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β-Adrenergic Stimulants and
Blockers
Presenter- Dr. Suresh PradhanModerator- Dr. Upendra Krishna Regmi
β1 receptor action
β2 receptor action
β3-receptors• are found in the gallbladder and brain adipose
tissue• role in gallbladder physiology is unknown• they are thought to play a role in lipolysis and
thermogenesis in brown fat
D1 receptor action
• β1 β2 D1 Receptors are Gs coupled
• Increase adenylyl cyclase---increased cAMP
• most of the adrenergic drugs are derivatives of β-phenylethylamine• substitutions on the benzene ring or on the
ethylamine side chains produce a variety of compounds with varying abilities to differentiate between α and β receptors and to penetrate the CNS
• Two important structural features of these drugs are
1) the number and location of OH substitutions on the benzene ring and 2) the nature of the substituent on the amino nitrogen
• Adrenergic Drugs can be:A. CatecholaminesB. Non-catecholaminesC. Substitutions on the amine nitrogen
A. Catecholamines• Sympathomimetic amines that contain the 3,4
dihydroxybenzene group are called catecholamines.• Includes epinephrine, norepinephrine, isoproterenol,
and dopamine
Substitutions at the R1, R2, and R3 sites affect
activity and selectivity
some important catecholaminescatechol is shown for reference
These compounds share the following properties:
1. High potency: Catecholamines (with –OH groups in the 3 and 4 positions on the benzene ring) show the highest potency in directly activating α or β receptors
2. Rapid inactivation: metabolized by COMT post-synaptically and by
MAO intra-neuronally, as well as by COMT and MAO in the gut wall, and by MAO in the liver
so , they have only a brief period of action when given parenterally, and they are inactivated when administered orally
3. Poor penetration into the CNS: are polar and, therefore, do not readily penetrate
into the CNS nevertheless, most catecholamines have some
clinical effects (anxiety, tremor, and headaches) that are attributable to action on the CNS
B. Non-catecholamines• compounds lacking the catechol hydroxyl groups have
longer half-lives, because they are not inactivated by COMT• include phenylephrine, ephedrine, and amphetamine
• are poor substrates for MAO and, thus, show a prolonged duration of action• increased lipid solubility of many of the non-
catecholamines (due to lack of polar hydroxyl groups) permits greater access to the CNS
examples of non-catecholamine sympathomimetic drugsthe isopropyl group is highlighted in color
C. Substitutions on the amine nitrogen• the nature of the substituent on the amine nitrogen is
important in determining β selectivity of the adrenergic agonist• epinephrine, with a –CH3 substituent on the amine
nitrogen, is more potent at β receptors than norepinephrine, which has an unsubstituted amine• isoproterenol, which has an isopropyl substituent –CH
(CH3)2 on the amine nitrogen is a strong β agonist with little α activity
Mechanism of action of adrenergic agonists
1. Direct-acting agonists:· act directly on α or β receptors, producing effects
similar to those that occur following stimulation of sympathetic nerves or release of epinephrine from the adrenal medulla
· Examples: epinephrine, norepinephrine, isoproterenol, and phenylephrine
2. Indirect-acting agonists:· may block the reuptake of norepinephrine or cause
the release of norepinephrine from the cytoplasmic pools or vesicles of the adrenergic neuron.
