COPD/Asthma Medium

Bronchodilators: Albuterol (Proventil)

• Therapeutic action: Causes bronchodilation by increasing cyclic adenosine monophosphate (cAMP) in bronchial tissue and stimulating beta-2 adrenergic receptors.
• Albuterol decreases airway resistance and facilitates airflow but has a limited role in suppressing histamine release.
• Indications: Used as a short-acting bronchodilator (SABA) or "rescue inhaler" for quick relief of acute bronchospasm in conditions like asthma and COPD.
• It is a selective beta2 agonist and a first-line therapy used as needed (PRN) for shortness of breath (SOB) associated with COPD
• Frequent use of SABA (more than 2-3 times a week) suggests that asthma is not well controlled and adjustments to baseline therapy may be necessary.
• Pharmacokinetics:
  • Inhaled (INH) form has a rapid onset (1-15 minutes), peaks in 30-60 minutes, and lasts for 3-6 hours.
  • Orally administered (PO) form's onset in 15-30 min, peaks in 2-3 hours, and lasts for 4-6 hours or more
  • The drug is well absorbed in the GI tract with PO administration and rapidly enters the bloodstream, but systemic concentration is low when inhaled.
  • Albuterol distributes widely in the body tissues, with small amounts appearing in breast milk.
  • It undergoes extensive metabolism by the liver
  • Excretion: Primarily excreted in urine as metabolites (~75%) and feces (~10%).
• Contraindications: Contraindicated in individuals with hypersensitivity to adrenergic amines.
• Use with caution in patients with cardiac disease, hypertension, hyperthyroidism, diabetes, glaucoma, and seizure disorders.
• Excessive inhaler use may lead to tolerance and paradoxical bronchospasm.
• Use during pregnancy and lactation: should be administered only if potential maternal benefit justifies potential fetal risks.
• Geri: Older adults have an increased risk of adverse reactions, and may require a decreased dose
• Adverse Reactions:
  • High doses lead to beta1 responses.
  • Reactions occur more often with oral (PO) administration.
  • Side effects may diminish after a week or longer.
  • May cause paradoxical bronchospasm, nervousness, tremors, insomnia, hyperactivity (in children), headache, tachycardia, heart palpitations, increased BP, angina, arrhythmias, chest pain, nausea/vomiting, hyperglycemia, and hypokalemia.
• Drug-to-drug Interactions:
  • Concurrent use with other adrenergic agents may increase adrenergic side effects.
  • Use with MAO inhibitors may lead to hypertensive crisis.
  • Beta blockers may negate the therapeutic effect.
  • It may decrease serum digoxin levels
  • Tricyclic antidepressants may potentiate cardiovascular effects.
  • Concurrent use of potassium-losing diuretics increases risk of hypokalemia
  • Drug-Natural Products: Use with caffeine-containing herbs (cola nut, guarana, tea, coffee) can increase the stimulant effect.

Bronchodilators: Salmeterol (Serevent Diskus)

• Therapeutic action: Similar MOA to SABA. Produces accumulation of cAMP at beta2-adrenergic receptors, leading to bronchodilation.
• Indications: Long-acting bronchodilator (LABA) used for the long-term maintenance and prevention of bronchospasm in conditions like asthma, COPD, and exercise-induced asthma.
• It is used concomitantly in patients who are currently taking but are inadequately controlled on an inhaled corticosteroid; typically combined to control asthma symptoms.
• Pharmacokinetics:
  • For inhalation use only: onset in 10-25 minutes, peaking in 3-4 hours, and lasts for 12 hours (9 hours in adolescents).
  • It has a half-life of 3-4 hours.
  • Slow absorption with minimal systemic absorption when inhaled.
  • Action primarily local.
  • The drug is metabolized in the liver via the CYP3A4 isoenzyme
  • Sixty percent is excreted in feces, 25% in urine.
• Contraindications:
  • Not suitable for the relief of acute symptoms.
  • Should not be used more than twice daily (BID).
  • LABAs are not indicated for abortive therapy for bronchospasm
  • Salmeterol is contraindicated in cases of Hypersensitivity to salmeterol or milk proteins, acute attack of asthma (onset of action is delayed), Patients whose asthma is currently controlled on low- or medium-dose inhaled corticosteroid therapy
• Use cautiously in patients with cardiovascular disease, seizure disorders, diabetes, glaucoma, hyperthyroidism, and pheochromocytoma
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk; may inhibit contractions during labor
• Adverse Reactions: Palpitations, and tachycardia
  • GI: abdominal pain, diarrhea, nausea
  • MS: muscle cramps/soreness
  • Neuro: headache, nervousness, tremor
  • Resp: cough, PARADOXICAL BRONCHOSPASM
• Drug-to-drug Interactions:
  • Beta blockers may decrease therapeutic effects.
  • MAO inhibitors and tricyclic antidepressants may potentiate cardiovascular effects.
  • Strong CYP3A4 inhibitors may increase levels and the risk of toxicity.
  • Drug-Natural Products: Use with caffeine-containing herbs
• Should not be used more than BID.
• LABAs should be only used in patients taking a recommended medication for long-term control and only if that medication has been inadequate by itself

