Drugs for Bronchial Asthma “May the force be with you” -Yoda

Description Triggers Pathophysiology Symptoms Lab Results Status Asthmaticus

Asthma Chronic obstructive lung
disease
Disease of the airways
characterized by:
▪ Bronchial
hypersensitivity
▪ Airway obstruction
▪ Airway inflammation
▪ Airway remodelling
o Epithelial injury and
edema
o Changes in
mucociliary function
Often starts during
childhood; affects all ages
Develop their first symptoms
before 5 years old
Has no cure
Atopic disease
Parents who have asthma
▪ Cold air, weather changes,
exercise
▪ Emotion (anxiety, stress, hard
laughter or crying)
▪ Allergens (pollens, dust mites,
animal dander, mold, food)
▪ Bronchial irritants (cigarette
smoke, air pollution, chemicals
such as hairspray)
▪ Medicines (NSAIDS, non-
selective -blockers)
▪ Sulfites in food and drinks
▪ Occupational factors (laundry
detergent, textile dust)
Early response
▪ 10-20 minutes after exposure
to inhaled antigen or irritant
▪ Bronchoconstriction
▪ IgE mediated
▪ Tx: bronchodilators
Cause of smooth muscle
contraction
▪ Histamine
▪ Tryptase
▪ PGD2
▪ Leukotrine C4
▪ Platelet activating factor
(PAF)
Late response
▪ 3-5 hours after exposure
▪ Inflammation and increased
airway responsiveness
▪ Few hours to days or weeks
▪ IgE mediated: inflammatory
mediators and inflammatory
cells from the mast cells,
macrophages and epithelial
cells
Frequently nocturnal or in Decreased
the early mornings ▪ FEV (Forced expiratory asthma that is refractory
volume) – the amount
Sudden or episodic of air that can be
▪ Shortness of breath forcible expired in 1
▪ Wheezing sec
▪ Chest tightness or pain ▪ PEFR (Peak expiratory
▪ Cough w/ or w/out flow rate)
sputum ▪ IRC
▪ Breathing that requires ▪ Ventilation → hypoxia
increased work
▪ Tachycardia Hyperinflation of the lungs
Increased FRV
(Functional residual
volume)
Severe, prolonged
to conventional methods
of therapy
Symptoms
▪ Persistent shortness of
breath
▪ Inability to speak in
complete sentences
▪ Extreme difficulty in
breathing
▪ Bluish discoloration of
the lips and face
▪ Agitation, confusion, or
inability to concentrate

Respiratory infections during Inflammatory mediators

childhood ▪ Eosinophils
➢ ECP (eosinophilic
Contact with airborne cationic protein)
allergens or exposure to ➢ MBP (major basic
viral infection in infancy protein)
▪ Neutrophils
➢ Proteases
➢ PAF
▪ Cytokines
➢ Interleukins 4 & 5
➢ GM –CSF
➢ TNF
TGF

Drug Description Route of administration Indication MOA Adverse effects

Drugs for Bronchial Asthma “May the force be with you” -Yoda
-agonists ▪ Most important sympathomimetics used Acute asthma attack 1. Stimulate - adrenergic
to reverse asthmatic Bronchoconstriction Prompt relief receptors
▪ Quickly reduce airway constriction and ▪ Bronchodilation
restore normal airflow 2. Activates adenyl cyclise and
▪ Almost given exclusively by inhalation increasing cAMP in
▪ Decrease the systemic dose and adverse bronchial smooth muscles
effects ▪ Airway smooth muscle
relaxation →
Ephedrine ▪ Rapidly acting ▪ SC or microaerosol Bronchodilation ▪ Tachycardia, arryhtmias
▪ Onset: 15 min ▪ Worsening of angina
▪ Duration of action: 60-90 min pectoris

