PHM - Adrenergic Agents

ADRENERGIC AGENTS Drugs Affecting the Autonomic Nervous System Adrenergic Agents and Adrenergic-Blocking Agents CNS PHYSIOLOGY Nervous System  a group of tissue composed of highly specialized cells possessing the characteristics of excitability and conductivity. MORPHOLOGICAL DIVISONS 1.

Central Nervous system Brain, spinal cord

2.

Peripheral Nervous System Cranial Nerves (12 pairs) Spinal Nerves (31 pairs) Autonomic Nervous System

Types of cells in the nervous system  the nervous system is composed of a special tissue containing two major types of cells. Neurons the active conducting element Neuroglia the supporting elements NEURON  basic unit of the nervous system which conduct electrical impulses from one part of the body to another  Consist of a cell body (perikaryon), containing a single nucleus, and processes transmitting impulses to and from the cell body.

NEUROTRANSMITTERS Main neurotransmitters:  Epinephrine (adrenalin), norepinephrine (nor adrenalin), acetylcholine  All are released by autonomic fibers. Acethylcholine released at neuromuscular junction. CENTRAL NERVOUS SYSTEM  Central nervous system includes the BRAIN and SPINAL CORD  Each division is further divided grossly gray matter white matter Gray Matter Nucleus Ganglion Regions of the Brain

Cerebrum Lobes of the Cerebral Cortex: 1. Frontal lobe Center of motor function and personality 2. Parietal lobe Center for ordinary sensory function 3. Temporal lobe Center of hearing and olfaction 4. Occipital lobe Visual center 5. Insula (Island of Reil) Synapse  synapses are points of connection between neurons.  The axon of one neuron make functional contact with dendrites of another neuron .  neurotransmitters are released from axon endings for impulse to leap the synaptic junction:

Functional area of the cerebral cortex  Motor speech area/Broca’s area  Sensory speech area/ Wernicke’s area  Auditory/Hearing Area (Transverse gyri of Heschl)  Visual area  Olfactory/ smell area  Taste area

Basal Ganglia  Caudate nucleus (medial portion)  Lentiform nucleus (lateral portion) Putamen Globus pallidus  Control of motor function  Unintetional, unecessary movement Thalamus  Located below the corpus callosum  Highest subcortical sensory integrating system  All sensory impulses passes to it except olfactory Hypothalamus  Where the pituitary gland is attached  Functions in regulation of; Body temperature feeding activities Concentration volume of extracellular fluid autonomic nervous system response endocrine function Cerebellum  Vermis and hemisphere  Aids the motor cortex in integration of voluntary movements  Injury- loss of coordination of motor activity Pons 

Bridge like structure

Medulla oblongata  Vital regulatory and reflex center  Circulatory system, breathing, swallowing. Vomiting, coughing, sneezing Functions of the Nervous System 1. Sensory input – gathering information  To monitor changes occurring inside and outside the body (changes = stimuli) 2. Integration  To process and interpret sensory input and decide if action is needed. 3. Motor output  A response to integrated stimuli  The response activates muscles or glands Functional Classification of the PNS 1.

Sensory (afferent) division Nerve fibers that carry information to the central nervous system

2.

Motor (efferent) division Two subdivisions: Somatic nervous system = voluntary Autonomic nervous system = involuntary

The Reflex Arc  Reflex – rapid, predictable, and involuntary responses to stimuli  Reflex arc – direct route from a sensory neuron, to an interneuron, to an effector Types of Reflexes and Regulation  Autonomic reflexes Smooth muscle regulation Heart and blood pressure regulation Regulation of glands Digestive system regulation  Somatic reflexes Activation of skeletal muscles Autonomic Nervous System  The involuntary branch of the nervous system  Consists of only motor nerves  Divided into two divisions - Sympathetic division - Parasympathetic division Autonomic Functioning Sympathetic – ―fight-or-flight‖ Response to unusual stimulus Takes over to increase activities Remember as the ―E‖ division = exercise, excitement, emergency, and embarrassment Parasympathetic – housekeeping activities Conserves energy Maintains daily necessary body functions Remember as the ―D‖ division - digestion, defecation, and diuresis