· norepinephrine then traverses the synapse and binds to α or β receptors
· Examples: cocaine and amphetamines
3. Mixed-action agonists: · Includes Ephedrine and its
stereoisomer, pseudoephedrine
· stimulate adrenoceptors directly and release norepinephrine from the adrenergic neuron
Epinephrine• prototype drug among the sympathomimetics• Its natural functions on release from the adrenal
medulla include regulation of (a) myocardial contractility,(b) heart rate,(c) vascular and bronchial smooth muscle tone,(d) glandular secretions, and (e) metabolic processes such as glycogenolysis and lipolysis
• the most potent activator of alpha-adrenergic receptors• two to ten times more active than norepinephrine
and more than 100 times more potent than isoproterenol• Epinephrine interacts with both α and β receptors• At low doses, β effects (vasodilation) on the
vascular system predominate, whereas at high doses, α effects (vasoconstriction) are the strongest• Epinephrine also activates beta 1 and beta 2
receptors
• oral administration is not effective because it is rapidly metabolized in the gastrointestinal mucosa and liver• administered SC or IV• absorption after SC injection is slow because of local
epinephrine-induced vasoconstriction• is poorly lipid soluble, preventing its ready entrance
into the CNS and accounting for the lack of cerebral effects
Effects• Cardiovascular• result from epinephrine-induced stimulation of
alpha- and beta-adrenergic receptors• Small doses of epinephrine (1 to 2µg/minute IV)
stimulate principally beta2 receptors in peripheral vasculature• Stimulation of beta receptors occurs at intermediate
doses (4 µg/minute IV)
• large doses of epinephrine (10 to 20 µg/minute IV) stimulate both alpha- and beta-adrenergic receptors with the effects of alpha stimulation predominating in most vascular beds, including the cutaneous and renal circulations• A single rapid injection of epinephrine, 2 to 8 µg IV,
produces transient cardiac stimulation lasting 1 to 5 minutes, usually without an overshoot of systemic blood pressure or heart rate
Drug Dependent effects of Epinephrine
Effect of Low-dose Epinephrineon Heart Rate and Blood Pressure
Effect of medium-dose Epinephrineon Heart Rate and Blood Pressure
Effect of high-dose Epinephrineon Heart Rate and Blood Pressure, is similar to action of norepinephrine
• Airway Smooth Muscle/Respiratory• causes powerful bronchodilation by acting directly
on bronchial smooth muscle (β2 action)• also inhibits/decreases release of vasoactive and
allergy mediators such as histamines from mast cells
• Metabolic Effects• has the most significant effects of all the
catecholamines on metabolism• Beta receptor stimulation due to epinephrine
increases liver glycogenolysis and adipose tissue lipolysis• Alpha receptor stimulation inhibits release of
insulin
• Infusions of epinephrine usually increase plasmaconcentrations of cholesterol, phospholipids, and LDL• Release of epinephrine and resulting glycogenolysis
and inhibition of insulin secretion is the most likely explanation for the hyperglycemia that commonly occurs during the perioperative period
• Electrolytes• activation of the sodium-potassium pump in skeletal
muscles, leading to a transfer of potassium ions into cells• epinephrine-induced hypokalemia could contribute
to cardiac dysrhythmias that occasionally accompany stimulation of the sympathetic nervous system
• Ocular Effects• contraction of the radial muscles of the iris,
producing mydriasis• contraction of the orbital muscles produces an
appearance of exophthalmus• adrenergic receptors responsible for these ocular
effects are probably alpha receptors because norepinephrine is less potent than epinephrine and isoproterenol has practically no ocular effects
• Gastrointestinal and Genitourinary Effects• relaxation of gastrointestinal smooth muscle• activation of beta-adrenergic receptors relaxes the
detrusor muscle of the bladder, whereas activation of alpha-adrenergic receptors contracts the trigone and sphincter muscles
• Coagulation• is accelerated by epinephrine, presumably due to
increased activity of factor V• a hypercoagulable state present during the
intraoperative and postoperative period may reflect stress-associated release of epinephrine• increases the total leukocyte count but at the same
time causes eosinopenia
Pharmacokinetics• has a rapid onset but a brief duration of
action (due to rapid degradation)• preferred route is intramuscular (anterior
thigh) due to rapid absorption• in emergency situations, epinephrine is
given intravenously for the most rapid onset of action• may also be given subcutaneously, by
endotracheal tube, and by inhalation • rapidly metabolized by MAO and COMT,
and the metabolites metanephrine and vanillylmandelic acid are excreted in urine
Adverse effects• can produce adverse CNS effects that include anxiety,
