Asthma is a chronic inflammatory disorder of the airways that is characterized by increased responsiveness of the tracheobranchial tree to a variety of stimuli resulting in widespread spasmodic narrowing of the air passages which may be relieved spontaneously or by therapy. Cough is a protective reflex, its purpose being expulsion of respiratory secretions or foreign particles from air passages. It occurs due to stimulation of mechano or chemoreceptors in throat, respiratory passages or stretch receptors in the lungs. Act peripherally in the respiratory tract to reduce tussal impulses. They aim to control rather than eliminate cough. Many H-1 anti histamines have been conventionally added to antitussive /expectorant formulations. Antihistamines afford relief in cough due to their sedative and Anticholinergic actions but lack selectivity for cough centre. Analeptics stimulate respiration and can have resuscitative value in Coma or fainting. They stimulate respiration in sub convulsive doses, but margin of safety is narrow.

1. ANTIASTHMATICS
EXPECTORANTS
ANTITUSSIVES
RESPIRATORY STIMULANTS
BY
NADIKATLAANUSHA
M.Pharm

2. ANTI ASTHMATIC DRUGS
 Bronchodilators
 Leukotriene antagonists
 Mast cell stabilizers
 Corticosteroids
 Anti-IgE antibody
EXPECTORANTS
 Bronchial secretion enhancers
 Mucolytics
ANTITUSSIVES
 Opioids
 Nonopioids
 Antihistamines
RESPIRATORY STIMULANTS
ANUSHA NADIKATLA

3. ASTHMA
ANUSHA NADIKATLA

4. ASTHMA
• Asthma is a chronic inflammatory disorder of the airways that is
characterized by increased responsiveness of the tracheobranchial tree to a
variety of stimuli resulting in widespread spasmodic narrowing of the air
passages which may be relieved spontaneously or by therapy.
• Asthma literally means ‘Panting’.
 EXTRINSIC ASTHMA : It is mostly episodic , less prone to
Status asthmaticus.
 INTRINSIC ASTHMA : It tends to be perennial , status
asthmaticus is more common
ANUSHA NADIKATLA

5.  ASTHMA IS CHARACTERISED BY:
 Inflamation of air ways.
 Bronchial hyper-reactivity.
 Reversible airways obstruction
SYMPTOMS : Dyspnoea
Wheezings
Cough
ANUSHA NADIKATLA

6. ASTHMA MECHANISM OF ACTION
ANUSHA NADIKATLA

7. ANTIASTHMATICS CLASSIFICATION
 BRONCHODILATORS :
 β2- SYMPATHOMIMETICS: Salbutamol, Terbutaline,
Bambuterol, Salmeterol.
 METHYL XANTHINES : Theophylline,
Aminophilline,
Doxophylline.
 ANTICHOLINERGICS : Ipratropium bromide,
Thiotropium bromide.
 LEUCOTRIENE ANTAGONISTS : Montelukast,
Zafirlukast. ANUSHA NADIKATLA

8. MAST CELL STABILIZERS : Sodium cromoglycate,
Ketotifen.
 CORTICOSTEROIDS:
 Systemic : Hydrocortisone,
Prednisolone and others.
 Inhalational : Beclomethasone dipropionate, Budesonide,
Fluticasone propionate, Flunisolide,
 ANTI- IgE ANTIBODY: Omalizumab
ANUSHA NADIKATLA

9. BRONCHODILATION
BRONCHIAL TONE
BRONCHO
CONSTRICTION
cAMP
AC
PDE
ATP
AMP
β-Agonist
Theophylline
+
-
-
Adenosine
TheophyllineMuscarinic Antagonists
ACH
+
-
+
-
BRONCHODILATORS MECHANISM
ANUSHA NADIKATLA

