Autonomic Drugs - Adrenergic Agonists - Ch 6 .docx

Autonomic Drugs -- Adrenergic Agonists Overview: - Adrenergic drugs affect receptors that are stimulated by norepinephrine (noradrenaline) or epinephrine (adrenaline) - Drugs that activate adrenergic receptors are termed sympathomimetics - Direct-acing agonists directly activate ad...

Autonomic Drugs -- Adrenergic Agonists Overview: - Adrenergic drugs affect receptors that are stimulated by norepinephrine (noradrenaline) or epinephrine (adrenaline) - Drugs that activate adrenergic receptors are termed sympathomimetics - Direct-acing agonists directly activate adrenergic receptors - Indirect-acting agonists act indirectly by enhancing release or blocking reuptake of norepinephrine - Drugs that block activation of adrenergic receptors are termed sympatholytic The Adrenergic Neuron - Adrenergic neurons release norepinephrine as the primary neurotransmitter - These neurons are found in the CNS and in the sympathetic nervous system where they sever as links b/w ganglia and the effector organs - Adrenergic drugs act on adrenergic receptors, located either presynaptically on the neuron or postsnaptically on the effector organ - Neurotransmission at adrenergic neurons: 6 steps - 1\. Synthesis of Norepinephrine - Tyrosine is transported by a carrier into the adrenergic neuron, where it is hydroxylated to dihydroxyphenylalanine (DOPA) by tyrosine hydrolase - This is the rate-limiting step in the formation of norepinephrine - DOPA is then decarboxylated by the enzyme aromatic I-amino acid decarboxylase to form dopamine in the presynaptic neuron - Tyrosine DOPA Dopamine - 2\. Storage of norepinephrine in vesicles - Dopamine is transported into synaptic vesicles - Next, dopamine is hydroxylated to form norepinephrine by the enzyme dopamine β-hydroxylase - Dopamine norepinephrine - The amine carrier system is blocked by reserpine (transport blocker) - 3\. Release of norepinephrine - An action potential arriving at the nerve junction triggers an influx of calcium ions from the extracellular fluid into the cytoplasm of the neuron - The increase in calcium causes synaptic vesicles to fuse with the cell membrane and to undergo exocytosis and expel their contents into the synapse - Drugs such as guanethidine block this release - 4\. Binding to receptors - Norepinephrine released from the synaptic vesicles diffuses into the synaptic space and binds to postsynaptic receptors on the effector organ or to the presynaptic receptors on the nerve ending - Binding of norepinephrine to receptors triggers a cascade of events within the cell, resulting in the formation of intracellular second messengers that act as links (transducers) in the communication b/w the neurotransmitter and the action generated within the effector cell - Norepinephrine also binds to presynaptic receptors (mainly α2 subtype) that modulate the release of the neurotransmitter - Adrenergic receptors use both the cyclic adenosine monophosphate (cAMP) second messenger system and the phosphatidylinositol cycle to transduce the signal into an affect - 5\. Removal of norepinephrine - Norepinephrine may... - Diffuse out of the synaptic space and enter the systemic circulation - Be metabolized to inactive metabolites by catechol-O-methyltransferase (COMT) in the synaptic space - Undergo reuptake back into the neuron - Reuptake of norepinephrine into the presynaptic neuron is the primary mechanism for termination of its effects - The reuptake by the neuronal membrane involves a sodium--chloride (Na+/Cl−)--dependent norepinephrine transporter that can be inhibited by tricyclic antidepressants (TCAs), such as imipramine; by serotonin--norepinephrine reuptake inhibitors such as duloxetine; or by cocaine and amphetamines. - 6\. Potential fates of recaptures norepinephrine (including metabolism) - Once norepinephrine reenters the adrenergic neuron, it may be taken up into synaptic vesicles via the amine transporter system and be sequestered for release by another action potential, or it may persist in a protected pool in the cytoplasm - Alternatively, norepinephrine