This document discusses the pharmacotherapy of cough and bronchial asthma. It begins by describing the etiology and types of cough, as well as the cough reflex process. It then covers the types of drugs used to treat cough, including expectorants, mucolytics, antitussives, and pharyngeal demulcents. The mechanisms and examples of each drug type are provided. The document also discusses the pathophysiology and classification of drugs used to treat bronchial asthma, including bronchodilators, leukotriene receptor antagonists, glucocorticoids, and monoclonal antibodies. The mechanisms and examples of the major drug classes used for asthma treatment are summarized.

1. Pharmacotherapy of cough

2. • Cough –a physiologically useful protective reflex that clears
the respiratory tract of the accumulated mucus & foreign
substances.
• Etiology:- Irritant triggers cough from different source
Exogeneous source
 Smoke
 Dust
 Infection
 Tumor
 Foreign body
Endogenous source
 Airways secretion
 Gastric content
Drug induced cough
 ACE-I
 Amiodarone
 Iodine
 Inhaled medication include
e.g.-ether, cromolyn sodium, glucocorticoids

3. Types of cough
Productive Cough/
tenacious/Purulent
Non-Productive Cough/Dry cough
Should be suppressed
Use Anti-tussive drugs-
Drug that suppress cough
center
 Should be drain the airways
 Should never be suppressed
Use Expectorants/ Mucokinetics
Rx- Rx-
Consequences:-
 ↑ discomfort to the pt.
 Pt. unable to sleep
 Serious in pt. of cardiac disease,
after ocular surgery or hernia
Production of mucous secretion
that helps in expulsion of harmful
materials

4. Cause Treatment
Bacterial infection Anti-bacterial drugs
Pulmonary TB Anti-bacterial drugs
URTI-upper respiratory tract
infection
Anti-bacterial if bacterial infection
Viral infection Symptomatic
Bronchitis Stream inhalation, drainage
bronchiectasis
Pulmonary eosinophilia Diethylcarbamazine
Asthma Inhaled bronchodilators,
corticosteroids
Smoking Avoid smoking
Drug induced Change the drug
e.g. ACE-I induced case change to
ARBS
Common cause of cough & Treatment Protocol

5.  Cough reflex:- is complex & comprises of three main
stages.
1.An inspiration
2.Building up of pressure in the lungs by contraction of
expiratory muscle against a closed glottis
3.Forceful expiration through narrowed airway with high
linear velocity of airflow which sweeps irritant material up
towards the pharynx.

6. Drugs Used in symptomatic Treatment of Cough
Antitussives
(cough centre
suppressants)
 Codeine,
 Pholcodine,
 Noscapine,
 Dextromethorphan
 Antihistamines,
 Benzonatate
Pharyngeal
demulcents
• Lozenges,
• linctuses,
• liquorice
Expectorants
 Sodium and potassium
citrate,
 potassium iodide,
 guaiphenesin,
 ammonium chloride.
Mucolytics
 Bromhexine,
 Acetylcysteine
 Carbocisteine
 Ambroxol

7. • Pharyngeal demulcents:-
 Coat the pharynx & provide Soothing effect
 ↓afferent impulses from the inflamed/irritated pharyngeal mucosa.
 ↓frequency & severity of cough
 Provide symptomatic relief in dry cough arising from throat.(above
the larynx)
 Dosage form-syrup, lozenges, linctus,
 Syrup:-conc. Solution of sugar containing the drug to mask the bitter
taste of the drug
 Lozenges-solid dosage form placed in the mouth and sucked it
dissolves slowly to liberate the active ingredient.It soothes the irritated
mucosa of the throat,e.g.-dyclonine (local anaesthetic) lozenge for
sore throat

8. Expectorants/Mucokinetics:-
• Use in productive cough
 Bronchial secretion enhancer:-
• Sodium/potassium citrate-by salt action
• Potassium iodide-irritation of mucosa
• Ammonium chloride-It is a gastric irritant which reflexly
↑bronchial secretions
• Guaiphenesin
• Balsum of tolu
• vasaka
Expectorants acts via two ways
↑↑Bronchial secretions/Bronchial
secretion enhancer
Reduces its viscosity/Mucolytics
These are plant products, they increases
bronchial secretion & mucocilliary
function