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Causes dilation of the following blood vessels, resulting in INCREASED blood flow Renal Mesenteric Coronary Cerebral Adrenergic Receptor Responses to Stimulation

ADRENERGIC MEDICATION Adrenergic Agents  Drugs that stimulate the sympathetic nervous system (SNS)  Also known as adrenergic agonists or sympathomimetics  Mimic the effects of the SNS neurotransmitters: norepinephrine (NE) epinephrine (EPI) Adrenergic Receptors  Located throughout the body  Are receptors for the sympathetic neurotransmitters Alpha-adrenergic receptors: respond to NE Beta-adrenergic receptors: respond to EPI Alpha-Adrenergic Receptors Divided into alpha1 and alpha2 receptors Differentiated by their location on nerves Alpha1-Adrenergic Receptors  Located on postsynaptic effector cells (the cell, muscle, or organ that the nerve stimulates) Alpha2-Adrenergic Receptors  Located on presynaptic nerve terminals (the nerve that stimulates the effector cells)  Control the release of neurotransmitters The predominant alpha-adrenergic agonist responses are:  Vasoconstriction  CNS stimulation Beta-Adrenergic Receptors All are located on postsynaptic effector cells Beta1-adrenergic receptors  located primarily in the heart Beta2-adrenergic receptors  located in smooth muscle of the bronchioles, arterioles, and visceral organs The beta-adrenergic agonist response results in:  Bronchial, GI, and uterine smooth muscle relaxation  Glycogenolysis  Cardiac stimulation Dopaminergic Receptors  An additional adrenergic receptor  Stimulated by dopamine

Catecholamines Substances that can produce a sympathomimetic response Endogenous: epinephrine, norepinephrine,dopamine Synthetic: isoproterenol, dobutamine, phenylephrine Adrenergic Agents Mechanism of Action: 1. Direct-acting sympathomimetic:  Binds directly to the receptor and causes a physiologic response 2. Indirect-acting sympathomimetic:  Causes the release of catecholamine from the storage sites (vesicles) in the nerve endings  The catecholamine then binds to the receptors and causes a physiologic response 3. Mixed-acting sympathomimetic:  Directly stimulates the receptor by binding to it AND  Indirectly stimulates the receptor by causing the release of stored neurotransmitters from the vesicles in the nerve endings

Drug Effects of Adrenergic Agents Stimulation of alpha-adrenergic receptors on smooth muscles results in:      

Vasoconstriction of blood vessels Relaxation of GI smooth muscles Contraction of the uterus and bladder Male ejaculation Decreased insulin release Contraction of the ciliary muscles of the eye (dilated pupils)

Stimulation of beta2-adrenergic receptors on the airways results in:   

Bronchodilation (relaxation of the bronchi) Uterine relaxation Glycogenolysis in the liver

Stimulation of beta1-adrenergic receptors on the myocardium, AV node, and SA node results in CARDIAC STIMULATION:   

Increased force of contraction (positive inotropic effect) Increased heart rate (positive chronotropic effect) Increased conduction through the AV node (positive dromotropic effect)

THERAPEUTIC USES Anorexiants: adjuncts to diet in the short-term management of obesity Examples:

benzphetamine phentermine dextroamphetamine Dexedrine

Bronchodilators: treatment of asthma and bronchitis Agents that stimulate beta2-adrenergic receptors of bronchial smooth muscles causing relaxation These agents may also affect uterine and vascular smooth muscles. Examples: albuterol isoetharine metaproterenol

ephedrine isoproterenol salmeterol

epinephrine levalbuterol terbutaline

Reduction of intraocular pressure and mydriasis (pupil dilation): treatment of open-angle glaucoma Examples:

epinephrine and dipivefrin

Nasal decongestant: Intranasal (topical) application causes constriction of dilated arterioles and reduction of nasal blood flow, thus decreasing congestion. Examples: epinephrine phenylephrine

