PCOL UNIT 2 - Pharmacology of the Respiratory System

Asthma

a chronic condition marked by hyper-responsive airways

dyspnea, cough, and wheezing

asthma is characterized by these symptoms

Asthma exacerbation

often referred to as an asthma flare-up or asthma attack

Asthma exacerbation

this condition involves an acute or sub-acute worsening of symptoms and lung function, in contrast to the individual’s normal state

COPD

irreversible airway blockage

COPD

refers to a group of diseases that cause airflow blockage and breathing-related problems

• frequent coughing or wheezing

• increased phlegm production

• shortness of breath

Symptoms of COPD include

Chronic bronchitis

is inflammation of the lining of the bronchial tubes, which carry air to and from the air sacs (alveoli) of the lungs

Chronic bronchitis

it’s characterized by a daily cough and mucus (sputum) production

Emphysema

is a condition in which the alveoli at the end of the smallest air passage (bronchioles) of the lungs are destroyed as a result of damaging exposure to cigarette smoke and other irritating gases and particulate matter

Beta Adrenoreceptor Agonist

MOA: relax bronchial smooth muscle by stimulating B-2 adrenergic receptors

Short-Acting β2 Agonists (SABAs)

Salbutamol (Albuterol )

Short-Acting β2 Agonists (SABAs)

Terbutaline

Short-Acting β2 Agonists (SABAs)

Metaproterenol

Short-Acting β2 Agonists (SABAs)

Pirbuterol

Long-Acting β2 Agonists (LABAs)

Salmeterol

Long-Acting β2 Agonists (LABAs)

Formoterol

Ultra-long-acting Beta Adrenoreceptor Agonist

Indacaterol

Ultra-long-acting Beta Adrenoreceptor Agonist

Olodaterol

Ultra-long-acting Beta Adrenoreceptor Agonist

Vilanterol

Ultra-long-acting Beta Adrenoreceptor Agonist

Bambuterol

Short-Acting β2 Agonists (SABAs)

DOC for Acute asthma attack

Short-Acting β2 Agonists (SABAs)

Rescue medication (“Reliever”)

Short-Acting β2 Agonists (SABAs) and Leukotriene Modifiers

Exercise-induced bronchospasm

Short-Acting β2 Agonists (SABAs)

Mild intermittent asthma (as-needed use)

Short-Acting β2 Agonists (SABAs)

Acute bronchospasm in COPD

Short-Acting β2 Agonists (SABAs)

Route:

• Inhalation (preferred)

• Nebulizer Oral tablets (rarely used)

• Terbutaline: Subcutaneous injection

• Onset: 5–15 minutes

• Peak: Around 15–30 minutes

• Duration: 3–6 hours

Terbutaline

subcutaneous injection SABAs

Long-Acting β2 Agonists (LABAs)

Used for maintenance therapy, NOT rescue.

Long-Acting β2 Agonists (LABAs)

Moderate-to-severe persistent asthma

Long-Acting β2 Agonists (LABAs) and Inhaled Corticosteroids (ICS)

Long-term asthma control

Long-Acting β2 Agonists (LABAs)

COPD maintenance therapy

Long-Acting β2 Agonists (LABAs)

drug class that should never be alone in asthma

Formoterol

B2 agonist drug that is

• Rapid onset

• Long duration

Bambuterol

B2 agonist drug that is

• oral prodrug

• converted to terbutaline

• Slowly released by pseudocholinesterase

• Duration: About 24 hours

Terbutaline

Bambuterol is converted

Beta Adrenoreceptor Agonist

AE: Skeletal muscle tremor

Beta Adrenoreceptor Agonist

AE: Palpitations

Beta Adrenoreceptor Agonist

AE: nervousness

Beta Adrenoreceptor Agonist, Leukotriene Modifiers, Methylxanthines, PDE - 4 Inhibitor

AE: Headache

• Skeletal muscle tremor (most common)

• Tachycardia

• Palpitations

• Nervousness

• Headache

Common AE of B2 Agonists

• Hypokalemia

• Hyperglycemia

• Hypomagnesemia

Metabolic AE of B2 agonists

• Muscle weakness

• Cardiac arrhythmias (rare)

Less common AE of B2 agonists

Beta Adrenoreceptor Agonist

Toxicities: Tachyphylaxis

• repeated frequent use may decrease responsiveness

Beta Adrenoreceptor Agonist and Corticosteroids

AE: Muscle weakness

Corticosteroids

Controller (Preventer) medication

Cortocosteroids

DOC for long-term control of persistent asthma

Corticosteroids

Not bronchodilators

• they do no provide immediate relief during an acute asthma attack

Phospholipase A2

Corticosteroids inhibit this enzyme that converts eicosanoids into arachidonic acid

• persistent asthma (mild, moderate, severe)