9. • Mucolytics:-
• These agents break the thick tenacious sputum
• lower the viscosity of sputum →sputum comes out easily
with less effort
Drugs include- Bromhexine, Acetylcysteine, Carbocisteine,
Ambroxol
 Bromhexine:-
 It is a semisynthetic agent used orally
 Derivatives of alkaloid vasicine(vasaka)
 Process mucolytic and mucokinetic effects
MOA:- Bromhexine
↓↓
Liberate Lysosomal enzyme

10. ↓↓
Digests the mucopolysaccharides
↓↓
↓viscosity of sputum
↓↓
Cough becomes less tiring and productive
 SE:- rhinorrhoea and lacrimation
 Acetylcysteine and carbocisteine:- metabolites of
bromhexine
 MOA:- Acetylcysteine and carbocisteine
↓↓
open disulphide bonds in mucoproteins of sputum
↓↓

11. sputum becomes thin and less viscid
↓↓
cough becomes less tiring and productive
 Carbocysteine- can be given orally
 Ambroxol-is a metabolite of Bromhexine
 A metabolite of bromhexine & has similar action, uses &
side effects.
 It is more useful if mucus plugs are present

12. Anti-tussives
• Use in symptomatic treatment of non-productive cough
• MOA:-
• ↑cough threshold by directly acting on cough center
(medulla oblongata)
• Act peripherally in the respiratory tract to reduce tussel
impulses or both these actions.
• Should be avoided in children below the age of 1 year
Narcotics/opioids Antitussives:-
 Codeine-Like morphine but less potent than morphine as
they are semi-synthetic derivatives
• Dose administered lower than analgesic dose(10 mg B.D.)-
lesser addiction liability or lesser constipation.

13. • Over dosage-respiratory depression, convulsions, postural
hypotension & tachycardia.
• contraindicated in asthmatics & in patients with diminished
respiratory reserve
Pholcodein:-
• Structurally related to codeine but slightly
• More potent & longer acting & better tolerated (No
addiction liability) than codeine.
• Non-Narcotics/Non-opioids:-
• Noscapine:-
• It suppress cough but has no narcotic, Analgesic or
dependance tendency
• Equipotent anti-tussive as codeine especially in spasmodic
cough

14. • Dextromethorphan:-
• D-isomer of codeine
• Efficacy → equal to codeine
• Advantage over codeine-
• Non-opioids action-so no constipation, no addiction
• Doesn’t ↓mucociliary clearence
• Side effect:- dizziness, nausea, drowsiness, ataxia etc.
• Peripherally acting antitussives:-
• Prenoxdiazine-
• It acts in contrast to other antitussives, it acts peripherally,
desensitizes the pulmonary stretch recep & reduces tussel
impulses originating in the lungs.
• Useful in cough of bronchial origin.

15.  Antihistaminics:-
• Drugs:- Diphenhydramine, dimenhydrinate, promethazine
• H1 antihistamines- First generation H1 blockers acts via
sedative & Anti-cholinergic action
• Anti-cholinergic action-↓secretion
• Effective in allergic cough (Productive cough)
• Second generation anti-histaminics- ineffective
• Role of other agents in cough:-
1. Role of hydration in cough:-
 by adequate intake of water/fluid ↓viscosity of bronchial
secretion/mucus secretion/sputum
2.Role of steam inhalation in cough:-
• steam inhalation-treating the cough particularly with
tenacious below the larynx.

