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63 Cards in this Set
- Front
- Back
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Which branch of the ANS utilizes thoracolumbar outflow?
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Sympathetic (fight or flight)
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Which branch of the ANS utilizes craniosacral outflow?
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Parasymp (conservation of energy, rest and digest)
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Sympathetic NS:
NTs involved Result of Stimulation Receptors Involved |
Pregang: ACh to activate Nicotinic receptors
Postgang: NE released except in adrenal medulla (Epi: 80%) Target Cell receptors: adrenoreceptors: alpha-1, alpha-1, beta1, beta2, beta3 |
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NE:
Synthesis Storage Termination of Effect |
-Synthesized from DA (which is synthesized via Tyrosine and Tyrosine Hydroxylase) in preganglionic nerve terminal
-Must be stored in vesicles or would be metabolized by monoamine oxidase (MAO) -Termination via: 1) Removal from synaptic cleft: reuptake via NET 2) Negative feedback via presynaptic alpha-2 receptors 3)Co-transmitters (modulators) |
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Reserpine:
Mechanism |
Blocks uptake of NE into vesicles
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Gunethidine:
Mechanism |
Blocks release of NE into synaptic cleft
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Effect of cocaine and trycyclic antidepressants on NE.
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Cocains inhibits NET and inhibits reuptake of NE
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Describe the mechanisms of sympathetic signal transduction for alpha-1, alpha-2, beta-1, and beta-2 receptors.
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All autonomic receptors are coupled to GTP-binding proteins with second-messenger systems!!
Alpha-1: activate phospholipase C, inc IP3 and intracell Ca2+ Alpha-2: Inhibit adenylyl cyclase, decrease cAMP Beta-1/Beta-2: stimulate adenylyl cycalse, inc cAMP |
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What are the relative receptor potencies of NE and Epi for alpha and beta receptors?
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Alpha-1/2: EPI>NE
Beta-1: EPI = NE Beta-2: EPI>>>NE (BIG DIFFERENCE) |
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What are the physiologic effects of stimulation of beta-1 receptors?
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Mostly heart, little bit of kidney
SA node: inc'd heart rate AV node: inc'd conduction velocity HIS-purkinje cells: Inc'd conduction velocity and automaticity Cardiac muscle: inc'd contractility Kidney juxtaglomerular cells: inc'd renin |
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What are the physiologic effects of stimulation of beta-2 receptors?
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Smooth muscle:
Arteriolar, bronchiolar, intestinal, uterine relaxation Other: Ciliary muscle (eye) relaxation, skeletal muscle: inc'd K+ uptake Liver: inc'd glycogenolysis Panc Isleta beta cells: inc'd insulin secretion |
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What are the physiologic effects of stimulation of alpha-1 receptors?
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Smooth Muscle
Arteriolar, venous, genitourinary CONTRACTION Intestinal RELAXATION Eye: Radial muscle contraction Lacrimal gland secretion Liver: inc'd glycogenolysis Kidney Juxtaglomerular cells: dec'd renin secretion |
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What are the physioloic effects of stimulation of alpha-2 receptors?
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Pancreatic Isleta (beta cells): dec'd insulin secretion
Presynaptic receptors: dec'd release of NE |
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A 30 year old patient is diagnosed with pheochromocytoma generated by a benign tumor in her right adrenal gland causing excessive release of epinephrine and norepinephrine.
What signs and symptoms would you expect in this patient? If you were designsin a drug to treat the signs and symptoms, what would be it mechanism of action? |
Syx: HTN (alpha-1 receptors), tachycardia
Drug: alpha then beta block |
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Parasympathetic Nervous System:
Neurotansmitters Involved Result of Stimulation Receptors Involved |
PNS:
Pre-gang neurons: ACh which activates Nicotinic receptors Postgang: Release ACh, which binds MUSCARINIC receptors of TARGET CELLS |
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Acetylcholine:
Synthesis Storage |
Choline uptake, combined with acetylCoA
Choline Acetyltransferase combines to two into ACh Storage into vesicles Release through exocytosis |
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Vesamicol:
Mechanism |
Reduced uptake of ACh into vesicles
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Botulinum Toxin:
Mechanism |
Blocks release of Ach via inhibition of exocytosis
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Hemicholinium:
Mechanism |
Reduces choline uptake (reduced synthesis of Ach)
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Acetylcholine:
Termination |
Acetylcholinesterase degrades ACh in synaptic cleft (reuptake is relatively small)
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Describe the second messenger signal transduction of muscarinic receptors.
