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 whereby

1. airflow = blood flow2. gas pressure = fluid pressure3. resistance of airway = resistance of

blood pressure

Airflow, pressure and resistance relationships

ohm’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

Pressure Gradient and 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 parasympathetic

2.Adrenergic drugs – acts on the receptors that are stimulated by norepinephrine and epinephrine – stimulates the sympathetic

Effects of catecholamines and cholinergic agonists on the airflow

1. Norepinephrine• Post-ganglionic Neurotransmitter for the sympathetic Nervous system

2. Acetylcholine• Pre-ganglionic Neurotransmitter for both systems Post-ganglionic neurotransmitter for the parasympathetic nervous system

Adrenergic agonists and cholinergic agonists

Adrenergic Agonists

Albuterol

Dopamine

Epinephrine

Isoproterenol

Norepinephrine

Salmeterol

Terbutaline

Cholinergic Agonists

Bethanechol

Carbachol

Neostigmine

Physostigmine

Tacrine

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 β

α adrenergic order of potency Epinephrine > norepinephrine > isoproterenol

β adrenergic order of potencyIsoproterenol > epinephrine > norepinephrine

Cathecolamines receptorsα 1 α 2 β 1 β 2

Vasoconstriction Inhibition of norepinephrine release

Tachycardia Vasodilation

Increased peripheral resistance

Inhibition of insulin release

Increase lipolysis Slightly Decrease in peripheral resistance

Increase in blood pressure

Increase in contractility of myocardium

BRONCHODILATION

Mydriasis Increse release of renin

Increase muscle and liver glygogenolysis

Increased closure of spinchter of internal spinchter and bladder

Relaxed uterine smooth muscle

Drugs and Receptor Interaction

α 1 α 2 β 1 β 2

ADRENALINE ++ ++ +++ +++

NORAD ++++ + ++ +

DOPAMINE >10 µg/kg/min 5- 10 µg/kg/min

ISOPROTERENOL ++++ +++

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 airflow

1. Catecholamine effect : isoproterenol and epinephrine – adrenergic receptor – sympathetic stimulation – bronchodilation – decrease resistance

2. 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 airflow

H1 receptors effect :Increased production of nasal and bronchial mucous

Constriction of bronchioles

Mucosal edema from increased microvascular permeability

Itching 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.

Prostaglandins effect on airflow

Prostaglandins effect on airflow

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