Respiratory pharmacology:

Bronchial asthma

Pharmacology-88 685
 Bronchial asthma: As thma is an intlammatory disease ol' th e airway ~ characterized by . cp_isocles of' acute
bronchoconstriction causing shortm;ss of' breath, co ugh, chest ti ghtn_t:~s, wheezin g, and rap,? respirut, on. Asthma is a
chronic cli sc:ase wi th ·.111 und~rl ying inllammatory pathophysiology that , if untreated, may 1n ctir airway rem ode ling, rcsulti n,
in increased severity and incidence or exacerbations and/or death . Deaths clue lo asthma are _relativ~~y infreque nt, bu~
significant morbidit y res ults in hi gh outpatient costs, numero us hospitali zations, and decreased quality of Ide .
(Ref: Lippincott ·s-6th
. . h I t· 1
Role of inflammation in asthma: Airllow obstruction in asthma is due to bronchoconstrictl on t at resu ts mm contractio
of bronchiaf s111ooth musc le, inflammation of the bronchial wall, and increased mucous secreti~n._Asthm_atic attac ks may b:
related to recent ex posure to allergens or inhaled irritants, exercise leading to bronchial hyperactivity and i~flammation of the
airway mucosa. The symptoms of asthma may be effectively treated by several drugs, but no age nt provides a cure for thi ~
obstructive lung disease.
(Ref Lippincott 's-6thJ
Causes of airway narrowing in acute asthmatic attacks include-
! . Bronchoconstriction (contraction of airway smooth muscle)
2. lnspissation of thick, viscid mucus plugs in the airway lumen
3. Thickening of the bronchial mucosa from edema, cellular infiltration
4. Hyperplasia of secretory, vascular, and smooth muscle cells
Approach to treatment:
I. Prevention of exposure to allergen
2. Bronchodilators: To reverse acute bronchoconstriction. Sho11-term relief is thus most effectively ach ieved by
bronchodilators, of which ~-agonists are the most effective and most widely used. Theophylline and antimuscarin ic
agents are also used for reversal of airway constriction.
3. Anti-inflammatory agents: Long-term control is most effectively achieved with an anti-inflammatory agent such as
an inhaled corticosteroid .
(Ref Katzung-l 3th edition)

Q. Classify anti-asthmatic drugs. (DU-06S; CU-06S, SU-16Ju)

.Q. Classify the drugs l).Sed in the management of bronchial asthma. (DU-12Ju, CU-
. 17M, 15J, 14J, 13Ju/J, l 1Ju,08Ju, RU-09Ju; SU~ l 7J,1 5J,09Ju) .
Q. · Classify anti-asthmatic drugs according to their mechanism of action. (CU-1 0J,07J)
Q. - Name,.the short-term reliever and long-term controller drugs used in bronchial asthma. (DU -1 lJu)

_
n
,
A
tµline antiinflammatory agents used in bronchial asthma . (RU-1lJ)
Q <;(assify I Categorize/ Name bronchodilators. (RU-16Ju, lSJ, l 3J, SU-16J,l 1J)
/ Lists the group wise important non-bron.chodilator agents used in bronchial asthma . (CU-08J)
Q, Name clinically useful bronchodilators . (DU-l 0J, CU-06S; SU-07J)
Q. Enlist the ~ntimuscarinic drugs used in bronchial asthma. (CU~ lSJu) .
Ans.
Anti-asthmatic Drugs:
A. Bronchodilator: Reverses bronchoconstriction and prov ides short-term relief (short-term reliever).
1. Selective P2-agonists a. Short acting (2-6 hours) f I
.-Salbutamo l ~
)
'I • Albuterol
.r, .: , ,.--,. . l. "'- •Terbuta line )
• Metaprotereno l
t' r, \,
~ •Pirbutero l
b. Long acting(> 12 hours)
, •Salmetero l
• Fo rmotero l
2. Anti-muscarinic agent ,,,,- Ipratropium bromide ( ~) '\
• Tiotropium
•Atro ine
- J. Methylxanthi nrs
687
. • J\ 111i11ophyllinc
Drugs used in Bron chia l Asthma

•Thcophyllinc
• Doxophyll ine
• Enprophyll inc
• Pentoxi fy lline (used in intcrrnill cnt cl audica ti on)
• Theobromine l '- cu·c)
•'Caffe ine

B. Anti-inflammatory drugs: Suppress chronic inflamm ation of bronchial asthma (long-term contro ll er) .
1. Corticosteroids / Glucocorticoids
//
I -1-lyd roco rti so nc (lnj) r ~

_y' Predni so lonc (tab let)

,,11 Bec lometh aso ne (in haler)
.
Ac . _L'i }-,,,___..
( < '---
)'
f e" Betamethasone ( in haler) ( -'j
/ . Triamcin olone (inhaler)
/ Budesonide
• Ciclesonid e
/ • Flun isol ide
Fluticasone
L, "' ,rl. l_ -j n--V-
c... \:'\
\.1--1\
_,/ Mometasone
2. Leukotriene receptor antagonists: These drugs also • Za fir lukast
competitively prevent bronchoco1~s.ry cti on caused by leukotrienes
(C4, 0 4 and E4) le ,..~t- <· ,-,.,,,y \ L\
Mo nte lu kast /.
3. Leukotriene synthesis in hibitor y Zileuton
4. Mast cell stabilizers: Prevents mast cell degranulation. Cromo lyn sodi um . D-, (
1
, , .