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G-protein coupled but slower response than nicotinic receptors
M1/3/5: increase release of intracell Ca2+ and protein phosphorylation M2/4: inc K+ permeability, dec cAMP M2: inc'd K+ perm (inhibitory), dec'd adenylyl cyclase activity (dec'd cAMP), dec'd Ca2+ perm; located in heart; effect: SLOWS CONDUCTION M3: Smooth muscle contraction, relaxation of sphincters, dilation of vessels through NO production, inc'd secretion of glands |
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What is the general effect of stimulation of muscarinic receptors?
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SA Node: dec'd heart rate
AV: dec'd conduction velocity Muscle: dec'd contractility Vasc SM: relaxation if endothelium intact, contraction if endothelium removed Other SM: GI, bronchiolar contraction Eye: sphincter/ciliary muscle: contraction Glands: inc'd secretion (salivary, lacrimal, nasopharyngeal, bronchiola, GI, panc, skin sweat glands) Sphincters: Urinary/GI: relaxation |
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What nerve is responsible for the decreased contractility of the heart?
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VAGUS
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Which of the following statements is correct regarding the parasympathetic nervous system?
Acetylcholine is synthesized in the postganglionic neuron and is released passively into the synaptic cleft. Activation of presynaptic M4 receptors decreases release of acetylcholine into the synaptic cleft. Removal of acetylcholine from the synaptic cleft is primarily through reuptake and the process is inhibited by cocaine. Stimulation of M3 receptors in the heart result in decreased calcium permeability and slowing of heart rate and AV nodal conduction. |
Activation of presynaptic M4 receptors decreases release of ACh into the synaptic cleft.
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List 3 catecholamines.
Can be they delivered orally? Why or why not? |
Epi, NE, DA
Cannot be given orraly because rapidly inactivated by COMT and MAO in liver |
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I.V. Epinephrine:
Receptors acted on Effects |
Agonist of a-1, b-1, b-2
a-1: BP incrcrease at higher doses b-1: inc in chronotropic (inc SA firing), dromotropic (inc AV conduction), inotropic (inc contractility) of heart b-2: bronchodilation |
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I.V. Norepinephrine:
Receptoprs acted on Effects |
POTENT Agonist of a-1, moderate agonism of b-1
No beta-2 to counteract, so get significant inc in BP and sig inc in inotropy |
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Dopamine:
Receptors acted on Effects |
Precursor of NE but direct agonist for b-1 and a-1, in addition to D-1 (mesenteric, renal, coronary vasodilation)
Dose-related effect! Low dose (1-2 mcg/kg/min): renal/mesenteric vasodilation Medium (5-10 mcg/kg/min): inc'd heart rate, inotropy High (10-20 mcg/kg/min): inc'd vasoconstricion, HR, inotropy (low dose: improves renal fn, high dose: vascular effects dominate) |
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Isoproterenol:
Drug Class Receptors Affected Uses |
Sympathomimetic
Beta-1, Beta-2 IV: inc in contractility (treat cardiogenic shock), inc heart rate Inhaled: asthma patients (but cardiac effects) |
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Dobutamine:
Drug Class Receptors Affected Uses |
Sympathomimetic
a-1,b-1,b-2 IV: inc contractility (treat cardiogenic shock) DOBUTAMINE LESS LIKELY TO CAUSE REFLEX TACHYCARDIA |
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Pseudophedrine:
Drug Class Receptors Affected Uses |
Sympathomimetic
A-1, b-1, b-2 Nasal decongestant, precursor for methamphetamine Can significantly raise BP increasing risk of stroke due to potent a-1 stimulation |
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Terbutaline:
Drug Class Receptors Affected Uses |
Sympathomimetic
beta-2 Inhalation: bronchodilator to tx asthma, COPD |
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Albuterol:
Drug Class Receptors Affected Uses |
Sympathomimetic
beta-2 Inhalation: bronchodilator to tx asthma, COPD |
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Salmeterol:
Drug Class Receptors Affected Uses |
Sympathomimetic
beta-2 Inhalation: bronchodilator to tx asthma, COPD NOTE: SALMETEROL CANNOT BE USED FOR ACUTE MANAGEMENT OF ASTHMA BECAUSE OF ITS SLOW ONSET |
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What sympathomimetic cannot be used for acute management of asthma because of its slow onset?
