DROGAS ANTITUSIGENAS MUCOLITICAS y EXPECTORANTES (mucoquineticos) Cough is a reflex response to mechanical, inflammatory and chemical irritation of the tracheobronchial tree. It is a normal mechanism for the maintenance of a healthy respiratory system.

TOS = MECANISMO de DEFENSA * Receptores xa la irritación Centro tusígeno Reg lateral de medula oblonga y región pontina N vago (X) Musc Intercostales y abdominales Cierran la glotis y contraen el diafragma *Pleura *Diafragma *Vías respiratorias Síntoma molestoso

Antitusígenos. Clasificación: de acción central (umbral xa el reflejo de la tos en centro de la tos o depresión sensibilidad). Narcóticos: Deriv Opio: morfina y heroína. Hidrocodona. +Grupo fenantreno: codeína. No narcóticos: Grupo morfinano: Dxmetorfano, clobutinol, folcodina. de acción periférica (bloquean a los R periféricos) Anestésicos locales: lidocaina, tetracaina y cocaina. Benzonatato Broncodilatadores: metilxantinas y B2-adrenergicos. Antihistamínicos: clorfedianol. Expectorantes o Mucokineticos.

NARCÓTICOS Gr. Fenantrenico: morfina y codeína ANTITUSÍGENOS de ACCION CENTRAL: NARCÓTICOS DERIVADOS del OPIO (analgésicos) Gr. Fenantrenico: morfina y codeína Gr. Benzilisoquinolonicos: Papaverina y noscapina. Bloquean liberación de histamina = ↓broncoespasmo MORFINA Y HEROÍNA Tos grave y persistente Producen adicción y depresión. * Depresores del centro respiratorio

CODEINA VENTAJAS VS. MORFINA Mejor tolerancia Menor adicción y euforia Metil éter de morfina Alivia el dolor. Analgésico 65 mg = 650 mg de ASA y acetaminofen. Antitusigeno ¼ o ½ parte. Disminuye el reflejo tusígeno central. VENTAJAS VS. MORFINA Mejor tolerancia Menor adicción y euforia Bajo riesgo de broncoespasmo Moderado fecto constipante y emético. VO, poco riesgo de sobredosis.

FDA. August the 15th. 2012. FDA is reviewing reports of children who developed serious adverse effects or died after taking codeine for pain relief after tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome. Recently, three pediatric deaths and one non-fatal but life-threatening case of respiratory depression were documented in the medical literature. These children (ages two to five) had evidence of an inherited (genetic) ability to convert codeine into life-threatening or fatal amounts of morphine in the body. All children had received doses of codeine that were within the typical dose range. When codeine is ingested, it is converted to morphine in the liver by an enzyme called cytochrome P450 2D6 (CYP2D6). Some people have DNA variations that make this enzyme more active, causing codeine to be converted to morphine faster and more completely than in other people. These “ultra-rapid metabolizers” are more likely to have higher than normal amounts of morphine in their blood after taking codeine. High levels of morphine can result in breathing difficulty, which may be fatal. The estimated number of “ultra-rapid metabolizers” is generally 1 to 7 per 100 people, but may be as high as 28 per 100 people in some ethnic groups.

CODEINA FARMACOCINÉTICA - Absorción rápida por v. oral -Metaboliza enHígado x glucoronoconjugacion -Concentración mx en plasma de 1 h T ½: 3.5 h Elimina orina 10% es desmetilada a morfina.

