Presentation gives basic information about the drugs used for respiratory system.

1. Drugs Acting on
respiratory system
-Hemanth.KG
AL-AMEEN COLLEGE OF PHARMACY
BANAGLORE.

2. TYPES OF RESPIRATORY DISEASES
■ RESTRICTIVE RESPIRATORY DISEASE
Condition which makes it difficult to get the air into
lungs(INSPIRATION), and expiration is not affected.
Ex: Myasthenia gravis, Polio,Flail chest(broken ribs).
■ OBSTRUCTIVE RESPIRATORY DISEASE
Condition which makes it difficult to push the air outside
the lungs(EXPIRATION).
Ex:Asthma,Chronic bronchitis & Emphysema(COPD).

3. ASTHMA

5. Definition
Bronchial asthma is the respiratory
disease characterized by difficult
breathing with wheezing(whistling type of
respiration), caused due to bronchiolar
smooth muscle constriction leading to
obstruction of air passage.
■ The obstruction is further exaggerated by the
edema of mucous membrane
i.e.,accumulation of mucous in the lumen of
bronchioles.

6. ■ During the attack ,there is difficulty in both
inspiration and expiration. Bronchioles have
inherent tendency to dilate during inspiration
and constrict during expiration.
■ Due to asthma condition(i.e.,constricted
bronchioles) greater effort is needed during
expiration causing compression of chest.

7. TYPES
1. Extrinsic(Allergic,Atopic) asthma.
■. This is the most common type of asthma. It usually begins in
childhood or in early adult life.
■. Patients of this type of asthma have personal and/or family
history of allergic diseases.
■. Hyper-sensitivity(Type-1) to various extrinsic antigenic
substances or‘allergens’ is usually present in these cases.
Most of these allergens cause ill-effects by inhalation e.g.
House dust,pollens, moulds etc.

8. 2.Intrinsic Asthma(idiosyncratic, non-atopic) asthma.
■. This type of asthma develops later in adult life with no family history of
allergy and normal serum levels of IgE.
■.Most of these patients develop typical symptom-complex after an
upper respiratory tract infection by viruses. Associated nasal polypi
and chronic bronchitis are commonly present.
■.There are no recognisable allergens but about 10% of patients
become hypersensitive to drugs,most notably to small doses of aspirin
(aspirin-sensitive asthma).

9. 3. Status asthmaticus(severe acute asthma)
■ Condition where an acute attack is severe , persistent and
does not respond to standard treatment.
■ Most common site of infection is upper respiratory tract.

10. PROGRESS OF HYPERSENSITIVITY
TYPE-1
■ The mast cells(in lungs) and inflammatory cells(neutrophil,
macrophage,monocyte, eosinophil, or basophil ) are activated, as a result
of initial reaction they produce various chemical mediators by the following
processes:
1. Degranulation (neutrophil,eosinophils,basophils), immediately release:
Histamine,Protease enzymes,TNF-α.
2. Release of phospholipids(Arachidonic acid) followed by mediator(PGG2)
synthesis: Prostaglandins(PGs), Leukotrienes(LKs), Platelet activating
factor(PAF)
3. Release of Cytokines: TNF-α, Interleukins(ILs)
■. THESE MEDIATORS TOGETHER CONSTRICT BRONCHIAL SMOOTH
MUSCLE,CAUSE MUCOSAL EDEMA &PRODUCE VISCID SECRETIONS

11. COPD
Chronic Obstructive Pulmonary disease

12. ■COPD is characterized by “Air flow resistance that is not reversible”,it includes:
1.Emphysema- Respiratory disease in which the lung tissues are extensively damaged.
2.Chronic bronchitis- It is a progressive inflammatory disease resulting from prolonged
irritation of bronchial epithelium
Casuses:
3.Cigarette smoking
4.Exposure to oxidant gases
5.Untreated bronchitis

