Pharmacology of the Respiratory System, Part 1, PDF

Part 1 1: Age ents use ed to tre eat coug gh █ Bas sic inform mation  Couugh is one of the mos st commo n symptom ms seen in clinical prractice.  Thee initial...

Part 1 1: Age ents use ed to tre eat coug gh █ Bas sic inform mation  Couugh is one of the mos st commo n symptom ms seen in clinical prractice.  Thee initial stimulus arisses in thee bronchia al mucosa,, where irrritation results in stim mulation of o “Cough” recepto ors, which are specialized sstretch rec ceptors. Affeerent impulses reachh the coughh center in n the medu ulla via thee vagus nerve and trigg ger a coug gh reflex.  Cou ugh may be acute (8 wee eks). Causes s of cough h:  Acu ute cough: respiratory infection n is the mo ost commo on cause.  Chrronic coug gh:  Upper airwway coug gh syndrom me (post--nasal drip p): due to o allergic rhinitis, c chronic sin nusitis or to onsillitis. Itt is the mo ost commo on cause off chronic cough. c  Bronchial asthma: th nd he 2 mostt common cause.  G Gastoesop phageal reflux diseasse (GERD)..  O Other causses: ACEIs s, lung tum mors, CHF. █ MAN NAGEMEN NT OF COU UGH Speecific trea atment: directed d tto the ca ause of cough c e.g g. antibiottics for resp piratory inffections. Non n-specific c treatmen nt:  A ves: are us Antitussiv sed to stopp dry cough h.  M Mucolyticcs and ex xpectoran nts: are used in prroductive cough to liquefy b bronchial secretions s and facilittate their re emoval. 231  █ COU UGH SUPP PRESSAN NTS (ANTIT TUSSIVES S) Definittion: they are a drugs that t reduce e the frequ uency or in ntensity of coughing. ▌Perip pheral an es: they ↓ afferent im ntitussive mpulses of the coughh reflex. Ste eam inhala ation with menthol o or tincture e benzoin compoun nd  It iss one of the best and d easy wayys to relievve acute cough. c Inhaaling water steam with h or withouut medications (e.g. m menthol) helps h flush out mucu s and moisturizes dry,, irritated air a passagees. The effficacy of ad dded mediication is nnot proved. Ben nzonatate  It iss a glycero ol derivativ ve chemica ally related d to the lo ocal anesthhetic proc caine. It dep presses peeripheral coough recep ptors at the e lung by lo ocal anestthetic effec ct. ▌Centtral antitu ussives: they inhibiit cough ce enter in the e medulla. Opiioids: Cod deine and hydrocod done  Theey are natu ural derivattives of mo orphine. Th hey directly y inhibit thhe cough center c in the medulla at a doses that are lowe er than tho ose needed d for analg gesia.  Theey are geneerally not recommend ded becauuse of adveerse effectts. Advers se effects  Droowsiness and a constip pation.  Druug depende ence if use ed for long duration.  Resspiratory depression d in large d doses. Chilldren lesss than 5 years old d are morre sensitivve to resppiratory depression d n so, co odeine is not recoommended d to childre en < 5 yeaars. Opiioid isome ers: Dextro omethorp phan  It iss synthetic L-isomer of o opioids..  It has selectivve central antitussive e action with w very few f opioidd effects (i.e. less add diction liability, analgesic action n, respirato ory depres ssion, or co onstipationn).  High doses ca an cause neuropsych n hiatric effe ects e.g. se edation and d hallucina ations. COLYTICS █ MUC S Definittion: they are agents that red duce viscosity of res spiratory ssecretions without increassing their amount. a 232  Bromhexine  Bromhexine acts on the mucus at the formative stages within the mucus- secreting cells. It disrupts the structure of acid mucopolysaccharide fibers in mucoid sputum and produces a less viscous mucus, which is easy to expel.  Because bromhexine can disrupt the gastric mucosal barrier, it should be avoided in patients with peptic ulcer. Ambroxol  It stimulates synthesis and release of surfactant by type II pneumocytes. Surfactant acts as an anti-glue factor by reducing the adhesion of mucus to the bronchial wall. N-Acetylcysteine and carbocyseine  Acetylcysteine has free sulfhydryl (-SH) groups that break disulfide bonds in mucus and reduces its viscosity.  Unlike acetylcysteine, carbocysteine does not act directly on mucus but rather, it affects the structural components of mucus. Therapeutic uses of mucolytics  Chronic respiratory diseases: chronic bronchitis, emphysema, bronchiectasis and cystic fibrosis.  Post-operative and post-traumatic pulmonary complications.  Chronic sinusitis and chronic otitis media.  N.B. Intravenous N-acetylcysteine is used as an antidote for acetaminophen (paracetamol) toxicity (quite apart from its mucolytic activity). █ EXPECTORANTS Definition: drugs that increase water content and amount of the respiratory secretions. This action facilitates the removal of respiratory secretions. Adequate hydration is the single most important measure to encourage expectoration. Using an expectorant in addition may produce the desired result. Potassium iodide  Iodides accumulates in the bronchial glands and stimulate secretion of low viscosity watery mucous.  The use of iodides is accompanied by wide range of side effects including unpleasant (metallic) taste, increase lacrimal and salivary secretions, painful salivary swelling, hypothyroidism, and skin eruptions (rash). 233  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