1

3.

RESPIRATORY DRUGS
A. EXPECTORANT
Actions: A medicine that promotes the secretion of sputum by the air
passages, used especially to treat coughs. A type of medication that is
used to loosen mucus in the lungs, throat and bronchi so easier to
expel the mucus when coughing.
Uses: Respiratory difficulty in children, bronchitis, persistent
coughs, mucus plugs, influenza, common cold
Major side effects - Rare, may include GI upset
O

SH

OH

H3C

OH

Guaifenesin
(Glyceryl guaiacolate)
3-(2-methoxyphenoxy)propane-1,2-diol
sulfanylpropanoic acid

N
H

OH

Acetylcysteine
(also a Mucolytic drug)
2-acetamido-3-

B. ANTITUSSIVES
Action: Suppress the cough reflex center in the medulla. Some are
peripherally acting and some are centrally acting.
Uses:
Ssuppress nonproductive cough and/or assist in nighttime
sleep in children with productive cough. It can be combined with a
narcotic or non-narcotic agent.
Major Side Effects: Dry secretions, drowsiness without respiratory
depression, constipation, narcotic abuse
Interactions: A synergistic effect with alcohol and CNS
depressants.
1. Narcotic Antitussive opiate drug acting on the central nervous
system.
H3C

Codeine (or Methylmorphine)

7,8-didehydro-4,5-epoxy-3-mthoxy17- methylmorphinan-6-ol

O
H

H
N CH
3

HO

Structure Activity Relationship:

a. Modifications on the aromatic ring system:
- aromatic phenyl ring is essential for activity
- C3 phenolic hydroxyl group decreases analgesic activity
- 3-OH group gives compounds more active than morphine
b. Modifications on the alicyclic ring system:
- saturation of double bond at C8 position gives more potent
compounds
- bridging of C6 and C14 through ethylene linkage gives
etorphine which is
200 times more potent than
morphine.

2
- introduction of any new substituents at 5th position does not
enhance the
activity except 5-methyl dihydro
morphine and azidomorphines.
c. Modifications on Nitrogen:
- replacement of N-CH3 by N-C2H5 results into slight fall in
analgesic response.
d. Modification on ether bridge:
- breaking of the ether bridge and opening of piperidine ring
decreases the activity.
2.
Non-narcotic Antitussive non-opiate drug acting on the
peripheral nervous
system.
Dextromethorphan is a cough suppressant. It affects the
signals in the brain that trigger cough reflex It will not treat a cough
that is caused by smoking, asthma, or emphysema.
Diphenhydramine is used to treat allergic symptoms and
itchiness, the common cold, insomnia, motion sickness, and
extrapyramidal symptoms. It is a first-generation antihistamine drug.
OCH3

CH3
N

CH3

N
H3C

Diphenhydramine
2-(diphenylmethoxy)N,Ndimethylethanamine

Dextromethorphan
3-methoxy-17-methyl-(9, 13,
14)morphinan
C.

MUCOLYTICS

Mucolytic agents are used to dissolve or breakdown mucus in

the respiratory tract. They make the mucus less viscous so that it can
be coughed up with more ease. They are used to treat respiratory
conditions, which have excessive or thickened mucus secretion, such
as a chesty cough. It does so by hydrolyzing glycosaminoglycans,
tending to break down/lower the viscosity of mucin-containing body
secretions/components. The viscosity of mucous secretions in the
lungs is dependent upon the concentrations of mucoprotein, the
presence of disulfide bonds between these macromolecules and DNA.
Mucolytics break down the chemical structure of mucus molecules.
The mucus becomes thinner and can be removed more easily through
coughing.
Br

Br

H
HO

N
H

Br

Br

NH2

Ambroxol
4-[(2-amino-3,5-dibromophenyl)methyl amino]
{[cyclohexyl(methyl)

NH2

Bromhexine
2,4-dibromo-6-

3
cyclohexan-1-ol
amino]methyl}aniline
HO

O
S

OH
NH2

Carbocisteine
(R)-2-amino-3-(carboxymethylsulfanyl)propanoic acid
D.

BRONCHODILATORS
- are substances that dilates the bronchi and bronchioles, decreasing
resistance in the respiratory airway and increasing the airflow to the
lungs. They are used in the treatment of obstructive lung diseases of
which asthma and chronic obstructive pulmonary disease (COPD) are the
most common conditions.
1.

B2 Selective Adrenergic Agonist

- The main effect of this drug is to dilate the bronchi by a direct
action on B2-adrenoceptors on the smooth muscles. It stimulates
the production of cyclic adenosine monophophate (cAMP), which
relaxes smooth muscle These drugs are usually given by inhalation
of aerosol, powder or nebulized solution but some may be given
orally or by injection. Terbutaline and Salbutamol are short
acting agents.
- They are used in bronchospasms, chronicpulmonary diseases,
asthma, and airway obstruction.
- The major side effects are: anxiety, restlessness, insomnia,
tremors
palpitations,
dysrhytmias,
headache,
rebound
OH
bronchospasm,
and
urinary
retention.
OH
H
N

HO

HO

HO
OH

Salbutamol
Terbutaline
1hydroxyethyl]-2
5-(1-Hydroxy-2-tert-butylamino-ethyl)
(hydroxymethyl)phenol
benzene-1,3-diol

4-[2-(tert-butylamino)-

The tertiary butyl group in terbutaline makes it more selective for

B2-receptors. Since there is no hydroxyl group on the 4 position of
the benzene ring, the molecule is less susceptible to metabolism by
COMT enzyme.
2.

Xanthine Derivatives
- They inhibit phosphodiesterase, an enzyme responsible for
breaking down cAMP. Because this enzyme is inhibited, more cAMP
is available for bronchodilation. These agents also stimulate
cardiac muscles and the central nervous system (CNS), increase
cardiac output, produce diuresis and decrease peripheral vascular
resistance (PVR).

4
- They are used for bronchospasm, asthma, wheezing and
dyspnea associated with pulmonary diseases chronic obstructive
pulmonary disease (COPD) or chronic airway limitations (CAL).
The xanthine molecule showing some pharmacological
consequences of alkyl substitution: 2
O

H3C
O

N
N
CH3

H
N
3

N
4

1.
2.
3.
4.
5.

R1, important for adenosine antagonism and for many nonbronchodilator effects.
R3, decreased bronchodilator potency
Toxic potency and adenosine antagonism may increase
General loss of potency
R2, augmented bronchodilator potency
O

H3C
O

N
N
CH3

O
H
N
N

H3C
O

N
N

H
N
N

CH2NH2
CH2NH2

CH3

Theophylline
Aminophylline
1,3-Dimethylxanthine
Theophylline
with
ethanediamine
1H-Purine-2,6-dione, 3,7-dihydro-1,3-dimethyl,
monohydrate or anhydrous

1,2-