CODEINA FARMACOPATOLOGÍA Sequedad de boca n-v Hiperhidrosis, Agitación Viscosidad de secreciones bronquiales Constipación n-v Mareo Somnolencia Dosis  = depresión Respiratoria. Tx NALOXONA

< constipación, pero …> riesgo adicción. HIDROCODONA + potente que codeína y < constipación, pero …> riesgo adicción. FDA, Dec 9,2012. Qualitest Hydrocodone Bitartrate and Acetaminophen Tablets 10 mg/500 mg: Recall - Potential for Oversized Tablets ISSUE: Qualitest, a subsidiary of Endo Health Solutions, issued a voluntary nationwide recall for 101 lots of Hydrocodone Bitartrate and Acetaminophen Tablets, USP 10 mg/500 mg. Bottles from the affected lots may contain tablets that have a higher dosage of acetaminophen, and as a result, it is possible that consumers could take more than the intended acetaminophen dose. Unintentional administration of tablets with increased acetaminophen content could result in liver toxicity, especially in patients on other acetaminophen containing medications, patients with liver dysfunction, or people who consume more than 3 alcoholic beverages a day. Taking a higher dose of hydrocodone than intended could result in an increase in the severity or frequency of side effects, such as sedation or respiratory depression, particularly in patients who are elderly, have severe kidney or liver impairment, or are also taking interacting medications, for example other sedating medications or certain antidepressants. BACKGROUND: Hydrocodone bitartrate and acetaminophen 10mg/500 mg tablets are indicated for the relief of moderate to moderately severe pain.

ANTITUSIGENOS NO NARCOTICOS Derivados del morfinano (poca acción sedante y analgésica). Dxmetorfano, Clobutinol, folcodina. En general, no producen adicción.

DEXTROMETORFANO Dextro isomero del narcótico morfinano. Potencia = codeina umbral de percepción a estímulos tusígenos. Fármacopatología: NAUSEA, MAREO. Dosis : depresión SNC y efectos causados por liberación de histamina.

CLORFEDIANOL (antihistaminico) Estructuralmente parecido a difenhidramina (benadryl) EFECTOS: antihistaminicos, anticolinergicos y leve anestesicos. Dosis terapéuticas=sedacion Dosis : excitación central con irritabilidad y alucinaciones. VENTAJA?: acción duradera y estimular centro respiratorio.

NO NARCOTICOS NO CLOBUTINOL FOLCODINA (silomat) - Potencia leve a moderada NO Hábito NO depresión del centro respiratorio Nausea Sueño FOLCODINA Su efecto NO es mediado por R opiaceos NO se metaboliza a morfina = NO efecto narcótico NO adicción NO deprime la respiración y SNC. Acción: 12 h. NO

ANTITUSIGENOS de ACCION PERIFERICA Anestésicos locales. Broncodilatadores Mucoliticos-Mucokineticos. Antihistamínicos.

Anestésicos locales -Se instalan en las vías respiratorias Lidocaina, Cocaína o tetracaina PARA SEDAR la TOS en PROCEDIMIENTOS: Endoscópicos (broncoscopía) o Diagnósticos (broncografía) -Se instalan en las vías respiratorias anestésicos tópicos ( cocaína o tetracaína) -Efectos tópicos e infiltrativos (lidocaína) PARA SEDAR la TOS en PRESENCIA de: Cuerpo extraño en las vías respiratorias Tos severa en el asma Micronebulización de lidocaína 0.5-1.0 % (broncodilatador)

Carafen Difenhidramina Oxolamine Son otros medicamentos que pueden disminuir la tos por tener ligera acción anestésica local

Relacionado con la tetracaína La sobredosis estimula el S.N.C La sobredosis produce convulsiones o coma Acción central antitusígena NO DEPRIME EL CENTRO RESPIRATORIO Disminuye los I.V.A de los receptores de la tos (Acido butilaminobenzoico)

BENZONATATO. EFECTOS ADVERSOS Cefalea, mareos Tiene mal sabor y produce anestesia bucal. Produce molestias G-I Rash cutáneo con prurito

Estimulantes B2-adrenergicos BRONCO DILATADORES Metilxantinas y Estimulantes B2-adrenergicos Al  el espasmo bronquial calman la tos

EXPECTORANTES (mucoquineticos) 1. INHALACION: ClNa, ClNa hipertonico1.8-20% y propilenglicol. 2. VO: Acetilcisteina, Guayacolato de glicerilo o guayfenesina, Ipecacuana, Yoduro de K, Bromhexina, carboximetilcisteina, Ambroxol.

