Chronic inflammatory disease of the bronchial tubes and lung tissue

• indued by multiple mediators
• Bronchial hyper-responsiveness

• muscles surrounding bronchial tubes constrict, airways narrow
• lining of airway becomes inflamed, swollen and there is an increase in mucous production

• cough
• wheezing
• chest tightness
• shortness of breath
• increased mucous production
• speech may be impacted by breathing changes
• fatigue

• Respiratory infections: viral, pneumonia
• allergens: pollen, dust mites, animal dander
• Gastroesophageal reflux (GERD)
• Environment: cold air, tobacco smoke  (adrenergic hyperactivity)
• Emotions: anxiety, stress
• exercise: especially in cold dry climate
• drugs/preservatives: ASA, Sulfites, β blockers
• Occupational stimulation: flour, farmers hay mold

• prevent troublesome symptoms - cough, breathlessness in night, am, after exercise
• maintain normal lung function
• maintain normal activity
• prevent recurrent exacerbations/hospitalizations
• optimal drug therapy with no side effects

Intermittent

Persistent or chronic

Seasonal allergic

do not exist on their own, types of asthma overlap in patients

daily symptoms or symptoms several times per week without extended symptom free periods

• most patients seen

• any patient not responding to therapy can be considered to be in status asthmaticus
• an acute emergency
• need bronchodilators and oxygen right away

• waking up at night > 2/month with severe breathlessness
• refilling salbutamol (ventolin) > 1/month
• exercise-induced bronchoconstriction
• missing school/work
• hospitalization
• need to adjust therapy

Quick relief Asthma Therapy 

• Short acting β₂ agonists (Salbuterol)
• anticholinergics (Spiriva)
• Systemic corticosteroids (tablets, used only temp. for anti-inflammatory effects, bad side effects with long term use)

• Inhaled Conicosteroids
• Long-acting β₂ agoists (ie salmeterol)
• Theophylline
• Leukotriene modifiers
• Cromolyn and nedocromil

In asthmatic person:

• muscles of bronchial tubes tightnen and thicken
• ari passage become inflammed and mucus filled
• air flow becomes difficult

Quick relief asthma Medication

Reliever/Rescue

• Inhaled β₂ selective agonist ie, Salbutamol (ventolin)
• Terbutaline (Bricanyl)
• Systemic corticosteroids (Prednisone)

i.e. Salbutamol

• relax airway smooth muscle or relieve bronchospasm
• Treat intermittent episodes of bronchospasm and prevention of exercise induced asthma
• Quickest for acute asthmatic attack
• Give systemic corticosteroid 1st (will not take effect for around 2 hrs), then these

• ↓Ipratropium (Atrovent), Tiotropium (Spiriva)
• Blockad of colinergic receptors ↓ the formation of cGMP, resulting in ↓ contractility of smooth muscle
• Bronchodilation
• Used for patients with pollen, allergic induced asthma

)Anticholinergic asthma durgs

• not well absorbed into circulation (advantage, stays topical) b/c are quaternary ammonium compounds
• max bronchodilation reached in 2 hrs (vs 30 mim for β₂ agonists) (disadvantage)
• given by inhalation or nasal spray
• minimal side effects (b/c topical)

• Used for moderate to severe exacerbations to speed recovery adn prevent recurrence
• ↓ inflammation and improve mucus production
• oral or IV

controller or preventer

• inhaled corticosteroids (local inflammation)
• long acting β₂ agonists
• leukotriene modifiers
• slow release Theophylline (a zantine like caffiene)

1st line treatment for asthma, even in patients < 5 years of age 

Studies show they:

• control symptoms
• improve lung function
• decrease hospitalization
• decrease risk of death
• decrease cost of care

Budesonide

Beclomethasone

Fluticasone

Triamcinolone

• Deposition of drugs in mouth and upper airway
• May lead to oral Candidiasis (thrush)
  • decrease local immune system in mouth 

• administer with a spacer (Nebulizer)
• Rinse and spit after use

• adjunct therapy to inhaled steroids
• available alone and as combo therapy with steroids
• Especially helpful for night time symptoms and exercise induced asthma
• not to be used to treat acute symptoms or exacerbations

The arachidonic acid pathway

and Arthritis

Membrane phospholipids are injured→ phospholipase A₂ released→ Arachidonic acid released→ (Cyclooxygenase acts to form)→ Prostaglandins and Thromboxanes 

= Inflammation

Corticosteroids

• blockage of phospholipase A₂ inhibits the production of arachidonic acid and FLAP and therefore the activation of both the arthritis and asthma pathways

membrane phospholipids are injured→

5-Lipoxygenase activating protein (FLAP)→ activates 5-Lipoxygenase → activates Leukotrienes (LTB₄, LTC₄)

Leads to asthma

• block leukotriene receptors that mediate airway inflammation, edema, bronchoconstriction and secretion of thick, viscous mucus
• administered orally
• Zileuton, Montelukast, Zafirlukast

5-lipoxygenase inhibitor

• prevents activation of leukotrienes

Montelukast (Singulair) and

Zafirlukast (Accolate)

