Pharmacology

1. PHARMACOLOGY OF DRUGS ACTING ON
RESPIRATORY SYSTEM
Mr. Shaikh Akhil. M.
M.Pharm(Pharmacology)
Assist. Professor
Balwantrao Chavan College of Pharmacy, (B.Pharm)
Naigaon (BZ) Dist. Nanded

2. CONTENT
 Expectorants & Antitussives
 Nasal Decongestants
 Respiratory Stimulants
 Antiasthmatic drug
 Drug used in the management of COPD

5. EXPECTORANT AND ANTITUSSIVES
 Cough- Protective reflex.
 Intended to remove irritants and accumulated secretion.
 Occurs due to stimulation of- mechanoreceptor or chemoreceptor in
throat or respiratory path stretch receptor in lungs
 Types of cough:
1. Non productive cough: Useless and should be suppressed. .
2. Productive cough: helps to clear the airway, suppression is harmful
may leads to infection
 On the basis of duration
 1. acute – less than 02 to 3 weeks
 Chronic – more than 3 weeks

6.  Causes of cough
 Acute- infection of upper respiratory tract- cold, sinus
infection. Pneumonia,whooping cough.
 Chronic- environmrntal iritants, smoking, chronic bronchitis,
dust pollen, pet dander, industrial chemical, pulmonary T.B.
 Classification drug for cough
A. Pharyngeal demulcents: logenges, glycerine,syrup,
liquorice
B. Expectorants(Mucokinetics):
1. Secretion enhancer: sodium and potassium citrate,
potassium iodide, vasaka, ammoniumchloride.
2. Mucolytics: bromhexine, acetylcysteine, carbocysteine,
ambroxol

7. C. Antitussives (cough center suppressants):
• Opioids-codeine, Pholcodeine, ethyl morphine
• non opioids- noscapine, dextromethorphan,
• Antihistaminics- chlorpheniramine, diphenhydramine.
D. Adjuvant antitussive- bronchodilators-
salbutamol, terbutaline

9. PHARYNGEAL DEMULCENT MOA
 Demulcent- demulcere to caress soothingly.
 Produce protective soothing effect on inflamed mucosa.
 Increase flow of saliva- produce soothing effect on mucosa.
 Reduce afferent impulses from irited mucos.
 Dry non productive cough got reduced by demulcent.
 Symptomatic relief- by decrease sensation arising from throat
 Known as- mucoprotective – act for – less than -30 minutes
 Ex lozenges, glycerine, honey, syrup
Explanation
Irritant throat afferent nerve brain cough centre
cough

11. EXPECTORANTS ( MUCOKINETIC )MOA
Ex. Secretion enhancer: sodium and potassium citrate,
potassium iodide, vasaka, ammonium chloride.
Mucolytics: Bromhexine, Carbocysteine, Ambroxol
1. Expectorant- To drive from the chest.
• Action given by- by increasing bronchial secretion
• Decrease viscosity the help removal by coughing
• Expectorant increase secretion by –
• Direct stimulation- increase secretion when inhaled by
steam
volatile oil,
• Reflex expectorant – given orally and these are gastric
irritant and increase respiratory secretion (cause vomiting)

12. Mucolytics- respiratory secretion is watery
• These agents break the thick tenacious sputum.
• Lowers viscosity of sputum.
• Open disulphide bond in mucoprotein of sputum, so the sputum
becomes
• So the sputum comes out easily with less effort
• Side effects are nausea, vomiting and bronchospasm.

15. ANTITUSSIVES (COUGH CENTER
SUPPRSSANTS)
 Produce their antitussive effect on CNS by
-Inhibits cough reflex by suppressing cough center in medulla.
-Act peripherally in respiratory center – decrease tussal impulse.
 They should use only for- non productive cough or it is
problematic in sleep.
Codeine:
• Cough center suppressant effects.
• Cause mild CNS depression.
• Constipation by decreasing intestinal movements.
• Should be avoided in children and asthmatics.
• Administered orally, mild analgesic, less addiction.