10. BRONCHODILATORS
 β2-SYMPATHOMIMETICS:
 SALBUTAMOL (ALBUTEROL):
 Inhaled Salbutamol: It bronchodilation with in 5mins
and the action lasts for 2-4hrs.
 DOSE: 100-200 µ gm.
 ADVERSE EFFECTS: Muscle tremors, palpitation, restlessness,
nervousness, throat irritation, ankle edema.
 Oral salbutamol :
• oral bio availability is 50%.
• Duration of action is 4-6hrs.
• Side effects are more frequent.
Dose:2-4 mg.
ANUSHA NADIKATLA

11.  TERBUTALINE:
• It is similar to salbutamol in properties and use.
• Inhaled salbutamol and terbutaline causes quick reversal or bronchospasum.
• Ragular use of these drugs does not reduce bronchial hyper reactivity: may
even worsen it.
• β2 agonist inhalers are restricted to symptomatic relief of wheezing.
ANUSHA NADIKATLA

12.  BAMBUTEROL:
• It is bicarbamate ester prodrug of terbutaline
• It is hydrolised by pseudo choline esterase to release the active drug over
24hrs.
• It is indicated in chronic bronchial asthma in a single evening dose of
10-20mg.
 SALMETEROL:
• It is first long acting selective
β2 agonist with slow on set of action.
• It is more lipophillic which
probably accounts for its longer action.
ANUSHA NADIKATLA

13.  FORMOTEROL:
• It has faster onset of action compared to salmeterol.
• It is used on a regular
morning-eveningschedule for round the
clock bronchodilation.
• It acts for 12hrs when inhaled.
 EPHEDRINE:
• It has α+β1+β2 actions.
• It causes mild slowly developing
bronchodilation lasting for 3-5hrs.
• Because of low efficacy and frequent
side effects it is not preffered now.
ANUSHA NADIKATLA

14. METYHL XANTHINES
 MECHANISM OF ACTION:
ANUSHA NADIKATLA

15.  PHARMACOLOGICAL ACTIONS:
 CNS:
• Stimulate the CNS increasing alertness.
• Stimulation of vagal, respiratory and vasomotor centers.
 CVS:
• Directly stimulate heart.
• Increase in force of myocardial contraction.
• +ve chronotropic and inotropic actions.
• Tachycardia is more common.
• High doses : Cardiac arrhythmias.
ANUSHA NADIKATLA

16.  SMOOTH MUSCLE :
• Relaxation of smooth muscles.
• Most prominent effect is exerted on bronchi especially in asthmatics.
 KIDNEYS:
• Methyl xanthines are mild diuretics.
• They inhibits tubular reabsorption of Na+ and water.
 SKELITAL MUSCLE:
• Theophylline enhances diaphramatic contractility in therapeutic
concentrations.
 STOMACH:
• Enhanced secretion of acid and pepsin.
• Theophilline acts as gastric irritant.
ANUSHA NADIKATLA

17.  THEOPHYLLINE:
MECHANISM OF ACTION:
• Inhibition of phosphpdiesterase which degrades cyclic nucleotides
Intracellularly.
• Blockade of adenosine receptors.
ANUSHA NADIKATLA

18. PHARMACOKINETICS:
• It is well absorbed orally.
• Only 10% is excreted unchanged in urine.
• t 1/2 : 7-12hrs.
ADVERSE EFFECTS :
• CNS toxicity in children.
• Gastric pain (oral).
• Rectal inflammation (suppositories).
• Ventricular arrhythmias.
INTERACTIONS:
• Plasma conc. of theophylline is decreased by rifampicine ,
Phenytoin and phenobarbitone (Induces p450 enzyme).
• Plasma conc. of theophylline is increased by erythromycin,
Clarithromycin and ciprofloxacin(Inhibits p450 enzyme).
ANUSHA NADIKATLA