fear, tension, headache, and tremor• can trigger cardiac arrhythmias, particularly if the
patient is receiving digoxin• can also induce pulmonary edema
• may have enhanced cardiovascular actions in patients with hyperthyroidism, and the dose must be reduced in these individuals• inhalation anesthetics also sensitize the heart to the
effects of epinephrine, which may lead to tachycardia• increases the release of endogenous stores of glucose
Clinical Uses• Clinical uses of epinephrine include
treatment of life-threatening allergic reactions administration during cardiopulmonary resuscitation
as the single most important therapeutic drug continuous infusion to increase myocardial
contractility addition to local anesthetic solutions to decrease
systemic absorption and prolong the duration of action of the anesthetic
Usual Adult Dose for Shock
• IV:• 2 to 10 mcg/min (1 mg in 250 mL of D5W or 4
mcg/mL)• May be increased as necessary to establish an
adequate heart rate and blood pressure• rarely doses as high as 20 mcg/min are required
• Endotracheal: 1 mg (10 mL of 1:10,000) once, followed by 5 quick insufflations• Intracardiac: 0.3 to 0.5 mg (3 to 5 mL of 1:10,000) by
direct injection into the left ventricular chamber once
Usual Adult Dose for Asystole
• IV:• 0.5 to 1 mg (5 to 10 mL of 1:10,000) once• may be repeated every 3 to 5 minutes as necessary• if there is inadequate response to 1 mg, then high dose
therapy (2 to 5 mg) every 3 to 5 minutes, escalating 1, 3, then 5 mg every 3 minutes, or 0.1 mg/kg every 3 to 5 minutes, has been used
• Endotracheal: 1 mg (10 mL of 1:10,000) once, followed by 5 quick insufflations• Intracardiac: 0.3 to 0.5 mg (3 to 5 mL of 1:10,000) by
direct injection into the left ventricular chamber once
Usual Adult Dose for Electromechanical Dissociation• IV: • 0.5 to 1 mg (5 to 10 mL of 1:10,000) once• may be repeated every 3 to 5 minutes as necessary• if there is inadequate response to 1 mg, then high
dose therapy (2 to 5 mg) every 3 to 5 minutes, escalating 1, 3, then 5 mg every 3 minutes, or 0.1 mg/kg every 3 to 5 minutes, has been used
• Endotracheal: 1 mg (10 mL of 1:10,000) once, followed by 5 quick insufflations• Intracardiac: 0.3 to 0.5 mg (3 to 5 mL of 1:10,000) by direct
injection into the left ventricular chamber once
Usual Adult Dose for AV Heart Block
• IV:• 0.5 to 1 mg (5 to 10 mL of 1:10,000) once• may be repeated every 3 to 5 minutes as necessary• if there is inadequate response to 1 mg, then high
dose therapy (2 to 5 mg) every 3 to 5 minutes, escalating 1, 3, then 5 mg every 3 minutes, or 0.1 mg/kg every 3 to 5 minutes, has been used
Usual Adult Dose for Asthma - Acute• Subcutaneous:• 0.1 to 0.5 mg (0.1 to 0.5 mL of 1:1000 solution)• may be repeated every 20 minutes to once every 4 hours
as needed• IM:• 0.1 to 0.5 mg (0.1 to 0.5 mL of 1:1000 solution)• May be repeated every 20 minutes to once every 4 hours
as needed• Inhalation aerosol:• 160 to 220 mcg (1 inhalation) once• additional inhalation may be used after at least one
minute• it is recommend that subsequent doses not be
administered for at least three hours
• Nebulized:• 1 to 3 inhalations (8 to 10 drops of a 1% 1:100 solution)
once• if relief does not occur within 5 minutes, the dose may
be repeated once• it is recommended that subsequent doses not be
repeated more often than every 3 hours• Intermittent positive pressure breathing:• 0.3 mg (0.03 mL of a 1:100 solution) once• the least amount of tolerated inhalations required to
provide relief is the recommended dose• most patients respond within 15 minutes• this dose may be repeated once every 3 to 4 hours as
needed
Usual Adult Dose for COPD- Acute
• Subcutaneous:• 0.3 mg (0.3 mL of 1:1000) every 20 minutes for up
to 3 doses• may be repeated once every 2 hours as needed
• IM• Inhalation aerosol• Nebulized• Intermittent positive pressure breathing
Usual Adult Dose for Allergic Reaction
• Subcutaneous:• 0.1 to 0.5 mg (0.1 to 0.5 mL of 1:1000 solution)• may be repeated every 20 minutes to once every 4
hours as needed• IM: • 0.1 to 0.5 mg (0.1 to 0.5 mL of 1:1000 solution)• May be repeated every 10 to 15 minutes
• IV:• 0.1 to 0.25 mg (1 to 2.5 mL of a 1:10,000 solution)
once slowly and cautiously over 5 to 10 minutes• the dose may be repeated every 5 to 15 minutes as
needed and tolerated• in some cases of severe anaphylaxis, an intravenous
infusion of epinephrine (1 mg in 250 mL of D5W, or 4 mcg/mL) can be started to run at 1 to 4 mcg/min (15 to 60 mL/hour)
Usual Adult Dose for Pupillary Dilation
• Induction and Maintenance of Mydriasis during Intraocular Surgery• Use the irrigating solution as needed for the
surgical procedure• Dilute 1 mL of epinephrine 1 mg/mL (1:1000) in
100 mL to 1000 mL of an ophthalmic irrigation fluid to a concentration of 1:100,000 to 1:1,000,000 (10 mcg/mL to 1 mcg/mL)• Do not use if solution is colored, cloudy or contains
particulate matter.