16. ANTITUSSIVES…
Pholcodeine:
• Similar action as codeine
• No analgesic.
• No addiction liability.
• Administered orally.
• Has long duration of action.
Noscapine:
• Opium alkaloid.
• Potent antitussive effect.
• Useful in spasmodic cough.
• No analgesic effect.
• Does’t cause constipation, CNS depression or addiction
• Side effects are nausea and headache.

17. ANTITUSSIVES…
Dextromethorphan:
1. Centrally acting antitussive agent.
2. No analgesic property.
3. Does’t cause constipation and addiction; mucuciliary function is
not affected.
Antihistamines:
Diphenhydramine, chlorpheniramine, promethazine are useful in
cough because:
1. Sedative, antiallergic, anticholinergic effects.
2. Produce symptomatic relief in cold and cough associated with
allergic condition of respiratory tract.

21. NASAL CONGESTANT

22. NASAL DECONGESTANT
Nasal decongestant – alpha 1 agonist- cause vasoconstriction
Example – 1) orally – Ephedrine, pseduephedrine, phenylephrine
2)Nasal spray – oxymetazoline, xylometazoline, naphazoline
MOA-
• They stimulate alpha 1 receptor in blood vessels ofnasal mucosa.
• They cause vasoconstriction of nasal mucosa- shrinkage and decrease
mucus
• Thus they decrease congestion and resistance to air low through nose
• They also reduce nasal secretion- stop congestion
• Adverse effect-
• Orally – insomnia, tremors and irritability
• Topical agent- nasal irritation

25. RESPIRATORY STIMULANT OR
ANALEPTICS
 They stimulate respiration – treat respiratory failure
 Respiratory stimulants- increase to breathing
 Stimulate CNS – increase in respiratory rate and tidal volume
 Ex. Doxapram, nikethamide, theophylline, caffeine.
 Useful in- emphysema, asthma, chronic bronchitis, coma
 They have low safety margine- may produce convulsion ( high
dose)

26. DOXAPRAM
 Act on brainstem and spinal cord- increase activity of
medullary respiratory and vasometer centers
 Given as I.V. Infusion
 ADR- nausea, cough, restlessness, hypertension, tachacardia
 Useful in situation of-
 Respiratory depression due to hypnotic drug poisoning
 Failure to ventilate after genral anaesthesia
 MOA
 Respiratory stimulant --- increase chemoreceptor --- increase
CNS --- Increase H.R. + breathing –relax bronchi

27. BRONCHIAL ASTHMA
 Impairment of airflow due to construction of
bronchial smooth muscle (bronchospasm)
 Swelling of bronchial mucus secretion.
Factors:
 Allergy, infection, psychological factors,
 Air way obstruction may be due to release of
the mediators from sensitized mast cells in
the lungs.

28. BRONCHIAL ASTHMA…
 Acute asthma
 Chronic asthma
 Status asthmaticus (acute severe asthma)

29. DRUGS FOR BRONCIAL ASTHMA…
 Histamine
 5-HT (serotonin)
 Prostaglandins
 Leukotriens (LTC4 and LTCD4)
 Protease
 Platelet activation factor (PAF)
 Bronchial asthma may be episodic or
chronic.

30. CLASSIFICATION OF ANTIASTHMATIC
DRUGS
1. Bronchodilators
A. Sympathomimetics:
i) Selective B2-adrenergic agonists:
salbutamol, terbutaline (short acting), salmeterol,
and formetrol (long acting).
ii) Non selective : adrenaline
B. Methylxanthine: theophylline, aminophylline,
etophylline

31. CLASSIFICATION OF ANTIASTHMATIC
DRUGS….
C. Anticholenergics: Ipratropium bromide, tiotropium
bromide.
2. Leukotriene receptor antagonist: zafirlukast, montelukast.
3. Mast cell stablizers: sodium chromoglycate, nedochromil
sodium, ketotifen.
4. Glucocorticoids:
a) Inhaled glucocortecoids: beclomethasone, budesonide, fluticasone.
b) Systemic glucocortecoids: hydrocortisone, prednesolone,
methylprednesolone.
5. Anti-Ig-E monoclonal antibody: omalizumab.