19.  ANTICHOLLINERGICS:
• Atropinic drugs cause bronchodilation by blocking cholinergic
constrictor tone.
 IPRATROPIUM BROMIDE:
• Patients with asthmatic bronchitis , COPD and psychogenic asthma
respond better to anticollinergics.
 DOSE: 2-4 puffs 6 hourly.
• Combination of inhaled ipratropium
with β2 agonist produces more
marked and long lasting bronchodilation.
 ADVERSE EFFECTS : Dry mouth,
• Systemic anticholinergic effects such as
urinary retention and constipation.
ANUSHA NADIKATLA

20. LEUKOTRIENE ANTAGONIST
MECHANISM OF ACTION:
ANUSHA NADIKATLA

21.  MONTELUKAST:
• It antagonises cys LT1 receptor mediated bronchoconstriction.
• Bronchodilation , Reduced sputum eosinophill count ,
Suppression of bronchial inflammation,
hyperreactivity occur in asthma patients.
• Cys LT1 receptors are effective in
aspirin induced asthma.
 ADVERSE EFFECTS : Abdominal pain,
head-ache, Diarrohoea, Dizziness, Acute
hepatitis.
ANUSHA NADIKATLA

22. ANUSHA NADIKATLA

23.  MAST CELL STABILIZERS:
 KETOTIFEN:
• It is an antihistaminic drug.
• It is not a bronchodilator but produces sedation
 PHARMACOKINETICS:
• It is absorbed orally.
• Bio availability is 50% due to first pass metabolism.
• t1/2 is 22hrs.
 ADVERSE EFFECTS: Sedation.
Dry mouth,
Dizziness,
Nausea,
Weight gain.
ANUSHA NADIKATLA

24.  CORTICOSTEROIDS:
• Glucocorticoids are not bronchodilators.
• They reduce broncheal hyperactivity, mucosal edema.
• They improve air flow, reduce asthma and may influence air way
remodeling.
 SYSTEMIC CORTICOSTEROIDS:
 HYDROCORTISONE
 PREDNISOLONE
• Severe chronic asthma :
start with prednisolone 20-60mg daily.
• Status asthmaticus :
• This is otherwise called acute asthma exacerbation.
• Start with high dose of a rapidly acting
i.v. glucocorticoid which generally acts in 6-24 hrs.
ANUSHA NADIKATLA

25.  INHALED CORTICOSTEROIDS:
• These are glucocorticoids with typical and low systemic activity.
• Inhaled steroids suppress bronchial inflammation.
 BECLOMETHASONE DIPROPIONATE:
• Intra nasal spray is effective in
perennial rhinitis.
 BUDESONIDE:
• It is non halogenated gluco corticoid
with high topical systemic activity.
 ADVERSE EFFECTS: Nasal irritation,
sneezing,
crusting,
Itching of throat.
ANUSHA NADIKATLA

26.  FLUTICASONE PROPIONATE:
• It is Inhaled glucocorticoid.
• High potency
• Longer duration
• It is having negligible oral bioavailability.
 DOSE:100-250µ gm.
ANUSHA NADIKATLA

27. ANTI IgE ANTIBODY:
 OMALIZUMAB:
• It is a humanized monoclonal anti-IgE anti body.
• It is effective in patients with allergic asthma and allergic rhinitis.
• Administered i.v (or) s.c it neutralises free IgE in circulation with out
activating mast cells and other inflammatory cells.
 Duration: 2-4 days.
 Toxicity: Injection site reactions.
ANUSHA NADIKATLA

28. COUGH
• Cough is a protective reflex, its purpose being expulsion of respiratory
secretions or foreign particles from air passages.
• It occurs due to stimulation of mechano or chemoreceptors in throat,
respiratory passages or stretch receptors in the lungs.
• Cough may be : Use ful ,Useless.
 Useful-Productive cough:
• This cough serves to drain the air way.Its suppression is not desirable,
may even be harmful.
 Useless-Non productive cough:
This cough should be suppressed.
ANUSHA NADIKATLA