Ephedrine Vs. epinephrine ▪ PO

▪ Has longer duration of action
▪ More pronounces central effects
▪ Lower potency
▪ Used infrequently due to advent of
selective  agonists
Isoproterenol Potent bronchodilator ▪Microaerosol Cardiac arrhythmias
▪Onset: 5-15 min
▪Duration of action: 60-90 min
Selective -agonists More preferred than non selective: 2 > 1 ▪Active by all routes DOC acute asthma Significant 1 effects at high
Short acting (Relievers, ▪ Rapid onset, short duration: ➢ Inhalation: MDI or attack doses
Rescue medications) ➢ FTS neublizer ▪ Tachycardia
▪ Albuterol ▪ Slow onset, long duration ➢ PO – MAT ▪ Arrhythmias
▪ Levalbuterol ➢ SB ➢ SC – terbutaline ▪ Skeletal muscle tremor
▪ Metaproterenol ▪ Rapid onset, long duration Short acting ▪ Tolerance, tachyphylaxis
▪ Terbutaline ➢ Formoterol Duration of action: 4-8 hours
▪ Pirbuterol Drug-drug interactions
▪ Bitolterol Long acting ▪  blockers – bronchospam
DOA: 10-12 hours and increased dose to
Long acting (Controllers, produce Bronchodilation
Prophylaxis) ▪  agonists – cardiovascular
▪ Salmeterol effects
▪ Formoterol
▪ Bambuterol

Drug Description Route of administration MOA Pharmacodynamics Adverse effects Cautions/

Drugs for Bronchial Asthma “May the force be with you” -Yoda
Contraindications
Methylxanthines ▪ Purine derivatives ▪ Microcrystalline (anhydrous form) ▪ Increase levels of CNS effects Nausea & vomiting
▪ Plant alkaloids o Increased SA for absorption CAMP by competitive ▪ Increased alertness ▪ GI distress
▪ Medium potency bronchodilators ▪ Sustained release preparations inhibition of PDE → ▪ Deferral of fatigue ▪ Diarrhea &
▪ Narrow TI (Theo-Dur) Bronchodilation ▪ Nervousness anorexia
➢ Aminophylline o Can maintain blood levels of ▪ Inhibition of adenosine ▪ Insomnia ▪ Palpitations &
➢ Oxtriphylline theophylline for 12 hrs or receptors ▪ Termor tremor
➢ Theophylline more o Adenosine – ▪ Insomnia
o For control of nocturnal mediator of Cardiovascular
asthma bronchospasm ▪ Positive inotropic Over dosage
▪ IV therapy and chronotropic ▪ Severe nausea &
o For hospitalized patients w/ ▪ * can also inhibit vomiting
whom PO is not possible histamine release GI tract ▪ Hypotension
▪ PO ▪ Stimulate gastric ▪ Cardiac
o Effective route acid secretion arrhythmias
o Dose: 3-4 mg/kg every 6hrs ▪ Activates digestive ▪ convulsion
(theophylline) enzymes

Kidney
▪ Weak diuretic

Airway smooth muscle

▪ Bronchodilation –
major therapeutic
action
▪ Inhibit histamine
release from lung
tissue
Anticholinergics ▪ Reverses Bronchoconstriction ▪ Aerosol Inhibition of acetylcholine Local drying effect in
▪ Decreases bronchial secretions ▪ Dose: 2 mg by blocking M2 receptors the mouth
▪ Slightly less effective than -
agonists as bronchodilators in Systemic adverse
asthma effects
▪ Not effect on the inflammatory Urinary retention
aspects ▪ Loss of visual
▪ Useful in many COPD patients accommodation
Atropine sulfate ▪ Aerosol ▪ Agitation,
▪ Dose: 2mg tachycardia
Ipratropium bromide ▪ Quaternary ammonium ▪ inhalations QID (max: 12 Not indicated in the
derivative of atropine inhalations/ day) initial treatment of
▪ Preferred over atropine sulfate bronchospasm
due to lesser systemic adverse Prostatic
effects hypertrophy
▪ Used in combinations w/  glaucoma
agonists (Ipra + albuterol)

Glycopyrrolate ▪ Quaternary ammonium

compound
▪ Used in combination w/ 
agonists for the treatments of
severe, acute asthma

