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46 Cards in this Set
- Front
- Back
adrenergic neurons synthesize, store, and release mainly...
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Norepinephrine (NE)
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_____ is synthesized and released from adrenal medulla into blood stream and acts as a ______
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Epinephrine (EPI); hormone
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Receptors that respond to NE/EPI
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α-1, α-2, β-1
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sympathomimetic drugs mimic and sympatholyic drugs block the effect of...
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EPI/NE
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α-1 receptor
(G-protein, 2nd msgr, ligands, tissue/organ/gland, effect of agonist) |
1. G-protein- Gq
2. 2nd messenger - ↑IP3, ↑DAG, ↑Ca2+ 3. ligands - EPI/NE 4. tissue/organ/gland - artery/vein, EYE, smooth muscles (constriction) 5. effect of agonist - vasoconstrict (↑BP), mydriasis |
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α-2 receptor
(G-protein, 2nd msgr, ligands, tissue/organ/gland, effect of agonist) |
1. G-protein- Gi
2. 2nd messenger - ↓cAMP 3. ligands - EPI/NE 4. tissue/organ/gland - none 5. effect of agonist - ↓SANS activity |
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special action of ACh in SANS
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innervation of M3 by ACh releases NO to relax smooth muscle arterioles that supply skeletal muscle
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α-1 receptor mechanism
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α-1 couples to Gq to ↑Ca2+
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α-1 activation tissue responses
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contraction of vascular smooth muscle = ↑PVR and ↑BP
contraction of iris radial muscles = dilates pupil contraction of urinary and GI sphincters contraction of prostate |
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clinical use of α-1 AGONIST drugs
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1. treatment of shock to ↑BP
2. ↑BP in hypotension 3. topically as mydriatic 4. topically as nasal decongestant 5. topically for allergeic ocular hyperemia |
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Clinical use of α-1 ANTAGONIST drugs
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1. ↓BP
2. relief of benign prostatic hyperplasia 3. pheochromocytoma |
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Presynaptic α-2 receptors mechanism
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α-2 binds to Gi, ↓cAMP, hyperpolarizes terminal and block nerve transmission
NE activates α-2 to inhibit its own release (negative feedback control) α-2 receptors contract vascular smooth muscle; peripheral effect |
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Clinical use of α-2 AGONIST drugs
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1. α-2 receptors in brain are used as anti-hypertensive agents
2. reduce SANS symptoms during opioid withdrawal 3. skeletal muscle relaxants 4. topically ↓IOP to treat glaucoma |
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Clinical use of α-2 ANTAGONIST drugs
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1. orthostatic hypotension
2. reverses hypotension caused by α-2 agonists 3. erectile dysfunction |
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ß-1 Receptor
(G-Protein, 2nd msgr, ligand, tissue/organ/gland, effect of agonist) |
1. G-Protein - Gs
2. 2nd Messenger - ↑cAMP 3. Endogenous Ligand - NE, EPI 4. Tissue/Organ/Gland - Heart, Kidney 5. Effect of Agonist - ↑HR, ↑force of atrial contraction, ↑renin release |
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ß-2 Receptor
(G-Protein, 2nd msgr, ligand, tissue/organ/gland, effect of agonist) |
1. G-Protein - Gs
2. 2nd Messenger - ↑cAMP 3. Endogenous Ligand - EPI 4. Tissue/Organ/Gland - Lungs, Artery/Vein, Liver 5. Effect of Agonist - dilate bronchioles, vasodilate (↓BP), ↑blood glucose |
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ß-3 Receptor
(G-Protein, 2nd msgr, ligand, tissue/organ/gland, effect of agonist) |
1. G-Protein - Gs
2. 2nd Messenger - ↑cAMP 3. Endogenous Ligand - EPI 4. Tissue/Organ/Gland - Adipose tissue 5. Effect of Agonist - ↑Lipolysis (free fatty acids) |
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Norepinephrine binds to...
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α-1, α-2, ß-1
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Epinephrine binds to....