16. Pharmacotherapy of Bronchial asthma

17. Definition-A state of bronchial hyper reactivity resulting
from a persistent inflammatory process on response to a
number of stimuli in a genetically susceptible individual
 Pathophysiology:-
Persistence inflammatory process in response to a number
of stimuli (allergens,virus,environmental pollutants, irritant
chemicals, cold air, kitchen fumes, dust)
Bronchoconstriction→ due to inflammatory process
Bronchi become hyperactive→↑level of Ig E
Exposure to allergens→ activation of mast cells
Airway obstruction -due to the release of mediators from
sensitized mast cells in the lungs
Mediators includes-histamine, serotonin (5-HT), PGs,
leukotrienes (LTC4 and LTD4), proteases, PAF, etc

18. • Types:-
1.Acute Asthma:-
 It is characterized by episode of dyspnoea associated with
expiratory wheezing
 Mediators release-histamine & Leukotrienes release from
mast cells
2.Chronic Asthma:-
 There is continuous wheeze and breathlessness on exertion.
 cough and mucoid sputum with recurrent respiratory
infection are common
 Mediators release-histamine & Leukotrienes release from
mast cells & from basophils (IL-4 & IL-13)

20. Status asthmaticus (acute severe asthma):-
 Prolonged attack of asthma with severe intractable
wheezing
 Life threatening form of asthma (Emergency condition)-
leading to pulmonary insufficiency
 Airway obstruction is unresponsiveness to usual therapy

21. Classification of antiasthmatic drugs
1.Bronchodilators:-
A. Sympathomimetics:-
(i)Selective β2-adrenergic agonists:-
 Salbutamol, terbutaline (short acting)
 Salmeterol, formoterol (long acting)
(ii) Nonselective:- Adrenaline
B. Methylxanthines:-
Theophylline, aminophylline, etophylline
C. Anticholinergics:-
Ipratropium bromide, tiotropium bromide.
2. Leukotriene receptor antagonists
Zafirlukast, montelukast.

22. 3. Mast cell stabilizers:- Sodium cromoglycate, ketotifen.
4. Glucocorticoids:-
A. Inhaled glucocorticoids:-
Beclomethasone, budesonide, fluticasone.
B. Systemic glucocorticoids:-
Hydrocortisone, prednisolone, methylprednisolone.
5. Anti-IgE monoclonal antibody:- Omalizumab
Bronchodilators
Drugs for acute use quick relievers, use on demand as
needed to suppress symptoms


23. MOA:- Sympathomimetics
↓↓
Acts by stimulating β2-receptors
in the bronchial smooth muscle
and mast cells
↓↓
↑↑cAMP
Leading to
– Bronchodilatation
– Inhibit the release of histamine,LTC4 and LTD4 from mast
cells
– Promote mucociliary clearance
• Also they ↑K+ conductance in bronchial smooth muscle-
Hyperpolarization & relaxation of Bronchial smooth
muscle

24. • Adrenaline (nonselective sympathomimetic):-
• It produces prompt and powerful bronchodilatation by
acting through β2-adrenergic receptors.
 USES:-acute attack of asthma – 0.2–0.5 mL of 1:1000
solution is given S.C.
 Use has declined - dangerous cardiac side effects
Selective β2-adrenergic agonists:-
 They are the first-line drugs for bronchial asthma.
 They are well tolerated when inhaled.
 At high doses, they may cause tremors, tachycardia,
palpitation, hypokalemia and rarely cardiac arrhythmias
 Short acting Agents- Provides rapid relief due to fast onset
of action- effective for acute attack of asthma
 Most effective when use via inhalational route(MDI)
 Not suitable for prophylaxis

25. • Salbutamol:-
• Highest selectivity (about 10 time more) for β2 receptor
• ↑ selectivity→ use via inhalational route
• BA-50% due to High first pass metabolism in gut
• Onset of action-within 5min (inhalational route) & persist
for 3-6hrs.
• Not suitable for prophylaxis-due to short action
• SE:-Tremor, tachycardia, palpitation, hypokalaemia,
restlessness
• Prolong use-development of tolerance due to
downregulation of β2 receptor
• Terbutaline- similar action like salbutamol
• Prodrug- is bambuterol (long acting bronchodilator)
• Long acting bronchodilators:-
• They can improve lung function