29.  EXPECTORANTS(MUCOKINETICS):
• Expectorants are drugs believed to increase bronchial secretion or reduce its
viscosity,facilitating its removal by coughing.
CLASSIFICATION
 BRONCHIAL SECRETION ENHANCERS : Sodium citrate
Potassium citrate
potassium iodide
guiphenesin
balsum of tolu
vasaka
ammonium chloride
 MUCOLYTICS : bromhexine
ambroxol
acetyl cysteine
carbocisteine
ANUSHA NADIKATLA

30.  BRONCHIAL SECRETION ENHANCERS:
 SODIUM & POTASSIUM CITRATE:
• They are considered to increase bronchial secretion by salt action
 POTASSIUM IODIDE:
• It is secreted by bronchial glands and can irritate the air way mucosa
Prolonged use can affect thyroid function and produce iodism.
It is rarely used now.
ANUSHA NADIKATLA

31.  GUAIPHENESIN , VASAKA , TOLU BALSUM:
• These are plant products which are
supposed to enthnce bronchial secretion and
mucociliary function while being
secreted by tracheobronchial glands.
 Adverse effects: G.I.irritation,
decreases viscosity of sputum.
 AMMONIUM CHLORIDE:
• These are nausating – reflexly
increase respiratory secretions.
 Adverse effects: nausea , acidosis, vomiting.
 Contra indication: In hepatic and renal impairment.
 Use : Metabolic alkalosis.
ANUSHA NADIKATLA

32.  MUCOLYTICS
 BROMHEXINE:
• It is a derivative of alkaloid vasicine obtained from Adhatoda vasica.
• It is potent mucolytic and mucokinetic, capable of inducing thin
copious bronchial secretion.
• It depolymerises mucopoly saccharides directly as well as by
liberating lysosomal enzymes.
• The network of fibers in tenacious sputum is broken.
• It is particularly used when mucous plugs are present.
 ADVERSE EFFECTS : Rhinorrhoea
Lacrimation
Gastric irritation
Hypersensitivity
 DOSE: 8mg.
ANUSHA NADIKATLA

33.  AMBROXOL:
• It is metabolite of bromhexine.
• DOSE:15-30mg.
 ACETYL CYSTEINE:
• It opens di sulfide bonds in muco
proteins present in sputum makes it less viscid.
• It has to be administered directly
in to the respiratory tract.
ANUSHA NADIKATLA

34.  CARBOCYSTEINE:
• It liquefies viscid sputum in the
same way as acetyl cysteine.
• It is administered orally .
• Some patients of chronic bronchitis
have been shown to benefit.
 ADVERSE EFFECTS: G.I.irritation
Rashes.
ANUSHA NADIKATLA

35. ANTITUSSIVES
• They act on CNS to raise the threshold of cough centre
(or)
Act peripherally in the respiratory tract to reduce tussal impulses.
• They aim to control rather than eliminate cough.
• Antitussives should be used for dry unproductive cough or if
cough is unduly tiring, disturbs sleep or is hazardous.
ANUSHA NADIKATLA

36. ANTITUSSIUE CLASSIFICATION
OPIOIDS : Codeine , pholcodeine.
NONOPIOIDS: Noscapine
Dextromethorphan
Chlophedianol.
ANTIHISTAMINES : Chlorpheniramine
Diphenhydramine
Promethazine.
ANUSHA NADIKATLA

37. OPIOIDS
 CODEINE: It is an opium alkaloid.
• It is qualitatively similar to but less potent than morphine.
• It is more selective for cough centre and is treated as standard
antitussive.
• It suppresses cough for about 6 hrs.
• Antitussive action action of codeine is
blocked by Naloxone indicating that it is
exerted through opioid receptors in brain.
ANUSHA NADIKATLA

38.  ADVERSE EFFECTS: Constipation
respiratory depression
drowsiness
driving may be impaired.
 CONTRAINDICATION : Codeine is contraindicated in asthmatics
and in patients with diminished respiratory reserve.
 DOSE: 10-15mg.
ANUSHA NADIKATLA