13. CLASSIFICATION

14. • SYMPATHOMIMETICS
1. Salbutamol(Albuterol)
■. It is a highly selective ß2 agonist.
■. It is delivered mostly through pressurised metered dose inhaler
such that selectivity is increased.
■. Produces bronchodilation within 5mins and action lasts for 2-
4hours.
■. Pharmacokinetics- Resistant to COMT and has longer duration of
action and undergoes metabolism in gut wall.
■. Oral Bioavailability – 50% and action lasts for 4-6 hours

15. ■ ADR- Restlessness, palpitation, nervousness,
throat irritation, hypokalemia, ankle edema.
■ Dose: 2-4mg oral, 0.25-0.5mg i.m/s.c, 100-
200micro gm by inhalation.
2. Terbutaline
■. It is similar to salbutamol in properties and uses

16. 3. Bambuterol (Prodrug of Terbutaline).
■ It is hydrolysed by psuedo cholinesterase to give active drug.
■ Reversible inhibition of enzyme occurs on the basis of dose.
■ Uses: Nocturnal and chronic asthma as single evening dose
of 10-20mg oral.
4. Formoterol
■ It is a long acting selective ß2 agonist .
■ Duration of action:12hrs
■ Has a faster onset of action compared to salmeterol.
■ Used as round the clock(morning and evening) bronchodilator

18. • METHYL XANTHINES
■ THEOPHYLLINE , CAFFEINE , THEOBROMINE.
■ These are used more often in COPD.
■ The above mentioned drugs are naturally occurring
methylated xanthine alkaloids.

19. Pharmacological actions
1. CNS: Caffeine and theophylline are CNS stimulants.
Caffeine is more active than theophylline in producing the following effects
■. Caffeine(150-250mg)-
1. Euphoria,alertness, dullness vanishes and thinking become
clearer.
2. Tends to improve performance and motor activity.
■. Higher doses- Nervousness, restlessness, panic ,insomnia and
excitement.

20. ■ Still higher doses- Delirium,tremors, and convulsions.
■ Theophylline produce these adverse effects at higher doses
and is more toxic than Caffeine.
■ These alkaloids also stimulate vagal,respiratory and
vasomotor centres
■ Vomiting at high doses is due to both gastric irritation and
CTZ stimulation.
2. CVS:
■ +Ve Inotropic effect
■ Tachycardia(Theophylline) due to cardiac action but
bradycardia(Caffeine) due to vagal stimulation.

21. ■ C.O is increased, at higher doses cardiac arrhythmias may
occur.
■ Theophylline-Dilate the systemic blood vessels including
coronaries by direct action.
■ Caffeine-Constrict the cranial vessels ,hence used in
treatment of migraine (Dilated cranial nerves)
■ BP-Variable and unpredictable,
1. Vasomotor centre & direct cardiac stimulation -Raise in BP
2. Vagal stimulation & direct vasodilation- lowers the BP
■. Systolic BP -increases , Diastolic BP- Decreases

22. 3. SMOOTH MUSCLES:
■ They are relaxed,most prominently bronchi, especially in
asthmaticus
■ THEOPHYLLINE IS MORE POTENT THAN CAFFEINE.
■ Effect is less marked compared to inhaled ß2 agonist.
4. KIDNEY:
■ Methyl xanthines are mild diuretics,which act by inhibiting
tubular reabsorption of Na+ and water .
■ Increased renal blood flow and g.f.r is observed.

23. 5.STOMACH:
■ Enhance the acid and pepsin secretion,even on parenteral
injection.
■ Theophylline is more gastric irritant than Caffeine.
6.SKELETAL MUSCLES:
■ At high concentration caffeine increases the release of Ca2+ from
sarcoplasmic reticulum by direct action.
■ Augmented twitch response to nerve stimulation at low doses.
■ At toxic doses contracture (abnormal muscle contraction) is
produced.