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Salmeterol
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Sympathomimetics:
Adverse Events |
Due to beta-1 over simulation: tachycardia, arrythmia, cardiac damage, inc'd myocardial O2 demand
Use beta-1 agonists in short term management of heart failure, not chronically Beta-2 over-stimulation: skeletal muscle tremors, tachycardia, arrhythmia, hypokalemia (less common with inhaled drugs, but possible) alpha-1 stimulation: severely elevated BP, inc'd myocardial O2 demand, predisposing to stroke and cardiac damage |
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Prazosin:
Drug Class Receptors Affected Uses |
Sympatholytic
Alpha-1 receptor antagonist: Dec vascular resistance in HTN, improves urinary flow in BPH MAY CAUSE ORTHOSTATIC HYPOTN, SYNCOPE |
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Terazosin:
Drug Class Receptors Affected Uses |
Sympatholytic
Alpha-1 receptor antagonist: Dec vascular resistance in HTN, improves urinary flow in BPH MAY CAUSE ORTHOSTATIC HYPOTN, SYNCOPE |
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Doxazosin:
Drug Class Receptors Affected Uses |
Sympatholytic
Alpha-1 receptor antagonist: Dec vascular resistance in HTN, improves urinary flow in BPH MAY CAUSE ORTHOSTATIC HYPOTN, SYNCOPE |
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Tamsulosin is an Alpha-1 selective blocking agent. It is very effective for the treatment of benign prostatic hyperplasia but is not effective as an antihypertensive agent. Why is this true?
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(Block alpha receptors-->relax urinary muscle tone)
For prostate, alpha-1a is receptor In vessels have alpha-1a and alpha-1b tamsulosin affects alpha-1a so has less of an effect on BVs |
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Phentolamine:
Drug Class Receptors Affected Uses Adverse Effects |
Alpha sympatholytic
Blocks alpha-1 and alpha-2 Use: pherohromocytoma AE: significant hypotn causing reflex stimulation of heart resulting in tachycardia, arryhtmias and myocardial ischemia |
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Phenoxybenzamine:
Drug Class Receptors Affected Uses Adverse Effects |
Alpha sympatholytic
Blocks alpha-1 and alpha-2 Use: pherohromocytoma AE: significant hypotn causing reflex stimulation of heart resulting in tachycardia, arryhtmias and myocardial ischemia |
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What properties are considered when selecting beta-blockers?
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Blocks only beta-1 receptors (selectivity)
Can act as beta-agonist (intrinsic sympathomimetic activity) Can cause alpha-1 blockade Can cross into CNS (lipophilicity) |
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Why would selectivity be an important factor in choosing a beta-blocker?
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When you want to avoid bronchoconstriction (when act beyond beta-1, and block beta-2); selectivity is dose-related (max dose = low selectivity)
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Why would intrinsic sympathomimetic activity be an important factor in choosing a beta-blocker?
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Can act as beta-agonist at times of low sympathetic tone (while sleeping)
Can be advantageous in pts with HTN on beta-blockers that have excessively low heart rates at night Not useful in pts w/ischemic heart dz |
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Propranolol:
Drug Class Receptors Affected Uses |
Beta-blocker
beta-1, beta-2 block |
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Metoprolol:
Drug Class Receptors Affected Uses |
Beta-blocker
beta-1 blockade |
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Carvedilol:
Drug Class Receptors Affected Uses |
Beta-blocker
beta-1, beta-2, alpha-1 blockade |
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Labetalol:
Drug Class Receptors Affected Uses |
Beta-blocker
beta-1, beta-2, alpha-1 blockade HAS BETA-2 AGONIST INTRINSIC ACTIVITY |
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Beta-1 blockade:
Uses |
HTN (reduces cardiac output)
Ischemic Heart Dz: reduces cardiac workload (dec syx) Acute Coronary sndromes (decreases workload, ischemia) Systolic heart failure (blocks effects of NE)--doses must be titrated slowly to avoid exacerbation of heart failure symptoms Arrythmias (blocks effects of symp NS) Glaucoma (decreases intraocular pressure), Thyroid Storm, Performance Anx, Migraine Prophylaxis |
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What drug class must be titrated slowly in treating patients with heart failure in order to avoid an exacerbation of heart failure symptoms?
