pharma fouda 2_p141-144.pdf

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