32. BRONCHODILATORS
 Adrenaline: produce prompt and powerful
bronchodilation by acting through β2
adrenergic receptors.
 Useful in acute attack of asthma (0.2-0.5 ml
of 1:1000 solution given s.c.
 Its use decline due to serious cardiac side
effects.

33. MECHANISM OF BRONCHODILATION…

34. BRONCHODILATORS…
 Selective β2- adrenergic agonists
 The first line drugs for bronchial asthma.
 Well tolerated when inhaled.
 At high doses may cause tremor,
tachycardia, palpitation, hypokalaemia.

35. BRONCHODILATORS…

36. BRONCHODILATORS…
Methylxanthines:
 Their uses are markedly reduced due to their narrow therapeutic index
and available of better antiathmatic drugs.
 Methylxanthine are third or fourth line drugs in the treatment of asthma.
 Methylxanthines are well absorbed after oral and parenteral
administration.
 Food delays the rate of absorption of theophylline, well distributed, cross
placenta & BBB, metabolised in liver and excreted in urine.

37. METHYLXANTHINE
BRONCHODILATORS…
 Theophylline: poorly water soluble, hence not
suitable for injection, available for oral
administration.
 Aminophylline: water soluble but highly irritant.
Administered orally or slow i.v.
 Etophylline: given by oral, i.m., i.v. routes.
 Adverse effects: have narrow margin of safety,
tachycardia, palpitation, hypotension, death due to
cardiac arrhythmias.

38. MECHANISM OF ACTION OF
METHYLXANTHINE

39. ADVERSE EFFECTS OF
METHYLXANTHINE

40. DRUG INTERACTIONS WITH
METHYLXANTHINES
Drug interactions
 Phenytoin/ rifampicin/phenobarbitone x
theophylline
 Cimetidine/ciprofloxacin/erythromycin x
theophylline.
 Uses:
 Bronchial asthma and COPD
 Premature apnoea in infants.

41. DRUG INTERACTIONS

42. ANTICHOLINERGICS
 Ipratopium bromide and tiotropium bromide are
atropine substitutes.
 Selectively blocks the effects of Ach in bronchial
smooth muscle and cause bronchodilation.
 Slow onset of action and are less effective.
 These drugs are preferred in COPD.
 Administered by inhalation route.
 Combination with B2- adrenergic agonist have
better effects.

43. LEUKOTRIENE ANTAGONISTS
 Example- Montelukast,Zafirlukast
 Cysteinyl leukotrienes produced by – macrophage, eosinophils
and inflammatory cells in lungs- causes bronchial asthma.
 MOA
 They competitively antagonize cysLT1 receptor mediated
bronchoconstriction, increased airways mucus secretion, increased
vascular permeability and requirement of eosinophils.
 Antagonism result into –bronchodilation, secretion, decrease
inflammation, decrease eosinophil count and reduction of
hypersensitivity = Asthma

44. Leaukitriene cys-LT1 receptor
bronchospasm, Inflammation
Mucosal oedema,
increase respiratory mucus
, drug bind cys- LT1 receptor ( Montelukast)
Decrease bronchospasm,
Decrease inflammation mucosal oedema,
decrease respiratory mucus

45. MECHANISM

46. MAST CELL STABILIZERS
 Sodium chromoglucate, nedocromil sodium,
kitotefen.
 They are not bronchodlators.
 Inhibits release of various mediators-
histamine, LTs.
 Stabilizes the mast cell membrane.
Sodium chromoglycate: is not effective orally
as it poorly absorbed from gut, given by
inhalation route.

47. MAST CELL STABILIZERS….
Uses of sodium chromoglycate
1. As prophylactic agent to prevent
bronchospasm induced by allergens and
irritants.
2. Can be used in allergic conjunctivitis,
allergic rhinitis, allergic dermatitis, etc.
3. Used by topical route as prophylactic agent.