26. • Drug must never be used for emergency rescue
from an acute attack-slow onset of action
• Salmeterol-
• Partial agonist + partial antagonist in β2 receptor
• Commonly use long acting drug
• Highly lipophilic
• USES:-
 Prophylaxis of asthma
 Nocturnal asthmatic attack
 Exercise induced asthma
 Formoterol-similar to salmeterol
 Full agonist at β-receptor

27. Adverse effect of inhalational β2 agonist:-
 Higher dose systemic absorption & side effect occurs due
to activation of β-adrenergic receptor
1. Muscle tremor & palpitation (most common)
2. Hypokalemia-shifts potassium into cells
3. Hyperglycemia-due to β2 mediated gluconeogenesis &
glycogenolysis
4. Tolerance:- due to down regulation of β2 receptor cause
by continuous exposure of tissue to β-agonist. this may
cause tachyphylaxis (rapidly development of tolerance)-
so,β2 agonist should not be used on regular basis
5. Throat irritation
6. Ankle edema

28. Anti-cholinergic Drug
• Drugs-Ipratropium bromide and tiotropium bromide are
atropine substitutes
• They selectively block the effects of acetylcholine in the
bronchial smooth muscles and cause bronchodilatation
• Relax the airways & prevent them from getting narrower
→this makes it easier to breath
• They may protect the airways from spasms that can
suddenly cause the airways to become
narrower(bronchospasm)
• They also ↓amount of mucus produced by airways
• Ipratropium bromide-short-acting anti-cholinergic
• Tiotropium-long-acting Anticholinergic
• Work after 1-2hr. Usually last upto-6hr

29. • Preferred in COPD and can also be used in bronchial
asthma
• Administered by inhalational route.
• In acute severe asthma- ipratropium +β2-adrenergic
agonists→produce greater and more prolonged
bronchodilatation
• Anticholinergics acts on→ larger central airways where as
sympathomimetics primarily acts on peripheral bronchioles
• Vagal tone in major reversible factor in COPD-Ipratropium
bromide and tiotropium bromide-DOC
• Use in pt. of bronchial asthma exacerbation due to β-
blocker→β2 agonist in effective due to blocked of β2
receptor
• Less effective in acute bronchial asthma
• SE:- Dryness of mouth, scatching in trachea,cough,bad taste

30.  3rd or 4th line drugs in the treatment of asthma
 Limited use due to-
 Narrow margin of safety
 Availability of better antiasthmatic drugs (selective β2-
agonists, inhaled steroids and LT-blockers)
 Theophylline:-methylated xanthine alkaloids
• MOA:- Theophylline & Aminophylline
↓↓
Inhibition of Phosphodiesterase
↓↓
↓degradation of cAMP or cGMP
↓↓
↑Intracellular cAMP→Bronchodilatation
Methylxanthines

31. • Also cause blocked of adenosine receptor
• Release of Ca++ from sarcoplasmic reticulum especially in
skeletal & cardiac muscle
• Low dose exert-Anti-inflammatory action(PG & TNF-α
inhibition )
• Pharmacological Action:-
 CNS stimulation-may cause convulsion which is treated by BZDs i.e.
diazepam
 Heart-stimulation(positive chronotropic & ionotropic )
cause tachycardia –Rx by β-blockers
 Blood vessel & bronchi-dilatation
 Kidney-diuresis
 Skeletal muscle-↑contractility
 Gastric mucosa-irritation (↑secretion of acid & pepsin)

32. • ↑BMR-↑plasma free fatty acid
• ↓release of histamine & other mediators from mast cells &
activated inflammatory cells
• Interaction of theophylline:-
Drug inhibiting Theophylline
metabolism & ↑Its plasma level
Drug increasing Theophylline
metabolism by CYP1A2 & ↓Its plasma
level
 Erythromycin
 Ciprofloxacin
 Cimetidine
 OC pills
 Allopurinol
 Phenytoin
 Phenobarbitone
 Rifampicin
 Smoking
Theophylline enhances the effects of Theophylline decreases the effects of
 Furosemide , Digitalis, Hypoglycemia
,Oral Anti-coagulants
,Sympathomimetics
Phenytoin , lithium

