2. ASTHMA
Definition:
Asthma is derived from Greek word meaning difficulty in
breathing.Asthma is a chronic disease that inflames the airways(i.e. the
small tubes,called bronchi)which carry air in and out of the lungs.
In asthmatic patient,the bronchi will be inflamed and more sensitive
than normal and produce extra mucus.
Asthma literally meaning’Panting’
3. Classification of Asthma
Based on the stimuli initiating bronchial asthma,broad etiologic types
are;
vExtrinsic(allergic,atopic)asthma
vIntrinsic(idiosyncratic,non-atopic)asthma
vMixed types
4. Symptoms of Asthma
qEarly Warning Signs:
Breathing changes
Sneezing
Runny/stuffy nose
Coughing
Chin or throat itches
Feeling tired,trouble sleeping
Dark circles under eye
q Asthma Episode Symptoms:
Wheezing
Shortness of breathe
Tightness in the chest
5. qSevere Asthma Episode Symptoms
Personal severe coughing,wheezing difficulty
Shortness of breath or tightness in the chest
Difficulty in talking or concentrating
Walking cause shortness of breath
Breathing may be shallow and fast or slower than usual
Hunched shoulder(posturing)
Nasal flaring
Cyanosis
6.
7. Pathophysiology of
asthma
§ The early reaction is immediate
bronchoconstriction produced
by histamine,tryptase,and other
neutral proteases,leukotrienes
C4 and D4 and prostaglandins.
§ These agents diffuse throughout
the airways wall and cause
vascular leakage.
•
8. • Late
bronchoconstricti
on occurs after 2-
8 hours by TH2
lymphocytes and
interleukins 4,5,9
&13,attracting
and activating
eosinophils and
stimulating IgE
production by B
lymphocytes.
9. Causes of asthma
• Allergens
Dust mites, mold spores, animal dander,
cockroaches, pollen, indoor and outdoor
pollutants, irritants (smoke, perfumes, cleaning agents).
• Pharmacologic agents: ASA, beta-blockers.
• Physical triggers: (exercise, cold air, distilled
water, and sulfur dioxide).
• Diseases: GERD, viral and bacterial URI,
rhinitis
• Genetic(inherited):usually occurs in children.The chances of
developing asthma are increased if
the patients’ family members or relatives have asthma and other allergic
conditions such as atopic dermatitis and hay fever.
10. Treatment
• Treatment is based on two important goals;
ü Specific regimens for the treatment of acute attaks by opening
swollen airways that are limitimg breathing ,and
üProphylactic measures to reduce inflammation and airways resistant
and to maintain airflow
ü
Treatment and prevention involves a combination of
medicines,lifestyles advises,and identification and then avoiding
potential asthma triggers.
13. SYMPATHOMIMETICS
• Cause bronchodialation through B2 receptor stimulation
increased cAMP formation in bronchial muscle cell
Relaxation.
• In addition,increased cAMP in mast cells and other inflammatory cells
decreases mediator release.
• Adrenergic drugs are the mainstay of treatment of reversible airway
obstruction,but should be used cautiously in
hypertensives,ischaemic heart patients and in those receiving
digitalis.
• Though adrenaline(B1+B2+alpha agonist)and isoprenaline(B1+B2
agonist) are effective bronchodialators,it is selective B2 agonist that
are now used in asthma to minimize cardiac side effects.
14. Salmutamol(Albuterol)
ØHighly selective B2 agonist,cardiac side effect are less prominent.
ØInhaled salbutamol delivered mostly from Pressurized Meter Dose
Inhaler(PMDI) produced Bronchodilation within 5 minutes and lasts
for 2-4 hours.
ØUsed to abort and terminate attaks of asthma,but is not suitable for
round-the-clock prophylaxis.
ØSide effects: Muscle tremors(dose related),palpitation,restlessness,
nervousness,throat irritation and ankle edema.Hypokalaemia(possibl
e complication).
ØMetabolism:Presystemic in gut wall,Oral bioavailability 50%,Acts for
4-6 hours.
15. Terbutaline
• Properties and use similar to Salbutamol.
Inhaled salbutamol and terbutaline are currently the popular
drugs for quick reversal or bronchospasm,but should not be
used on any regular schedule.
16. Methylxanthines
• Use of methylxanthines in asthma has markedly diminished because of their
narrow margin of safety and availability of better antiasthmatic
drugs(selective B2 agonist ,inhaled steroids,leukotriene antagonists).
• Third or Fourth line drugs.
• MOA:
Theophylline Inhibit Phosphodiesterase Increase
Aminophylline (PDP) cAMP
Bronchodilation
Inhibit the release of histamine and SRS-A from mast cells.
Improve mucocilliary clearance in respiratory passage.
17. Methylxanthines Effects
A) CNS effects:
• Mild cortical arousal with increased alertness and deferral of
fatigue.
• Caffeine containing beverages cause nervousness and insomnia
in unusually sensitive patients and bronchodilation in patients
with asthma.
• Medullary stimulation and convulsions .
• Nervousness and tremors are toxic effects of larger doses.
18. (B) Cardiovascular effects:
• Direct positive chronotropic and inotropic effects on the heart.
