Pharmacology

department
FACULTY OF MEDICINES
LAMPUNG UNIVERSITY

DRUGS USED IN
ASTHMA
BRONCHODILATORS

AGONISTS
MUSCARINIC
ANTAGONISTS

ANTI-INFLAMMATORY
AGENTS

RELEASE
INHIBITORS
STEROIDS

METHLYXANTHINES

LEUKOTRIENE
ANTAGONISTS

LIPOXYGENASE RECEPTOR
INHIBITORS
INHIBITORS
ANTIBODIES

SLOW ANTIINFLAMMATORY DRUGS

BRONCHIAL ASTHMA
Airway inflammation
Episodic, reversible bronchospasm
Chronic inflammation that leads to

marked bronchial hyperreactivity

BRONCHIAL ASTHMA

AC

BRONCHIAL
ASTHMA

Dilatation
CAMP

Bronchial Tone

Acetylcholine

Leukotrienes

Adenosine

Constriction

PDE

ATP
AMP

BRONCHIAL ASTHMA
Release of several mediators from IgE-

sensitized mast cells and other cells

involved in immunologic responses
Mediators include
Leukotrienes
Chemoattractants
Cytokines
Enzymes

DRUGS USED IN
ASTHMA
STRATEGIES OF ASTHMA THERAPY
ACUTE ASTHMATIC ATTACKS
Treated promptly and effectively with

bronchodilators
2 agonist
Muscarinic

antagonists
Theophylline and its derivatives

DRUGS USED IN
ASTHMA

STRATEGIES OF ASTHMA THERAPY

CHRONIC ASTHMA
Long term preventive treatment
Requires control of inflammatory process in

the airways

Corticosteroids
Cromolyn

DRUGS USED IN
ASTHMA
BRONCHODILATORS

AGONISTS
MUSCARINIC
ANTAGONISTS

ANTI-INFLAMMATORY
AGENTS

RELEASE
INHIBITORS
STEROIDS

METHLYXANTHINES

LEUKOTRIENE
ANTAGONISTS

LIPOXYGENASE RECEPTOR
INHIBITORS
INHIBITORS
ANTIBODIES

SLOW ANTIINFLAMMATORY DRUGS

DRUGS USED IN
ASTHMA
BETA-ADRENOCEPTOR AGONISTS
Mechanism of action
Stimulate adenyl cyclase and increasing cAMP

in smooth muscle cells bronchodilatation

ATP

Relaxation
CAMP

Bronchial Tone
Acetylcholine

Leukotrienes

Adenosine

Constriction

PDE

AMP

DRUGS USED IN
ASTHMA

BETA-ADRENOCEPTOR AGONISTS
Most important sympathomimetic used
to reverse asthmatic bronchoconstriction
Almost given exclusively by inhalation
Decreases the systemic dose and adverse

effects
Occasionally by nebulizer

DRUGS USED IN
ASTHMA
BETA-ADRENOCEPTOR AGONISTS
Albuterol, terbutaline, metaproterenol
Short-acting
Drug of choice for acute asthma

DRUGS USED IN
ASTHMA
BETA-ADRENOCEPTOR AGONISTS
Salmeterol and formoterol
Long-acting
12 h or more
Used for prophylaxis

DRUGS USED IN
ASTHMA
BETA-ADRENOCEPTOR AGONISTS
Epinephrine and isoproterenol
Still used occasionally

Used for chronic obstructive pulmonary

disease (COPD) patients

DRUGS USED IN
ASTHMA
BETA-ADRENOCEPTOR AGONISTS
TOXICITY
Skeletal muscle tremor
Significant 1 effects (tachycardia) at high

clinical dosage
Arrhythmias may occur when used excessively

DRUGS USED IN
ASTHMA
BETA-ADRENOCEPTOR AGONISTS
TOXICITY
Tolerance, tachyphylaxis (loss of

responsiveness) is an unwanted effect

COPD patients often with concurrent cardiac
disease may have arrhythmias at normal
dosage

DRUGS USED IN
ASTHMA
METHYLXANTHINES
Purine derivatives
MOA
Inhibit phosphodiesterase (PDE), the enzyme

that degrades cAMP to AMP, thus increases

cAMP
Anti-PDE effect requires high concentration of
the drug

Relaxation
ATP
CAMP

Bronchial Tone
Acetylcholine

Leukotrienes

Adenosine

Constriction

PDE

AMP

DRUGS USED IN
ASTHMA

METHYLXANTHINES
Found in plants and provide the stimulant
effect of 3 common beverages
Caffeine (coffee)
Theophylline (tea)
Theobromine (cocoa)

