ANTI-ASTHMATIC

DRUGS
HUZAIFAH, DAWOOD, ZUBAIR, BASIT
CONTENTS:
• INTRODUCTION
• SYMPATHOMIMETICS (B2 agonists)
• LEUKOTRINE RECEPTOR ANTAGONISTS
• LEUKOTRINE SYNTHESIS INHIBITOR
INTRODUCTION:
• Asthma is a chronic lung disease that inflames and narrows the
airways.
• Asthma causes recurring periods of wheezing (a whistling sound when
you breathe), chest tightness, shortness of breath, and coughing.
• The coughing often occurs at night or early in the morning.
SYMPATHOMIMETICS (Beta2
Agonists):
These are those drugs that activate the Beta 2 adrenergic receptor
present on the lungs and lead to the relaxation of the smooth muscles
causing bronchodilation.
They work by Gs stimulatory pathway (cyclic adenosine
monophosphate pathway).
This cAMP is further responsible for causing relaxation of smooth
muscles.
Beta2 Agonists:
They perform their function by causing:

• Decreased intracellular Calcium level

• Inactivation of Myosin Light Chain Kinase
• Activation of Myosin Light Chain Phosphatase
• Increased potassium conductance
MECHANISM OF ACTION:
Activation of β adrenergic receptors leads to relaxation of smooth
muscle in the lung, and dilation and opening of the airways.

• β adrenergic receptors are coupled to a stimulatory G protein of

adenylyl cyclase.
• This enzyme produces the second messenger cyclic adenosine
monophosphate (cAMP).
• In the lung, cAMP decreases calcium concentrations within cells and
activates protein kinase A.
MECHANISM OF ACTION:
• Both of these changes inactivate myosin light-chain kinase and
activate myosin light-chain phosphatase.
• In addition, β2 agonists open large conductance calcium-activated
potassium channels and thereby tend to hyperpolarize airway smooth
muscle cells.
• The combination of decreased intracellular calcium, increased
membrane potassium conductance, and decreased myosin light chain
kinase activity leads to smooth muscle relaxation and
bronchodilation.
TYPES OF B2 AGONISTS:
Short Acting:
Also known as rescue medicines. They are used for quick relief of asthma symptoms,
such as wheezing, "feeling tight" when breathing, coughing and shortness of breath.
Short-acting beta agonists act within minutes to temporarily relieve these symptoms.
E.g. Salbutamol and terbutaline
Long Acting:
Long-acting are usually prescribed for moderate-to-severe persistent asthma
patients. They are designed to reduce the need for shorter-acting β2 agonists such as
salbutamol (albuterol), as they have a duration of action of approximately 12 hours in
comparison with the 4-to-6-hour duration of salbutamol. E.g. formoterol and
salmerterol.
LEUKOTRIENES:
• Leukotrienes are a family of eicosanoid inflammatory mediators
produced in leukocytes by the oxidation of arachidonic acid (AA) by
the enzyme arachidonate 5-lipoxygenase. The production of
leukotrienes is usually accompanied by the production of histamine
and prostaglandins, which also act as inflammatory mediators.
• One of their roles (specifically, leukotriene D4) is to trigger
contractions in the smooth muscles lining the bronchioles; their
overproduction is a major cause of inflammation in asthma and
allergic rhinitis. Leukotriene antagonists are used to treat these
disorders by inhibiting the production or activity of leukotrienes.
ANTI-LEUKOTRIENES:
• An antileukotriene, also known leukotriene receptor antagonist, is a
medication which functions as a leukotriene-related enzyme inhibitor
(arachidonate 5-lipoxygenase) or leukotriene receptor antagonist
(cysteinyl leukotriene receptors) and consequently opposes the
function of these inflammatory mediators.
ANTI-LEUKOTRIENES:
LEUKOTRIENE RECEPTOR ANTAGONIST:

Antagonism of cysteinyl-leukotriene type 1 receptors

LEUKOTRIENE SYNTHESIS INHIBITOR:

Inhibition of the 5-lipoxygenase pathway

LEUKOTRIENE RECEPTOR
ANTAGONIST :
• Agents that block the actions of cysteinyl leukotrienes at the
CysLT1 receptor on target cells such as bronchial smooth
muscle via receptor antagonism results in the blocking of the
receptor that is responsible for the production of
Leukotrienes causing Bronchoconstriction.
• montelukast and zafirlukast are the drugs that are
Leukotriene receptor antagonists.
LEUKOTRIENE SYNTHESIS
INHIBITOR:
• Arachidonate 5-lipoxygenase inhibitors are compounds that slow or
stop the action of the arachidonate 5-lipoxygenase (5-lipoxygenase or
5-LOX) enzyme, which is responsible for the production of
inflammatory leukotrienes. The overproduction of leukotrienes is a
major cause of inflammation in asthma and allergic rhinitis and
Osteoarthritis.
LEUKOTRIENE SYNTHESIS
INHIBITOR:
• Drugs that inhibit the 5-lipoxygenase enzyme will inhibit the synthetic
pathway of leukotriene metabolism; drugs such as MK-886 that block
the 5-lipoxygenase activating protein (FLAP) inhibit functioning of the
5-lipoxygenase enzyme.
• Examples of 5-LOX inhibitors include drugs, such as meclofenamate
sodium[10] and zileuton.