can be oxidized by monoamine oxidase (MAO) present in neuronal mitochondria - Adrenergic Receptors (adrenoceptors) - 2 main families: α and β - α-adrenoceptors - weak response to isoproterenol (synthetic) - responsive to epinephrine and norepinephrine, naturally occurring catecholamine - catecholamines are the hormones produced and released by the adrenal glands -- responsible for sympathetic stimulation - α~1~ receptors - present on the postsynaptic membrane of effector organs - activates second messengers - causes constriction of smooth muscle - α~2~ receptors - present on sympathetic presynaptic nerve endings - control the release of norepinephrine - stimulation of α~2~ receptors decreases intracellular cAMP - also found on parasympathetic presynaptic nerve endings -- inhibit the release of ACh - further subdivisions - useful for more selective drug targets - examples: Tamsulosin -- α~1A~ antagonist for BPH - β-Adrenoceptors - strong response to isoproterenol (synthetic) - less responsive to epinephrine and norepinephrine (natural) - 3 types of β-receptors - β ~1~ -- equal affinity for epinephrine and norepinephrine - β ~2~ -- higher affinity for epinephrine - β ~3-~ ? - binding of a neurotransmitter at any of the 3 subtypes results in activation of adenylyl cyclase and increase concentrations of cAMP within the cell - Distribution of receptors: - Adrenergically innervated organs and tissues usually have a predominant type of receptor - Characteristic responses mediated by adrenoceptors - In general -- stimulation of a α~1~ receptor produces vasoconstriction and increase in total peripheral resistance and blood pressure - Stimulation of β ~1~ receptors causes cardiac stimulation (increase in HR and contractility) (1 = heat) - Stimulation of β ~2~ receptors produces vasodilation (skeletal muscle vascular beds) and bronchial smooth muscle relation (2 = lungs) - β ~3~ Receptors are involved in lipolysis (found in adipose tissue) and have affects on the bladder - Desensitization of receptors - Prolonged exposure to the catecholamine reduced the responsiveness of these receptors- desensitization - 3 mechanisms involved: - Sequestration of the receptors make them unavailable for interaction - Down regulation -- disappearance by destruction of decreased synthesis - Inability to couple G-protein d/t phosphorylation on the cytoplasmic side A diagram of a medical procedure Description automatically generated with medium confidence  Know these charts Characteristics of Adrenergic Agonists - Catecholamines - Sympathomimetic amies that contain the 3,4-dihydroxynemzene group and have the following characteristics - Show the highest potency in directly activating α or β receptors - Are metabolized by COMT and MAO- have only a brief period of action when given parenterally and are completely inactivated if given orally - Are polar and do not cross the CNS well -- few CNS effects - Noncatecholamines - Have longer half-lives -- prolonged duration of action - Not inactivated by COMT, poor substrates for MAO - Increased lipid solubility permits greater access to the CNS - Lacks the hydroxyl groups - Substitution on the amine nitrogen - The nature of the substituent on the amine nitrogen is important for determining β selectivity - Mechanism of action of adrenergic agonists - Direct-acting agonists -- act directly and α or β receptors, producing effects similar to those that occur following stimulation of sympathetic nerves or release of epinephrine from the adrenal medulla - Indirect-acting agonist -- may block the reuptake of norepinephrine or cause. The release of norepinephrine from the cytoplasmic pools or vesicles of the adrenergic neuron - Mixed-action agonist -- both stimulate adrenoceptors directly and enhance release of norepinephrine from the adrenergic neuron +-------------+-------------+-------------+-------------+-------------+ | **Drug** | **Mechanism | **Actions** | **Therapeut | **Adverse | | | of Action / | | ic | Effects** | | | Pharmacokin | | Uses** | | | | etics** | | | | +=============+=============+=============+=============+=============+ | Direct-Acti | | | | | | ng | | | | | | Adrenergic | | | | | | Agonists | | | | | | | | | | | | *Bind to | | | | | | adrenergic | | | | | | receptors | | | | | | on effector | | | | | | organs | | | | | | without | | | | | | interacting | | | | | | with the | | | | | | presynaptic | | | | | | neuron* | | | | | +-------------+-------------+-------------+-------------+-------------+ | Epinephrine | In the | Cardiovascu | Bronchospas | CNS effects | | | adrenal | lar: | m | -- anxiety, | | (Nasal | medulla, | primary | | fear, | | spray, | norepinephr | site of | -primary | tension, | | injection, | ine | action | drug used | headache, | | | is | | in the | and tremor | | Inhalation) | methylated | -strengthen | emergency | | | | to yield | s | treatment | Can trigger | | | epinephrine | contractili | of | cardiac | | | | ty | respiratory | arrythmias | | | On | of the | conditions | and angina, | | | stimulation | myocardium | when | esp in pts | | | , | (positive | bronchocons | w/ CAD or | | | the adrenal | inotrope: | triction | HTN | | | medulla | β~1~)(↑ | has results | | | | releases | force) | in | Can induce | | | 80% | | diminished | pulmonary | | | epinephrine | -increases | respiratory | edema | | | and 20% | rate of | fxn | | | | norepinephr | contraction | | Pts w/ | | | ine | (positive | -Drug of | hyperthyroi | | | | chronotrope | choice for | dism | | | Epinephrine | : | anaphylacti | may have | | | interacts | β~1~)(↑ | c | enhanced | | | w/ both α | rate) | shock | response | | | and β | | | d/t | | | receptors | -overall | Anaphylacti | increased | | | | cardiac | c | receptors | | | -low doses | output | shock | | | | β effects | increases | | Hyperglycem | | | (vasodilati | and oxygen | -Drug of | ia | | | on) | demands on | choice for | may occur | | | on the | the | type I | and insulin | | | vascular | myocardium | hypersensit | may be | | | system | increase | ivity | required | | | predominate | | reactions | | | | | \- β~1~ | | Tachycardia | | | -high doses | receptors | Cardiac | may occur | | | α effects | cause the | arrest: | w/ | | | (vasoconstr | kidneys to | | coadministr | | | iction) | release | -may be | ation | | | are the | renin | used to | of inhaled | | | strongest | production | restore | anesthetics | | | | of | cardiac | | | | Rapid onset | angiotensin | rhythm in | Increase BP | | | but brief | II -- a | pts with | and | | | duration of | potent | cardiac | peripheral | | | action d/t | vasoconstri | arrest | vascular | | | rapid | ctor | (ACLS) | resistance | | | degradation | and results | | may occur | | | | in | Local | when given | | | Preferred | decreased | Anesthesia: | with | | | rout in | renal blood | | nonselectiv | | | outpatient | flow | -increases | e | | | setting is | | the | β-blockers | | | IM d/t | -Constricts | duration of | | | | rapid | arterioles | local | | | | absorption | in the | anesthesia | | | | | skin, | by | | | | Emergency | mucous | producing | | | | -- may be | membranes, | vasoconstri | | | | given IV | and viscera | ction | | | | (fastest) | and dilates | at the site | | | | or by | vessels | of | | | | interosseou | going to | injection, | | | | s, | the liver & | reduces | | | | subcutaneou | skeletal | systemic | | | | s, | muscles | absorption | | | | endotrachea | | of the | | | | l | -cumulative | anesthetic, | | | | tube, or | effect is | and | | | | inhalation | an increase | promotes | | | | | in systolic | local | | | | Rapidly | BP and a | homeostasis | | | | metabolized | slight | | | | | by MAP and | decrease in | Intraocular | | | | COMT | diastolic | Surgery: | | | | | | | | | | | Respiratory | -used to | | | | | : | induce and | | | | | | maintain | | | | | -powerful | mydriasis | | | | | bronchodila | during | | | | | tion | surgery | | | | | | | | | | | -inhibits | | | | | | the release | | | | | | of allergic | | | | | | mediators | | | | | | such as | | | | | | histamine | | | | | | from mast | | | | | | cells | | | | | | | | | | | | Hyperglycem | | | | | | ia: | | | | | | | | | | | | -produces | | | | | | significant | | | | | | hyperglycem | | | | | | ic | | | | | | effects | | | | | | though | | | | | | increased | | | | | | glycogenoly | | | | | | sis. | | | | | | Increased | | | | | | release of | | | | | | glucagon, | | | | | | and | | | | | | decreased | | | | | | release of | | | | | | insulin | | | +-------------+-------------+-------------+-------------+-------------+ | **Drug** | **Mechanism | **Actions** | **Therapeut | **Adverse | | | of Action / | | ic | Effects** | | | Pharmacokin | | Uses** | | | | etics** | | | | +-------------+-------------+-------------+-------------+-------------+ | Norepinephr | α-adrenergi | Cardiovascu | Used to | Similar to | | ine | c | lar: | treat shock | epinephrine | | | receptor is | | (septic | | | (injection) | most | vasoconstri | shock) b/c | Potent | | | affected | ction | it | vasoconstri | | | | | increases | ctor | | | *the weak | -causes a | vascular | -- may | | | β~2~ | rise in | resistance | cause | | | activity | peripheral | and | blanching | | | explains | resistance | increase BP | and | | | why it is | d/t intense | | sloughing | | | not useful | vasoconstri | | of skin | | | in the | ction | | along an | | | treatment | of most | | inject4ed | | | of | vascular | | vein | | | bronchospas | beds, | | | | | m | including | | Extravasati | | | or | the kidney | | on | | | anaphylaxis | (α~1~ | | can cause | | | * | effects) | | tissue | | | | (little to | | necrosis | | | When | no β~2~ | | | | | atropine | activity) | | Avoid | | | (blocks the | | | peripheral | | | transmissio | -both | | veins -- | | | n | systolic | | central | | | of vagal | and | | line | | | effects) is | diastolic | | preferred | | | given | pressure | | | | | before | increases | | Impaired | | | norepinephr | | | circulation | | | ine, | Barorecepto | | cause by | | | stimulation | r | | norepinephr | | | of the | reflex | | ine | | | heart by | | | may be | | | norepinephr | -increases | | treated | | | ine | BP, which | | with | | | is evident | stimulates | | phentolamin | | | as | the | | e | | | tachycardia | barorecepto | | (alpha | | | | rs, | | antagonist) | | | Given IV | which | | | | | for rapid | creates a | | | | | onset of | rise in | | | | | action -- | vagal | | | | | duration of | activity | | | | | action is | | | | | | 1-2 mins -- | -increased | | | | | given as | vagal | | | | | continuous | activity | | | | | infusion | produces a | | | | | | reflex | | | | | Rapidly | bradycardia | | | | | metabolized | , | | | | | by MAP and | which is | | | | | COMT | sufficient | | | | | | to | | | | | | counteract | | | | | | the local | | | | | | action of | | | | | | norepinephr | | | | | | ine | | | | | | on the heat | | | | | | (lowers | | | | | | rate, not | | | | | | force) | | | +-------------+-------------+-------------+-------------+-------------+ | Dopamine | Immediate | Stimulate | Used for | Produces | | | metabolic | β~1~ | cardiogenic | same | | (injection) | precursor | cardiac | and septic | effects as | | | of | receptors, | shock and | sympathetic | | | norepinephr | both | is given by | stimulation | | | ine | inotropic | continuous | | | | and occurs | and | infusion | Rapidly | | | naturally | chronotropi | | metabolized | | | in the CNS | c | Raises BP | by MAP and | | | and adrenal | | by | COMT- | | | medulla | Dilates | stimulating | adverse | | | | renal and | β~1~ | effects are | | | Can | splanchnic | receptors | short lived | | | activate | arterioles | on the | | | | both α and | by | heart to | | | | β-adrenergi | activating | increase | | | | c | dopaminergi | cardiac | | | | receptors | c | output and | | | | | receptors, | α~1~ | | | | -higher | thereby | receptors | | | | doses = | increasing | on blood | | | | vasoconstri | blood flow | vessels to | | | | ction | to the | increase | | | | by | kidneys and | total | | | | activating | other | peripheral | | | | α~1~ | viscera | resistance | | | | receptors | | | | | | | | Increased | | | | -lower | | blood flow | | | | doses = | | to the | | | | stimulate | | kidney | | | | β~1~ | | enhances | | | | cardiac | | the GFR