/ Nedocromil sodium (_ \ - ' I >

5. Anti-IgE monoclonal antibody: Inhibits the binding of IgE to mast / Omalizumab
ce ll s & prevents mast ce ll degranulation.
1 ~' -- , - ->-, ,. \- «c':-, r, /
''v' L ,--0\c~~ -, (Re/ Kat:ung-13th)
;----. '-' cs',''(.\ :.. 'i'¾- O · ) <2 -~ o r-- -=, C. '-0.rt c- -r,--c.. l.<.q_\ ,1)-,-,,,

BronchOdilation ~ ATP( Botaagon;sts ]

~cAMP

Bronchial to1ne
~~ Theophylllne ]

AMP
Acetylcholine -B7 ~)- Adenosi ne
Muscari_n k
antagonists
- "'t;._r1 Th h Hin )
eop Y e _

Bron ch oconstriction

Fig. Bronchodilation is promoted by cAMP. Intracellular levels of cAMP can be increused by /-J-adrenoceptor
agonisls, which increase !he rate of its synthesis by adeny/y/ eye/use (AC): or hy phosphodiesterase (PDE)
inhibitors such as theophylline, which slow the rate cf .i ts degradotion. Bro11choconstrictio11 cm, be inhibited by
muscarinic antagonists and possihlv by adenosine antagonists.
l', ,. ,'-'',\~
Q. Name the drugs used to decrease bronchia l responsiveness to exogenous stimu li. Ex plain th eir action.
(S U-12Ju)
- '',o C c. \ )'•

<. - , ( c_.., / L ),-1 Jl • r \ C>- -,-

 T:\I
)Jlueprint · Pharmacology 688
Ans.
Drugs used to decrease bronchial responsiveness to exogenous stimuli
I. Co11icosteroids
2. Leukotriene receptor antagonists
3. Leukotriene synthesis inhibitor
4. Mast cell stabilizers
5. Anti-lgE monoclonal antibody.

Write name of the individual class of drugs from above. Write their action.from below.

Q. Name the drugs used by inhalation route in the treatment of bronchial asthma . (DU-1 OJu)
Q. Name the inhalational drugs used to treat bronchial asthma. (DU-] 6Ju, 14J, RU-l 5Ju)
Q. Enumerate inhalers of different groups used in bronchial asthma. (RU-131)
Af}i.
l1rugs used bv inhalation route in the treatment of bronchial asthma
' ·; 1. Selective P2-agonists: Salbutamol, Salmeterol
2. Anti-muscarinic agent: lpratropium bromide
3. Corticosteroids: Beclomethasone, betamethasone, triamcinolone
4. Mast cell stabilizers: Cromolyn sodium, nedocromil sodium .
(Ref Katzung-13'h edition)

Q. How to differentiate meter dose and dry powder inhaler? (RU-1 SJu)
r Ans.
Differences between meter dose and dry powder inhaler:
Traits Meter dose inhaler (MDI) Drv powder inhaler (DPI)
1. Definition A MDI is a device that delivers a specific A DP! is a device that delivers medication
amount of medication to the lun gs, in the form to the lungs in the form of a dry powder.
of a short burst of aerosolized medicine that is
usually self-administered by the patient via
inhalation .
2. Propellant Propellant based (HF A/CFC) Non- propellant based .
3. Consistency Solution / suspension Solid particles
4. Other Contains surfactants and lub ricants. Mi ght contain lactose.
constituents
5. Coordination Required. Not required.
of actuation-
inhalation
6. Cost Less expensive . More ex pens ive .

metered dose inhaler (MDI) Dry Powder Inhaler

Q. Name the drugs used in the treatment of acute bronchial asthma. (DU-07J, SU-IJJ)
 689 Dru~s u.-.cd in Bronchial Asthma
Q. Name the drugs used in the treatment of status asthmaticus. (RU-09.lu/.1 )
Q. Enlist the drugs used in acute severe bronchial astlnna. (RU- 13.lu)
Q. Name 4 drugs used in the lreattm~nt of acute bronchial asthma . (DU - 16.1 )
,l\ns.
Drugs used in acute severe bronchial asthma/ status asthmaticus
A. Bronchodilator
I. Selective ~2-agonists: Sa lbutamol, Tcrbutalinc, !\l butc ro l
2. Anti-muscarinic agent: lpratropium bromide
3. Methylxanthines: Aminophylline, Theophylline

B. Anti-inflammatory drugs:
1. Corticosteroids: Hydrocorti sone, Beclomethasone, betamethasone, tri amcinolon e

~
,
.J? r- .Oe \ ~
. \ (Ref Kaizung-1 3'" edil ion)
<._' _ /\1-)() I' 0 U ' ./'

Q. Stat5 the management of severe acute bronchial asthma/ status asthmaticus. (SU- I I Ju )
Q. ouy-rne the pharmacological approach to treat status asthmaticus. (RU-\ 5J u)
QJJate the drug management of status asthmaticus. (RU-1 7J)
An .
~ cute severe asthma/ status asthmaticus : Thi s is a life-threatening emergency req uiring rap id aggress ive
treatment. t is c 1aracteri zed-6y sev~ eeze, preathlessness to such extent that the~ ient cannot comp lete
sentences in 1 breath, tachycardia, central cyanosis and sometimes pulsu s paradoxus . -
- (R ef Davidson 's-22nd edition)
Treatment of acute bronchial asthma:
I . Oxygen :
r,c.rr~ ~-r re~
• Give high flow oxygen.
• Maintai n oxygen saturatio n above 92% .
2. High doses of inhaled bronchodilators:
• Salb utamol by nebu li ser in a dose of 2.5-5 mg over about 3 min, repeated in \ 5 min .
• Terbutaline 5-1d mg is an alternative. - -
• ~-;:-atropium 0.5 mg may be added to the nebul ised ~2-agonist.
3. Systemic corticosteroids:
• Hydroco! tisone 200 mg IV 4-6 hourly, then switch to-
• Pred'Esolo ne 30-60 1n g orally '-: _ -, .J. J )
4~ Avoid sedation of any kin d. ------- r .. I \ 0' . 0"'-Cf~,>-
, '\ \' ,-,.,;
L ' I ' I,~
5. Chest x-ray to exc lude pneumothorax.