EXPECTORANTES (mucoquineticos) Inhalación Propilenglicol Cl Na hipertónica 1.8 - 20% aerosol Cl Na Nausea, vomito, Broncoespasmo, irritación de mucosa bucal y faringeas

PROPILENGLICOL (inhaloterapia) Propiedades higroscopicas, se disuelve en H20, sabor dulce, no irritante. humectante y demulcente. Soluciones 2-5% en fibrosis quística de páncreas. 15-20% con solución salina hipertónica para inducir esputo.

Acetil Cisteina mucolítico MEC ACCION: Rompe los puentes de unión de disulfuro de las mucoproteínas. Liquificar.  viscosidad del esputo, no rompe el DNA. No acción sobre fibrina o coágulos sanguíneos Se usa por instilación directa al árbol bronquial. No se debería usar por inhalación y NO es efectiva por VO. Evita progresión de enfisema

Expectorantes administrados por vía oral Irritan la mucosa gástrica que provoca un reflejo vagal mucoquinetico gastro-pulmonar ↑ la secreción bronquial, requiriendo dosis eméticas. -Guayacolato de glicerilo o guayfenesina -Ipecacuana -Ioduro de K, Cloruro de amonio y Citrato de Na -Bromexina -Carboximetilcisteina -Ambroxol

Guayacolato de Glicerilo:Guayfenesina Expectorante ??? A dosis altas 2400mg diarios útil mucokineticos que por vía refleja (accion emetica) produce broncorrea Dosis empleadas es 800mg/d. Placebo !!

IPECACUANA Emética, el extracto contiene alcaloides emetina y cefalina En dosis subemeticas es estimulador del reflejo vagal gastropulmonar mucokinético Incremento de la secreción de glándulas bronquiales Caphelis acuminata

Ioduro de Potasio A largo plazo = bloque de la tiroides. Expectorante a dosis terapeutica? A largo plazo = bloque de la tiroides. Estimula el reflejo vagal gastropulmonar mucokinetico y secreción de glándulas bronquiales Estimula el movimiento ciliar. Estimula digestión del moco por las enzimas proteolíticas naturales. FARMACOPATOLOGÍA: nausea, vomito, rinorrea, eritema, acne, urticaria, hipotiroidismo.

Cloruro de amonio 200mg a un gramo en 5ml. Estimulando el reflejo vagal gastro-pulmonar Citrato de sodio Subemetica por vía oral nebulizaciones

Mucolytics -Bromexina - Oral mucolytics; loosen and thin bronchial secretions by reducing surface tension and viscosity of mucus. - Dizziness, headache, rash - these rarely occur at therapeutic doses. Nausea/vomiting, abdominal pain, diarrhoea.

BROMEXINA  expectoración  de viscosidad. (H2O y Obtenido de la planta Adhatoda basica Origen India (tos y asma)  expectoración  de viscosidad. (H2O y despolimerizacion de mucopolisacaridos).

CARBOXIMETILCISTEINA VO. (Acetilcisteina uso solo x local o inhalacion).  viscosidad del esputo rompiendo los puentes sulfhidrilos que unen los mucopolisacáridos.

AMBROXOL - Broncosecretolitico. - Estimulante del Surfactante -  la viscosidad del esputo - Antioxidante - Antiinflamatorio x interferencia con Ac araquidonico.

Cough and cold remedies for children Valerie Sung, University of Melbourn Key words: children, over-the-counter medicines. (Aust Prescr 2009; 32:122-4) Summary Over-the-counter cough and cold remedies for children under 2 years of age have recently been rescheduled to prescription-only. This will mean that doctors and pharmacists will encounter more consultations for such medicines. These drugs are no longer recommended in children because of the lack of efficacy and reports of serious adverse events.