Bronchodilators: Methylxanthines (Theophylline)

• Therapeutic action: Causes bronchodilation by increasing cAMP which relaxes the smooth muscles of the airways and pulmonary vessels;
• Has impact on CNS stimulation, CVS effects dilate coronary vessels, and causes a diuretic effect
• Indications:
  • Treatment option for COPD but not very frequently used in COPD and asthma
  • Often used in combination with other medications for better control of symptoms
  • Used to treat apnea of prematurity (AOP)
• Pharmacokinetics:
  • Onset 30 min (for SR caps: 1-2 hours), duration for SR 8-25 hours (6 hrs for IV or Oral theophylline)
  • Large volumes of fluid and high-protein meals may increase the rate of absorption
  • Distribution: distributes freely into fat-free tissues but poorly into body fat
  • Liver Metabolized by CYP450 enzymes (CYP 1A2, CYP 2E1, and CYP 3A4);
  • Meds that induce CYP450 can increase clearance of theophylline
  • Tobacco smoking increases metabolism of theophylline drugs, thereby decreasing the half-life of the drug
• Contraindications:
  • Those with cardiac d/t its stimulatory effects
  • Those with renal or hepatic dysfunction
• Adverse Reactions:
  • Nausea/vomiting, gastric pain (due to increased gastric acid secretion)
  • Tachycardia, Irritability
  • Seizures, Cardiorespiratory collapse
  • No antidote for theophylline toxicity
• Drug-to-drug Interactions:
  • Beta-blockers & erythromycin: decreases liver metabolism of theophylline, thereby increases the half-life of the drug and adverse effects
  • Barbiturates: induce CP450, stimulating theophylline metabolism which can result in subtherapeutic levels of theophylline
  • Macrolide antibiotics: inhibits metabolism of theophylline & increases renal clearance of erythromycin
  • Lithium: theophylline decreases the effects of lithium
  • SMOKING: decreases theophylline levels.
  • Caffeine: the effects of theophylline can be increased by foods containing caffeine
• Monitoring:
  • Serum theophylline levels
  • Toxicity is likely to occur when level exceeds 20 mcg/ml
  • If serum levels of theophylline have not been stabilized, screen diet, other medication, smoking habits,
  • Toxicity treatment: Charcoal, emesis, gastric lavage to decrease absorption of the oral medication, Lidocaine: to treat dysrhythmias, Diazepam: to control seizures

Bronchodilators: Anticholinergics: Ipratropium (Atrovent)

• Therapeutic action: Causes bronchodilation by antagonizing the action of acetylcholine by blocking muscarinic acetylcholine receptors in the airways
• Indications:
  • Long-acting muscarinic antagonist (LAMA)
  • Inhaled anticholinergic drugs are considered 1st treatment for COPD whose symptoms have become persistent
• Pharmacokinetics:
  • Onset 1-3 min, peak 1-2 hrs, duration 4-6 hrs
  • Minimal systemic absorption (1-2% for inhalation solution
  • Distribution: distributed throughout the body but does not significantly penetrate into body fat, 15% of dose reaches lower airways after inhalation
  • Metabolism: Ipratropium is metabolized in the liver by cytochrome P450 enzymes.
  • Excretion: It is excreted primarily in the urine, with a small amount excreted unchanged, Majority of swallowed dose excreted in feces unchanged
• Contraindications:
  • hypersensitivity to ipratropium, atropine, belladonna alkaloids, or bromide
  • Use cautiously in: Bladder-neck obstruction, prostatic hyperplasia, glaucoma, or urinary retention
• Adverse Reactions:
  • PARADOXIC BRONCHOSPASM with aerosol ipratropium (especially with 1st inhalation in newly opened MDI)
  • Dry mouth and irritation of the pharynx
  • CV: hypotension, palpitations
  • Drug-to-drug Interactions: Increases anticholinergic effects with other drugs having anticholinergic properties (antihistamines, phenothiazines, and disopyramide)
• Teaching: Beta-agonist inhalant should administer it 5 min before using ipratropium

Inhaled Glucocorticoid Steroids (ICS): Flunisolide (AeroBid)

