Section 9 - Drugs and Toxins Affecting the Respiratory System

Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Principles of Pharmacology and Toxicology (BIOL3020) Section 9 Drugs and Toxins Affecting the Respiratory System Rang et al 2007 (Chapter 23) Stine and Brown (2006) Principles of Toxicology The Control of the Air Ways SM Preganglionic neuron ganglion Postganglionic neuron CNS The Control of the Air Ways  SM The Control of the Air Ways Nitric Oxide (NO) In upper airways Activates guanylate cyclase Increase cGMP-activate protein kinase G Ca2 inhibited Activates K channels  Irritant receptors/C-fibres Chemical stimuli can act on receptors or C-fibers Cause bronchoconstriction and coughing C-fibres release neuropeptides that causes mucus secretion and constriction Asthma  Asthma Drugs Bronchodilators  Xanthine Drugs Theophylline, theobromine, caffeine theobromine (cocca) Inhibits phoshodiesterase (PDE) isoenzymes This increases cAMP Relaxes SM Given orally Side effects (heart, blood vessels) Asthma Drugs Bronchodilators Muscarinic Receptor antagonists Ipratroponium Blocks M3 receptors on SM It can block M2-autoreceptors thus increasing ACh release Decrease its effectiveness on M3 receptors on smooth muscle Given by inhalation not absorbed well SM Asthma Drugs Anti-inflammatory Agents f Cough Drugs Respiratory Toxicology d d Respiratory Toxicology Respiratory Toxicology The irritant response of toxicants Induce bronchoconstriction May interact directly with SM or receptors and nerves Respiratory Toxicology Examples of Irritant toxicants Lower air ways Nitrogen dioxide (NO2) and ozone produce fluid in alveoli Herbicide paraquat (LD50 30mg/kg) tends to accumulate in lungs Upper air ways Sulfur dioxide Formaldehyde Respiratory Toxicology Conditions caused by toxicants Asthma May involve injury to epithelial cells by free radicals May develop from toxicants such as toluene diisocyanate Byssinosis (Brown lung) Exposure to cotton dust in mills May be an allergic reaction to microoganisms on dust particles Or to reaction to irritant in the cotton dust itself Hypersensitivity pneumonitis Exposure to organic materials that trigger allergic reaction Response to moldy hay (farmers lung) Exposure to fungus on cheese particles (cheese washers lung) Respiratory Toxicology Conditions caused by toxicants