33. Pharmacokinetics of Methylxanthines:-
Absorption-well absorbed after oral and parenteral
administration
food delays the rate of absorption
Distribution-well distributed all over the body
cross placental and blood–brain barriers
Metabolism- in liver
Excretion- by kidney
USES:-
 1. Bronchial asthma and chronic obstructive pulmonary
disease (COPD).
 2. Apnoea in premature infants: Theophylline is used orally
or I.V. to reduce the duration of episodes of apnoea

34. Leukotriene Antagonist
• Leukotrienes→ pro-inflammatory mediators that play an
important role in pathophysiology of asthma
• LTs-derived from cell membrane
• Release following activation of mast cells & infiltrating
cells (eosinophils & neutrophils)
• LTs- potent bronchoconstrictor –cause airway edema,mucus
secretion & recruitment of eosinophils into airways
• LTs- Block by LT-receptor Antagonist, lipo-oxygenase
inhibitors, corticosteroids
• These drugs competitively block the effects of cysteinyl
leukotrienes (LTC4, LTD4 and LTE4) on bronchial smooth
muscle

35. • Montelukast & Zafirlukast:-
 Block cysteinyl leukotriene receptor(CysLT1)→Anti-
asthmatic action
 Cysteinyl leukotrienes(C4,D4,E4)-product of arachidonic
acid metabolism & release from mast cells & eosinophils
 CysLT-1 receptor-found in human airway smooth muscle &
airway macrophages & on other pro-inflammatory cells
 Montelukast:- block both CysLT-1 & CysLT-2 receptors
thereby interfering with inflammatory pathways that are
involve in pathogenesis of asthma & allergic rhinitis
 Montelukast has been shown to reduce symptoms of asthma
& allergic rhinitis & prevent acute attacks
 Uses:- prophylaxis & chronic treatment of asthma
 Allergic rhinitis & prevention of exercise induced asthma

36.  SE:-Dyspepsia, abdominal discomfort, headache, skin
rashes and rarely eosinophilia
 Pharmacokinetics:-
 Absorption-well absorbed after oral administration
 Distribution-body
 Metabolism-liver
 Excretion-urine
 Zafirlukast:-same to montelukast but longer acting
 Lipoxygenase inhibitor:-
 Zileuton:-inhibitor of the enzyme 5-lipoxygenase
Arachidonic acid
LT-A4
5-lipoxygenase Zileuton
Short duration of action
SE:-Hepatotoxicity

37. Corticosteroids
1. Systemic:- Hydrocortisone, prednisolone, methylprednisolone
2. Inhalational:- Beclomethasone, budesonide, fluticasone, etc.
 They are not bronchodilators
 MOA:-
 ↑synthesis of lipocortin→which inhibits phospholipase A2
and thereby prevent the formation of various mediators
such as PGs, TXA2, SRS-A, etc.
Advantages:-
 Complete & sustained symptomatic relief than bronchodilators
 Improve airflow
 Suppress inflammatory response to AG–AB reaction
 Reduce asthma exacerbation
 Decrease mucosal oedema.
 Retard disease progression

38. • Inhalational corticosteroids:-
• 1st line therapy for all pt. with persistent asthma
• These are glucocorticoids with high topical & low systemic
activity
• Not considered necessary for pt. With mild episodic asthma
• They have no role during acute attack or In status
asthmaticus
• Inhaled Long acting β2 agonist + Inhaled corticosteroids –
(synergistic action) improve pt. Compliance
• Safe during pregnancy
• Systemic steroids-
• use in sever chronic asthma & status asthmaticus
• Prednisolone-most commonly use steroids

39. Mast cell stabilizer
 Sodium cromoglycate and ketotifen are mast cell
stabilizers
 They are not bronchodilators.
 They inhibit the release of various mediators—histamine,
LTs, PGs, PAF, etc. by stabilizing the mast cell membrane
 They ↓bronchial hyperreactivity to some extent but
antigen–antibody reaction (AG–AB reaction) is not
affected.
 Uses:-
 long term prophylaxis in mild→moderate asthma
 Acute attack-not effective (degranulation of mast cells
with release of mediators has already occured )

