Pharmacology of Bronchial Asthma PDF
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This document discusses the pharmacology of bronchial asthma, including the various drugs and treatments used, and their mechanism of action. It describes the symptoms and pathogenesis of the condition, as well as factors that may predispose to or exacerbate the disease.
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Gua aifenesin It iss one of the mostt widely u used overr-the-countter (OTC) expectorants. It incrreases bro onchial fluid d secretion ear mechanism. ns by uncl...
Gua aifenesin It iss one of the mostt widely u used overr-the-countter (OTC) expectorants. It incrreases bro onchial fluid d secretion ear mechanism. ns by uncle Oth her expecttorants Man ny other traditiona al expecttorants (e e.g., ammmonium cchloride, tincture ipec cacuanha, herbal re emedies) a are found in numerrous OTC cough mixtures. m Theeir efficacy is doubtfu ul, particula arly in the dosages of o most preeparations. Part 2 2: The erapy off bronch hial asth hma ma is a chrronic inflam Definittion: Asthm mmatory disorder d of the airwayys causing g airflow obstrucction and recurrent episodes of wheezing, breath hlessness,, chest tig ghtness, and coughing. Pathog genesis Frequeent exposure to allergic stim muli causess infiltration of the bronchial b w wall by acu ute and chronic inflammat i tory cells. These cells re elease m many inflammmatory cy ytokines e.g. e histam mine, adenossine, PGs, LTs, PAF F, etc. lead ding to: Hypertroph hy of airway y smooth mms Increased mucus se ecretion tha at is difficu ult to expel. Congestio on and ede ema of the respiratory y mucosa. Predisposing fac ctors Rec current re espiratory n: the mo y infection ost impportant facttor. Gennetic facttors: asthm ma occurss in familiies with h positive history h of allergy. a Psyychologica al factors: are pressent in 40 % of a asthmatics. Clinica al presenta ation Chrronic asth hma Theere is dysp pnea, ches st tightnesss, coughing (parrticularly at night), and d expiratoryy wheezing g. 234 Patients can present with mild intermittent symptoms that require no medications or only occasional short-acting inhaled β2-agonists to severe symptoms despite multiple medications. Acute severe asthma Uncontrolled asthma can progress to an acute state in which inflammation, airway edema, mucus accumulation, and severe bronchospasm that is poorly responsive to bronchodilator therapy. There are severe dyspnea, inspiratory wheezing, cyanosis; the patient may be able to say only a few words with each breath. █ MANAGEMENT OF ASTHMA █ BRONCHODILATORS β-adrenergic agonists. 3 groups of Muscarinic receptor blockers: ipratropium. bronchodilator drugs: Xanthines: theophylline. ▌β-adrenergic agonists Classification Non-selective β-receptor agonists: e.g. adrenaline, isoprenaline and ephedrine. They are rarely used as bronchodilators. Selective β2 agonists: Short acting: salbutamol, terbutaline, fenoterol (duration 3-4 hrs). Long acting: salmeterol and formoterol (duration 12 hrs). Mechanism of action Stimulation of bronchial β2 receptors → ↑ cAMP → bronchodilatation. Stimulation of β2 receptors in the mast cells → ↓ histamine release They ↓ bronchial inflammation and wall edema. Administration In acute asthma: short acting β2 agonists are given by inhalation or i.v infusion. In chronic asthma: long acting β2 agonists are given orally or by inhalation. Adverse effects Tachycardia and arrhythmia due to: Reflex from hypotension (caused by VD of sk ms BV). 235 Directt activation n of cardiac c β1 (due to o loss of se electivity inn high dos ses). Trem mors of sk keletal ms and nervou usness. Tole erance with prolonge ed use (reqquiring tem mporary ces ssation of the drug). Hyp + pokalemia (due to shift of K froom blood tot cells). ▌Musc carinic an ntagonistts: Ipratro opium brromide Atro opine bloc cks M3 rec ceptors in a airway ms s leading to o bronchod dilatation through t uno opposed β2 action, bu ut it is not used for treatment t ma because t of asthm e: It is non-selective M3 blocker lleading to many sidee effects e..g. dry mouth and urine reten ntion. It can crosss BBB andd causes CCNS side effects e e.g. sedation.. It causes excessive e dryness off bronchiall secretions making iit difficult to t expel Ipra atropium is i more prreferred th han atropiine because: It is more selective s muscarinic m blocker th han atropinne. It is quaterrnary ammmonium com mpound th hat can't cross BBB. Does not cause c exce essive dryn ness of bro onchial seccretions. Ipra atropium is not sufficient s alone fo or bronch on. It is usually hodilatatio com mbined with β2 agonists to gett synergistiic effect. ▌Meth hylxanthin nes Classiffication Nattural: e.g. caffeine, th heophylline e, and theo obromine. Sem misynthetiic: e.g. am minophyllinee (salt of th heophylline e). anism and pharmac Mecha cological e effects Xan nthines are e adenosine e A recepttor antago onists lead ding to: Bronchodiilatation (block broncchoconstrictor effect of adenossine). C CNS stimuulation (blo ock the inh ibitory effe ect of aden nosine on tthe CNS) ↓ mediatorr release frrom mast c cells. ↑ AV conduction. Theey inhibit phosphodiestrase ennzyme (PD DE4) → ↑ cA DE3 and PD AMP leading g to: Bronchodilatation (PD DE4). ↑ cardiac contractility c y and arrhyythmogeniic action (PPDE3). V VC of cereebral and VD V of perippheral vesssels. Relaxationn of most smooth s mu T, biliary, ureteric, etcc). uscles (GIT Diuresis. 236 Therap peutic use es Res spiratory uses: u Acuute severe asthma: aminophyllline may be given by slow i.v. infusion 250 2 mg i.vv. (at least over 15 minnutes to avoid sy yncope orr cardiac arrest), follo owed by maintenanc m ce i.v infusiion of 0.7 mg/kg/h. m Chrronic broncchial asthm ma: sustain ned releas se tablets of theophylline 100 0-300 mg g/day orr rectal supppository of o aminoph hylline can be given. CNS S uses: To rreverse CN NS depression. To ddelay physsical and mental m fatig gue (caffein ne). Treaatment of migraine (caffeine ( + ergotamine): to increase VC of cerebra al blood vessels and inncrease abbsorption oof ergotam mine from GIT. G Neoonatal apnea syndrom me: caffeinne is the ag gent of cho oice. CVS S uses: Acu ute pulmon nary edema a due to ac cute left sided HF. Advers se effects CNSS: irritabilitty, headac che, insom nia, nervou usness and d convulsioons. CVSS: palpitations, tachy ycardia, an nd arrhyth hmias. Rap ection can pid i.v. inje n cause hyp potension, syncope and a cardia ac arrest. GIT T: nausea, anorexia, hyperacid h dity and rea activation of peptic uulcer. Precau utions Aminophyllinee must be e given byy slow i.v.ii. (at least over 15 minutes to o avoid sud dden synco ope or card diac arrestt). Use ed with caaution in se evere card diac diseasse, severe hypoxem mia, and renal and hep patic disease and in elderly e andd neonates s. The ey should not n be give en to patiennts with pe eptic ulcer. Drug in nteraction ns Enzzyme inhib bitors (cim metidine an omycin) → nd erythro ↑ s hines and ↑ their serum levvels of methylxanth m toxiicity (arrhyythmia). Enzzyme inducers (sm moking, riffampin) → ↓ their seru um levels and a reducee their effe ect. 237