39.  PHOLCODEINE:
• It has particularly no analgesic or eddicting property.
• It is similar in efficacy as antitussives to codeine.
• It is a long acting opioid drug.
• Its acts for 12hrs.
 DOSE: 10-15mg.
ANUSHA NADIKATLA

40. NONOPIOIDS
 NOSCAPINE:
•It is an opium alkaloid of benzo isoquinolone series.
•It depresses cough but has no narcotic ,
analgesic or dependence inducing properties.
•It is nearly equipotent antitussive as codeine.
•Especially useful in spasmodic cough.
 ADVERSE EFFECTS:
•It can release histamine and produce
bronchoconstriction in asthmatics.
•Head-ache
•Nausea.
 DOSE:15-30mg.
ANUSHA NADIKATLA

41.  DEXTROMETHORPHAN:
• It is a synthetic compound.
D-isomer Antitussive action.
L-isomer Analgesic action.
• It does not depress mucocilliary function of the airway mucosa.
• It is particularly devoid of constipating and addicting actions
• The antitussive action lasts for 6hrs and is not blocked by naloxone.
 ADVERSE EFFECTS: Dizziness
nausea
G.I disturbances
confusion
drousynes
ataxia.
 DOSE :10-20mg.
ANUSHA NADIKATLA

42. ANTIHISTAMINES
• Many H-1 anti histamines have been conventionally added to antitussive
/expectorant formulations.
• Antihistamines afford relief in cough due to their sedative and
Anticholinergic actions but lack selectivity for cough centre.
• They have no expectorant property , may even reduce secretions by Anti
cholinergic action.
• They have been specially promoted for cough in respiratory allergic states.
ANUSHA NADIKATLA

43. ANTIHISTAMINES:
CHLORPHENIRAMINE PROMETHAZINE
DOSE : 2-5mg. DOSE:15-25mg.
DIPHENHYDRAMINE
DOSE:15-25mg.
ANUSHA NADIKATLA

44. RESPIRATORY STIMULANTS
(ANALEPTICS)
• Analeptics stimulate respiration and can have resuscitative value in
Coma or fainting.
• They stimulate respiration in sub convulsive doses,
but margin of safety is narrow.
ANUSHA NADIKATLA

45. Respiratory stimulants are employed under following situations:
• As an expedient measure in hypnotic drug poisoning untill mechanical
ventilation is instituted.
• Suffocation on drowning, acute respiratory in sufficiency.
• Apnoea in premature infant.
• Failure to ventilate spontaneously after general anaesthesia.
ANUSHA NADIKATLA

46.  DOXAPRAM
• It is a short acting respiratory stimulant.
• It acts by promoting excitation of central neurons.
• At low doses it is more selective for the respiratory centre than other
analeptics.
• Respiration is stimulated through carotid and aortic chemoreceptors
ANUSHA NADIKATLA

47. • Falling B.P. raises
• Doxapram is excreted rapidly.
• Continuous I.V. infusion of doxapram has been found to abolish
episodes of apnoea in the premature infant not responding to
Theophilline.
 ADVERSE EFFECTS: Nausea
Coughing
Restlessness.
 DOSE : 40-80mg I.M. (or) I.V.
 USE : Treats acute respiratory failure.
ANUSHA NADIKATLA

48. REFERENCES
• Text book of PHARMACOLOGY by RANG AND DALE’S
(pg.no. : 361-364)
• Essentials of MEDICAL PHARMACOLOGY by KD Tripathi
(pg.no. : 213-226)
• Text book of PHARMACOLOGY by LIPPINCOTTS
(pg.no. : 319-328)
• Basic & clinical PHARMACOLOGY by LANGE
(pg.no. : 339-356)
• Text book of PHARMACOLOGY by S.D.SETH
(pg.no. : 181-184)
• CLINICAL PHARMACY & THERAPEUTICS by -WALKER
-WHITTLESIA
` (pg.no. :367-368) ANUSHA NADIKATLA

49. ANUSHA NADIKATLA