,onitoring respon se to treatment: By- ' 0. l ""

~--,
1. Peak expiratory fl ow rate (P EFR)
2. Oxygen saturation : maintain >_92%
3. A~'teri al blood gas (ABG) analysis: Maintain PaO2 > 8 kPa (60 mm Hg).
- (R~f- Benne/I & Brovvn- 1 I th : Davids un ·s-22nd)

Q. Enlist the receptors which after stimulation cause bronchoconstriction . (CU-17M)

Ans.
Receptors which after stimulation cause bronchoconstriction
1. ~2 adrenocepto rs
 BlueprintTM Pharmacology 690
Q. Outline the therapeutic approach to bronchial asthma. (SU-1 JJu)
Q. Outline the therapeutic approach to chronic bronchial asthma. (SU - I I Ju)
Ans.
A stepwise approach to the management of chronic bronchial asthma

Patients should start treatment at the step most

appropriate to the initial severity of their asthma.
Check concordanoe and reconsider diagnosis If
response due to treatment is unexpectedly poor

Use daily storoid tabk)t

:.. .·'
.. ..::· In kl west dos.a pr0Vld1ng
a equate control
1 Add inhal9d long- Maintain high-dos.g
acting Pz-agomst inhalocl steroid at
Add inhal9d steroid ~ 2000 µg/day'
200-800 JLQ!da~ 2 Assess control of
lnhalocl st,ort-acting 4-oo-µ-g-is-arT1Jpp ropriate asthma:
~ 2-agonist as requ1rocl Consider other
j
sf.ming dose for many • Good r0Sponse to treatments to minrmis.Q
patients tA~ use of steroid tablets
- continue LABA
• Booefit from LABA Refer patient for
Start at dose of lnhal9d b--u:rc-mrtrohti II speciaJist care
st&roid appropriate to inad uafu
severity of disease - continue LABA and
increase inhalocl
steroid dose to
800 µg. ay· , ot
----atmaoron this dose)
• Jlio response
to LABA---.
- _stop LA&i'>: and
increase inhaioo -
steroid to SOO µQI
~ If control still
in.adequhle,7rTStittJtB
~ ies,
IGUkotriene receptor
anta oms or ·Fr
thoophylline

11'.litlal add-on
therapy

/,.._________Sy
_m_pt_o_m : 1\
_s ________/1 \ -- - - - - - - , - - -Treatment
vs\ - - - - - - - - , - - - - - - -\

-----------------------~;r· ,
Figure. Management approach in adults based on asthma control. *Beclometasone diprupionate (BDP) or
equivalent. From British Thoracic Society and SIGN.
(R ej:. D av,'dson .s--?- ,.t)

Q. Name the drugs u_sed for long-term control of bronchial asthma. (DU-17J)
Q. Enlist three drugs used in chronic bronchial asthma. (DU-17M)
Ans .
Drugs used for long-term control of bronchial asthma
I. Inhaled Short acting P2-agonists, eg, Sa lbutamo l
2. Inhaled Long acting B2-agonists, eg, Salmetern
 691 Drugs used in Bronchial Asthma
J. Inhal ed Steroids, eg, Fluticasonc
4. Leukotriene receptor antagonists, cg, Montclukast
S. Meth ylxanthines, eg, Doxophyllinc
6. Oral steroid, eg, preclniso lone.

Q. How P2selective agouists (salbutamol / salmeterol) act in bronchial asthma? (DU- l 6J , CU-17M, RU-06J)
Q. How salbutamol produces bronchodilatation? (CU-l 4J, RU- l 6J)
Q. Explain the role of.salbutamol in bronchial asthma. (DU-17 J1 SU-l 7J)
Q. Write tl e MIA of salbutamol. (SU-16J)
Ans. /
M~ anism of action (M/A) of p2 selective agonists (salbutamol / salmeterol): Bronchial asthma 1s
-characterized by bronchoconstriction leading to severe respiratory distress.
~2 agonist drugs (salbutamol / salmeterol) bind with ~2 receptor of bronchial smooth musc le
t 1
Relaxation of bronchial smooth muscle (bronchodilatation)
• '1 -
t
Quick relief of acute bronchoconstriction and asthma.
(Ref Katzung-13th)

Q. What are the advantages of inhaled Pi-selective agonists?

Ans .
Advantages of inhaled ~2-selective agonists/ salbutamol:
l. Selective action on Prreceptor of bronchial smooth muscle.
2. Rapid onset of action (within 1-5 minutes).
3. Very low systemic absorption and so less/ no CVS & CNS (tremor) adverse effects.
4. Easy to use; even if can be used in office or during walking.
5. Top ical delivery (anatomical selectivity).
(Ref Goodman & Gilman 's-l lrh)
Q. What iS"the role of salmeterol in bronchial asthma? (SU-08J u,08J)
Q. Discuss the role of salmeterol in chronic bronchial asthma. (SU- l 7M, l 4J )
AQ.&'
-Role of salmeterol in bronchial asthma: Salmeterol is a potent selective ~2 agonists that pl ays important role in
long-term control of bronchial asthma. It is due to the fact that-
1. It has a long duration of action (12 hours or more) as a result of hi gh lipid solubility .
2. It interacts with inhaled corticosteroids to improve asthma control.
However, it is not recommended as the sole therapy for asthma.
(Ref Ka1::. 11ng-l 3rh)
Q. What is the advantage of salmeterol over salbutamol?
Ans. Salbutarnol has short duration of action (only 4 hours) whereas Salmeterol has long duration of ac tion ( \ 2
hours).