LTD₄ receptor antagonists

Prevent binding of Leukotrienes to target tissue preveting: Bronchoconstriction, mucosal edema, bronchial hyper-reactivity 

beneficial in patients with exercise induced bronchospasm (already on steroids) and patients with environmental allergies

1. bronchoconstriction
2. mucosal edema
3. bronchial hyper-reactivity

• Class of Methyl Xanthines (with Theobromine and caffeine)
• many are sustained release
• mild to moderate bronchodilator used principally as adjuvant to inhaled corticosteroids for prevention of nocturnal asthmatic symptoms
• may have mild anti inflammatory effects and immunosuppressant effects

Include:

• Bronchodilation
• improved respiratory muscle function
• improved gas exchange
• enhanced mucociliary clearance
• enhances catecholamine secretion
  • Risk of sympathetic stimulation
  • Serum levels measurable

• Variable half life: reduced in smokers and children age 1-9
• Metabolized by CYP 450 - Watch drug interactions
  • Ciprofloxacin- severely ↓ its clearance (can lead to toxicity)

• Watch for GI, CNS and cardiac stimulation
• CNS effects - headaches, anxiety, restlessness, insomnia, dizziness, seizures
• Death

Cromolyn sodium (Intal)

• maintenance drug
• prevents mast cells from rupturing and spilling histamine (degranulation) after it has contact with antigen
• administered via inhalation or intra-nasal spray

Mast cell stabilizers

• Taken daily regardless of absence of symptoms
• not effective during acute attack
• can also be used as preventive treatment prior to exercise or unavoidable exposure to known allergens

•  Induce bronchoconstriction
• blocking β₂ receptors in airways prevents Salbutamol from working
• Selective β blockers (Cardio-selective blockers i.e. Atenolol)
  • Less bronchoconstriction than nonselective β blockers

ASA and NSAIDS
can induce severe bronchospasm

Ace inhibitors

Can cause cough (Lisinopril)

Treated with Aspirin

Use these drugs cautiously in asthmatics (cough is a symptom of asthma and ACE inhibitors)

       Asthma               COPD

Age of onset   <40 > 40

Smoking not causal Usually >10 pk/yr

Sputum Infrequently Often

Allergies Often Infrequent

Course Stable Progressive

Spirometry Normalizes Never normalizes

Symptoms Intermittent/vary Perisitent

• enlarged mucus glands
• dilated bronchial gland ducts
• inflammation in bronchioles
• mucus plugged
• fibrotic distortion

• Bronchodilators: anticholinergics, β₂ agonists, methyxanthines
• Glucocorticoids
• Mucolytics
• Oxygen
• Respiratory stimulants
• antibiotics
• vaccinations (ie pneumonia)
• lifestyle modifications 

• Used to describe patients with 1 or more of:
  • chronic bronchitis
  • Emphysema
  • Asthma

Lung diseases that inflame airways, obstruct breathing and trap bad air in the lungs, including emphysema and chronic bronchitis

• steady ↑ prevalence, while other major causes of death ↓
• (largely due to increase in populations age)
• Rise in younger people and women, due to effects of smoking (even years after they quit) as well as exposure to 2nd hand smoke and pollutants

• new campaign to ↑ awareness of COPD by encouraging people over 45 who may be at risk to get spirometry
• test that determines lung fxn by measuring air a person can breath out and the time it takes

Iprotropium (Atrovent)

• relaxation of bronchial smooth muscle by inhibitio of cGMP
• Bronchodilating effects are equal to or more than beta agonists
• Tiotropium (Spiriva) once daily

• Combination more effective than either alone
• Combivent = Salbuterol + Ipratropium

Salmeterol (Serevent)

• Approved for use in COPD in 1997

• Long acting β₂ agonists
• used for COPD since 1997
• 2 puffs BID vs. Ipratropium QID
  • Equal or superior to ipratropium, greatest benefit in those with bronchodilator response

• Controversial
• Only appropriate for symptomatic patients with moderate and severe COPD
• Long term use with oral steroids not advised

• Long term oxygen
• Antibiotics
• flu and pneumonia vaccines

Breaks up thick, tenacious sputum in patients whose physical condition makes it difficult to cough them up

Antidote for severe Acetaminophen overdose(causes 2nd peak of tylenol to not go quite as high)

Usually given by Nebulizer

Fast acting, onset of action within 1 minute

Guaifenesien (Robitussin)

• ↓ viscosity of secretions so they can be coughed up
• Available in many OTC preperations

Dextromethorphan (DM)

• used to suppress the cough reflex (Acts centrally in the brain) when chronic nonproductive coughing accompanies a disorder of the respiratory tract
• not used in peds

• Sedating: Diphenhydramine (Benadryl)
• Non-sedating: Loratiadine (Claritin)
• Block the H₁ receptor site, preventin histamine action whtn an antigen is encountered
• Resotres normal air flow through the upper respiratory tract
• many available OTC

Local hormones

• Histamine
• Serotonin (5-Hydroxythyptamine)
• Prostaglandins
• Leukotrienes

Mediates a range of cellular responses:

• allergies
• inflammatory reactions
• gastric acid secretion
• Neurotransmission in CNS

No clinical application

Cliically we aim to block its effects (Antihistamines)