Term
Adrenergic junction (catecholamine synthesis) |
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Definition
| Tyrosine --> Dopa (via tyrosine hydroxylase) --> Dopamine --> NE (via dopamine beta hydroxylase) --> NE placed in storage vesicle --> released into junction to act on alpha and beta receptors |
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Term
What can happen to NE once released |
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Definition
Can bind to its receptor alpha or beta Can be metabolized by COMT enzyme Can be taken back up into neuron (MC b/c short 1/2 life) Can have neg. feedback on alpha2 auto recetpor |
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Term
Where can drugs effect the adrenergic junction (hint 8 places) |
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Definition
Methyl-p-tyrosine inhibits tyrosine to Dopa step MAOI's inhibits the free metabolism of NE keeping them around longer for use Amphetamines central release of NE, and DA via binding to the MAO transporters Cocaine/TCA's Na/K reuptake blocked leaving it in the junction longer Alpha 2 agonist/antagonists Reserpine destroys the storage vesicles for NE Guanethidine inhibits exocytosis Alpha and Beta agonists/antagonists |
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Term
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Definition
Eye -- contraction of radial muscle, mydriasis Arterioles/veins -- vasoconstricts, increases TPR/diastolic pressure/afterload from the aa and increases venous return/preload from the vv Bladder -- contraction, urinary retention Liver -- increases glycogenolysis kidney -- decreases renin release |
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Term
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Definition
Negative feedback Prejunctional nerve terminals (decrease NE release) Platelets -- aggregation Pancreas -- decrease insulin secretion |
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Term
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Definition
Heart SA node -- increase HR (positive chronotropy) AV node -- increase conduction velocity Atrial and ventricular muscle -- increase force of contraction (positive ionotropy), CV, CO, O2 consumption His-Pukinje -- increase automaticity and CV Kidney -- increase renin release |
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Term
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Definition
Mostly not innervated (Epi) Blood vessels -- vasodilation, decreases TPR/diastolic pressure,afterload Uterus -- inhibit contractions/relaxation Bronchioles -- dilation Skeletal muscle & liver -- increase glycogenolysis Pancreas -- increase insulin secretion |
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Term
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Definition
| Beta receptors are usu more sensitive to activators than alpha receptors so drugs that exert both effects like (Epi) the beta responses are dominant at low doses and alpha at high doses |
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Term
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Definition
Phenylephrine = nasal decongestant, ophthalmologic Methoxamine = paroxysmal atrial tachycardia (b/c cause reflex bradycardia but low on list of choices) Alpha 1 = increase TPR, BP, potential for reflex bradycardia (decreased HR) Increase in mean BP via vasoconstriction |
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Term
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Definition
Clonidine & Methyldopa = mild to moderate HTN Stimulate prejunctional receptors in the CNS to decrease sympathetic outflow |
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Term
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Definition
Isoproterenol = (B1=B2) used for bronchospasm, heart block, and bradyarrhythmias SE's: flushing, angina, arrhythmias Dobutamine = (B1>B2) used for CHF salmeterol, albuterol, terbutaline = B2 selective for asthma Ritodrine = B2 selective used in premature labor B1's = increase HR, SV, CO, and pulse pressure B2's = decrease TPR, BP |
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Term
Mixed-Acting Agonists (NE) |
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Definition
Alpha 1,2 and Beta 1 Alpha 1 = increase TPR, BP Beta 1 = increase HR, SV, CO, pulse pressure Potential reflex bradycardia Net effect on HR is initially increased followed by a decrease long term |
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Term
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Definition
Alpha 1,2 and Beta 1,2 Low dose Epi = all beta effects so increase HR, SV, CO, and pulse pressure and decrease TPR and BP Medium dose Epi = both betas and some alpha 1 get the increased HR, SV, CO and pulse pressure but then the Beta2 and alpha1 cancel eachother out (mean BP stays the same) High dose Epi = get mostly alpha effects, looks very similar to NE (increased TPR,BP w/ potential for reflex bradycardia and initial tachycardia from beta 1 at the beginning) |
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Term
Differentiate b/n NE and high dose Epi |