Q. ~·,a_y,re the toxicities of inhaled ~rselective agonists?

An J
,. . oxicities of inhaled ~2-selective agonists / sulbutamol: Chronic use of ~r se lective agoni sts / sulbutarnol by
~ ~ inhaler cause-
i I. Dryness of airway

t 2. _Irritation or airway
3. Oropharyngea_l canclidiasis.
Blueprmt· Ti\l Ph armaco l ogy 692
Q. What ~ adverse effects of systemic P2-selective agonists / salbutamol? (DU-16J , RU-06J , SU -l6J)
Ans . /
Ad\'erse effects of systemic P2-selective agonists / salbutamol: ( :Dv-Q_·~ s;n"f'· \ ~ r- ~ r,r-- r 0-\:.
l. Tremor r----, ~
2. Tachycardia 1>1'\,--oJ,e& ~ ~~./
3. Arrhythmia
4. Palpitation
5. Hypokalaemia
6. Hyperglycemia

Q. Ephedrine is no longer used in bronchial asthma- explain . (DU-03S)

Q. Briefly assign reasons why Salbutamol but not ephed rine is preferred as bronchodilator. (DU-05M )
Ans.
Ephedrine is no longer used in bronchial asthma, because-
l. Availability of new efficacious & ~rselective drugs such as sulbutamol, salmeterol.
2. It has more duration of action than adrenaline.
3. It has more cardiovascular effect.
4. It is less potent.

Q. Compare the consequences between oral and inhalational salbutamol. (CU- l 6J)
Ans.
Comparison between oral and inhalational salbutamol
Traits Oral salbutamol Inhalational salbutamol
1. Onset of action Slow Rapid (within 1-5 minutes)
2. Selective action on P2-receptor of bronchial smooth No Yes
muscle
3. Systemic absorption High Low
4. CVS & CNS (tremor) adverse effects Present Less or absent
5. D ryness of airway No Yes
6. Oropharyn2:eal candidiasis No Yes

Q . Discuss briefly the differences between salbutamol & aminophylline. (DU-09Ju)

Q. Compare salbutamol & theophylline as bronchodilator/anti asthmatic drug. (CU-15J,09Ju,05S)
Ans.
Differences between salbutamol & aminophylline
.- Traits I Salbutamol ,.,, ..... < ,. I ...., . Theophylline -· .,,_.,·, ,- '

1. Mechanism Selectively stimulates ~2 receptors Inhibits phosphodiesterase enzyme

on bronchial tree
2. Onset of action Slow Rapid (due to IV route)
3. Duration of action Relatively lon ger Shorter
4. Route Inhaled, Oral IV , Oral
5. In acute asthma Nebulized / inhaled form IV route
6. Adverse effects • Tremor • Arrhythmia (Tachycardia)
• Tachycardia • Palpitation
• Hypotension • Insomnia
7. Therapeutic index Hi gh Narrow
8. Close observation Not needed Needed
durin2: administration
9. Cardiotoxic effect Absent, because sulbutamol has Present (Tachy-arrhythmia, tachycardia,
no BI effect hypertension, palpitation)
10. CNS toxicity Less More (insomni a, tremor, restlessness
 693 Drugs used in Bronchial Asthma
Q. Name the drugs used for nebulization. What are its advantages over inhalation? Mention the
mechanism of action of any drug. (RU- I4Ju)
Ans.
Drugs used for nebulization
I. Salbutamol
2. Terbutaline
3. lpratropium

Advantages over inhalation

I. Rapid onset of action.
2. Suitable for acute severe asthma.
3. Less chance of dryness of airway.

nti-muscarinic dru s in asthma

Q. Explain the action & role of Ipratropium bromide in bronchial asthma. (DU- l 6J , SU-09J)
Q. Justify he use oflpratropium bromide in obstructive airway disease. (CU-1 SJ)
Ans. /,.
Role o tpratropium bromide in bronchial asthma: Antimuscarinic agents are effective bronchodilators.

lpratropium bromide blocks Mrreceptors on bronchial smooth muscles & glands

!
!IP3 & DAG
!
Repolarization of muscles
!
Relaxation of bronchial smooth muscles & decreased bronchial secretion
!
Relief of bronchial asthma
(Ref Katzung-l 3th)

Anticholinergic agents are generally less effective than ~radrenergic agonists. Inhaled ipratropium is useful in
patients who are unable to tolerate adrenergic agonists. lpratropium is slow in onset and nearly free of side effects.
These agents are not traditionally effective for patients with asthma unless COPD is also present.

Clinical use of inhaled muscarinic receptor antagonists (e.g. ipratropium)

I. Asthma, as an adjunct to ~r agonists and steroids.
2. COPD, especially long-acting drugs (e.g. tiotropium).
3. For bronchospasm precipitated by ~r blockers.
(Ref Rang & Dale ·s-8th)

Methylxanthine dru s
Sources:
Theophylline - tea
Theobromine - cocoa
Caffeine - coffee.
(Ref Kat::ung-l 3th)

Q. Explain the mechanism of action & role of aminophylline in bronchial asthma . (DU- l6J, RU-1 SJ, SU-
09J)

Pharmacology-89
 I , . ~Yrv-
i -\)\.-,ch . 0 I ~ ('.!,,~ (.-' ' -

J \ 'y l ~ ~ 0 .s- I ,"' t>-.:.-1?__

BlueprintTM Pharmaco logy 694 (y>
_l ,,.
Q. Outline the mechanism of action of theophylline. (CU-16J , RU-14J)
-
Q. .,Ex.plain the role of theophylline in bronchial asthma . (RU-04J ;SU-07 J ;06M)
Q Write a short note on aminophylline . (SU-06S)
I
' p\95.
Mechanism of action of Theophylline in bronchial asthma: Several mechanisms have been proposed for the
actions of methylxanthines, but none has been firmly established.
I. Theophylline inhibits "phosphodiesterase (PDE)" enzyme - j cAMP - Relaxation of bronchial smooth
muscle - Bronchodilation.
2. Theophylline inhibits ' phosphodiesterase enzyme 4' (PDE4) - j cAMP - Reduces the release of
cytokines and chemokines from inflammatory cells - Decrease immune cell migration and activation .
3. Competitive inhibition of adenosine receptors - Prevents bronchoconstriction by adenosine and
histamine release from airway mast cells.
(R~[' Katzung-13th)
Q. ~iISs the pharmacological action of theophylline on respiratory system, CVS, CNS & kidney. (SU-
L J)