Examples: dobutamine epinephrine methoxamine

naphazoline tetrahydrozoline

dopamine fenoldopam norepinephrine

ephedrine isoproterenol phenylephrine

SIDE EFFECTS Alpha-Adrenergic Effects  CNS: headache, restlessness, excitement, insomnia, euphoria  Cardiovascular: palpitations (dysrhythmias), tachycardia, vasoconstriction, hypertension  Other: anorexia, dry mouth, nausea, vomiting, taste changes (rare) Beta-Adrenergic Effects  CNS: mild tremors, headache, nervousness, dizziness  Cardiovascular: increased heart rate, palpitations (dysrhythmias), fluctuations in BP  Other: sweating, nausea, vomiting, muscle cramps INTERACTIONS  Anesthetic agents  Tricyclic antidepressants  MAOIs  Antihistamines  Thyroid preparations  Antihypertensives  Will directly antagonize another adrenergic agent, resulting in reduced effects Adrenergic-Blocking Agents  Bind to adrenergic receptors, but inhibit or block stimulation of the sympathetic nervous system (SNS)  Have the opposite effect of adrenergic agents  Also known as adrenergic antagonists or sympatholytics Sympatholytics inhibit—or LYSE—sympathetic neurotransmitters (norepinephrine and epinephrine) Classified by the type of adrenergic receptor they block  Alpha1 and alpha2 receptors  Beta1 and beta2 receptors Drug Effects and Therapeutic Uses 

ephedrine naphazoline tetrahydrozoline

Ophthalmic: Topical application to the eye surface affects the vasculature of the eye, stimulating alpha receptors on small arterioles, thus relieving conjunctival congestion. Examples: epinephrine phenylephrine

Vasoactive sympathomimetics (pressors, inotropes), also called cardioselective sympathomimetics: Used to support the heart during cardiac failure or shock.

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Ergot Alkaloids (Alpha-Blockers) Constrict dilated arteries going to the brain (carotid arteries) Used to treat vascular headaches (migraines) Stimulate uterine contractions by inducing vasoconstriction Used to control postpartum bleeding Alpha-Blockers Cause both arterial and venous dilation, reducing peripheral vascular resistance and BP Used to treat hypertension Effect on receptors on prostate gland and bladder decreased resistance to urinary outflow, thus reducing urinary obstruction and relieving effects of BPH

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Phentolamine  Quickly reverses the potent vasoconstrictive effects of extravasated vasopressors such as norepinephrine or epinephrine.  Restores blood flow and prevents tissue necrosis.

SIDE EFFECTS

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Beta Blockers Block stimulation of beta receptors in the SNS Compete with norepinephrine and epinephrine Selective and nonselective beta blockers

Beta Receptors Beta1 Receptors Located primarily on the heart Beta blockers selective for these receptors are called cardioselective beta blockers Beta2 Receptors Located primarily on smooth muscles of bronchioles and blood vessels Nonspecific Beta Blockers Beta blockers that block both beta1 and beta2 receptors Mechanism of Action Cardioselective (Beta1) Decreases heart rate Prolongs SA node recovery Slows conduction rate through the AV node Decreases myocardial contractility, thus decreasing myocardial oxygen demand Nonspecific (Beta1 and Beta2) Effects on heart: Same as cardioselective Bronchioles: Constriction, resulting in narrowing of airways and shortness of breath Blood vessels: Vasoconstriction Therapeutic Uses Anti-angina: decreases demand for myocardial oxygen Cardioprotective: inhibits stimulation by circulating catecholamines Class II antidysrhythmic Antihypertensive Treatment of migraine headaches Glaucoma (topical use)