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Slide 1-

Adrenergic and anti-adrenergic drugs By Linda Self NUR 3703
Slide 2-

Divisions of human nervous system
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Nervous system
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Sympathomimetic or adrenergic in sympathetic nervous system—neurotransmitters are ____________ Parasympathomimetic or cholinergic are used to describe parasympathetic system—neurotransmitter is _____________
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Sympathetic nervous system Fight or flight response results in: Increased BP Increased blood flow to brain, heart and skeletal muscles Increased muscle glycogen for energy Increased rate of coagulation Pupil dilation
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Adrenergic receptors Alpha—A1 and A2 Beta—B1, B2, B3 Dopamine—subsets D1-5
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Review of functions of sympathetic nervous system receptors Alpha 1—smooth muscle contraction Alpha 2-negative feedback causes less norepinephrine to be released so BP is reduced Beta 1—increased heart rate Beta 2—bronchodilation Beta 3—actual site for lipolysis
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Mechanisms of action and effects of adrenergic drugs Direct adrenergic drug action Affects postsynaptic alpha 1 and beta receptors on target effector organs Examples: epinephrine, Isuprel, norepinephrine, phenylephrine
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Mechanisms of action cont. 2. Indirect adrenergic drug action occurs by stimulation of postsynaptic alpha 1, beta 1 and beta 2 receptors.Cause release of norepinephrine into the synapse of nerve endings or prevent reuptake of norepinephrine. Examples include cocaine and TCAs
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Mechanisms of action cont. 3. mixed action. Combination of direct and indirect receptor stimulation Examples are ephedrine and pseudoephedrine
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Mechanisms of action cont. Stimulation of alpha 2 receptors in CNS is useful in decreasing BP Most body tissues have both alpha and beta receptors Effect occurs 2ndary to receptor activated and number of receptors in the particular body tissue
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Mechanisms of action cont. Some drugs act on both receptors--dopamine Some are selective--Isuprel
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Indications for use Emergency drugs in treatment of acute cardiovascular, respiratory and allergic disorders In children, epinephrine may be used to treat bronchospasm due to asthma or allergic reactions Phenylephrine may be used to treat sinus congestion
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Indications of adrenergics cont. Stokes Adams Shock Inhibition of uterine contractions For vasoconstrictive and hemostatic purposes
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Contraindications to use of adrenergics Cardiac dysrhythmias, angina pectoris Hypertension Hyperthyroidism Cerebrovascular disease Distal areas with a single blood supply such as fingers, toes, nose and ears Renal impairment use caution
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Individual adrenergic drugs Epinephrine—prototype Effects include: increased BP, increased heart rate, relaxation of bronchial smooth muscle, vasoconstriction in peripheral blood vessels
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epinephrine Increased glucose, lactate, and fatty acids in the blood due to metabolic effects Increased leukocyte and increased coagulation Inhibition of insulin secretion
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epinephrine Affects both alpha and beta receptors Usual doses, beta adenergic effects on heart and vascular smooth muscle will predominate, high doses, alpha adrenergic effects will predominate Drug of choice for bronchospasm and laryngeal edema of anaphylaxis
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epinephrine Excellent for cardiac stimulant and vasoconstrictive effects in cardiac arrest Added to local anesthetic May be given IV, inhalation, topically Not PO
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epinephrine Physiologic antagonist to histamine Those on beta blockers may need larger doses Drug of choice in PEA. Vasopressin has now become drug of choice in ventricular tachycardia Single dose of Vasopressin, 40 units IV
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Other adrenergics Ephedrine is a mixed acting adrenergic drug. Stimulates alpha and beta receptors. Longer lasting than epinephrine. See in Primatene mist
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Pseudophed Used for bronchodilating and nasal decongestant effects
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isuprel (Isoproterenol) Synthetic catecholamine that acts on beta 1 and 2 receptors Stimulates heart, dilates blood vessels in skeletal muscle and causes bronchodilation No alpha stimulation Used in heart blocks (when pacemaker not available) and as a bronchodilator
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Neosynephrine (Phenylephrine) Pure alpha Decreases CO and renal perfusion No B1 or B2 effects Longer lasting than epinephrine Can cause a reflex bradycardia Useful as a mydriatic
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Toxicity of adrenergics in critically ill patients Affects renal perfusion Can induce cardiac dysrhythmias Increases myocardial oxygen consumption May decrease perfusion of liver Tissue necrosis with extravasation
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Toxicity Do not give epinephrine and Isuprel at same time or within 4 hours of each other. Could result in serious dysrhythmias.
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Anti-adrenergics Sympatholytic Block or decrease the effects of sympathetic nerve stimulation, endogenous catecholamines and adrenergic drugs
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Antiadrenergic s—mechanisms of action and effects Can occur by blocking alpha 1 receptors postsynaptically Or by stimulation presynaptic alpha 2 receptors. Results in return of norepineprhine to presynaptic site. Activates alpha 2 resulting in negative feedback. Decreases release of additional norepinephrine.
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Alpha-Adrenergic Agonists and blocking agents Alpha 2 agonists inhibit release of norepinephrine in brain; thus, decrease effects on entire body Results in decrease of BP Also affects pancreatic islet cells, thus some suppression of insulin secretion
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Alpha 1 adrenergic blocking agents Act on skin, mucosa, intestines, lungs and kidneys to prevent vasoconstriction Effects: dilation of arterioles and veins, decreased blood pressure, pupillary constriction, and increased motility of GI tract
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Alpha 1 adrenergic blocking agents May activate reflexes that oppose fall in BP such as fluid retention and increased heart rate Can prevent alpha medicated contraction of smooth muscle in nonvascular tissues Thus, useful in treating BPH as inhibit contraction of muscles in prostate and bladder
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Alpha 1 antagonists Minipress (prazosin)—prototype. Hytrin (terazosin) and Cardura (doxazosin)—both are longer acting than Minipress.
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Alpha 1 antagonists cont. Flomax (tamsulosin). Used in BPH. Produces smooth muscle relaxation of prostate gland and bladder neck. Minimal orthostatic hypotension. Priscoline (tolaxoline) used for vasospastic disorders. Pulmonary hypertension in newborns. Can be given sub Q, IM or IV.
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Alpha 2 agonists Catapres (clonidine). PO or patch. Tenex (guanfacine) Aldomet (methyldopa). Can give IV. Caution in renal and hepatic impairment.
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Beta adrenergic blocking medications Prevent receptors from responding to sympathetic nerve impulses, catecholamines and beta adrenergic drugs.
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Effects of beta blocking drugs Decreased heart rate Decreased force of contraction Decreased CO Slow cardiac conduction Decreased automaticity of ectopic pacemakers
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Effects of beta blocking drugs Decreased renin secretion from kidneys Decreased BP Bronchoconstriction Less effective metabolism of glucose. May result in more pronounced hypoglycemia and early s/s of hypoglycemia may be blocker (tachycardia)
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Effects of beta blocking agents Decreased production of aqueous humor in eye May increase VLDL and decrease HDL Diminished portal pressure in clients with cirrhosis
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Indications for use Alpha 1 blocking agents are used for tx of hypertension, BPH, in vasospastic disorders, and in persistent pulmonary hypertension in the newborn May be useful in treating pheochromocytoma May be used in Raynaud’s or frostbite to enhance blood flow
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Regitine (phentolamine) Used for extravasation of potent vasoconstrictors (dopamine, norepinephrine) into subcutaneous tissues
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Indications for use Alpha 2 agonists are used for hypertension—Catapres Epidural route for severe pain in cancer Investigationally for anger management, alcohol withdrawal, postmenopausal hot flashes, ADHD, in opioid withdrawal and as adjunct in anesthesia
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Beta blocking medications Mainly for cardiovascular disorders (angina, dysrhythmias, hypertension, MI and glaucoma) In angina, beta blockers decrease myocardial oxygen consumption by decreasing rate, BP and contractility. Slow conduction both in SA node and AV node.
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Beta blockers Possibly work by inhibition of renin, decreasing cardiac output and by decreasing sympathetic stimulation May worsen condition of heart failure as are negative inotropes May reduce risk of “sudden death”
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Beta blockers Decrease remodeling seen in heart failure In glaucoma, reduce intraocular pressur by binding to beta-adrenergic receptors in ciliary body, thus decrease formation of aqueous humor
Slide 45-