M ~·rmacological actions of theophylline

A. CVS: Directly stimulates the heart & dilates systemic blood vessels including coronary vessels & reduces
peripheral resistance.
• Increase heart rate (tachycardia /tachyarrhythmia)
• Increase force of contraction
• Increase cardiac output
• Usually a rise in SBP & fall in DBP is observed with aminophylline.
B. CNS: Stimulatory effects including-
• Insomnia (most common adverse effects)
• Nervousness
• Restlessness
• Excitement
• Agitation
• Tremor
• Very high doses, from accidental or suicidal overdose, cause medullary stimulation and convulsions and
may lead to death .
C. Kidney: Inhibits tubular reabsorption of Na+ & water & thus causes mild diuresis.
(Ref Katzung- 1Jth)

Q. Mention the indications of aminophylline. (RU-04S/J)

Ans.
Indications of aminophylline:
I. Severe acute bronchial asthma
2. Chronic asthma
3. COPD
4. Apnea in preterm baby
5. Ordinary headache (caffeine+ aspirin)
6. Migraine
7. Emergency treatment of left ventricular failure.
(Ref Katzung-l 3th)

Q. Mention the adverse effects of aminophylline. (DU-16J, RU- l 4J)

Q. Mention the adverse effects of theophylline. (RU-l 4J)
 /
695 Drugs used in Brond1ial Asthma
Ans. I'
· A~erse effects of theo phyllinc / amino phyllinc:
I. Cardio-vascular: Tac hycardi a, palpitation, hypotcnsion, prccordial pain
2. CNS (stimulatory): Insomnia, headac he dizzin ess, server restl essness, agitati on.
3. Overdose may cause se izures or potenti ally fatal arrh ythmi as .
4. Others: Nausea, vomitin g.
(Ref Katzung-1 Jth, Ciood111an & (1i/111t111 's- l 2tlt, l.ip;1inrnlt ·.1- rith;

Q. Mention the advantage and disadvantages of thcophyllinc

Ans.
Advantage of theophylline
I . Theophylline is an effective bronchodilator, and it has been shown repeatedly both to relieve airn ow
obstruction in acute asthma and to reduce the severity of symptoms and time lost from work or schoo l in
patients with chronic asthma.
2. Theophylline improves long-term control of asthma when taken as the so le maintenance treatment or
when added to inhaled corticosteroids.
3. It is inexpensive.
4. It can be taken orally, by IV infusion and per-rectally .
(Ref Kat::ung-! JthJ

Disadvantages of theophylline: Previously the mainstay of asthma therapy, theophylline has been largely
replaced with ~2 agonists and corticosteroids due to-
1. Narrow therapeutic window.
2. High side-effect profile.
3. Potential for drug interactions.
(Ref Kat::ung- 1JthJ

Q. Why theophylline should be used with caution in IN form?

Ans.
Theophylline should be used with caution in IN form: Aminophylline/ theoph ylline has pos iti ve chro notro pic
& inotropic effect. Rapid IV administration of aminophylline/ theophylline som etimes cau ses sudden death du e
to cardiac arrhythmia. So, the drug should be injected slowly over 20-40 minutes or with infusion drip slowly to
avoid severe toxic symptoms.
(Ref Goodman & Gilman-1 2th)

Q. Name the glucocorticoids used in bronchial asthma. (D U- I3Ju )

Q. Categorize glucocorticoids used in bronchial asthma with indication and routes in special situation.
(SU-I 5Ju)
Q. Enlist inhalation Glucocorticoids. (CU -1 7J)
Ans. /
Ghicocorticoids used in bronchial asthma
1. IV
a. Hydrocortisone
2. Oral
a. Predni so lone
3. Inhalation Glucocorticoicls
a. Fluticaso ne
b. Budesonide
c. Becl ometh aso ne
d. Ciclesonide
 TI\I
Blueprint Phairmacology 696
e. Flunisolide
f. M ometasone
g. Tiriamcinolone

Q. Expla~n the )pharm~~olog!c~I·~~~i?n~J{o(u,!1~~-;~~~:~~;~~~f!~oid~·t~lt9~f:h J~F.asthma. tCU-07J) ·

Q. Explam the 1'}ech~msiµ of actio.n of,.beclome_th~~one·.1n b1.;onch1~l asth_ma.:(Dl!:-10iu, RU-09! u,06M)
Q. Discuss the .role. of :glucocor.ticoids'
~ .·:t
.:·i.i.;bronchial asthnial~hron'ic /~1stiim'a·.'·(DU-17M,1'1 Ju, :·CU-17J,09Ju,
•' ,I~ ..i• 4 • l -''"·'\ •;:\. • ~ . ~ • •• I I, ,, • " ,_ '\ ,o ! --'·
1

'.,.t~·- .. ·. -'.·j,.:. ·.·.: ·. :··._ .· ·, ,. • . , :'._··. -_.. .

f

RU-12Ju ) STJ-16Ju , 14Ju)' ,i·~·-

' •
-·:"'
• :f·
-~'tt.
'-; ,.. , • ,. • '• • " ., . • I' ;

