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Drugs in Respiratory System

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Drugs in Respiratory System DRUGS IN RESPIRATORY SYSTEM Pharmacology Department FACULTY OF MEDICINE – UNISSULA INTRODUCTION Symptom of respiratory system : no sputum---antitussives Cough sputum --- expectorants Asthma ----- antiasthmatic drugs PHYSIOLOGY OF COUGH • Batuk disebabkan oleh aktivasi reseptor sensorik di laring dan saluran pernapasan bagian bawah, mengirimkan impuls ke batang otak. • Ada banyak agen bervariasi yang bisa menimbulkan batuk: asam sitrat, bradikinin, air suling, SO2, capsaicin, metabisulfite, asap rokok dan inhibitor ACE. • Sensitivitas ujung saraf sensoris, yang menengahi refleks batuk yang ditimbulkan oleh agen tussive meningkat pada penderita asma dengan batuk, mengikuti infeksi saluran pernapasan bagian atas pada individu sehat dan pada pasien dengan batuk yang diinduksi ACE. PHYSIOLOGY OF COUGH • Batuk biasanya terjadi ketika reseptor sensorik di saluran pernapasan menerima rangsangan dengan intensitas yang cukup untuk membangkitkan peningkatan aktivitas impuls saraf sensorik / aferen. Refleks batuk dapat dipicu dengan mudah oleh rangsangan mekanis dan kimia yang terjadi di laring atau trakeobronkial, karena di sinilah perlindungan terbesar terhadap masuknya bahan asing diperlukan. • Informasi sensorik dari saluran pernafasan yang memulai refleks batuk melalui nervus vagus. COUGH IN DISEASE • Batuk sering terjadi pada asma dan selama infeksi saluran pernafasan bagian atas disertai dengan pembengkakan saluran udara. • Etiologi batuk pada anak berbeda dengan orang dewasa: virus URTI, bronkitis bakteri dan asma yang berkepanjangan sering menjadi penyebab anak- anak batuk. Jadi, pendekatan empiris yang biasa digunakan pada orang dewasa tidak sesuai untuk anak-anak. Evaluasi klinis batuk pada anak juga harus mencakup penilaian faktor lingkungan. ANTITUSSIVE AGENTS SITE AND MECHANISMS OF ACTION OF ANTITUSSIVE AGENTS • Batuk dikaitkan dengan kelebihan produksi lendir di dalam paru-paru, penekanan refleks batuk umumnya tidak diperlukan, karena retensi lendir dapat terjadi yang dapat menyebabkan komplikasi serius. • Bila batuk tidak produktif dan menjadi gangguan, tidur dan istirahat, penekanan menjadi diperlukan, meski penekanan menyeluruh bisa berbahaya karena paru-paru kemudian kehilangan mekanisme pertahanan yang esensial SITE AND MECHANISMS OF ACTION OF ANTITUSSIVE AGENTS • Obat ideal akan mengurangi peningkatan sensitivitas refleks batuk normal, sebaiknya dengan mengeluarkan proses penyakit atau dengan mengurangi responsivitas reseptor sensorik saluran napas. • Reseptor sensori nafas yang paling jelas untuk ditargetkan adalah RAR. Obat yang mempengaruhi batuk juga bisa diberikan secara tidak langsung. Misalnya, obat yang menyebabkan bronkodilatasi, seperti agonis reseptor dan antagonis kolineptor yang digunakan pada asma, mengurangi refleks batuk tanpa memiliki efek sentral yang signifikan. SITE AND MECHANISMS OF ACTION OF ANTITUSSIVE AGENTS • Obat dengan aktivitas antitusif secara longgar dikelompokkan menjadi dua kelompok: perifer atau pusat. • Obat antitusif sentral bertindak di dalam sistem saraf pusat untuk menekan satu atau lebih komponen jalur batuk sentral. • Agen yang bertindak secara periferal menggunakan cara kerjanya di luar sistem saraf pusat, mungkin dengan menghambat aktivasi reseptor sensorik saluran napas yang bertanggung jawab untuk memulai refleks batuk. • Penekan batuk yang paling sering digunakan adalah opiat, anestesi lokal, demulcents, ekspektoran, antihistamin dan dekongestan. SITE AND MECHANISMS OF ACTION OF ANTITUSSIVE AGENTS • Antitussive effects of the classical opiates, such as codeine and morphine, were generally reported to be mediated centrally. • Opioid receptors on the afferent / sensory neurones of the vagus nerves. • Codein & morphine with opioid-receptor-mediated antitussive actions can modulate impulse activity in airway sensory neurones originating from RARs and C- fibre receptors. • Antitussive activity of drugs such as codeine is not restricted entirely to the central nervous system, but that some of its activity is also exerted peripherally. ANTITUSSIVES Classification : A. Central Antitussives / Cough Supressants 1. Dependent Central Antitussives (Opioid) 2. Independent Central Antitussives (Non Opioid) B. Peripheral Antitussives Note : codeine, dextromethorphan and cloperastine are among the most common central agents that inhibit cough primarily by their effect on the cough center. DEPENDENT CENTRAL ANTITUSSIVES • Centrally acting antitussives opioid / narcotic alkaloids. • Mechanism : suppressing of cough center. • Morphine is the most effective drug for the suppression of cough, but have addiction. • Ex : codeine, hydrocodone. INDEPENDENT CENTRAL ANTITUSSIVES • Non opioid / narcotic alkaloids. • Stereoisomers of opioid molecules that are devoid of analgesic effects and addiction liability. • Classification : 1) Orphan – antitussives : dextromethorphan 2) Amido – antitussives : pentoxyverine, clofedanol 3) Piperidine – antitussives : cloperastine 4) Morpholine – antitussives : promolate, fominoben 5) Others : eprazinone, zipeprol PERIPHERAL ANTITUSSIVES Inhibiting receptor, afferent nerve, efferent nerve of cough reflex arc → cough suppression. 