DRUGS USED IN
ASTHMA

METHYLXANTHINES
Theophylline and several analogs
Orally active
Available as salts and base

Slow-release theophylline
For control of nocturnal asthma
Most important in clinical use

DRUGS USED IN
ASTHMA
METHYLXANTHINES
Clearance varies
Highest in young adolescents
Higher in smokers
Concurrent use of other drugs that inhibit or

induce hepatic enzyme

DRUGS USED IN
ASTHMA

METHYLXANTHINES
Bronchodilation is the most important
therapeutic effect
CNS stimulation, cardiac stimulation,
vasodilation and slight increase in BP (due
to release of NE from adrenergic nerves

DRUGS USED IN
ASTHMA
METHYLXANTHINES
Eliminated by Cytochrome P450-drug
metabolizing enzyme in the liver
Pentoxifylline
Used for treatment of intermittent

claudication

DRUGS USED IN
ASTHMA
METHYLXANTHINES
TOXICITY

Common adverse effects

GI

distress
Tremor
Insomnia

DRUGS USED IN
ASTHMA
METHYLXANTHINES
TOXICITY
Overdosage
Severe

nausea and vomiting

Hypotension
Cardiac arrhythmias
Convulsion

DRUGS USED IN
ASTHMA
MUSCARINIC ANTAGONISTS
MOA
Competitively blocks muscarinic receptors in

the airways
Prevents bronchoconstriction mediated by
vagal discharge

ATP

Relaxation
CAMP

Bronchial Tone
Acetylcholine

Leukotrienes

Adenosine

Constriction

PDE

AMP

DRUGS USED IN
ASTHMA
MUSCARINIC ANTAGONISTS
Reverses bronchoconstriction
Useful in 1/3 to 2/3 of asthmatic patients

(especially children)
No effect on the inflammatory aspects of
asthma
Useful in many COPD patients
More

effective and less toxic than

agonists

DRUGS USED IN
ASTHMA
MUSCARINIC ANTAGONISTS
Atropine and other naturally-occurring

belladona alkaloids were used for asthma

DRUGS USED IN
ASTHMA
MUSCARINIC ANTAGONISTS
Ipatropium
Quaternary antimuscarinic drug
Delivered to the airways by pressurized aerosol
Have little systemic action

Tiotropium
Newer longer-acting analog

DRUGS USED IN
ASTHMA
MUSCARINIC ANTAGONISTS
TOXICITY
Delivered directly to the airway, minimally

absorbed
Systemic effects are small
In excessive dosage, minor atropine-like toxic
effects may occur
Does not cause tremor or arrhythmias

DRUGS USED IN
ASTHMA
CROMOLYN AND NEDOCROMIL
No bronchodilator action but can prevent
bronchoconstriction caused by a challenge
with antigen to which the patient is allergic

DRUGS USED IN
ASTHMA

CROMOLYN AND NEDOCROMIL

MOA
Decrease in the release of mediators

(leukotrienes and histamine) from mast cells

Prevents both early and late responses to
challenge

DRUGS USED IN
ASTHMA
CROMOLYN AND NEDOCROMIL
Cromolyn prototype drug
Unusual chemicals
Extremely insoluble
Massive doses given orally or by
aerosol result in minimal systemic levels
(local effects)
Given by aerosol for asthma

DRUGS USED IN
ASTHMA

CROMOLYN AND NEDOCROMIL

Food allergy
Given orally

Asthma in children
Most important use

Hay fever
Nasal and eyedrop formulations

DRUGS USED IN
ASTHMA
CROMOLYN AND NECRODOMIL
TOXICITY
Cough and irritation of the airway when given

by aerosol
Drug allergy is rare

DRUGS USED IN
ASTHMA
BRONCHODILATORS

AGONISTS
MUSCARINIC
ANTAGONISTS

ANTI-INFLAMMATORY LEUKOTRIENE
AGENTS
ANTAGONISTS

RELEASE
INHIBITORS
STEROIDS

METHLYXANTHINES

LIPOXYGENASE RECEPTOR
INHIBITORS
INHIBITORS
ANTIBODIES

SLOW ANTIINFLAMMATORY DRUGS

DRUGS USED IN
ASTHMA
CORTICOSTEROIDS
MOA
Reduces the synthesis of arachidonic acid by

phospholipase A2

Inhibit the expression of COX-2 (anti-

anflammatory action)
Postulated that: this drugs increases the
responsiveness of beta agonists in the airway