Q. Discuss the.
<
benefidal• effects' giuf~corticoids
~ ' t,; . ~·
·of
.. -•
in asthrit.a t_ic·
• ' ... ,, ., .i
patient.
. I' ,
JDU-13fo)
• -
' l' .
. -- f-
Q. Explain _th,e· role of hydroco1 isorie. in·t~\ maJii~gein~nfoflfro!1~hial'as!.h m,a. (C~J?q} u) . . . . . . , ,
Q. How corticosteroids act in asthma? (D~-06,S;;~U-06M/S). ;::. . <·;~. < :;:> ...:< · . ·· ,· , 1·,
Q. Discuss th,e role of ster oids inrbrom;}lfal as_tliffi a~
' '"'j;J
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1

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ti;.JlU~'
.
i OJ) ,·.,:W; %~-k;f;t¥t···;
•.\~ ~\'"· • '>·
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,ti
.f__ i
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" ;. ••! ·, t -..J• • • • ' •--~-:'"·\,I.• • l •

Q . Mention tine role,of fluticasone hd lie~t'reatmeiit-of·til:onchiaha:sthina.,,(SU-'BJ,l lJ} ·:~".\;, ... ·~< -:.'-:'\ ~-~- .

-c
An~. ---~-- · ·· - -· -~-') -~-----"{~~f-e;~~-, . . ,.. ~. c-~- ...---- . ·· ·-- . .... _ --·· -- ...
Role of glucocorticoids / beclomethasone/prednisolone in asthma: Asthma 1s associated with -
• Airway inflammation C O''f' -~ ~ fCA 1.. t
• Airway hyperactivity & 9 L 7' bit\ ·
• Acute bronchoconstriction L](. -----7" . ~ l T Bl-\.., C' ~~
"~ ~ ; s ~ A 0 \o,,_;, ,---,Q_\-'u-~ ..!, ....b,s-\-~, 1
Glucocorticoids do not relax airway smooth muscle directly & thus have little effect on acute bronchoconstriction.¾<>~-/ ~
On the other hand they are effective to inhibit airway inflammation & hyperactivity. The mechanisms include: ~
• Inhibition of the influx of inflammatory cells into the lung after allergen exposure;
• Inhibition of the release of mediators from macrophages and eosinophils and reduction of the
rnicrovascular leakage which these mediators cause . 3) f--2~.;,s1"e.. c ~ ~x,.'.\ e:,,-.\;~ --r
~ ~Cfo'- cJl.- ~ ~-VO-

The glucocorticoids are effective in improving all indices of asthma control-severity of symptoms, tests of
airway caliber and bronchial reactivity, frequency of exacerbations, and quality of life.

Inhaled corticosteroids (ICS) are the drugs of first choice in patients with any degree of persistent asthma (mild,
moderate, or severe). No other medications are as effective as ICS in the long-term control of asthma.
Severe persistent asthma may require the addition of a short course of oral glucocorticoid treatment.
(Ref Kalzung-13th + Bennett & Brown-I I th; Lippincott 's-6th)

Q. Mention the role of glucocorticoids in acute bronchial asthma. (DU-07 J,06S ; CU-04M ; RU-OSS)
Ans.
Role of glucocorticoids in acute bronchial asthma: Glucocorticoids do not relax airway smooth muscle directly
& thus have little effect on acute bronchoconstriction.
But, Glucocorticoids potentiate the action of acute bronchodilators by their antiinflammatory action & thus used
in acute asthma with the bronchodilator agents.
Urgent treatment is often begun with an oral prednisone (30-60 mg/day) or IV methylprednisolone ( 1 mg/kg 6
hourly); the daily dose is decreased after airway obstruction has improved. In most patients, systemic
corticosteroid therapy can be discontinued after 7- 10 days .
(Ref Goodman & Gilman 's-12th: Katzung-1 Jth)

Q. Discuss the role of fluticasone in bronichial asthma. (SU-17 J)

Q. Discuss the role of fluticasone in chronic bronchial asthma. (SU- l 7M , I 4J)
Q. Mention the role of fluticasone in acute bronchial asthma. (SU-09Ju)
Ans .
Role of fluticasone in chronic bronchial asthma: Fluticasone is effective in long-term control of chronic
bronchial asthma. It is usually given in inhalation route along with a long-acting Pragonist, eg, salmeterol.
(write the actions of glucocorticoid in asthma from above.)

Q. Why inhalational steroids are better than that of oral ones? (DU- l 2Ju)
 I 697 Drugs used in Bronchial Asthma
Q. JY!ention the advantages of beclomethasone inhaler in treating bronchial asthma. (DU-I 0Ju)
,l ~

Inhalational steroids are better than oral steroids / Advantages of beclomethasone inhaler in treating
bronchial asthma: To prevent bronchial asthma, long-term corticosteroid therapy is needed. 1f corticosteroids are
given orally or parenterally, they produce severe adverse effects like Cushing 's syndrome, adrenal suppression.
But if they are given through inhalation, there is minimal systemic absorption and there will be few systt:mic
effects. Thus aerosol treatment (inhalation) is the most effective way to avoid the systemic adverse effects of
corticosteroid therapy. This is why some corticosteroids such as beclomethasone are given by inhalation to
prevent asthma. An average daily dose of four puffs twice daily of beclomethasone (400 mcg/d) is equivalent to
about I0-15 mg/d of oral prednisone for the control of asthma, with far fewer systemic effects.
(Ref Katzung-13th)