• Therapeutics Action: ANTIINFLAMMATORY
• Functions by decreasing airway inflammation
• Indications: First line treatment for persistent asthma
• Pharmacokinetics:
  • Inhalation: onset 5-10 min, peak 30-60 min, duration 12-24 hours, half-life 1.3-1.7 hours
  • Absorption: absorbed through the lungs into bloodstream with minimal systemic absorption (↓ systemic side effects)
  • Distribution: extensively distributed throughout the body reaching various tissues and exert its anti-inflammatory effects throughout the body
  • Metabolism: metabolized by the liver
  • Excretion: primarily in the urine
• Contraindications:
  • Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required
  • Use in children younger than 6 years of age
• Adverse Reactions:
  • During inhalation (especially when a spacer is not used) flunisolide is deposited in the mouth and pharynx
  • Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is possible with long term daily use, but this effect is very rare. ***
  • sore throat (Pharyngitis), Hoarseness
• Drug-to-drug Interactions: Desmopressin: can increase risk of hyponatremia
• Oral Medications: Oral Corticosteroids (e.g., Prednisone)

Leukotriene Receptor Antagonists: Zafirlukast (Accolate)

• Therapeutic Actions: PREVENT BRONCHOCONSTRICTION AND VASODILATION
• Leukotriene receptor antagonist (LTRA) that works by blocking the action of leukotrienes, which are inflammatory chemicals the body releases in response to allergens
• helps decrease inflammation, mucus production in the airways, making it effective in managing asthma symptoms
• Primarily for the prophylaxis and chronic treatment of asthma in adults and children aged 5 years and older
• Pharmacokinetics:
  • PO: Onset 1-2 hours, peak 3 hours, duration 24 hours, half-life 10 hours
  • Absorption: rapidly absorbed after oral administration
  • Distribution: highly protein bound in plasma (>99%, primarily to albumin) with moderate volume of distribution
  • Metabolism: extensively metabolized by the liver, primarily by CYP2C9
  • Excretion: mainly in the feces
  • The bioavailability of zafirlukast is decreased when taken with high-fat or high-protein meals.
• Contraindications:
  • Use with patients with known hypersensitivity to the drug
  • Should not be used to control acute asthma/asthma attack
• Adverse Reactions: elevated liver enzymes

Mast Cell Stabilizers: Cromolyn (Intal)

• Therapeutic Action: ANTIINFLAMMATORY
• Functions by inhibiting the release histamine and other inflammatory mediators of Type-I allergic reactions from mast cells, thereby preventing allergic reactions
• Indications: Asthma: Prophylaxis of allergic and exercise-induced Asthma
• Pharmacokinetics:
  • To be administered via nebulizer, Onset 15 min, peak 30-60 min, duration 8-12 hours
  • Absorption: absorbed through the lungs into the bloodstream; Approx 8% is absorbed systemically
  • Distribution: minimally distributed
  • Metabolism: not extensively metabolized
• Contraindications: SHOULD NOT BE USED DURING ACUTE ASTHMA ATTACK: may worsen symptoms
• Adverse Reactions: GI: Nausea, vomiting, diarrhea, abdominal pain, Bitter taste, CNS: Headache, dizziness, difficulty speaking
• Patient Education: Effective use requires regular administration and will not STOP an attack in progress

Differentiating Drug Classes for COPD and ASTHMA

• Beta-Agonists (SABA/LABA): Used in asthma & COPD for bronchodilation, symptom relief, and improved airflow.
• Anticholinergics (SAMA/LAMA): Used in COPD & asthma exacerbations for bronchodilation, decreased mucus production, and symptom control.
• Inhaled Corticosteroids: Used in asthma & severe COPD for anti-inflammation, prevention of exacerbations, and airway remodeling control.
• Leukotriene Modifiers: Used in asthma (some COPD cases) for anti-inflammation, reduced bronchoconstriction, and prevention of exercise-induced bronchospasm.
• PDE4 Inhibitors: Used in COPD to reduct inflammation
• Immunomodulators: Used in severe asthma to reduce exacerbations and can control symptoms in allergic or eiosinophilic asthma
• Methylxanthines: Used in asthma & COPD for long-term bronchodilation and symptom reduction, but used less frequently.
• Systemic Corticosteroids: Used in asthma & COPD exacerbations for quick relief from inflammation and control during exacerbations.

Key treatment differences for COPD vs ASTHMA

• COPD management focuses on long-term control, symptom relief, and reducing exacerbations, mainly with bronchodilators + CS
• Asthma Management is focused on preventing inflammation, controlling acute exacerbations, + minimizing airway hyperresponsiveness, using ICS + beta-agonists + leukotriene modifiers.