24. ■ Caffeine facilitates the neuromuscular transmission by
increasing the ACh release, relieves fatigue and increases
muscular work.
■ Theophylline increases the diaphragmatic contractility in
the therapeutic concentration which is useful in dyspnoea
(shortness of breath)and COPD.
7. METABOLISM
■ Caffeine and to a smaller extent theophylline increases
BMR-Basal metabolic rate (BMR) is the amount of energy
expended while at rest in a neutrally temperate environment, in
the post-absorptive state (meaning that the digestive system is
inactive, which requires about twelve hours of fasting)

25. 8.MAST CELLS AND INFLAMMATORY CELLS
■ Theophylline decreases the release of histamine and other
mediators from mast cells and activated inflammatory cells
which is useful in treatment of bronchial asthma.

26. MECHANISM OF ACTION
■ The slow-reacting substance of anaphylaxis or SRS-A is a mixture of the
leukotrienes LTC4, LTD4 and LTE4. Mast cells secrete it during the
anaphylactic reaction, inducing inflammation.

27. ■ The three distinct cellular actions of methylxanthines have been
defined-
1. Release of Ca2+ from sarcoplasmic reticulum (in skeletal and cardiac
muscles)
2. Inhibition of phosphodiesterase (PDE) which degrades cyclic
nucleotides intracellularly.
3. Blockade of adenosine receptor: adenosine acts as a local mediator
in CNS, CVS and other organs:
■. Smooth muscles-contraction, especially bronchial
■. Cerbral blood vessels- dilates
■. Depresses cardiac pacemaker and inhibits gastric secretion.

28. ■ Action 1 occurs at higher concentration much higher than
therapeutic plasma concentrations of caffeine and
theophylline.
■ Action 2&3 occur at therapeutic range and appear to
contribute to bronchodilation.
■ Raised cAMP levels in inflammatory cells inhibits the
mediator release and promote apoptosis of eosinophils
adding to the therapeutic effect of theophylline in asthma.

31. Uses:
1. Bronchial asthma and COPD.Theophylline is ised as an
additional drug in moderate or severe persistent bronchial
asthma.
2. Apnoea in premature infants: theophylline is used orally or
intravenously to reduce the duration of apnoea episodes.

32. • ANTICHOLINERGICS
1. IPRATROPIUM BROMIDE.
■. Short acting inhalation bronchodilator.
■. It acts selectively on bronchial muscle without altering the
volume or consistency of the respiratory secretions.
■. Dose: 40-80μg,by inhalation.
■. Peak plasma concentration- 40-60mins.
■. Duration of action- 4-6hours.

33. ■ It mainly acts on receptors located in larger central airways..
■ More effective in COPD than in bronchial asthma.
■ Side effects: (Transient) Dryness of mouth, scratching
sensation in trachea, cough, bad taste and nervousness.

34. 2.TIOTROPIUM BROMIDE
■ Long acting inhalation bronchodilator.
■ Has high bronchial selectivity hence more effective than the
former.
■ Anticholinergics are more suitable for prophylactic use than
for the symptomatic relief during the attack.
■ Combination of Beta2 & anticholinergics produce more
marked and long lasting bronchodilation.

35. • MAST CELL STABILIZERS
■ Sodium cromoglycate and Ketotifen.
1. SODIUM CROMOGLYCATE
■. It is not a bronchodilator ,do not inhibit the constrictor action
of histamine,ACh,LTs,etc.
■. It inhibits the degranulation of mast cells by the stimuli.
■. Chemotaxis of inflammatory cells is inhibited.
■. Bronchospasm induced by allergens, irritants,cold air,
exercise can be treated.

36. Pharmacokinetics:
■ Not absorbed orally, administered as an aerosol through
metered dose inhaled delivering 1mg per dose:2puffs
4times a day.
■ Rapidly excreted unchanged in urine and bile.
Uses
■ Allergic asthma :as a prophylactic agent to prevent
bronchospasm induced by allergens and irritants.
■ Can be used in allergic conjunctivitis, allergic rhinitis,
allergic dermatitis etc.

38. 2. KETOTIFEN
■ It is an antihistaminic with Some cromoglycate like action.
■ Stimulation of inflammatory cells(mast cells, macrophages,
eosinophils, lymphocytes, neutrophils) and mediator release
are reduced.
■ It is not a bronchodilator , produces sedation.
ADR: Sedation ,dry mouth, dizziness, nausea&weight gain.

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