and | | | | receptors | | causes | | | | | | diuresis | | | | Has | | | | | | additional | | Used to | | | | actions at | | treat | | | | D~1~ and | | hypotension | | | | D~2~ | | , | | | | dopaminergi | | severe HF, | | | | c | | and | | | | receptors | | bradycardia | | | | which are | | unresponsiv | | | | found in | | e | | | | their | | to other | | | | peripheral | | treatments | | | | mesenteric | | | | | | and renal | | | | | | vascular | | | | | | beds and | | | | | | cause | | | | | | vasodilatio | | | | | | n. | | | | | | D~2~ | | | | | | receptors | | | | | | located on | | | | | | presynaptic | | | | | | adrenergic | | | | | | neurons | | | | | | interfere | | | | | | w/ | | | | | | norepinephr | | | | | | ine | | | | | | release | | | | +-------------+-------------+-------------+-------------+-------------+ | Phenylephri | Synthetic | Vasoconstri | Induces | Lawsuits | | ne | agonist | ctor | reflex | r/t oral | | | | that rises | bradycardia | decongestan | | (nasal, | Binds | both | -- useful | t | | ophthalmic, | primary to | systolic | for the | sales | | injection, | the α~1~ | and | treatment | | | oral, | receptors | diastolic | of | | | topical) | | BP | paroxysmal | | | | Topical -- | | supraventri | | | | preparation | | cular | | | | H | | tachycardia | | | | | | \* | | | | | | | | | | | | Used to | | | | | | treat | | | | | | hypotension | | | | | | in | | | | | | hospitalize | | | | | | d | | | | | | or surgical | | | | | | patients | | | | | | (especially | | | | | | those with | | | | | | rapid HR) | | | | | | | | | | | | Also acts | | | | | | as a nasal | | | | | | decongestan | | | | | | t | | | | | | (poor) and | | | | | | is used in | | | | | | ophthalmic | | | | | | preparation | | | | | | for | | | | | | mydriasis | | +-------------+-------------+-------------+-------------+-------------+ | Naphazoline | Synthetic | Directly | | Oxymetazoli | | | agonists | stimulate α | | ne | | \[naf-AZ-oh | | receptors | | -- may | | -leen\] | Stimulate | on blood | | produce | | | both α~1~ | vessels | | nervousness | | (oral) | and α~2~ | supplying | | , | | | receptors | the nasal | | headaches, | | Oxymetazoli | | mucosa and | | and trouble | | ne | Found in | conjunctiva | | sleeping | | | OTC nasal | , | | | | (oral, | spays and | thereby | | Use for | | nasal, top) | ophthalmic | producing | | greater | | | drops | vasoconstri | | than 3 days | | Tetrahydroz | | ction | | is not | | oline | Oxymetazoli | and | | recommended | | | ne | decreasing | | , | | (oral, | is absorbed | congestion | | as rebound | | nasal) | in the | | | congestion | | | systemic | | | and | | | circulation | | | dependence | | | regardless | | | may occur | | | of the | | | (Rhinitis | | | route | | | medicamento | | | | | | sa) | +-------------+-------------+-------------+-------------+-------------+ | Midodrine | Selective | Acts in the | Used in the | avoid | | | α~1~ | periphery | treatment | within 4hrs | | (oral) | agonist | to increase | of | of bedtime | | | | arterial | orthostatic | to avoid | | | Given 3x | and venous | HTN | supine HTN | | | daily at | tone | | | | | 3-4hr | | | | | | intervals | | | | +-------------+-------------+-------------+-------------+-------------+ | **Drug** | **Mechanism | **Actions** | **Therapeut | **Adverse | | | of Action / | | ic | Effects** | | | Pharmacokin | | Uses** | | | | etics** | | | | +-------------+-------------+-------------+-------------+-------------+ | Dobutamine | Synthetic | Increases | Used to | | | | catecholami | HR and | increase | | | (injection) | ne | cardiac | cardiac | | | | | output w/ | output in | | | | Primarily | few | acute HF | | | | β~1~ | vascular | | | | | receptor | effects | Increases | | | | agonist | | atrioventri | | | | | Does not | cular | | | | | elevate | (AV) | | | | | oxygen | conduction | | | | | demands of | -- caution | | | | | the | in AFib | | | | | myocardium | | | | | | as much as | | | | | | other | | | | | | sympathomim | | | | | | etics | | | +-------------+-------------+-------------+-------------+-------------+ | Isoproteren | Synthetic | Produces | | | | ol | catecholami | intense | | | | | ne | stimulation | | | | (injection) | | of the HR, | | | | | Stimulates | increasing | | | | | both β~1~ | HR, | | | | | and β~2~ | contractili | | | | | receptors | ty | | | | | | and cardiac | | | | | Non | output | | | | | selectivity | | | | | | is a | Dilates the | | | | | disadvantag | arterioles | | | | | e | of skeletal | | | | | -- rarely | muscle, | | | | | used | resulting | | | | | | in | | | | | | decreased | | | | | | peripheral | | | | | | resistance | | | | | | | | | | | | May | | | | | | decrease | | | | | | systolic BP | | | | | | slightly, | | | | | | but greatly | | | | | | reduces | | | | | | mean | | | | | | arterial | | | | | | and | | | | | | diastolic | | | | | | blood | | | | | | pressure | | | +-------------+-------------+-------------+-------------+-------------+ | Albuterol | Short | | Albuterol | Most common | | | acting β~2~ | | and | is tremor | | (injection | agonists | | levalbutero | | | & PO) | (SABAs) | | l | Restlessnes | | | | | are the | s, | | Levalbutero | Effects | | SABA of | apprehensio | | l | last about | | choice for | n, | | | 3 hrs | | the mgt of | anxiety | | (injection) | | | acute | | | | | | bronchospas | Monoamine | | Terbutaline | | | m | oxidase | | | | | | inhibitors | | (injection | | | Injectable | (MAOIs) | | & PO) | | | terbutaline | increase | | | | | is used | the risk of | | | | | off-label | adverse | | | | | as a | cardiovascu | | | | | uterine | lar | | | | | relaxant to | effects and | | | | | suppress | concomitant | | | | | premature | use should | | | | | labor and | be avoided | | | | | cannot be | | | | | | used more | | | | | | than 72hrs | | +-------------+-------------+-------------+-------------+-------------+ | Formoterol | Long acting | | Mgt of | Not | | | β~2~ | | respiratory | recommended | | Olodaterol | agonists | | disorders | as | | | (LABAs) | | such as | monotherapy | | Salmeterol | | | asthma and | for asthma | | | Effects | | COPD | b/c they | | | last 12 | | | have been | | | hours | | | shown to | | | | | | increase | | | Salmeterol | | | the risk of | | | has a | | | asthma-rela | | | delayed | | | ted | | | onset of | | | deaths | | | action | | | | +-------------+-------------+-------------+-------------+-------------+ | Mirabegron | Β~3~ | | Used for | Mirabegron | | | agonists | | overactive | may | | (oral) | that relax | | bladder | increase BP | | | the | | | -- do not | | Vibegron | detrusor | | | use in pt | | | smooth | | | with | | (oral) | muscle and | | | uncontrolle | | | increases | | | d | | | bladder | | | HTN | | | capacity | | | | +-------------+-------------+-------------+-------------+-------------+ | Direct-Acti | | | | | | ng | | | | | | Adrenergic | | | | | | Agonists | | | | | | | | | | | | *Bind to | | | | | | presynaptic | | | | | | neurons* | | | | | +-------------+-------------+-------------+-------------+-------------+ | Clonidine & | α~2~ | Acts | Used in the | Abrupt | | | agonist | centrally | treatment | discontinua | | Guanfacine | | on | of HTN | tion | | | | presynaptic | | must be | | (oral) | | α~2~ | Minimize | avoided to | | | | receptors | the | prevent | | | | to produce | withdrawal | rebound HTN | | | | inhibition | from | | | | | of | opioids, | | | | | sympathetic | tobacco | | | | | vasomotor | smoking, | | | | | centers, | and | | | | | decreasing | benzodiazep | | | | | sympathetic | ines | | | | | outflow to | | | | | | the | Used in mgt | | | | | periphery | of ADHD | | +-------------+-------------+-------------+-------------+-------------+ | Indirect-Ac | | | | | | ting | | | | | | Adrenergic | | | | | | Agonists | | | | | | | | | | | | *Cause the | | | | | | release, | | | | | | inhibits | | | | | | the | | | | | | reuptake, | | | | | | or inhibit | | | | | | the | | | | | | degradation | | | | | | of | | | | | | epinephrine | | | | | | or | | | | | | norepinephr | | | | | | ine* | | | | | | | | | | | | *Potentiate | | | | | | the effects | | | | | | of | | | | | | endogenous | | | | | | epi or | | | | | | norepi, but | | | | | | do not | | | | | | directly | | | | | | affect | | | | | | postsynapti | | | | | | c | | | | | | response* | | | | | +-------------+-------------+-------------+-------------+-------------+ | Amphetamine | Can | Actions are | Central | | | | increase BP | mediate | stimulatory | | | (oral) | significant | though the | action -- | | | | ly | increase on | used in | | | | by α~1~ | nonvesicula | ADHD | | | | agonist | r | | | | | activity on | release of | Also | | | | the | norepinephr | inhibit MAO | | | | vasculature | ine | | | | | and β~1~ | and | | | | | stimulatory | dopamine | | | | | effects on | | | | | | the heart | | | | +-------------+-------------+-------------+-------------+-------------+ | Tyramine | Not a drug | Normally | | | | | but found | oxidized by | | | | | in | MAO -- | | | | | fermented | causes | | | | | food | serious | | | | | | vasopressor | | | | | | episodes in | | | | | | pt taking | | | | | | MAOIs | | | +-------------+-------------+-------------+-------------+-------------+ | Cocaine | Blocks the | Can | | | | | sodium-chlo | increase BP | | | | | ride | by α~1~ | | | | | (Na^+^ / | agonist | | | | | Cl^-^) -- | activity | | | | | dependent | and β~1~ | | | | | norepinephr | stimulatory | | | | | ine | effects | | | | | transporter | | | | | | required | Small doses | | | | | for | of | | | | | cellular | catecholami | | | | | uptake of | nes | | | | | norepinephr | produce | | | | | ine | greatly | | | | | into the | magnified | | | | | adrenergic | effects and | | | | | neuron | prolonged | | | | | results in | duration of | | | | | the | action in | | | | | accumulatio | an | | | | | n | individual | | | | | of | taking | | | | | norepinephr | cocaine | | | | | ine | | | | | | in the | | | | | | synaptic | | | | | | space and | | | | | | increased | | | | | | sympathetic | | | | | | activity | | | | +-------------+-------------+-------------+-------------+-------------+ | Mixed-Actio | | | | | | n | | | | | | Adrenergic | | | | | | Agonists | | | | | | | | | | | | *Enhance | | | | | | release of | | | | | | norepinephr | | | | | | ine | | | | | | and | | | | | | directly | | | | | | stimulate | | | | | | adrenergic | | | | | | receptors* | | | | | | | | | | | | -less | | | | | | potent than | | | | | | epinephrine | | | | | | | | | | | | -poor | | | | | | substrates | | | | | | for COMT | | | | | | and MAO, | | | | | | have a long | | | | | | duration of | | | | | | action | | | | | | | | | | | | -Excellent | | | | | | oral | | | | | | absorption | | | | | | and | | | | | | penetrate | | | | | | the CNS | | | | | | | | | | | | -NOT | | | | | | catecholami | | | | | | nes | | | | | +-------------+-------------+-------------+-------------+-------------+ | Ephedrine | | Raises | Indicated | Ephedrine-c | | | | systolic | in | ontaining | | (Injection | | and | anesthesia- | herbal | | & PO) | | diastolic | induces | supplements | | | | BP by | hypotension | have been | | | | vasoconstri | | banned by | | | | ction | Produces | the FDA | | | | and cardiac | bronchodila | because of | | | | stimulation | tion | life-threat | | | | | -- slower | ening | | | | | and less | cardiovascu | | | | | potent than | lar | | | | | other | complicatio | | | | | agents | ns | | | | | | | | | | | Produces | | | | | | mild CNS | | | | | | stimulation | | | | | | -- | | | | | | increases | | | | | | alertness, | | | | | | decreases | | | | | | fatigue, | | | | | | and | | | | | | prevents | | | | | | sleep | | | | | | | | | | | | Improves | | | | | | athletic | | | | | | performance | | | | | | -- but not | | | | | | sage | | +-------------+-------------+-------------+-------------+-------------+ | Pseudoephed | | | Used for | Fewer CNS | | rine | | | nasal and | effects | | | | | sinus | | | (oral) | | | congestion | Sales are | | | | | -- OTS | limited d/t | | | | | | use in | | | | | | production | | | | | | of | | | | | | methampheta | | | | | | mine | +-------------+-------------+-------------+-------------+-------------+ A chart of medication used to treat a patient Description automatically generated with medium confidence