Side effects of beta2-adrengeric agonists

• commonly used as bronchodilators for conditions like asthma and COPD
• can have side effects due to stimulation of beta2-adrenergic receptors
• Side effects may diminish after a week or longer
• The bronchodilating effects may decrease with continued use
• Adverse effects are more frequent when administered orally.

Methylxanthines Side Effects and Interactions (Theophylline)

• Narrow therapeutic index with modest alterations in metabolism can lead to subtherapeutic effects or toxic side effects
• Side effects: Central Nervous System Stimulation:
  • Insomnia, Nervousness, and Anxiety (overstimulation)
  • Tremors (common)
  • Seizures (toxic levels)
  • Gastrointestinal Disturbances: (higher doses)
  • Nausea, Vomiting, and Abdominal Discomfort: (higher doses)
• Drug-to-Drug Interactions: Because methylxanthines are primarily metabolized by cytochrome P450 enzymes, several drugs can alter their metabolism:

Levels of Theophylline

• Theophylline has a narrow therapeutic index (range between an effective dose and a toxic dose is small). Max dose typically 600mg/day
• Therapeutic Levels:
  • Target Serum Concentration: maintained between 10–20 mcg/mL
  • Clinical Effects: effective bronchodilation with minimal side effects.
• Toxic Levels:
  • Mild-Moderate: Approx 20-25 mcg/mL
    • Symptoms: Nausea, vomiting, diarrhe, insomnia
  • Severe: >30 mcg/mL
    • Symptoms: severe dysrhihythmias
    • May result in cardiorespiratory collapse
• Monitoring is critical due to the narrow therapeutic range
• Regular monitoring of serum levels is important, starting or adjusting doses
• Individual Variability: Age, smoking status, concurrent medications, and liver function affect theophylline metabolism

Differentiate general client teaching related to drugs commonly used for COPD and asthma; inhaler technique and when to use medications and what to monitor

Client Teaching Points

• Inhaled Bronchodilators:
  • Short-Acting Beta2-Agonists (SABAs) - e.g., Albuterol
  • Use for rapid relief of acute bronchospasm
  • Technique: Demonstrate correct inhaler or nebulizer use,importance of shaking the inhaler and using a spacer if recommended
  • May include tremors, tachycardia, and nervousness
• Inhaled Corticosteroids (ICS):
  • Purpose: Reduce airway inflammation and prevent exacerbations
• Medications:
  • Check if PRN or scheduled for best usage

General Client teaching points

• Medication Adherence:
  • Consistency: Emphasize the importance of taking medications exactly as prescribed, even when feeling well.
  • Daily Routine: Encourage integrating medication routines into daily life.
• Recognizing Symptoms: Educate about recognizing symptoms and what steps to take during worsening symptoms

Review the “GOLD” standards in COPD

• Diagnosis
  • Spirometer confirms diagnosis
  • COPD is comfirmed when post-bronchodilator Force expiratory Volume (Fev1); / Forced Vital Capacity (FVC) ratio is <.70 Symptoms
  • History including smoking exposure and environmental factors must be evaluated

Assessment and Classification; management

• Symptom and Exacerbation Risk Assesment (ABCD Groups)
  • Group A: low symtpom burden, low exacerbation risk
  • Group B: more symptoms, but low exacerbation risk
• Management Strategies:
  • Pharmacologic treatment; vaccines and smoking cessation
  • Bronchodilators: SABA and LABA and also LAMA
  • Inhaled Corticosteriods in combination with LABA
  • Combination Thearpeutics for increased affectivity

Key aspects of exacertion management

Exacerabtion recognition and management

Long term monotoring

• Educate patients to identify worsening symptoms and seek timely medical intervention Treatment: Ongoing pharmacologic and non-pharmacologic strategies are aimed at reducing the frequency and severity of exacerbations Review action plans

General client teaching review

1st gene antistamines

▪ H1 antagonist: ○ Preventing action of H1 ▪ useful in motion sickness ▪ can cause excitation and depression of CNS ▪ useful in treating allergic disorders: 1st generation H1 Antagonists (Non-Selective): diphenhydramine, promethazine, chlorpheniramine: ☐Also interacts with muscarinic receptors, which contributes to anticholinergic effects (dry mouth, blurred vision, urinary retention) []May affect alpha-adrenergic receptors, contributing to

Differences with 2nd gene

▪2nd generation: ☐Primarily targets the peripheral H1 receptors with minimal or no action on muscarinic, alpha-adrenergic, or serotonin receptors Less Sedation: Designed to minimize drowsiness and other CNS side effects Summary of 1st vs 2nd Generation Antihistamines: • 1st Generation: Blocks H1 receptors but is non-selective, affecting additional receptor sites (muscarinic, alpha-adrenergic, etc.), which results in significant sedation and anticholinergic side effects

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