Cough and cold remedies for children Valerie Sung, University of Melbourn Key words: children, over-the-counter medicines. (Aust Prescr 2009; 32:122-4) Summary Over-the-counter cough and cold remedies for children under 2 years of age have recently been rescheduled to prescription-only. This will mean that doctors and pharmacists will encounter more consultations for such medicines. These drugs are no longer recommended in children because of the lack of efficacy and reports of serious adverse events. Introduction Upper respiratory tract infections are common in children and it is not surprising that cough and cold symptoms can be a major burden to many families. Until recently, over-the-counter (OTC) cough and cold remedies were widely available in Australia, and extensively used in young children. They include antitussives, antihistamines, expectorants and decongestants (Table 1). However, since September 2008 cough and cold medicines for children less than two years have been rescheduled to S4 to become prescription-only. The USA and the UK introduced similar restrictions in response to reports of adverse effects, accidental overdoses and lack of evidence of their efficacy for acute and chronic cough in children. Cough in children Cough is a reflex response to mechanical, inflammatory and chemical irritation of the tracheobronchial tree. It is a normal mechanism for the maintenance of a healthy respiratory system. Diagnosis When a child presents with cough or cold symptoms, the most important first step is to make the correct diagnosis and exclude serious pathology. Most causes of cough are self-limiting and do not require investigations. A detailed history and physical examination are most important, followed by specific investigations only when clinically indicated. Causes of cough Management of a cough should be directed at the underlying cause. Cough that is accompanied by other upper respiratory tract infection symptoms, such as rhinorrhoea and sore throat, is usually due to viral infections and is rarely bacterial. If such a cough lingers, it may be a postinfective cough. A barking or brassy cough may suggest croup or tracheomalacia. Cough accompanied by respiratory distress suggests pneumonia or bronchiolitis. Asthma may present as nocturnal cough, while cough that disappears when the child is asleep may suggest a psychogenic cause. A coughing infant or child with paroxysms of cough may have pertussis. Suppurative lung disease should be considered if the cough is most vigorous in the morning. If there is a temporal association with feeding or with positioning, gastro-esophageal reflux should be considered. The presence of a foreign body should be suspected after an acute episode of choking, while aspiration may occur in children with hypotonia or pharyngeal incoordination. Chlamydia trachomatis is an uncommon but serious cause of cough that should be considered especially if the infant has conjunctivitis or whose mother has evidence of chlamydial infection. Structural anomalies causing cough are usually associated with other symptoms such as stridor or cyanosis.

Symptomatic treatments for colds and cough Cough and cold symptoms can cause significant distress to children and their families, and this is reflected in the vast array of OTC medications marketed over the years. Most cough and cold remedies are a combination of antitussives, antihistamines, expectorants and decongestants.

Antitussives Pholcodine Centrally acting opioid derivative; directly suppresses medullary cough centre Dizziness, sedation, nausea Opioid dependence, potential abuse, serotonin syndrome, lethargy, stupor, aspiration Dextromethorphan Narcotic analogue; directly suppresses medullary cough centre Antihistamines Diphenhydramine Brompheniramine Chlorpheniramine Histamine H1-receptor antagonists; prevent histamine-induced reactions in cells of the respiratory tract, gastrointestinal tract and blood vessels Sedation, headache, dizziness, nervousness, restlessness, irritability, palpitations Hallucinations, seizures, central nervous system depression, cardiovascular collapse, apnoea, death, anticholinergic effects Decongestants Pseudoephedrine Phenylephrine Sympathomimetic drugs, adrenergic receptor agonists; produce vasoconstriction within the respiratory tract mucosa, and cause increased heart rate and cardiac contractility Nervousness, restlessness, insomnia, trembling, headache, anxiety Tachycardia, palpitations, dysrhythmias, hypertension, hallucinations, agitation, central nervous system depression, seizures Expectorants Guaifenesin Ipecacuanha Expectorants; promote the expulsion of mucus and other materials from the respiratory tract Drowsiness, dizziness, headache, rash - these rarely occur at therapeutic doses Nausea/vomiting, abdominal pain, nephrolithiasis