48. MAST CELL STABILIZERS…
 Nedocromil sodium: mechanism of action
pharmacological effects are similar to sodium
chromoglycate.
 Approved for use in patients above 12 years
of age in bronchial asthma.
 Ketotefen: mechanism is similar to sodium
chromoglycate, has H1-blocking effect. It is
orally effective but has a slow onset of action.

49. MECHANISM

50. GLUCOCORTICOIDS
Systemic: hydrocortisone,prednisolone, methylprednisolone, and
others
Inhalational: beclomethasone, budesonide and fluticasone.
 Glucocoticods – decrease inflammatory cytokines production
 Inhibit infiltration of eosinophilic and lymphatic cell in lungs
 Inhibit bronchial hyperactivity, mucosal oedema and
inflammmatory response to AG:AB tection.
 Have antiallergic, antiinflammatory and immunosuppressant
effects.

51. GLUCOCORTICOIDS…
 Decrease mucosal oedema.
 Reduced bronchial hyperreactivity.
 Do not have direct bronchodilating effect but potentiates the
effects of B-adrenergic agonists
 They have no role during acute asthma attack
 They have synergistic action used in COPD and bronchial
asthma.
 Adverse effects: gastric irritation, Na+ and water retention,
hypertension, muscle weakness, osteoporosis, HPA-axis
suppression etc.

52. ANTI-IG-E ANTIBODY
Omalizumab: prevents binding of IgE to mast cell,
thus prevent mast cell de-granulation.
 It has no effects on IgE already bound to mast
cells.
 Administered parenterally.
 Used in moderate to severe asthma and allergic
disorders such as nasal allergy, food allergy, etc.
approved for use in patient above 12 years of age.

53. INHALATIONAL DEVICES
 Metered dose inhaler (MDI)- used with
spacer device.
 Dry powder inhalers- spinhaler and
rotahaler
 Nebulizers- useful in acute severe asthma,
COPD, and children.

54. TREATMENT OF ACUTE SEVERE
ASTHMA
 Humidified oxygen
 Nebulized β2- adrenergic agonist (salbutamol 5
mg/terbutaline 10 mg) + anticholinergic agents
(ipratropium bromide 0.5 mg).
 Systemic glucocorticoids: i.v. hydrocortisone 200
mg stat followed by 30-60 mg prednisolone/day.
 I.V. fluid to correct dehydration.
 K+ and sodium bicarbonates supplements.
 Antibiotics.

55. DUGS TO BE AVOIDED IN ASTHMA
 NSAIDs
 β-adrenergic blockers.
 Cholinergic agents.

56. COPD- CHRONIC OBSTRUCTIVE PULMONARY
DISORDER/DISEASE
• Air flow resistance which is not reversible
• COPD include – chronic bronchitis, chronic broncholitis
( small airway disease)
• Emphysema- damaged air sac in lungs
• COPD associated with – impaired nutrition, weight loss and
skeletal muscle dysfunction, obstruction of air way for long time
• Risk factor- tobacco smoking, fuel fire smoke, air pollution,
industrial exhaust fumes, working in coal mines, other respiratory
infection.

59. Pathophysiology –
• Enlargement of mucus secreting gland
• Increase no. Of goblet cells in larger airway.
• Loss of elastic tissue surrounding the smaller airway.
• Inflammation and fibrosis in airway wall and mucus in airway
lumen
• Management of COPD
• Symptoms- Peristant cough, sputum, breathlessness and other
feature like= asthma , bronchitis and T.B.

60. TREATMENT OF COPD
 Inhaled bronchodilator-B2 sympathomimetic, anti cholinergic
 Inhaled glucocorticoid
 Oxygen inhalation
 Prophylatic antibiotic- when triggered by bacteria virus
 Prevention of dehydration
 Physiotherapy and pulmonary rehabilation
 Mucolytic agent- need long term treatment
 Avoidance of respiratory irritant- smoking dust, pillution

61. THANK YOU