Bronchodilators

Bronchodilators: A bronchodilator or broncholytic  is a medication that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs.

Indication: Rapid relief of bronchospasm in asthma. Prophylactic or maintenance therapy in asthma, COPD(Chronic obstructive pulmonary disease).

Classification:

 

Sympathomimetics b2 - adrenoceptor agonists

: Beta₂-adrenergic agonists, also known as adrenergic β₂ receptor agonists, are a class of drugs that act on the β₂ adrenergic receptor. Like other β adrenergic agonists, they cause smooth muscle relaxation.

Mechanism of Action

Ø  Direct b₂ stimulation  ¾® stimulate adenyl cyclase ¾® ­ cAMP ®  bronchodilation.

Ø  Increase mucus clearance by (increasing ciliary activity).

Ø  Stabilization of mast cell membrane (inhibit release of allergic mediators)

Classification:

Non Selective:  Ex: Epinephrine – isoprenaline

•      Epinephrine: is a Potent bronchodilator

Mechanism of action: stimulation  of alpha, beta1 and beta 2 receptors¾® stimulate adenyl cyclase ¾® ­ cAMP ®  bronchodilation.

•      Pharmacokinetics:

Route of administration	Subcutaneous.
Half – life	of < 5 minutes.
Onset of action	Rapid action (maximum effect within 15 min).
Duration of action	60-90 min
Elimination	mostly degraded by conjugation with glycuronic acid sulhuric acid and eliminated in urine.

•      Disadvantages:

•      It is Not effective orally.

•      Causes Hyperglycemia and Skeletal muscle tremor

•      CVS side effects: tachycardia, arrhythmia, hypertension

•      Not suitable for asthmatic patients with    hypertension or heart failure.

•      Contraindications: CVS patients, diabetic patients

Ø  Selective b2 – agonists (Preferable):

Short acting selective b2 – agonists: relieve acute asthma symptoms/attacks very quickly by opening airways.

Ex:   Salbutamol (albuterol),Terbutaline

Salbutamol: route of administration: Oral, Subcutaneous

Pharmacokinetics:

Bioavailabilty	Oral  50%
T half life	4 hours
Onset of action	Oral : 30 minutes  Inhalation 5-15 min.
Duration of action	8-12 hrs.
Metabolism	Liver(Oral)
Excretion	Urine as metabolite and unchanged drug.

Adverse reactions: Inhalation: Palpitation, anxiety, tremors.

Oral: Anxiety and tremors.

Contraindication: Hyperthyroidism, Cardiovascular diseases, Diabetes, Renal impairment.

Terbutaline: route of administration: Oral and Subcutaneous

 

Bioavailabilty	Oral  50%
T half life	Oral: 3 hours, Subcutaneous: 2 Hours.
Onset of action	Oral: 30 min.   Inhalation 5-15 min.
Duration of action	8-12 hrs.
Metabolism	Liver(Oral)
Excretion	50% of administered drug excreted unchanged in urine.

Side effects: Hypotension, Hypokalamia, Hyperglycemia, headache, tremors, anxiety and nervousness.

Long acting selective b2 – agonists: Long acting bronchodilators (12 hours) due to  high lipid solubility (creates depot effect). They are not used to relieve acute episodes of asthma but used for nocturnal asthma. And are combined with inhaled corticosteroids to control asthma (decreases the number and severity of asthma attacks).

Ex:   Salmeterol, Formeterol

Salmeterol: route of administration: Inhalation.

Salmeterol is a long-acting medication that provides bronchodilation for at least 12 hours. It is a selective β2-adrenergic agent that is structurally related to albuterol and has greater receptor selectivity but decreased intrinsic activity.

Indication: Salmeterol is commonly used to reduce variation in diurnal peak expiratory flow rates, decrease nocturnal symptoms and asthma exacerbations, and increase overall lung function. 

Bioavailabilty	Oral  50%
T half life	The half life of salmeterol is 5.5h
Onset of action	Inhalation 10-15 min.
Duration of action	8-12 hrs.
Metabolism	Liver(Oral)
Excretion	Salmeterol is 57.4% eliminated in the feces9 and 23% in the urine.1 Less than 5% of a dose is eliminated in the urine as unchanged salmeterol.

Contraindication: Hypersensitivity.

Side effects: Dizziness, sinus infection, migraine headaches, tremor, tachycardia and cardiac dysrhythmia.

Formeterol: Inhaled formoterol works like other β₂ agonists, causing bronchodilation by relaxing the smooth muscle in the airway so as to treat the exacerbation of asthma.

Bioavailabilty	Oral  50%
T half life	Oral: 3.4 hours, Inhalation: 1.7-2.3 Hours.
Onset of action	Inhalation 2-3 min.
Duration of action	12 hrs.
Metabolism	Liver(Oral)
Excretion	Urine and feces

 

Methyle xanthenes:

Theophylline: Theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.

Route of administration: Oral and Intravenous.

Pharmacokinetics:

Bioavailabilty	Oral  96%
T half life	4-8 hours.
Onset of action	1-2 hours
Duration of action	12 hrs.
Metabolism	Liver(Oral)
Excretion	Urine and feces

Indication: Acute asthma, COPD

Side effects: Insomnia, tremors, nervousness, cardiac dysrhythmia, nausea and vomiting.

Anticholinergics(Muscarinic receptor antagonists): They bind to the Acetylecholine receptor and block muscarinic receptors resulting into airway dilation and reduces mucus secretion.

Ex: Ipratropium: has short duration of action(3-5 hrs)

Tiotropium: has long duration of action(24 hrs)

Route of administration: Inhalation.

Onset of action: Delayed.

Indication: Asthma, COPD.