1. ASTHMA AND ANTI ASTHAMIC DRUGS PRESENTED BY karnaker reddy M. Pharmacy Pharmacology.

2.  CONTENTS:  Introduction  Definition  Investigation  Drugs used to treat asthma  MOA  Adverse effects and uses  Reference

3.  INTRODUCTION:  Spontaneous rhythms controlled by respiratory system.  Regulation of airway  Afferent pathway:  Irritantant receptor and unmylenated c fibers respond to inflammatory stimuli cause bronchoconstriction through ach.

4. Efferent pathway:  Parasympathetic: bronchocostriction trough M 3 receptor.  Sympathetic:B.V(Constriction),gland (decrease),but not airway smooth muscle  Circulating adrenaline act on beta two and relax smooth muscle  The NANC relax air way trough NO

5. Definition:  Defined as recurrent reversible air way obstruction of air flow trough the air way.  Characteristics:  Asthma is two types  Chronic asthma dyspnoea,wheezing,and cough. Reversible  Acute(status asthmatics) irriversible.hospilization

9. Investigation: FEV(forced expiratory volume) FVC(forced vital capacity) FEV/FVC 75%Of total capacity PEFR(peak expiratory flow rate)

10. Drugs used to treat bronchial asthma: I.Bronchodilators: Β2 agonist : 1.Shortacting:salbutamol,terbutaline(inj.0.25mg), bambuterol. 2.Longacting:salmeterol,formoterol,fenoterol, pirbuterol(0.2mg/puff),reprotelol. ll.Xanthine drugs-theophylline (50mg),aminophylline (100to200mg).

11. III) Muscarnic receptor antagonist: ipratropium,tiotropium(18mcg/puff) lV) cystenyl leukotriene receptor antagonist: montelucast,zafirlucast(10to20mg). V) H1 Receptor antagonist: loratidine. Vl) anti inflammatory agent: glucocorticoids:beclometasone(40to80mg), dipropionate, budesonide,fluticasone, cromoglycate:nedocromil sodium(5.2mg).

12. Bronchodilator: Β 2 adrnoreceotor agonist MOA:  Direct Β 2  Decrease mediator release of mast cell.  Short acting-30min.duration 4to6hr.  Long acting-12hr.twice a day.  Unwanted effects:  Tremor  Shakiness and fever, cardiac arrhythmias

13. Xanthine drugs : Theophylline(1,3dimethyl xanthine) Used as theophylline ethylene di amine (amynophylline) Actions: CNS actions:stimulation CVS actions :positive chronotropic and inotropic actions and vasodilatation. Renal system: methyl xanthenes weak diuretic decrease renal absorption in the tubes and increases GFR.

14. MOA: Relax effect on smooth muscles by inhibition of phosphodiesterase(PDE) increases cAMP and effect on cGMP. And increases ca+2. PDE4 inhibitors- Roflumilast and Tofimilast. Another action is competitive antagonism of adenosine receptor. PDEinhibitor enprofylline is not a adenosine antagonist.

15. Unwanted effect: 30-100microm/l no effect >110microm/l GIT disturbance. >200microm/l CNS effects (dysarrhythmia) Metabolized in liver t 1/2 8hr. The plasma concentration decreased by increase cytocrome P 450 RIFAMPICIN,phenobabitol,phenytoin. Increase by decrease cytocrome P 450 with contraceptive,erythromycin,cimetidine Use: second line drug,iv acute severe asthma. Decrease symptoms of COPD.

16. Muscarnic receptors antagonist: Iptratropium, oxitropium. Cause relaxation by action of parasympathetic's N iso propylatropine cause M 2 auto receptor Blocked increase ach release Decrease M3 antagonism Uses:- used with B2 agonist As a bronchodilator.

17. Cysteinyl leukotriene receptor antagonist: Mantelucast, zafirlukast. Action:- decrease aspirin sensitive asthma, inhibit exercise induced asthma & decrease both early & late respond allergen. Unwanted effect:- Head ache GIT disturbance Mantelucast (daily Once), Zafirlukas (daily twice).

18. Histamine H1 – receptor antagonist: No place in therapy Non sedating antihistamines Loratidine mild. Anti Inflammatory agents: Glucocorticoids. Cromoglicate & nedocromil Glucocorticoids used only in management

19. Action & MOA: Decrease prostaglandin Decrease COX II Decrease IL 1,2,3,4, TNF & NO Decrease IgG production

20. Oropharyngeal candidacies, first pass metabolism. Uses: Require regular bronchodilators for gluco corticoids treatment Severe affected patients High potency inhaled drug (budenosid) & slow release theophyline. Any severe cause require gluco corticoids

21. Cromoglicate : first tested in human. Action & MOA: Not a bronchodilator if give prophylactically Decrease both late & immediate phase effective for exercise, allergic antigen induced asthma MOA: Mast cell stabilizer Decrease Histamine release Not absorbed by GIT, inhalation t1/2 – 90mins Excreted in urine Unwanted effect irritate upper respiratory tract

22. Severe asthma (acute): O2 & inhalation of salbutamol iv – hydrocortisone followed by a course of oral prednisolone. Iprotropium, iv salbutamol / aminophylline & ab. Other drugs in the treatment of asthma: anti IgE monoclonal antibodies. Omalizumab(anti IgE Ab)

23. Possible future therapies: Direct action on antagonism of cell adhesion Protease inhibitor Immune modulator Selective inhibition of TH2 Infection Chlamydia pneumonia/ mycoplasma pneumonia Macrolide antibiotics are used.

24. References  Barriors R et al: Asthma: Pathology and pathophysiology. Arch Pathol Lab med 2006;130:447.  Kelly HW: Levalbuterol for asthma: A better treatment? Curr Allergy Asthma Res Rep 2007:7:310.  Ito K et al: A molecular mechanism of action of theophylline: Induction of histone deacetylase to decrease inflammatory gene expression. Proc Natl Acad Sci USA 2002;99:8921.  Gross N: Anticholinergic agents in asthma and COPD. Eur J Pharmacol 2006:8:533.  Walker S et al: Anti-IgE for chronic asthama in adults and children. Cochrane Database Syst Rev 2006;2:CD003559.  Barnes J: Novel signal transduction modulations for the treatment of airway diseases. Pharmacol Ther 2006;109:238.

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