~Teachingcenter的醫學筆記~

氣喘用藥
Durgs Used in Asthma

Beta Agonists

Albuterol

1. Mechanism of Action:
   • Selective β2 agonist
2. Effects:
   • Prompt, efficacious bronchodilation
3. Clinical Applications:
   • Asthma, chronic obstructive pulmonary disease (COPD)
   • Drug of choice in acute asthmatic bronchospasm
4. Pharmacokinetics, Toxicities:
   • Aerosol inhalation
   • Duration: several hours
   • Also available for nebulizer and parenteral use
   • Toxicity:
     1. Tremor and tachycardia
     2. Arrhythmia in overdose

Salmeterol

1. Mechanism of Action:
   • Selective β2 agonist
2. Effects:
   • Slow onset
   • Primarily preventive action
   • Potentiates (enhanced) corticosteroid effects
3. Clinical Applications:
   • Asthma prophylaxis
4. Pharmacokinetics, Toxicities:
   • Aerosol inhalation
   • Duration: 12~24 hours
   • Toxicity:
     1. Tremor and tachycardia
     2. Arrhythmia in overdose

Metaproterenol, terbutaline: like albuterol, and terbutaline available as an oral drug

Formoterol: like salmeterol

Epinephrine

1. Mechanism of Action:
   • Non-selective α and β agonist
2. Effects:
   • Bronchodilation plus all other sympathomimetic effects on cardiovascular and other organ systems
3. Clinical Applications:
   • Anaphylaxis and asthma (rarely used for asthma while selective β2 agonists available)
4. Pharmacokinetics, Toxicities:
   • Aerosol, nebulizer or parenteral use

Isoproterenol

1. Mechanism of Action:
   • Non-selective β agonist (β1 and β2 agonist)
2. Effects:
   • Bronchodilation plus powerful cardiovascular effects
3. Clinical Applications:
   • Asthma, but selective β2 agonists preferred
4. Pharmacokinetics, Toxicities:
   • Aerosol, nebulizer, or parenteral use

Corticosteroids (inhaled)

Fluticasone

1. Mechanism of Action:
   • Alter gene expression
2. Effects:
   • Reduces mediator of inflammation
   • Powerful prophylaxis of exacerbations
3. Clinical Applications:
   • Asthma
   • Adjunct in COPD
   • Hay fever (nasal)
4. Pharmacokinetics, Toxicities:
   • Aerosol
   • Duration: hours
   • Toxicity: (limited by aerosol application)
     1. Candida infection
     2. Vocal cord changes

Beclomethasone, budesonide, flunisolide, others: like fluticasone

Corticosteroids (systemic)

Prednisone

1. Mechanism of Action:
   • Like fluticasone
2. Effects:
   • Like fluticasone
3. Clinical Applications:
   • Asthma
   • Adjunct in COPD
4. Pharmacokinetics, Toxicities:
   • Oral
   • Duration: 12~24 hours
   • Toxicity: multiple adverse effect
     1. Indigestion or heartburn
     2. Increased appetite, which could lead to weight gain
     3. Difficulty sleeping
     4. Changes in mood and behaviour, such as feeling irritable or anxious
     5. An increased risk of infections – especially chickenpox, shingles and measles
     6. High blood sugar or diabetes
     7. Weakening of the bones (osteoporosis)
     8. High blood pressure
     9. Cushing's syndrome – symptoms such as thin skin that bruises easily, stretch marks on the thighs, and fat deposits in the face
     10. Eye conditions, such as glaucoma and cataracts
     11. Mental health problems, such as depression or suicidal thoughts

Methylprednisolone: parenteral agent like prednisone

Stabilizers of Mast and Other Cells

Cromolyn, nedocromil

1. Mechanism of Action:
   • Alter function of delayed chloride channels
   • Inhibits inflammatory cell activation
2. Effects:
   • Prevents acute bronchospasm
3. Clinical Applications:
   • Asthma (other routes used for ocular, nasal, and gastrointestinal allergy)
4. Pharmacokinetics, Toxicities:
   • Aerosol
   • Duration: 6~8 hours
   • Toxicity: (minimal) cough
   • Not absorbed so other toxicities are minimal

Methylxanthines

Theophylline

1. Mechanism of Action:
   • Uncertain
   • Phosphodiesterase inhibition
   • Adenosine receptor antagonist
2. Effects:
   • Bronchodilation, cardiac stimulation, increased skeletal muscle strength (diaphragm)
3. Clinical Applications:
   • Asthma, COPD
4. Pharmacokinetics, Toxicities:
   • Oral
   • Duration: 8~12 hours but extended-release preparations often used
   • Toxicity: multiple
     1. Acid-base imbalance
     2. Chest pain or discomfort
     3. Dizziness
     4. Fainting
     5. Fast, slow, or irregular heartbeat
     6. Increase in urine volume
     7. Lightheadedness
     8. Persistent vomiting
     9. Pounding or rapid pulse
     10. Seizures
     11. Shakiness

Leukotriene Antagonists

Montelukast, zafirlukast

1. Mechanism of Action:
   • Block leukotriene D4 receptors
2. Effects:
   • Block airway response to exercise and antigen challenge
3. Clinical Applications:
   • Prophylaxis of asthma, especially in children and in aspirin-induced asthma
4. Pharmacokinetics, Toxicities:
   • Oral
   • Duration: hours
   • Toxicity: minimal

Zileution: inhibits lipoxygenase, reduces synthesis of leukotrienes

IgE Antibody

Omalizumab

1. Mechanism of Action:
   • Humanized IgE antibody reduces circulating IgE
2. Effects:
   • Reduces frequency of asthma exacerbations
3. Clinical Applications:
   • Severe asthma inadequately controlled by above agents
4. Pharmacokinetics, Toxicities:
   • Parenteral
   • Duration: 2~4 days
   • Toxicity: injection site reactions (anaphylaxis extremely rare)

皮質類固醇和氣喘
1.口服和靜脈注射的療效是一樣的
2.效果通常在給藥的12小時候開始，因此不會影響在急診室對於氣喘的評估
3.此療法沒有明顯的劑量反應曲線(dose-response)，prednisone每日給予超過100mg並不會有更好的療效
※在相對低劑量(prednisone 40~80mg QD)、十天內的類固醇治療，可以在療程結束後直接停止，不須遞減劑量