Eval Pharmaceutical

Sciences VIII

Medicinal Chemistry and

Pharmacology of Respiratory
Drugs
 Asthma
• Chronic inflammatory disorder of
the airways, ↑ airways
responsiveness, causes
reversible obstruction.
• In asthma eosinophils, mast cells
and T lymphocytes plays
significant role.
• ↑ Sensitivity, and
hypersensitivity of airways to
specific and non-specific stimuli,
such as:
– air, odour, allergens, and virus
etc.
 Asthma COPD

Airway (Bronchus) Progressive, partially reversible airway limitation. Increases frequency

and severity of exacerbations. COPD is preventable and treatable. The
cardinal symptoms are SOB and activity limitation, fatigue, and barrel
chest.
Terminal alveoli
Inflammatory disease Emphysema (permanent enlargement Chronic bronchitis
of
alveoli)
Esinophilic Neutrophil Neutrophil
Coughing with wheezing SOB (dyspnea), fatigue SOB (dyspnea) + sputum
during breath, and SOB.

DOC for acute asthma DOC bronchodilator ipratropium,
attacks is salbutamol, tiotropium, salbutamol, salmeterol,
anti- inflammatory formoterol (LABA).
Inhaled Inhaled corticosteroids are LEAST
corticosteroids (ICS). likely used. PSO2 <90% oxygen
therapy
Antibiotics are used to
manage exacerbations of
pneumonia.
Corticosteroid PO for less than
<2wks.
Drugs that cause bronchodilation Drugs that cause
bronchospasm
Examples of beta2 agonist Beta blockers
(sympathomimetics) € Salbutamol,
salmeterol, formoterol
Examples of mixed alpha & beta €
Examples of muscarinic antagonists€
 Beta2 Adrenergic Agonist
• MOA : beta2 stimulation causes increase
camp in smooth muscle leading to
bronchodilation

• Oral beta agonist have more SE and less

bronchodilation effect than inhaled
preparations.
 • Inhaled: Albuterol (salbutamol), and
terbutaline
• Onset: within 5 min
Short acting • Therapeutic use: relieve
bronchoconstriction, the acute
beta2 agonist symptoms of cough, wheezing and chest
(SABA) tightness, asthma emergencies and
exercise induced asthma
• SE: Tremors, nervousness, weakness,
flushing of face or skin, nausea and
vomiting.
• Regular use can lead to decline in lung
function.
 • Inhaled: Formoterol (full B2
agonist), salmeterol (partial agonist)
• Onset: 14 min and duration up to
24 hours. Regular BID treatment.
• Therapeutic use: Maintenance
Long acting therapy and EIA. Used in patients
already taking corticosteroids.
beta2 • Formoterol can be used for acute

agonist and maintenance. It has faster onset

of action 3 to 5 min.

(LABA)
 Anticholinergic
used as bronchodilators

• Ipratropium bromide is short

acting bronchodilator and is
used as alternative for patients
who are already susceptible to
tremors or tachycardia from B2
agonist.
• Tiotropium DPI (Spiriva,
Handihaler, and RESPIMAT
inhaler) 18 mcg/daily capsule for
inhalation.
• Long acting anticholinergic taken
once daily, it is administered by
handihaler.
 • Dry mouth, metallic taste,
Side mydriasis, and glaucoma if
effects released into eye.
 ANTICHOLINERGIC BRANCHODILATORS

Ipratropiun (Atrovant) Ipratropium 2puffs Q6-8h

Tiotropium (Spiriva handihaler, Respimat) Once daily

Glycopyrronium (Seebri Neohaler) Twice daily

Aclidinium (Tudorza Pressair) Twice daily
Umeclidinium (Incruse Ellipta) Once daily
Combinations: ICS + LABA.
Symbicort = budesonide/formoterol
Advair = Fluticasone/salmeterol
Zenhale = mometasone/formoterol
BREO = fluticasone + vilanterol
 Inhaled
Corticosteroids Oral

• Inhaled corticosteroids (ICS):

– Inhaled corticosteroids (ICS):
Fluticasone, mometasone, budosenide,
beclomethasone and ciclesonide.
– Used for mild to moderate asthma.
Benefit ↑ lung function, ↓ airway
hyper responsiveness, ↓ symptoms of
exacerbations.
– Max clinical effects in 2 to 4 wks. Corticosteroids
Fluticasone in few days, given 2 to 4 pf
BID.
 • Sore mouth and sore throat
• Oral pharyngeal candidiasis (oral
thrush)
Side • dysphonea (hoarseness) from vocal
cord myopathy and cough.
effects • Rinsing mouth and using spacer (aero
chamber) can minimize side effects.
• High dosages. Check bone
densitometry, patient with glaucoma
check IOP.
Oral corticosteroids (Po CST): Prednisone and prednisolone
• Therapeutic use: Severe asthma with intensive airway
inflammation.
• SEs: hyperglycemias, osteoporosis, hypothyroidism, hypertension,
weight gain, susceptible to infections.
 Leukotriene antagonist:
Montelukast and zafirlukast

OWEVER!
H

LTRAs are not as effective as

low dose inhaled
The montelukast and
corticosteroids for improving
zafirlukast have anti-
symptoms or exacerbations.
inflammatory action
It is considered as ad-on
therapy with ICS.

• Therapeutic use: Asthma maintenance (steroid sparing

agents), and the drug of choice for ASA induced and
beta blockers induced asthma.
• Montelukast 10 mg QHS po tablets is used in
children >2 yr age, available as granules and 4
mg, 5 mg chewable tablets.

• Zafirlukast 20 mg BID po at least 1 h before

and 2hr after meals is used in over >12 yr age
and only oral available.
• Advantage of
combinations. More
convenient, enhance
adherence, less expensive.

• Disadvantage. Loss in
dosing flexibility
 Chronic Obstructive
Pulmonary Diseases
• Chronic obstructive pulmonary
diseases (COPD) is due to chronic
obstruction of airway passage.

• COPD is two types:

1. Emphysema (high altitude
sickness)
2. chronic bronchitis.
 disease in which the small
air exchange sacs (alveoli)
in the lungs become
permanently enlarged and
damaged

alveoli walls destroyed

decreasing oxygen
absorption.
Emphysema

resulting in shortness of
breath
 Inflammation of the airways
in the lungs that causes lungs
to produce excessive
amounts of mucus (phlegm)

associated with chronic

Chronic productive cough

bronchitis

reduce the flow of air to the

lungs.
 Drug used for the
treatment of COPD

• Anticholinergics. Ipratropium and

tiotropium are muscarinic blocker and act
as bronchodilator.
• Beta adrenergic agonists
• Corticosteroids
• Theophylline
 Community acquired pneumonia
(CAP)

• Community acquired pneumonia (CAP) without risk factors:

Pneumonia in COPD patient is treated by amoxicillin, doxycycline,
cotrimoxazole, azithromycin, or clarithromycin.
• COPD with risk factors (FEV1 <50%,
Ischemic heart diseases, use of
home O2, chronic use of steroids,
antibiotic use <3m, >4
exacerbation/yr). Amoxi/clav,
cephalosporin's (1st, 2nd, and 3rd) or
fluroquinolones (levofloxacin and
moxifloxacin).
 Inhalational Drug
delivery devices
Aerosolized medications drug delivery
depends on:
 Drug formulation properties
(particle size distribution, selected
the delivery system)

Selection of appropriate device:

 with appropriate particle size and
lung delivery.

Inhalation technique:
 inspiratory flow rate, inspiratory
volume, and breath holding time
determines the dose of inhaled
drug that deposits in lung.