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beta-1 blockers
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Beta-blockers:
Adverse effects |
AEs may be dependent/modified by characteristics of beta-blocker, e.g., selectivity
Direct cardiac effects Bronchoconstriction (avoid in pts with asthma) Dyslipiedmias (dec'd HDL) Signs of hypoglycemia in DM may be harder to recognize (esp insulin-dependent) |
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Why shouldn't patients abruptly discontinue beta-blockers?
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Increased rick of ischemia due to up-regulation of beta-receptors during chronic therapy (severe hypertension, inc'd Q)
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Parasympathomimetics:
Direct vs Indirect Mechanisms of action |
Increase effect of parasymp NS by:
Direct mech: stimulation of muscarinig receptors Indirect mech: inhibition of Acetylcholinesterase |
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SLIDE 62, 40:52
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xxx
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What are the two kinds of direct acting muscarinic agonists? Provide examples of each.
Uses? AE's? |
Choline Esters:
Carbachol Bethanechol Methacholine Acetylcholine (can't be used clinically) Alkaloids: Pilocarpine Uses: Glaucoma (reduce intraoc pressure through inc outflow of aq. humor) Xerostomia (inc salivary secretion) Gastric atony/urinary retention (in patients without obstruction) AE: Bradycardia, Hypotn Bronchoconstriction, glandular hypersecretion GI distress, inc'd acid secretion |
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What are examples of indirect acting parasympathomimetics?
Uses? AE's? |
Edrophonium...
Physostigmine, neostigmine, pyridostigmine (-stigmine)--medium strenth binding -Organophosphates (insecticides, topical treatments, nerve gases)---STRONG binding Used for dry mouth, glaucoma Myasthenia gravis (for increase at NMJ') Prophylaxis against nerve gas poisoning AE: Bradycardia, Hypotn Bronchoconstriction, glandular hypersecretion GI distress, inc'd acid secretion |
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Organophosphate insecticide poisoning:
Signs Management |
CV: hypotn, bradycardia, arrythmia
Pulm: resp distress, failure GI: nausea, vomiting, cramps, diarrhea, incont Eyes: miosis, reduced vision, ocular pain CNS: confusion, seizures, coma Management: Decontamination--atropine for muscarinic side effects, Pralidoxime (cholinesterase reactivator) Respiratory support |
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Anti-Muscarinic Drugs:
Actions Effects |
Block exog/endog muscarinic agonists
Effects: Inc'd heart rate, conduction velocity, block of reflex bradycardia Bronchodilation, reduced bronchial secretions Inhibit GU/GI tone, inhibit gastric acid secretion Mydriasis (open eyes for eye exam) |
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Atropine:
Drug Class Effects Uses |
Antimuscarinic (Alkaloid)
opposite of muscarinic f/x Little CNS effects; used IV for significant bradycardia Effects are dose-related |
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Scopolamine:
Drug Class Effects Uses |
Antimuscarinic (Alkaloid)
OPP of muscarinic More BBB penetration than atropine so used for motion sickness |
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An 85 year old man with Alzheimer's Disease is given donepezil. Which of the following should you anticipate as an adverse effect of the drug?
Constipation Urinary incontinence Dry eyes Sinus tachycardia |
Donepezil inhibits Acetylcholinesterase, so get increased cholinergic effects
URINARY INCONTINENCE |
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Malathion poisoning:
A 6 year old child comes home from school with a note from the school nurse indicating that she has head lice. Her mother receives a prescription buys a bottle of malathion, an organophosphate. She mistakenly gives her child the malathion orally instead of using it as a topical application. What symptoms who you expect this child to exhibit and why? |
Worry about excess cholinergic and nicotinic activity (excess skeletal muscle activity?)
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