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).
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
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
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
17.
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.
29.
30.
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.
37.
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.