Drug Decription Route of Admin/ Indications MOA Adverse effects Precautions/ Contraindications
Drugs for Bronchial Asthma “May the force be with you” -Yoda
Dosage
ANTI-INFLAMMATORY AGENTS
Mast Cell Stabilizers ▪ Has no use in acute ▪ Cromolyn ▪ Exercise ▪ Inhibit mast cell ▪ Chest tightness, Warnings
asthma attacks o Adult: MDI (2- induced degranulation by stabilizing wheezing ▪ Hypersensitivity/ drug allergy
4 mg, 4x asthma the cell membranes thus ▪ Mouth dryness, taste (rare)
daily) ▪ Occupational preventing the release of change
o Children: asthma various substances that ▪ Irritation of the throat, ▪ Contraindicated for acute
aerosol (1% ▪ Drug induced cause bronchospasm cough exacerbations
solution) asthma ▪ Their beneficial effects in ▪ Therapeutic effects may not be
▪ Allergic rhinitis the Tx of asthma are seen for up to 4 weeks
▪ Nedocromil ▪ Hay fever largely prophylactic ▪ Teach patients to gargle and
o Adult: MDI 3.5 rinse the mouth with water
mg 4x daily or afterwards to minimize irritation to
2 inhalations the throat and oral mucosa
4x daily
Corticosteroids ▪ Inhaled are the most ▪ Systemic: ▪ Reduces the synthesis of Systemic effects (more than Contraindications
Systemic effective anti- status arachidonic acid by 2 weeks) ▪ Systemic fungal infections
▪ Hyrdocortisone IV inflammatory tx for asthmaticus inhibiting phospholipase A ▪ Reduced bone density ▪ Persistently positive of candida
▪ Prednisone PO asthma ▪ Inhibit (osteoporosis)
▪ Prednisolone IV ▪ All are potentially ▪ Inhaled o The expression of COX- ▪ Skin changes Warnings
▪ Methylprednisone beneficial in severe (aerosol): 2 ▪ Change in adrenal ▪ Adrenal suppression
IV asthma common first o Production of function ▪ Pregnancy: not proven although
line for leukotrienes which are ▪ Cataract formation shown teratogenic effects in
Inhaled (aerosol) moderate to potent rodents
▪ Beclomethasone severe asthma bronchoconstrictors Inhaled
▪ Dexamethasone o Production of cytokines ▪ Oral thrush Precautions
▪ Triamcinolone that initiates airway ▪ Use a spacer or holding ▪ Oropharyngeal candidiasis “oral
▪ Flunisolide inflammation chamber on your inhaler; thrush”
▪ Fluticasone helps prevent the ▪ Pharyngeal irritation, coughing
▪ Budesonide medicine from landing in ▪ Hoarseness, dry mouth
▪ Mometasone your mouth or on the ▪ Retarded growth in children
back of your throat

Rinsing mouth w/ water after

taking inhaled corticosteroids
LEUKOTRIENE ANTAGONISTS
Leukotriene antagonists
Zafrilukast & ▪ Newest anti- PO ▪ Zafrilukast – LTD4 receptor Montelukast Churg- Strauss Syndrome
montelukast inflammatory agents Dose: 20 mg antagonist ▪ Headache ▪ A clinical syndrome comprising
used in asthma twice daily ▪ Prevent leukotriene from ▪ Dizziness severe asthma associated w/
interacting with their ▪ Dyspepsia eosinophilic vasculitis
receptors ▪ Associated w/
Zafrilukast ✓ Zafrilukast
Pathophysiology ▪ Headache ✓ Monetlukast
▪ Leukortienes ▪ Dizziness ✓ Pranlukast (Japan)
a. Enhanced migration of ▪ Nausea ▪ Vasculitis rash
eosinophils and ▪ Diarrhea ▪ Eosinophilia
Neutrophils ▪ Increasing pulmonary, cardiac
b. Increased and neuropathic symptoms
c. Adhesion of leukocytes
d. Increased capillary
permeability
e. Smooth muscle
contraction
▪ LTB4- potent neutrophil
chemoattractant
Drugs for Bronchial Asthma “May the force be with you” -Yoda
▪ LTC4 & LTD4 causes
✓ Bronchoconstriction
✓ Increased bronchial
reactivity
✓ Mucosal edema
✓ Mucus hypersecretion
Lipoxygenase inhibitor
Zileuton ▪ PO ▪ Inhibits 5-lipoxygenase
▪ Dose: 600 mg 4x thereby preventing
daily leukotriene synthesis
OTHER DRUGS FOR ASTHMA
Calcium channel ▪ Inhibit
blockers Bronchoconstriction
▪ Verapamil &
nifedepine
NO Donors ▪ Relaxes airway ▪ Inhaled as gas &
smooth muscles dilates
pulmonary blood
vessels & airway
smooth muscles
Potassium channel ▪ CROMAKALIM
openers o Investigational
drug
▪ Relaxes airway
smooth muscles
Omalizumab ▪ Helps prevent body Parenteral – ▪ Used if other ▪ Humanized murine
from reacting to once/ twice a asthma monoclonal antibody
asthmatic triggers, month medicines have ▪ Prevents binding of IgE to
such as pollen & not worked well mast cells preventing
dust mites degranulation (Prophylaxis)