Q. Mention the risks of inhaled corticosteroids? How do you avoid risk? (DU-09Ju)

~~~t or inhaled glucocorticoids:

1. Oropharyngeal eandidiasis (most common)
2. Hoarseness of voice (direct local effect on vocal cords)
3. Dryness of airway
4. Irritation of airway
5. Long term complications: Osteoporosis, cataracts, slowing the rate of growth in children .
(Ref Katzung-13th)
Prevention/ How to avoid risk:
1. The risk of oropharyngeal candidiasis can be reduced by having patients gargle water and spit after each
inhaled treatment.
2. Counseling the patient about the user manual of the inhaler (e.g. correct positioning of the inhaler.
inhaling the drug substance by deep inspiration during puffing).
3. The patient should shake well the inhaler before use
(Ref Katzung-13th)

Mast cell stabilizers

Drugs that stabilize mast cells:
1. Cromolyn sodium (disodium cromoglycate)
2. Nedocromil sodium

Q. Explain the action & role of nedocromil sodium in bronchial asthma. (SU-09J)
Q. Discuss the role of cromolyn-Na in the management of bronchial asthma. (CU-08J ;RU-02J;SU-06M)
Ans.
Mechanism of action of mast cell stabilizers:
Cromolyn and nedocromil
J
An-a-Iteration in the-function ef delayed chloride channels in tne cell me mbrnne of ,rnrsnei±s__

Entry of er ions into the cel ls causes _hyperpola ization of the cel l
~ {'- . p r r - 1<..w: \-- v- . ~~ - .- '" -\ I )
No mast cell activalTon ·
J ,---;
No degranulation of mast cells no histamine release.
---I
No bronchoconstriction (as histamine causes bronchospasm)
J
Prevention of asthma
(Ref Kut::ung-l Jth)
BlueprintTM Pharmacology
I
698
linil'al use of romolyn & Nedocromil .
1. For prevention of bronchial asthma: To prevent bronchial asthma , cromolyn is taken shortl y before
~x 'r i e or before unavoidable exposure to an allergen.
llergic rhinoconjunctivitis.
(R4' Katzung-I31hJ

Q. \\ hy cromolyn sodium is used prophylactically?

Ans.
Cromolyn sodium is used prophylactically: Cromolyn sodium (disodium cromoglycate). and nedocromil
sodium have no effect on airway smooth muscle tone and are ineffective in reversing asthmatic bronchospasm;
they are only of value when taken prophylactically. When used as aerosols (by ne?ulizer or m~tered-d? e
inhaler), they effectively inhibit both antigen- and exercise-induced asthma, and chrome use (four tunes dally)
lightly reduces the overall level of bronchial reactivity.
(Ref Katzung-13th)
Q. Mention the adverse effects of mast cell stabilizers.
Ans.
Adverse effects of mast cell stabilizers: Because the drugs are so poorly absorbed, adverse effects of cromolyn
and nedocromil are minor and are localized to the sites of deposition.
~{\
I. Bronchospasm
,)
2. Cough or wheezing j
3. Laryngeal edema ('._ V )<·
4. Joint pain & swelling
5. Angioedema
6. Headache
7. Nausea
8. Rash

Leukotriene Pathway Inhibitors

Leukotriene (LT) B4 and the cystein I leukotrienes, LTC4, LTD 4, and LTE4, are products of the 5-lipoxygenase
pathway of arachidonic acid metabolism and part of the inflammatory cascade. 5-Lipoxygenase is found in cells
of myeloid origin, such as mast cells, basophils, eosinophils, and neutrophils._LTB 4 is a potent chemoattractant for
neutrophils and eosinophils, whereas the cysteinyl leukotrienes constrict bronchiolar smooth muscle, increase
endothelial permeability, and promote mucous secretion.

W at o you know about the status of leukotriene inhibitor in asthma? (RU- I 3Ju, 12Ju, I !Ju)
Q. J ttnote: Montelukast. (SU-17 J, I SJ , 14Ju)
A s.
~ eukotriene receptor antagonists: These drugs also competitively prevent bronchoconstriction caused by
leukotrienes (C4, D4 and E4)
• Zafirlukast
• Montelukast: Of these two, montelukast is the most prescribed, probably because it can be taken without
regard to meals and because of the convenience of once-daily treatment.

Leukotriene synthesis inhibitor

• Zileuton
 -
Advantages:
699 Drugs used in Bronchial Asthma

1. Can be given to children I year of age and older

2. Available in chewable tablets and granule formulations.

Indication: All three drugs are approved for the prophylaxis of asthma but are not effective in situations where
immediate bronchodilation is required . L' 1 \ , , _ ·)
\.O~ -\ e '"'-"f"\ ~'"'° fY
Adverse effects:
I. Liver toxicity (zileuton, so zileuton is the least prescribed of these agents)
2. Churg-Strauss syndrome (a systemic vasculitis accompanied by worsening asthma, pulmonary infiltrates,
and eosinophilia)
3. Zafirlukast may interact with warfarin & increase prothrombin times.
(Ref Goodman & Gilman 's-l 2th)

Q. Exp.Jain -he role of montelukast in the management of bronchial asthma. (DU-I 7J , 14Ju, CU-1 JJu, SU-
.a,-[) /
. J3· .plain the pharmacological basis of using montelukast in bronchial asthma. (CU-14Ju)
Q. Discuss the role of Leukotriene inhibitor/ montelucast in chronic bronchial asthma. (DU-16Ju, SU-
l 7M, 14J)
Q. Justify the use of Leukotriene receptor blockers in bronchial asthma. (CU-16J)
Ans.
Role of montelukast / Leukotriene receptor blockers in the management of bronchial asthma
I. Montelukast is indicated for the prophylaxis of asthma but are not effective in situations where
immediate bronchodilation is required .
2. It can be taken without regard to meals and because of the convenience of once-daily treatment.
3. It reduces the freq1Iency-nf-exacer6ation.
4. Very much effecfive in persistent asthma whether it is mild, moderate or severe.
5. It reduces inflammatory process and lacks of wide range . of adverse effects compared to oral
corticosteroids.
6. It is a steroid sparing agent.
7. Provides additional control of symptoms during exercise.
