APH1 PDF - Physiology Exam Notes

which system through responses behavioral regulation and viscromotor neusendocrine pain E integral component controls the brain of an internal , , essential for survival. , alls molecules signaling target Specialized endocrine cells secrete hormones into the bloodstream where they travel thr...

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F qy The somatic efferent neurons are involved in the voluntary control of functions such as contraction of the skeletal muscles essential for locomotion. Estefierent 6 c Cs openingsor 12 vertebrae Thespinal cord finishes 5 very at L1 fromthere is justramification Gy 5 vert Freation 3 Eat fanfare 991s.inlcord if qq.ua pygffeathed nerve cell brasifeen ᵗ of a fiftreganslionic trajectory p IEEE's p.EEIiEPIIie Areshort 4Th Aug 71 022 an hake Another name Sympathetic output (Diffuse because postganglionic neurons may innervate more than one organ) Parasympathetic output (Discrete because postganglionic neurons are not branched, but are directed to a specific organ. Ejemplos que puede defiler I a to a 3 ganglion nucleiThen releases epi and norepi EE 1 a If transmission is mediated by acetylcholine, the neuron is termed cholinergic When norepinephrine or em epinephrine is the transmitter, the fiber is Ef.io A A termed adrenergic. Cholinergic (red) Adrenergic (blue) 1 4 7 or When the signal is already postganglionic and is hitting the target organ. Those organs now have receptors. 4mpara The parasympathetic receptor is cholinergic. Anything postganglionic that is innervated by acetylcholine is a cholinergic receptor. Specifically a muscarinic receptor of the parasympathetic system. For the sympathetic system is called adrenergic receptor and the neurotransmitter is norepinephrine. Nicotinic receptor are not part of the autonomic system they are part of your voluntary skeletal system called nicotinic receptor. In the nicotinic receptor the neurotransmitter is acetylcholine. time iiÉii Receptor Befeptor decrease muscarinic Feceptor 498 Dilation I Emitter Lacrimal Gland If.it rye i have para and symp im parasympathetic chdings SEIBEL closes c muscarinic receptor contrae norepinephrine Ritatessympathetic innervation it isthitting a receptor In f ftp.hf faftes Beta 2 agonistAlbuterol Tepinephrine 2 Ten fathetic BqInemp ym Afferent Bloodflowbythe sympathetic MEus EYE sympathetic neuron trajectory 5 APH2 Exam #1 Adrenergic Agonist Agents: Detalles adicionales que mencionó el profesor y del capítulo del libro estarán escritos a mano Norepinephrine release at effector tissue/organ (Remember this is post-ganglionic synapses) o Norepinephrine (NE) is the primary neurotransmitter for postganglionic sympathetic adrenergic nerves. It is synthesized inside the nerve axon, stored within vesicles, then released by the nerve axon stored within vesicles, then released by the nerve when an action potential travels down the nerve. Below are the details for release and synthesis of norepinephrine (NE). Adrenergic Agonist Drugs: They act on receptors stimulated by epinephrine and norepinephrine. Activation of Alpha Adrenoreceptors Direct Acting Adrenergic Agonists Endogenous/Natural Occurring Synthetic Epinephrine Dobutamine Norepinephrine Isoproterenol Dopamine Epinephrine: Interacts with alpha and beta receptors Low dose/levels High dose Higher affinity for beta receptors Higher affinity for alpha receptors Beta receptor activity predominates 9vasodilation Alpha receptor predominates (vasoconstrictor by by beta 2 receptor activity) alpha 1 receptor activity) Pharmacokinetics of epinephrine o Rapid onset but brief duration: IV, SC o Orally ineffective o Metabolites excreted in urine (Metanephrine & Vanillylmandelic Acid) o Adverse effects: CNS disturbances intracerebral hemorrhage cardiac arrhythmias (digitalis) pulmonary edema o Interactions: Hyperthyroidism & Cocaine Actions of Epinephrine Cardiovascular System o (+) inotropic and chronotropic (B1) o Peripheral vasoconstriction with decrease renal blood flow (A1) o Peripheral vasodilation (B2) Respiratory system: Bronchodilation (B2) Liver: Glycogenolysis (B2) Pancreas: Low insulin (A2) Adipose tissue: Lipolysis (B3) Therapeutic use of Epinephrine o Bronchospasm (SC) o Anaphylactic shock: Type 1 hypersensitivity reactions (Anaphylaxis) o Glaucoma open angle (2% sol): Low intraocular pressure by increase uveoscleral outflow. o Anesthetics: Increased duration of local anesthetic effect due to vasoconstriction Norepinephrine: Affects mostly alpha receptors Actions: o Cardiovascular - vasoconstriction: Endogenous NE is reduced with baroreceptor reflex (stretching of baroreceptors due increased BP which cause decrease in sympathetic flow and thus NE levels) Therapeutic use: o Acute hypotension in a hemodynamically unstable patient o It can be use as atropine pre-treatment for acute hypotension (if given after atropine it will cause tachycardia) o Cardiac arrest (adjunct TX) Isoproterenol: Non-selective B1 and B2 agonist Actions o Cardiovascular: (+) inotropic (+chronotropic), decrease peripheral resistance o Pulmonary – Bronchodilation Therapeutic use: Bronchial Asthma & Heart block or cardiac arrest Dopamine: A1 and B1 receptors activity D receptors activity o Dopamine 1 receptors subserve vasodilation, especially in the renal, coronary, mesenteric, and cerebral vascular beds. o Dopamine 2 receptors have been located at the endings of postganglionic sympathetic nerves; upon activation norepinephrine release Actions Cardiovascular o (+) inotropic (+) chronotropic (B1) vasoconstriction (A) o Vasodilation of dilation of renal and splanchnic beds Therapeutic use: Primarily used for cardiogenic shock and acute HF Adverse effects: Short lived arrhythmias and nausea Other direct acting agents o Fenoldopam: IV D1 and D2 Rapid vasodilation for severe hypertension in hospitalized patients o Dobutamine (B1): (+) inotropic Use in congestive heart failure to high C.O. o Phenylephrine (A1) o Oxymetazoline (A): Nasal decongestant Ophthalmic (Upneeq) o Clonidine (A2): Essential hypertension due to CNS action (diminish central adrenergic outflow) o Beta-2 agonist (bronchodilators): Metaproterenol, Albuterol, Pirbuterol, Salmeterol and formoterol (long acting), Terbutaline-also for tocolysis (bronchodilator in low uterine contractions in premature labor (delay labor)) Indirect Acting Adrenergic Agents o Amphetamines (“up”): Causes release of norepinephrine from presynaptic terminals and increase NE release. Central stimulation High blood pressure and heart rate o Tyramine (an amino acid): Not a clinically useful drug found in cheese and Chianti wine. o Cocaine: local anesthetic that blocks Na/K pump required for reuptake of norepinephrine enhancing its sympathetic activity Mixed-Action Adrenergic Agents o Induce norepinephrine release from presynaptic terminals and activate adrenergic receptors in post synaptic membranes. o Ephedrine: enhance contractility and improve motor function in Myasthenia Gravis o Metaraminol: Alternative drug for shock treatment. May be used to treat acute hypotension. Adrenergic Agonists Side Effects: Arrhythmias, Headache, Hyperactivity, Insomnia, Nausea, Tremors Chapter 6 Review: Quizás hay diagramas repetidos a la presentación, pero aquí añadí más detalles del libro o Adrenergic drugs affect receptors that are stimulated by norepinephrine or epinephrine. Some adrenergic drugs act directly on the adrenergic receptor (adrenoreceptor) by activating it and are said to sympathomimetic. Those who block the action of the neurotransmitters at the receptors are known as sympatholytic. o Neurotransmission takes place at numerous varicosities and it involves five steps: o Types of adrenergic receptors Activation of alpha 1 receptor initiates a series of reactions through the G protein activation of phospholipase C: 1. Results in the generation of inositol-1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG) from phosphatidylinositol 2. IP₃ initiates the release of Ca²⁺ from the endoplasmic reticulum into the cytosol, and DAG turns on other proteins within the cell. In contrast to alpha 1 receptors, the effects of binding at alpha 2 receptors are mediated by inhibition of adenylyl cyclase and a fall in the levels of intracellular cAMP. Desensitization of receptors: Reduced responsiveness of these receptors because of the prolonged exposure to the catecholamines. There are three mechanisms that suggest this phenomenon: 1. Sequestration of the receptors so that they are unavailable for interaction with the ligand 2. Down-regulation, that is, a disappearance of the receptors either by destruction or decreased synthesis 3. An inability to couple to G protein, because the receptor has been phosphorylated on the cytoplasmic side by either protein kinase " or βadrenergic receptor kinase Characteristics of Adrenergic Agonists Most adrenergic drugs are derivatives of β-phenylethylamine. Two important structural features of these drugs are: 1) the number and location of OH substitutions on the benzene ring and 2) the nature of the substituent on the amino nitrogen. A. Catecholamines Sympathomimetic amines that contain the 3,4-dihydroxybenzene group 9such as epinephrine, norepinephrine, isoproterenol, and dopamine). These compounds share the following properties: 1. High potency: Drugs that are catechol derivatives (With -OH groups in the 3 and 4 positions on the benzene ring) show the highest potency in directly activating " or β receptors. 2. Rapid inactivation: Catecholamines can be metabolized by catechol-Omethyltransferase (COMT) postsynaptically and by monoamine oxidase (MAO) intraneuronally, but also can be metabolized in other tissues(COMT being in the gut wall and MAO in the liver and gut wall). Catecholamines have a brief period of action when given parenterally and they are ineffective when administered orally because of inactivation. 3. Poor penetration into the CNS: Catecholamines are polar and therefore do not readily penetrate into the CNS. Nevertheless, most of these drugs have some clinical effects (anxiety, tremor, and headaches) that are attributable to action on the CNS. B. Noncatecholamines Compounds lacking the catechol hydroxyl groups have longer half-lives because they are not inactivated by COMT. These include phenylephrine, ephedrine, and amphetamine. These are poor substrates for MAO and thus show a prolonged duration of action because MAO is an important route of detoxification. Increased lipid solubility of many of the non-acatecholamines (due to lack of polar hydroxyl groups) permits greater access to the CNS. NOTE: EPHEDRINE and AMPHETAMINE may act indirectly by causing the release of stored catecholamines. C. Substitutions on the amine nitrogen Epinephrine with a -CH₃ substituent on the amine nitrogen is more potent at β receptors than norepinephrine which has an unsubsituted amine. Similarly, isoproterenol, which has an isopropyl substituent -CH (CH₃)₂ on the amie nitrogen is a strong β agonist with little " activity. D. Mechanism of action of the adrenergic agonists