Beta blockers Inderal (propranolol) is prototype Useful in treatment of hypertension, dysrhythmias, angina pectoris, MI Useful in pheochromocytoma in conjunction with alpha blockers (counter catecholamine release) migraines
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Beta Blockers In cirrhosis, Inderal may decrease the incidence of bleeding esophageal varices Used to be contraindicated in heart failure, now are standard Known to reduce sudden death Often given with ACEIs Indications include: htn, angina, prevention of MI
Slide 47-

Receptor selectivity Acetutolol, atenolol, betaxolol, esmolol, and metoprolol are relatively cardioselective These agents lose cardioselection at higher doses as most organs have both beta 1 and beta 2 receptors Byetta is new agent that is cardioselective
Slide 48-

Non-Receptor selectivity Carteolol, levobunolol, metipranolol, nadolol, propranolol, sotalol and timolol are all non-selective Can cause bronchoconstriction, peripheral vasoconstriction and interference with glycogenolysis
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Combination selectivity Labetalol and carvedilol (Coreg) block alpha 1 receptors to cause vasodilation and beta 1 and beta 2 receptors which affect heart and lungs Both alpha and beta properties contribute to antihypertensive effects May cause less bradycardia but more postural hypotension Less reflex tachycardia
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Intrinsic sympathomimetic activity Have chemical structure similar to that of catecholamines Block some beta receptors and stimulate others Cause less bradycardia Agents include: Sectral (acebutolol), Cartrol (carteolol), Levatol (penbutolol) and Visken (pindolol)
Slide 51-

Specific conditions-alpha agonists and antagonists In tx for BPH, patient should be evaluated for prostate cancer With alpha 2 agonists, sudden cessation can cause rebound BP elevation With alpha 1 blockers, first dose syncope may occurr from hypotension. Give low starting dose and at hs. May also cause reflex tachycardia and fluid retention.
Slide 52-

Specific condtions-beta blockers With significant bradycardia, may need med with ISA such as pindolol and penbutolol Patient with asthma, cardioselectivity is preferred For MI, start as soon as patient is hemodynamically stable
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Special conditions—beta blocers Should be discontinued gradually. Long term blockade results in increase receptor sensitivity to epinephrine and norepinephrine. Can result in severe hypertension. Taper 1-2 weeks.
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Ethnic considerations Monotherapy in African Americans is less effective than in Caucasians. Trandate (labetalol) with both alpha and beta effects has been shown to be more effective in this population than Inderal, Toprol or timolol.