1. local anesthesia action : narcotine, benzonatate 2. Alleviative action : extractum glycyrrhizae liquidum PERIPHERAL ANTITUSSIVES •Levodropropizine is a non-opioid agent whose peripheral antitussive action may result from its modulation of sensory neuropeptide levels within the respiratory tract. •Locally acting agents (throat lozenges, cough drops) may suppress cough by increasing the flow of saliva and by containing demulcents or local anesthetics to decrease irritation of pharyngeal mucosa. ANTITUSSIVES Indication for use of antitussives : •A dry, hacking, nonproductive cough that interferes with rest and sleep. •It is not desirable to suppress a productive cough because the secretions need to be removed.. ANTITUSSIVES • Penekanan berlebihan terhadap refleks batuk dengan antitusif (ketidakmampuan untuk batuk efektif saat ada sekresi). • Ini adalah efek samping yang berpotensi serius karena sekresi yang ditahan dapat menyebabkan atelektasis, pneumonia, hipoksia, dan gagal napas. • Mual, muntah, sembelit, pusing, kantuk, pruritus, kehilangan kesadaran, insomnia, sulit bernafas dan ketergantungan obat: berhubungan dengan agen narkotika. Ketika narkotika diberikan untuk efek antitusif, namun diberikan dalam dosis yang relatif kecil dan tidak menimbulkan reaksi yang merugikan. ANTITUSSIVES Drug interactions • Drugs that increase antitussive effects of codeine : CNS depressants (alcohol, antianxiety agents, barbiturates, and other sedative-hypnotics) - Additive CNS depression. Codeine is given in small doses for antitussive effects, and risks of significant interactions are minimal. Drugs that alter effects of dextromethorphan : • MAO inhibitors This combination is contra- indicated. Apnea, muscular rigidity, hyperpyrexia, laryngospasm, and death may occur. ANTITUSSIVES GENERAL PRECAUTION : • Anti cough agents that include codeine, dextromethorphan, butamirat are not recommended for using in kids (to 2 years of age), during pregnancy and lactation. • Agents that include glaucini hydrochloridum may provoke decreasing of arterial blood pressure in kids. • Anti cough agents that include dextromethorphan may cause CNS and breathing depression if using in hight doses or for a long period. • Anti cough agents that include butamirat, dextromethorphan may cause weakness, sleepiness, dizziness. CODEIN • Codeine phosphate is an opioid analgesic with uses similar to those of morphine, but is much << potent as an analgesic & has only mild sedative effects. Mechanism of Action and Effects : • Selectively suppress cough center in medulla oblongata. Its primary site of action is at the opioid receptors distributed throughout the central nervous system. • Codeine phosphate reduces intestinal motility through both a local and possibly central mechanism of action. • Codeine phosphate also suppresses the cough reflex by a direct central action, probably in the medulla or pons. CODEIN Potency : • Analgesia : 1/7 of morphine • Suppression of cough : 1/10 of morphine • Respiratory depression, constipation, tolerance, dependence ＜ that of morphine Clinical Uses : • Dry cough & moderate pain Pharmacokinetic : • Codeine is readily absorbed from the GI tract & metabolised by O- and N-demethylation in the liver morphine & norcodeine which with codeine are excreted almost entirely by the kidney, mainly as conjugates with glucuronic acid. CODEIN • Codeine and its salts are absorbed from the gastro-intestinal tract and onset of analgesic action occurs 30 to 45 minutes after administration, when given orally. • Peak effect is reached within 1 to 2 hours and the duration of antitussive action is 4 hours and 4 to 6 hours respectively. CODEIN Dosage and administration : • Adults = for non-productive cough the usual dose is 10 mg – 20 mg every 4-6 hours to a maximum total of 120 mg in 24 hours. • Paediatric = for cough children may be given up to 0.25 mg per kg every 4 - 6 hours. • On the basis of available data, codeine and other opioid cough suppressants should rarely be administered to children less than 6 to 12 months old. • They should not be given in productive cough. CODEIN Contra Indications : • Known hypersensitivity to codeine • Acute respiratory depression (cyanosis and excessive bronchial secretion) • Obstructive airways disease • Acute alcoholism • Head injuries or conditions in which intracranial pressure ↑ • Patients at risk of paralytic ileus • Hepatic
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