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α-1, α-2, ß-1, ß-2, ß-3
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ß-1 receptor mechanism
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ß-1 couples Gs, ↑cAMP, activates kinases
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Clinical use of ß-1 receptor AGONIST drugs
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short term relief as cardiostimulant in acute heart failure
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ß-2 receptor mechanism
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ß-2 couples Gs, ↑cAMP, protein kinase A (PKA) inactivates myosin light chain kinase (MLCK) to RELAX smooth muscles
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Clinical use of ß-2 receptor AGONIST drugs
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1. relaxes bronchial smooth muscle -> asthma; physiological antagonist to histamine
2. relaxes uterine smooth muscle to prevent premature labor (physiological antagonist to oxytocin) |
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NE/EPI Metabolism
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Phase I - Oxidation - MAO
Phase II - Conjugation - Catechol O-Methyl Transferase (COMT) No COMT in synaptic cleft |
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selective α-1 agonists
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phenylephrine, midodrine
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selective α-2 agonists
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clonidine, methyldopa, guanabenz, aproclonidine, bromonidine, guanfacine
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mixed α, ß agonists
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NE, EPI, ephedrine
NE: α-1, α-2, ß-1 EPI: α-1, α-2, ß-1, ß-2 Ephedrine: same as EPI |
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selective α-1 antagonists
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"SINS" - prazosin, terazosin, doxazosin
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selective α-2 antagonists
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yohimbine
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non-selective α antagonists (α-1 = α-2)
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phentolamine, phenoxybenzamine
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mixed α antagonists
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labetalol, carvedilol
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Direct Mixed-Acting: NE
(Effects and Adverse Effects) |
released from SANS, administered as IV
Effects: 1. Heart - ↑HR, force of atrial contraction (↑CO) 2. Blood Vessels - ↑PVR and venous return Adverse Effects: hypertension, arrhythmias, hyperthyroidism |
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Direct Mixed-Acting: EPI
(Effects and Adverse Effects) |
released from adrenal medulla (hormone), administered as IV, local injection, oral inhalant, topical
Effects: 1. Heart - ↑HR, force of atrial contraction (↑CO) 2. Bronchioles - relaxes smooth muscle, bronchodilation 3. Blood Vessels - ß-2, low dose vasodilates, high dose vasoconstricts 4. Liver - glycogenolysis, ↑free glucose 5. Adipose - ↑free fatty acids (lipolysis) 6. Skeletal muscle - increase blood flow to contracting SKM Adverse Effects: hypertension, arrhythmias, hyperglycemia |
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Direct Mixed-Acting: Ephedrine
(Properties and Adverse Effects) |
Properties:
1. Same effects as EPI but weaker 2. Non-catechol resists metabolism by MAO and COMT 3. long duration and passes blood brain barrier 4. potent stimulant, good bronchodilator Adverse Effects: inomnia, hypertension, palpitations, ventricular tachyharrythias (FATAL) |
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Selective Acting: Phenylephrine
(Effects, Uses, Adverse Effects) |
α-1 AGONIST
Effects: constricts arteries and veins, ↑BP (systolic/diastolic) Uses: produce mydriasis, ↑BP in hypotension, runny nose, eye drops (allergies) Adverse Effects: hypertension, rebound congestion, reflex bradycardia |
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Selective Acting: Midodrine
(Effects, Uses, Adverse Effects) |
α-1 AGONIST
Effects: ↑BP Uses: orthostatic hypotension Adverse Effects: supine hypertension, urinary retention, goosebumps |
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Selective Acting: Clonidine, Guanabenz, α-Methyldopa
(Effects, Uses, Adverse Effects) |
α-2 AGONIST
Act at Vasomotor Center (VMC) in brain, inhibit SANS Effects: ↓BP by overriding peripheral effects of α-2 activation Uses - Hypertension Adverse Effects: CNS depression/drowsiness, must taper or rebound hypertension and tachycardia |
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Selective Acting: α-Methyldopa
(Effects, Uses, Adverse Effects) |
prodrug, metabolized to α-methyl NE
Effects: 1. activates α-2 in periphery and brain 2. False neurotransmitter when released from SANS Uses: ↓BP in pregnant women |
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Indirect Acting: Amphetamine
(Actions, Effects, Uses) |
Agonist
Actions: 1. displace NE from vesicles 2. blocks reuptake (Uptake-1) 3. Inhibits MAO Effects: 1. ↑NE in synapse Uses: ADHD, obesity, narcolepsy |
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Indirect Acting: Tyramine
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Comes from cheese and wine
Metabolized by MAO Outcomes: 1. Acute: consumption of large amount of Tyramine causes NE displacement and hypertensive crisis 2. Chronic - consumption while on MAOIs causes Tyramine -> Octopamine = orthostatic hypotension |
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Indirect Acting: Guanethidine
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Agonist
Displaces NE Clinically antihypertensive agent |
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Non-Selective Antagonist - Phenoxybenzamine
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α antagonist
long-acting, irreversible inhibition RARELY used clinically |
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Non-Selective Antagonist - Phentolamine
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α antagonist
short-active, reversible used clincally for pre-operative pheochromocyoma |
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Non-Selective α Antagonists - Reflex Tachycardia
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Drugs that nonselectively block α-1 and α-2 are very likely to cause reflex tachycardia because α-1 causes ↓BP and α-2 causes ↑NE
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Selective Antagonists: SINS
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α-1 Antagonists
Prazosin, Terazosin, Doxazosin Effects - reduce PVR and BP Adverse effects: hypotensions, rebound congestion, reflex tachycardia, urinary incontinence, miosis |
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Selective Antagonist: Yohimbine
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α-2 antagonist
↑NE release Effects: ↑HR and ↑PVR Uses: orthostatic hypotension, erectile dysfunction Adverse Effects: ↑release of insulin |