Faez Baherin MBBSMMed (Emergency) Training Programme USM Supervised by Dr T. Hairul
Outlines• Relationship between flow, pressure and resistance in regards to the conducting airway• Effects of catecholamines and cholinergic agonists on the airflow• Effects of histamine and prostaglandins on bronchial smooth muscles and air flow
Airflow, pressure and resistance relationships• Analogous to the relationship in cardiovascular system whereby1. airflow = blood flow2. gas pressure = fluid pressure3. resistance of airway = resistance of blood pressure
Airflow, pressure and resistance relationshipsohm’s law•Q = airflow (ml/min or L/min)• P = pressure gradient (mm Hg or cm H20)•R = airway resistance (cm H20/L/sec)
Pressure Gradient and Airflow• Pressure difference ( P) is the driving force for the airflow.• In a breathing cycle :- Rest : alveolar pressure = atmospheric pressure, no pressure difference, no driving force, no airflow- Inspiration : diaphragm contracts, increase lung volume, decrease alveolar pressure, presence of pressure gradient hence the airflow
Airway Resistance and Airflow• Flow is inversely proportional to resistance• Resistance determinants : Poiseuille’s Law
Airway Resistance and Airflow• Airway resistance is :-directly proportional to viscosity and length-inversely proportional to radius to the power of 4 (powerful relationship)• Airflow is :-directly proportional to the pressure gradient and radius-inversely proportional to the viscosity and length
Effects of catecholamines and cholinergic agonists on the airflow• Bronchial smooth muscle is innervated by parasympathetic cholinergic nerve fibers and by sympathetic adrenergic nerve• Sympathetic stimulation produces relaxation of bronchial smooth muscle via stimulation of β2 receptors – increase airway diameter – decrease resistance – increase airflow (adrenergic agonist)• Parasympathetic stimulation produces constriction of bronchial smooth muscle – reduce diameter – increase resistance – decrease airflow (cholinergic agonist)
Effects of catecholamines and cholinergic agonists on the airflow• Drugs affecting ANS are divided into 2 groups (depending to the type of neuron involved in the mechanism of action)1.Cholinergic drugs - acts on the receptors that are activated by Ach – stimulates the parasympathetic2.Adrenergic drugs – acts on the receptors that are stimulated by norepinephrine and epinephrine – stimulates the sympathetic
Effects of catecholamines and cholinergic agonists on the airflow1. Norepinephrine• Post-ganglionic Neurotransmitter for the sympathetic Nervous system2. Acetylcholine• Pre-ganglionic Neurotransmitter for both systems Post-ganglionic neurotransmitter for the parasympathetic nervous system
Effects of Catecholamines on airflow• Adrenergic neurons and receptors (stimulated by epi/nor epi) are the sites of effect of adrenergic drugs – catecholamines• Adrenergic receptors – α and βα adrenergic order of potencyEpinephrine > norepinephrine > isoproterenolβ adrenergic order of potencyIsoproterenol > epinephrine > norepinephrine
Cathecolamines receptors α1 α2 β1 β2Vasoconstriction Inhibition of Tachycardia Vasodilation norepinephrine releaseIncreased Inhibition of insulin Increase lipolysis Slightly Decrease inperipheral release peripheral resistanceresistanceIncrease in blood Increase in BRONCHODILATIONpressure contractility of myocardiumMydriasis Increse release of Increase muscle and renin liver glygogenolysisIncreased closure of Relaxed uterinespinchter of smooth muscleinternal spinchterand bladder
Cholinergic agonists• Cholinergic drugs - acts on the receptors that are activated by Ach• Carbachol, Bethanechol- Synthetic esters of choline - binds directly to cholinoreceptor - constriction of bronchial smooth muscle• Neostigmine- Cholinesterase inhibitor - allow accumulation of acetylcholine at the NMJ – prolongs effects -constriction of bronchial smooth muscle
Summary for the effects of catecholamine and cholinergic agonists on airflow1. Catecholamine effect : isoproterenol and epinephrine – adrenergic receptor – sympathetic stimulation – bronchodilation – decrease resistance2. Cholinergic agonist : - Carbachol, Bethanechol - cholinergic receptor – parasympathetic stimulation – bronchoconstriction – increase resistance
Histamine effect on airflow• Histamine- Chemical messenger that mediates a wide range of cellular responses including allergic and inflammatory rxn, gastric acid secretion and neurotransmissions in parts of the brain.- Occurs in all tissues but unevenly distributed, high amount found in lung, skin and GI tract- High concentration in mast cells or basophils- Component of venoms and in secretion from insect stings
Histamine effect on airflow• Histamine exerts its actions by combining with specific cellular histamine receptors.• The four histamine receptors that have been discovered in humans and animals are designated H1 through H4• Release of histamine may be from the response to some stimuli like cold, bacterial toxins, bee sting venoms, allergic and trauma.
Histamine effect on airflowH1 receptors effect :Increased production of nasal and bronchial mucousConstriction of bronchiolesMucosal edema from increased microvascular permeabilityItching and pain – sensory nerve ending
Prostaglandins effect on airflow• Any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the human body.• They are synthesized in the cell from the essential fatty acids.• Mediate a wide range of physiological functions, such as control of blood pressure, contraction of smooth muscle, and modulation of inflammation.• Found in most tissues and organs and produced by almost all nucleated cells.• They act upon platelets, endothelium, uterine and mast cells.
Prostaglandins effect on airflow• An intermediate arachidonic acid is created from diacylglycerol via phospholipase-A2, then brought to either the cyclooxygenase pathway or the lipoxygenase pathway to form either prostaglandin and thromboxane or leukotriene respectively.• The cyclooxygenase pathway produces thromboxane, prostacyclin and prostaglandin D, E and F.• The lipoxygenase enzyme pathway is active in leukocytes and in macrophages and synthesizes leukotrienes.
Summary• Airflow is directly proportional to the radius and pressure gradient, and inversely proportional to the length and viscosity• Catecholamine causes bronchodilation• Cholinergic agonist causes bronchoconstriction• Histamine causes increase in airway resistance• Prostaglandins have dual effects - Protacycline – bronchodilation - PGE2 – EP 1 – bronchoconstriction EP 2 - bronchodilation
Reference• Linda S Constanzo, 4th Edition 2006• Lippincott’s illustrated reviews of pharmacology, 3rd Edition 2006• Previous slide presentations