• In unusually sensitive patients few cups of coffee can cause
arryhthmias but in normal persons high doses administered
parenterally produce only sinus tachycardia and increased cardiac
output.
• Relaxation of vascular smooth on larger doses except cerebral
vessels where they cause contraction.
• Ordinary consumption raise peripheral vascular resistance and BP
slightly, probably by releasing catecholamines.
• Increases viscosity of blood in some cases.
19. (C)Effects on GIT:
Stimulation of gastric acid and digestive enzymes secretion.
(D) Effects on kidney:
Weak diuresis (especially theophylline).
(E) Effects on smooth muscles:
Bronchodilation.
Also inhibits antigen-induced histamine release.
(F) Effects on skeletal muscles:
Strengthening of contraction.
20. Pharmacokinetics:
• Theophylline: Poorly water soluble,hence not suitable for injection.Available
for oral administration.
• Aminophylline:Water soluble but highly irritant.Administered orally or slow
intravenously.
• Ethophylline:Water soluble and can be given by oral,i.m or i.v route.
qAdverse Effects:Have narrow margin of safety.Cause:Tachycardia,Palpitation,
hypotension and sudden death due to cardiac arrhythmias.
21. Anticholinergics:
• Ipratropium bromide and tiotropium bromide are atropine substitutes.
• Selectively block the effects of acetylcholine in bronchial smooth and
cause bronchodialation.
• Slow onset of action.
• Administered by inhational route.
• Combined use of ipratropium with B2 adrenergic agonists produce
greater and more prolonged bronchodialation,hence used in acute
severe asthma.
• Atropine is effective intravenously as well as aerosol, effect lasting for 5
hours.
• Adverse effects of antimuscarinics include urinary retention, tachycardia,
loss of visceral accommodation and agitation.
22. Leukotriene Antagonists
• These drugs competitively block the effects of cysteinyl leukotrienes
(LTC4,LTD4 and LTE4)on bronchial smooth muscle.
Montelukast Cysteinyl-LT1 Leukotrienes-LTC4,
Zafirlukast -receptor LTD4 and LTE4
(Antagonist) (Agonist)
• Produce bronchodilation,suppress bronchial inflammation & decrese
hyperreactivity.
• Well absorbed after oral administration,highly bound to plasma proteins and
metabolized extensively in the liver.
• Effective for prophylactic treatment of mild asthma.
• Well tolerated,few adverse effects:-headache,skin rashes and rarely
eosinophilia.
23. Mast cell Stablizers
• Sodium cromoglycate,nedocromil sodium and ketotifen are mast cell stabilizers.
• Bronchodialators.
• Inhibit the release of various mediators-histamine,LTs,PGs,PAF,etc by stabilizing mast
cell membrane.
• Reduce bronchial hyperactivity to some extent but AG:AB reaction is not affected.
qSodium cromoglycate:
Not effective orally as it is poorly absorbed from gut.
Inhalation route.
Uses:In allergic asthma as a prophylactic agent to prevent bronchospasm
induced by allergens or irritants.Allergic conjunctivitis,allergic rhinitis,
allergic dermatitis by topical route as a prophylactic agents.
24. qNedocromil Sodium:
MOA,Pharmacological effects and use similar to sodium
Cromoglycate.Nedocromil sodium is more effective than cromoglycate.Only
above 12 years old patients,
q Ketotifen:
MOA similar to sodium cromoglycate,has additional H1-blocking
effect.
It is orally effective but has a slow onset of action.
25. Corticosteroids (Glucocorticoids)
• Glucocorticoids induce synthesis of ‘lipocortin’,which inhibits phospholipaseA2
and there by prevent the formation of various mediators such as PGs,TXA2,SRS-
A,
etc.Glucocorticoids have antiallergic,anti-inflammatory and immunosuppressant
effects.They;
oSuppress inflammatory response to AG:AB reaction.
oDecrease mucosal oedema.
oReduce bronchial hyperactivity.
• Glucocorticoids do not have direct bronchodilating effect but they potentiate the
effects of B-adrenergic agonist.
26. • Inhaled glucocorticoids such as beclomethasone,budesonide and fluticasone
are used as prophylactic agents in bronchial asthma.
• Well tolerated,Rare systemic side effects.
• Common side effects:Hoarseness of voice,dysphonia and oropharyngeal
candidiasis.
• Reduced by:Using a spacer,rinsing the mouth after each dose and can be
treated effectively by topical antifungal agent,nystatin or hamycin.
• Combination of llong acting beta agonist(LABA)with steroid is
available,fluticasone+salmeterol;budesonide+formoterol.Synergistic
action;used in bronchial asthma and COPD.
• Systemic glucocorticoids:Acute and chronic severe asthma.Long term
sideeffect;gastric irritation,Na+ and water retention,hypertension,muscle
weakness, osteoporosis,etc.
27. Anti-IgE Antibody:Omalizumab
• Omalizumab prevents the binding of IgE to mast cell,thus prevents mast cell
degranulation.It has no ettect 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 patients above 12 years of age.
• Cause local side effects such as redness,stinging,itching,and induration.