8. Available as tablet form; children and elderly people can easily take it for whom inhaler is not suitable.
(Ref Goodman & Gillman-12th)

Omalizumab
Omalizumab is a recombinant DNA-derived monoclonal antibody that selectively binds to human
immunoglobulin E (IgE). It is the I st biological drug approved for the Rx of asthma. Due to the high cost of the
drug (approximately $600 for a 150-mg vial), limitations on dosage, and available clinical trial data, it is not
presently used as first-line therapy.

Mechanism of action of omalizumab:

I. Omalizumab binds with IgE.
!
IgE can't bind with lgE receptor on mast cell & basophil.
!
No degranulation of mast cells and basophils and no release of mediators of allergic reaction.
!
Prevention of asthma
BlueprintTM Pharmacology 700
2. Omalizumab may also inhibit IgE synthesis by B lymphocytes.
(Ref Katzung-13th)
Route: Parenteral route (intravenous or subcutaneous)

Clinical uses: As it is not a bronchodilator, it is used prophylactically. Omalizumab may be particularly useful for
treatment of moderate to severe allergic asthma in patients who are poorly controlled with conventional therapy.

Importance of Omalizumab:
l. Omal izumab lessens asthma severity and reduces the corticosteroid requirement in patients with moderate
to severe disease, especially those with a clear environmental antigen precipitating factor
2. It improves nasal and conjunctiva! symptoms in patients with perennial or seasonal allergic rhinitis.
3. Omalizumab's most important effect is reduction of the frequency and severity of asthma exacerbations
even while enabling a reduction in corticosteroid requirements. '

Adverse effects of omalizumab:

I. Hypersensitivity reaction
2. Injection site reactions: Redness, stinging, bruising, induration.
(Ref Goodman & Gi!man 's-12th)

};i:. .~; :, ::\'k;~ \ ... ·- Dru s u·s ed to treat Cou h Antitussives >.-: . .·· ·,_.-._,:
Cough: Cough is a protective reflex that removes foreign material and secretions from the bronchi and
bronchioles. Cough is the most frequent symptom of respiratory disease. It is caused by stimulation of sensory
nerves in the mucosa of the pharynx, larynx, trachea and bronchi.
(Ref Rang & Dale's-8th)

Causes of cough:
Origin Common causes
Pharynx • Post-nasal drip
Larynx • Laryngitis, tumour, whooping cough, croup
Trachea • Tracheitis
Bronchi • Bronchitis (acute) and COPD
• Asthma
• Eosinophi lic bronchitis
• Bronchial carcinoma
Lung parenchyma • Tuberculosis
• Pneumonia
• Bronchiectasis
• Pulmonary oedema
• Interstitial fibrosis -
Drug side-effect • ACE inhibitors -
(Ref Davidson 's-2211d)
 70 I Drugs used in Bronchial Asthma
;i_titussivcs: tuititussiws arc the dru gs that ca use suppression ol' cough .
"-- ~ \. Pniphcrally acting antitussivcs --
I. Li11ctuscs (ckrnulsa~ prcpmations, lozenges)
2. Water aerosol inhalation
3. Bcnzoin inhalation
4. Methanol and eucalyptus inhalation
B. Centrally acting antitussives
-
• Opioids (addicting, powerful respiratory
suppressant action):
I . Morphine
2. Diamorphine
3. Methadone
• Opioids (less-addicting, less respiratory
depression):
I. Codeine (methylmorphine)
2. Dextromethorphan a
3. Pholcodine
C. Sedative antihistamine: (Sedation I. Di phenhydram ine ( I v-'..> ..... >y \-"\
reduces cough) )
2. Ch lorphen iram ine

Codeine
Codeine is the go ld-standard treatment for cough suppression due to its long history of availability and use .
Codeine decreases the sensitivity of cough centers in the central nervous system to peripheral stimuli and
decreases mucosa! secretion. These therapeutic effects occ ur at closes lower than those required for ana lges ia but
still incur common sides effects like constipation, dysphoria, and fatigue, in addition to its addictive potential.
(Ref Lippincoll 's-6th)

Dextromethorphan
Dextromethorphan is a synthetic derivative or morphine that suppresses the response of the central cough center.
It has no anal gesic effects, has a low addictive profile, but may cause clysphoria at hi gh closes, which may explain
its status a a potential drug of abu se . Dextromethorph an has a significantly better side effect profile than codeine
and has been demon trated to be equally effective fo r co ugh suppress ion.
(Ref Lippincolf 's-6th)

Expectorant
!\n expectorant ( from the Lat in eX/)(! C:forar e, to expel from the chest) helps bring up mucus and other material
from the lun gs, bronchi. and trachea . /\n expectorant increases bronchial secretions and reduce th e thickness or
viscosity of bronchial secretions thu s increasin g mucus fl ow that can be removed more easi ly through coughing,
Expectorant are-
1. Iodide
2. Ch loride
3. Bicarbonate
4. /\cetates
5. Guaifenes in
Mucolytics
Mucolytics reduces the viscosity of the mucu s (sputum). The mucus becomes thinner and can be removed more
eas il y throu gh coughing. Mucolytic. are-
l. Acetylcysteine
2. Carbocysteine
3. Arnbroxol.
Pharrnarolon ,·-90
"'·'
Blul'printTl\t Pharmacology 702

MCQ
Q. Following arc bronchodilators- (DU -17.J )
a. sa llll etcrol
b. ipratropium bro mid e
c. hydrocort iso ne
d. nedocro mil sodium
e. th eophylline
a. 7~ b. T. c. F. cl. F. e. T

Q. Following arc bronchodilators- (DU-1 JJ)

a. sa lmeterol.
b. prednisolone.
c. chro moglycate.
d. ipratropiurn.
e. aminophylline.
a. 1~ b. F. c. F, d. T e. T

Q. Role of drugs in bronchial asthma include- (SU-I 3J)

a. Fluticasone decrease bronchial response
b. Montelukast is anti-inflammatory
c. Salmeterol inhibit bronchial secretion
d. Theopylline dilates muscle
e. Sodium cromoglycate is rapid acting
a. T, b. T; c. 1~ d. T e. F