• Long-term asthma control

• prevention of asthma exacerbations

Inhale Corticosteroids (ICS) is DOC for

Inhaled Corticosteroids (ICS)

Beclomethasone

Inhaled Corticosteroids (ICS)

Budesonide

Inhaled Corticosteroids (ICS)

Fluticasone

Inhaled Corticosteroids (ICS)

Mometasone

Inhaled Corticosteroids (ICS)

Ciclesonide

Inhaled Corticosteroids (ICS)

Flunisolide

Inhaled Corticosteroids (ICS)

Triamcinolone

Inhaled Corticosteroids (ICS)

Route:

• Metered-dose inhaler (MDI)

• Dry powder inhaler (DPI)

• Nebulized formulations

Inhaled Corticosteroids (ICS)

Onset:

• Not immediate

• Clinical improvement:

  • Several days

• Maximum benefit:

  • Weeks to months

Inhaled Corticosteroids (ICS)

Duration:

• requires regular daily use to maintain effectiveness

Inhaled Corticosteroids (ICS)

Distribution:

• High concentration delivered directly to the lungs

• Minimal systemic absorption

• Swallowed portion undergoes extensive first-pass hepatic metabolism, reducing systemic exposure

Inhaled Corticosteroids (ICS)

AE: Oropharyngeal candidiasis (oral thrush)

Inhaled Corticosteroids (ICS)

AE: Hoarseness (dysphonia)

Inhaled Corticosteroids (ICS)

AE: Throat irritation , cough

Systemic Corticosteroids

for acute severe asthma exacerbation

Systemic Corticosteroids

for status asthmaticus

Systemic Corticosteroids

Patients not responding adequately to bronchodilators

Prednisone and Prednisolone

Systemic corticosteroids that are oral

Methylprednisolone and Hydrocortisone

Systemic corticosteroids that is IV

Systemic Corticosteroids

Short-course therapy

• Usually 5–10 days

• Tapering is generally unnecessary after a short course because significant hypothalamic–pituitary–adrenal (HPA) axis suppression is unlikely

Systemic Corticosteroids

AE: adrenal suppression with prolonged use

Systemic Corticosteroids

AE: Weight gain

Systemic Corticosteroids

cushingoid appearance

Systemic Corticosteroids

Musculoskeletal AE

• Osteoporosis

• Muscle weakness

Systemic Corticosteroids

has immune AE that increased the risk of infetions

Systemic Corticosteroids

has eyes AE that causes

• cataracts

  • glaucoma

Systemic Corticosteroids

AE psychiatric (mood changes, insomnia, psychosis)

Leukotriene Receptor Antagonists (LTRAs)

Montelukast

Leukotriene Receptor Antagonists (LTRAs)

Zafirlukast

Leukotriene Receptor Antagonists (LTRAs)

MOA:

• Block CysLT1 (cysteinyl leukotriene-1) receptors

Leukotriene Receptor Antagonists (LTRAs)

MOA:

• prevent the actions of LTC4, LTD 4, and LTE4

Leukotriene Receptor Antagonists (LTRAs)

MOA:

• reduce bronchoconstriction, mucus production, and airway inflammation

Leukotriene Receptor Antagonists (LTRAs)

MOA:

• Block CysLT₁ (cysteinyl leukotriene-1) receptors

• Prevent the actions of LTC₄, LTD₄, and LTE₄

• Reduce bronchoconstriction, mucus production, and airway inflammation

5-Lipoxygenase Inhibitor

Zileuton

Zileuton

MOA:

• inhibits 5-lipoxygenase

Zileuton

MOA:

• Prevents synthesis of leukotrienes (LTB4, LTC4, LTD4, LTE4)

Zileuton

MOA:

• Inhibits 5-lipoxygenase

• Prevents synthesis of leukotrienes (LTB₄, LTC₄, LTD₄, LTE₄)

Leukotriene modifiers

for mild persistent asthma (alternative controller)

Leukotriene modifiers

Add-on therapy to ICS

Leukotriene modifiers

for prevention of exercise-induced bronchospasm

Leukotriene modifiers

for Aspirin-exacerbated asthma

Montelukast

Leukotriene modifiers drug for allergic rhinitis

Leukotriene modifiers

Pharmacokinetics:

• Administered orally

• Highly protein bound

• Extensive hepatic metabolism

Zafirlukast

Leukotriene modifier drug that decreases absorption with food

Zileuton

Leukotriene modifier drug that excreted through urine

Montelukast and Zafirlukast

Leukotriene modifier drug that excreted through bile/feces

• Headache

• Dyspepsia

Common AE of leukotriene modifiers

Zileuton

a drug that causes elevated liver enzymes

Leukotriene Modifiers

Serious AE hepatotoxicity (requires liver function monitoring)

CYP2C8, CYP2C9, CYP3A4

Zafirlukast inhibits