but the IV methylprednisolono is reserved in patients who are vomiting and adherence is a concern
2) Short courses or bursts are effective in establishing control and should be continued until patient achieves 80% PEF. The duration is 3-10 days but may requiere longer Prednisolone dose: 120-180 mg/ day in or 4 divided doses dor 48 hours, and then 60-80mg / day until PEF is achieved |
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Pharmacist role in asthma
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1) Educate patient on asthma triggers and method to decrease exposure
2) Familiarize patiens on the proper use of devices 3) Minimize the risk of drug toxicity and side effects 4)Monitor patients on primary outcomes and response to treatment 5) Use of asthma action plan |
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