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Definition
Give an alpha 1 blocker (eg: phenoxybenzamine) and if the pt had been given high dose Epi will actually see hypotension b/c the Beta 2 receptors have been unmasked (versus the alpha 1 causing initial HTN d/t the vasoconstriction of the blood vessels) Remember NE doesn't stimulate Beta 2 receptors at all so won't see the hypotension |
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Term
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Definition
Cardiac arrest Adjunct to local anesthetic Hypotension Anaphylaxis (epi only) Asthma (epi only) |
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Term
Indirect acting adrenergic receptor agonists (Releasers) |
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Definition
Displace NE form the mobile pool (more available) Major DI: MAO(a) inhibitors (can lead to a hyptertensive crisis) Tyramine (red wine, cheese) Amphetamines (eg methyl phenidate) used in ADHD & narcolepsy causes central release of DA, NE, 5HT Ephedrine (cold medication) These can ONLY work on effector tissues innervated by the sympathetic system b/c they do nothing to the alpha or beta receptors |
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Term
Indirect acting adrenergic receptor agonists (reuptake inhibitors) |
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Definition
Leave the NE around longer in the synapse Cocaine and TCA's |
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Term
Alpha receptor antagonists (effects and uses) |
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Definition
Decrease TPR and mean BP May cause reflex tachycardia and salt/H2O retention Uses: HTN, pheochromocytoma (nonselective), BPH (alpha 1 selective) |
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Term
Nonselective alpha blockers |
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Definition
Phentolamine = competitive inhibitor Phenoxybenamine = noncompetitive inhibitor (irreversibly binds) |
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Term
Selective alpha 1 blocker |
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Definition
| Prazosin, doxazosin, terazosin, tamsulosin (last one specifically blocks the 1a receptor found in the prostate |
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Term
Selective alpha 2 blockers |
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Definition
Yohimbine = postural hypotension and impotence (b/c w/o the negative feedback from the alpha 2 receptors the alpha 1 can continue) Mitazapine = used as an antidepressant |
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Term
Beta blockade (general effects) |
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Definition
Beta 1 blockade = decrease HR, SV, CO, renin release, aqueous humor production Beta 2 blockade = precipitate bronchospams, and vasospasm in pts w/ these disorders Also blocks glycogenolysis and gluconeogenesis (problem in diabetics) Can increase LDL's and TG's |
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Term
Beta blocker drugs (+general uses) |
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Definition
Acebutolol, Atenolol, Metoprolol (1st half of the alphabet is beta 1 selective) so safer in asthmatics, diabetics, and peripheral vascular dz Pindolol, Propranolol, Timolol (2nd half is nonselective) Acebutolol and Pindolol both have intrisic sympathomimetic activity and act as partial agonists causing slight vasodilation and minimal change in lipids Used for angina, HTN, post-MI Antiarrhythmics (propranolol, acebutolol, esmolol) Glaucoma (timolol) Migraine, thyrotoxicosis, performance anxiety, essential tremor (propranolol b/c overstimulation of beta 2 on skeletal mm) |
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Term
Combined alpha 1 and beta blocking |
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Definition
Labetalol & Carvedilol used for CHF |
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Term
K+ channel blockade and Beta blocking |
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Definition
Sotalol Used as an antiarrhythmic |
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Term
Open angle glaucoma (+treatment) |
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Definition
Chronic condition w/ increased intraocular pressure d/t decreased reabsorption of aqueous humor Leads to progressive painless visual loss Strategy in treatment = beta blockers (timolol) to decrease formation of fluid and muscarinic activators (pilocarpine) to improve drainage through the canal of Schlemm |
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Term
Closed angle glaucoma (+ treatment) |
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Definition
Acute, painful condition w/ increased IOP d/t the blockade of the canal of Schlemm Emergency treatment involving a cholinomimetic, carbonic anhydrase inhibitor, and/or mannitol Pilocarpine, Acetazolamide, Mannitol 1st = muscarinic agonist causes contraction of ciliary muscle which increases flow through canal 2nd = decreases aqueous humor formation 3rd = osmotic diuretic |
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