DRUGS USED IN
ASTHMA

Phospholipase
Membrane A2

Lipid

Arachidonic acid

Lipooxygenase

Cyclooxygenase

Hydroxypeptidase

Endoperoxidase

Leukotrienes

Prostacycline

Prostaglandin

Thromboxane A2

DRUGS USED IN
ASTHMA
CORTICOSTEROIDS
All are potentially beneficial in severe
asthma
Systemic (oral corticosteroids)
Used chronically only if other therapies fail

DRUGS USED IN
ASTHMA

CORTICOSTEROIDS
Local aerosol administration of surface
active corticosteroids are relatively safe
Beclomethasone
Budesonide
Dexamethasone
Flunisolide
Fluticasone
Mometasone

DRUGS USED IN
ASTHMA
CORTICOSTEROIDS
Inhaled corticosteroids
Common first-line therapy for moderate to

severe asthma
Appropriate (even in children) in cases of
moderate asthma that does not fully respond to
aerosol agonist

DRUGS USED IN
ASTHMA
CORTICOSTEROIDS
Prednisolone and hydrocortisone
Intravenous
For status asthmaticus

DRUGS USED IN
ASTHMA
CORTICOSTEROIDS
Reduced activity of phospholipase

A2

Leukotrienes that result from the

synthesis of prostaglandins are potent

bronchoconstrictors

DRUGS USED IN
ASTHMA
CORTICOSTEROIDS
Early use may prevent the severe,

progressive inflammatory changes of longstanding asthma

DRUGS USED IN
ASTHMA
CORTICOSTEROIDS
TOXICITY
Changes on oropharyngeal flora result to

candidiasis
For oral therapy
Adrenal

suppression can be reduced by

using alternate day therapy (give the
drug in slightly higher dosage every
other day)

DRUGS USED IN
ASTHMA
CORTICOSTEROIDS
TOXICITY
Systemic toxicities
Occur

if treatment is required for more

than 2 weeks
Regular use of inhaled steroids cause
mild growth retardation in children

DRUGS USED IN
ASTHMA
BRONCHODILATORS

ANTI-INFLAMMATORY

ANTAGONISTS

AGENTS

AGONISTS
MUSCARINIC
ANTAGONISTS

RELEASE
INHIBITORS
STEROIDS

METHLYXANTHINES

LEUKOTRIENE

LIPOXYGENASE RECEPTOR
INHIBITORS
INHIBITORS
ANTIBODIES

SLOW ANTIINFLAMMATORY DRUGS

DRUGS USED IN
ASTHMA

LEUKOTRIENE ANTAGONISTS
Interfere with the synthesis or action
of leukotrienes
Not as effective as corticosteroids in
severe asthma
Not recommended for acute asthma
Low toxicity

DRUGS USED IN
ASTHMA
Arachidonic acid

Lipooxygenase

Cyclooxygenase

Hydroxypeptidase

Endoperoxidase

Leukotrienes

Prostacycline

Prostaglandin

Thromboxane A2

DRUGS USED IN
ASTHMA

LEUKOTRIENE ANTAGONISTS
Zileuton
Orally active
Selectively inhibits 5-lipoxygenase,

a key enzyme in the conversion of

arachidonic acid to leukotrienes

DRUGS USED IN
ASTHMA
LEUKOTRIENE ANTAGONISTS
Zileuton
Effective in
Exercise-

and antigen-induced
bronchospasm
Aspirin allergy
Toxicity include occasional elevation of
liver enzymes

DRUGS USED IN
ASTHMA
LEUKOTRIENE ANTAGONISTS
Zafirlukast and montelukast
Antagonist at the LTD4 leukotriene receptor
Orally active

DRUGS USED IN
ASTHMA
LEUKOTRIENE ANTAGONISTS
Effective in preventing exercise-,
antigen-and aspirin-induced
bronchospastic attacks

DRUGS USED IN
ASTHMA
Anti-IgE antibody
Omalizumab
Humanized

murine monoclonal
antibody to human IgE
Prophylactic management of asthma
Given parenterally

DRUGS USED IN
ASTHMA
Anti-IgE antibody
Binds to IgE on sensitized mast cells
Prevents activation by asthma triggers
Subsequent release of inflammatory

mediators

Terima kasih . .