LABA and ultra LABA

Dr V Srujana
First year PG
Department of pulmonary medicine
 Introduction

• Beta 2 adrenergic agonists comes under the class of

bronchodilators primarily used for asthma and
COPD

• They mimic activity of catecholamines and

stimulates sympathetic nerve fibres which allow
relaxation of smooth muscles

• They specifically act on the smooth muscle of the

airway, uterus, intestine, and systemic vasculature
 Classification

Based on onset of action and duration

• Short acting beta agonist (SABA)
• Long acting beta agonist (LABA)
• Ultra long acting beta agonist (ultra LABA)
Mechanism of action
 Beta Agonists

• Routes of administration
• Inhalation
• Oral
• Parenteral
• Inhalation route is preferred due to
• Rapid onset of action
• Requirement of smaller doses
• Minimal side effects like tremors and tachycardia
• Drug is delivered directly to the target organ
• Painless and safe
Short Acting Beta Agonist (SABA)

• Examples include Salbutamol, levosalbutamol,

Terbutaline sulphate, Pirbuterol etc
• Route of administration: Inhalation
• Action starts within 5 minutes of inhalation and
lasts for 3-6 hours
• First-line agents for acute treatment in asthma and
COPD, also useful in treatment of hyperkalemia
 Adverse effects

• Headache
• Insomnia
• Anxiety
• Tremors (very common)
• Palpitations
• Tolerance to bronchodilator effect
Long Acting Beta Agonist (LABA)

• Examples include salmeterol, formoterol, and

arformoterol
• Route of administration: Inhalation
• Onset of action greater than 10 minutes and
duration of action 12 hours
• They should only be used in conjunction with
inhaled steroids (greater efficacy with dual therapy
versus monotherapy)
• Prolonged duration is achievable by decreasing the
susceptibility of the beta-2 agonists to catechol O-
methyl transferase (COMT) and monoxidase
enzymes which inactivate beta-2 agonist
• Two theories to explain long duration of effect of
LABA’s
Diffusion microkinetic theory (Formoterol)
Exosite theory (Salmeterol)
Long Acting Beta Agonist (LABA)

These beta adrenergic agonists provide following

advantages over SABA

• Due to long duration of action they need less

frequent dosing in asthma and COPD
• Provides Broncho dilatation and control of
nocturnal symptoms in asthma
• LABA’s are not to be used without a controller
medication (corticosteroids).
• LABA’s should not be used by patients who are
controlled on low dose or medium dose inhaled
corticosteroids
• LABA’s should be used for short term use only.
Once asthma is controlled they should be
discontinued
 Salmeterol

• Inhalational LABA with predominant beta 2 activity

• Broncho dilator effect

• Onset of action: 14 mins – 22 mins
• Peak by 3-5 hours
• Duration of action – 12 hours

• Metabolised by cytochrome p450 3A4 to hydroxyl

salmeterol which is eliminated primarily through
faeces
• Based on lipophilic side chain interact with beta
receptor via an exosite anchor that is its lipophilic
side chain allowing continuous stimulation of the
receptor via its active binding site (Head)
 Salmeterol

• Dose: 50mcg twice daily

• Drug interaction:

• Salmeterol + indinavir – increased levels of

salmeterol and increased toxicity

• Can be used in combination with fluticasone

 Formoterol

• Inhalational LABA with Broncho dilator effect

• Onset of action: 2-3 mins
• Peak by 2 hours
• Duration of action – 12 hours

• It is moderately lipophilic enter the bilipid cell

membrane which act as reservoir. It releases drug
slowly leading to prolonged effect
• Useful in:
• In maintenance treatment of asthma and nocturnal
asthama in adults and children (more then 5 years age)
• Prevention of exercise induced bronchospasm
• Treatment of COPD
 Formoterol

• Dose: 20mcg inhaled via nebuliser twice a day

• Drug interaction:

• Formoterol + CPZ – prolongation of QTc interval

• Formoterol + amiodarone/dronedarone --- prolongation
of QTc interval
 Arformoterol

• R enantiomer of formoterol
• Onset of action: 15 mins
• Peak by 30-60 minutes
• Duration of action – 12 hours

• Metabolised by direct conjugation to glucuronide or

sulfates

• Used in treatment in patients with COPD

 Arformoterol

• Dose: 15mcg twice a day

• Drug interaction:

Arformoterol + linezolid --- increase the effects of

former --- high risk of acute hypertensive episode
 Ultra LABA

• Term coined in 2005 to to indicate once-daily β2-

adrenoceptor agonists for the treatment of asthma
and COPD
• Duation of action up to 24 hours and better ß2: ß1
profile
• With once a day administration improvement in
compliance to therapy in COPD and Asthma
• Example include
• Indacaterol
• Vilanterol
• olodaterol
 Indacaterol

• Inhaled ultra LABA with significant beta 2

adrenoreceptor potency with fast and sustained
action

• Onset of action: 30 minutes

• Duration of action : 24 hours
• Better cardiovascular safety profile then salmeterol and
formeterol
• Dose: 75mcg inhaled once daily
INLIGHT -1 study
INLIGHT -2 study
INVOLVE study
 Vilanterol
• Potent, Selective inhaled ultra LABA
• Greater potency and greater beta2 selectivity than
indacaterol and salbutamol
• Highly lipophilic with duration of action >24 hours
• Onset of action – 5mins
• Peak levels – 10 miins
 Olodaterol

• Chirally pure
• Potent, highly selective inhaled ultra LABA
• Sustained duration of activity
• Rapid onset
• Greated selectivity for beta2 over beta 1 receptors
• Greater potency then indacaterol
• Sustained action not appear to be due to
lipophilicity
• A portion of the delivered molecules form semi
stable complexes with the receptor and its G-
coupled protein
• T1/2 – 17 hours
Comparison of LABAs
COPD
 Thank You

Next seminar by Dr Shravya on PMDT guidelines

on 19/7/2023