40. • MOA:-
Uses:-
1. Allergic asthma:- Sodium cromoglycate -prophylactic
agent to prevent bronchospasm induced by allergens and
irritants.
• Sodium cromoglycate-not absorbed orally(inhalational
route)
2. also used in allergic conjunctivitis, allergic rhinitis, allergic
dermatitis, etc. by topical route as a prophylactic agent.

41. • Ketotifen:-
• Additional H1-blocking effect-so indicated in pt. with
multiple disorders
• Mechanism of action is similar to sodium cromoglycate,
• Orally effective but has a slow onset of action.
• Omalizumab→ recombinant DNA derived humanized monoclonal
antibody
• MOA:-
• Omalizumab prevents the binding of immunoglobulin E (IgE) to mast
cell and thus prevents mast cell degranulation.
• Uses:-
• moderate-to-severe asthma and allergic disorders such as nasal
allergy, food allergy, etc
Anti-Ig-E Monoclonal Antibody: Omalizumab

42. • It has no effect on IgE already bound to mast cells
• It is administered parenterally
• It is approved for use in patients above 12 years of age.
• SE:-
• redness, stinging, itching and induration.
• Exercise induced asthma:-
• Defined as “transient narrowing of the lower airways
following exercise in the presence or absence of clinically
recognized asthma”
• Rx-
 Inhalational Short acting β2 agonist –most effective
 Inhalational corticosteroid therapy-↓frequency & severity

43. Status asthmaticus(acute severe asthma)
• Life-threatening form of asthma -leading to pulmonary
insufficiency
• Emergency condition-required quick management & pt.
should be hospitalized
• Prolonged attack of asthma with severe intractable
wheezing may lead to hypoxemia & acidosis
• Usually precipitated by→ sever upper respiratory tract
infection
• Airway obstruction is unresponsiveness to usual therapy-
due to obstruction by mucous plag.(drug may not reach at
the site of action)

44. Rx-
 General supportive measures:-
1. Humidified oxygen(60%) inhalation
2. Acidosis-corrected by I.V. sodium bicarbonate
3. Dehydration- corrected by I.V. fluid (NS)
4. K+ supplements:- To correct hypokalemia produced by
repeated doses of salbutamol/terbutaline
 Specific treatment:-
1. Nebulized salbutamol 5 mg or terbutaline 10 mg +
ipratropium bromide 0.5 mg
2. I.V. hydrocortisone 200 mg or prednisolone 30-60mg
orally depending on the patient’s condition
3. Suitable antibiotics-if there is evidence of infection such
as chlamydia pneumoniae,mycoplasma pneumoniae,H
influenzae

45. Stepwise treatment of bronchial asthma
Oral
corticosteroids
Long acting β2
agonist
Long acting β2
agonist
Long acting β2
agonist
Inhale
corticosteroids-
High dose
Inhale
corticosteroids-
High dose
Inhale
corticosteroids-
low dose
Inhale
corticosteroids-
low dose
Short acting β2 agonist for symptomatic relief
Mild intermittent Mild persistent Moderate
persistent
Severe
persistent
Very sever
persistent

46. THANK YOU

47. Question Paper
1.Discuss briefly the therapeutic uses & common Adverse effects of:
 Salbutamol
2.Discuss the drug treatment of the following conditions:- (3M)
Acute attack of bronchial asthma
3.Discuss the pharmacological basis of :- Steroids in bronchial
asthma(4M)
4.Write drug treatment of : Status asthmaticus
5.Disuss the drug treatment of the Following:- status asthmaticus (5M)
6.Discuss the pharmacological basis of the use of the following:-(5M)
 Salbutamol in bronchial asthma
 Steroid in bronchial asthma
7.Discuss the rational of using:- Beta-2 Agonist with Methylxanthines