• Renal Dose Adjustments• no dosage adjustments are recommended for
patients with renal dysfunction.• Liver Dose Adjustments• it is recommended that multiple doses or dose
increments be given cautiously to patients with liver dysfunction
Norepinephrine• endogenous neurotransmitter released from
postganglionic sympathetic nerve endings• approximately equal in potency to epinephrine for
stimulation of beta 1 receptors, but unlike epinephrine, norepinephrine has little agonist effect at beta 2 receptors
• a potent alpha-agonist that produces intense arterial and venous vasoconstriction in all vascular beds and lacks bronchodilating effects on airway smooth muscle• hyperglycemia is unlikely to occur
Effects• Cardiovascular• causes a rise in peripheral
resistance due to intense vasoconstriction of most vascular beds, including the vasculature of skeletal muscles, liver, kidneys, and skin
• decreases venous return to the heart and increases systolic, diastolic, and mean arterial pressure
• decreased venous return to the heart combined with baroreceptor-mediated reflex decreases in heart rate tend to decrease cardiac output despite beta 1 effects of norepinephrine
• extravasation during infusion can produce severe local vasoconstriction and possible necrosis
Pharmacokinetics• is given IV for rapid onset of action• duration of action is 1 to 2 minutes, following the
end of the infusion• it is rapidly metabolized by MAO and COMT• inactive metabolites are excreted in the urine
Adverse effects• are similar to epinephrine• in addition, norepinephrine is a potent vasoconstrictor
and may cause blanching and sloughing of skin along an injected vein• if extravasation of drug from the vessel into tissues
surrounding the injection site occurs, it can cause tissue necrosis• impaired circulation from norepinephrine may be
treated with the α receptor antagonist phentolamine
Therapeutic uses• used to treat shock, because it increases vascular
resistance and, therefore, increases blood pressure
Dopamine• is the immediate metabolic precursor of norepinephrine• regulates cardiac, vascular, and endocrine function• is an important neurotransmitter in the CNS and
peripheral nervous system• occurs naturally in the CNS in the basal ganglia, where it
functions as a neurotransmitter, as well as in the adrenal medulla
• the pharmacology of dopamine is complex• differentially stimulates a variety of dopaminergic
and adrenergic receptors• at higher doses, it causes vasoconstriction by
activating α 1 receptors, whereas at lower doses, it stimulates β1 cardiac receptors
• Dopamine receptors are located post-synaptically and when activated • elicit vasodilation (renal, mesenteric, coronary,
cerebral vessels) and• inhibition of sodium-potassium adenosine
triphosphate• activation of these receptors is mediated by
adenylate cyclase
• Dopamine 2 receptors are principally presynaptic and inhibit adenylate cyclase activity and release of norepinephrine• Nausea and vomiting produced by dopamine reflect
stimulation of dopamine 2 receptors• Dopamine receptors - associated with the neural
mechanism for "reward " that is associated with cocaine and alcohol dependence
• rapid metabolism of dopamine mandates its use as a continuous infusion (1 to 2µg/kg/minute) to maintain therapeutic plasma concentrations• dopamine should be dissolved in 5% glucose in
water for IV administration• extravasation of dopamine produces intense local
vasoconstriction, which may be treated with local infiltration of phentolamine
• Dopamine is not effective orally and does not cross the blood-brain barrier in sufficient amounts to cause CNS effects• immediate precursor of dopamine, L-dopa, is
absorbed from the gastrointestinal tract and readily crosses the blood-brain barrier• Hyperglycemia that is commonly present in patients
receiving a continuous infusion of dopamine is likely to reflect drug-induced inhibition of insulin secretion
Actions• Cardiovascular:• Depending on the dose, dopamine stimulates
different receptors• dopamine 1 receptors (0. 5 to 3µg/kg/ minute IV) in
the renal vasculature to produce renal vasodilation• beta 1 receptors (3 to 10µg/kg/ minute IV) in the
heart- having both positive inotropic and chronotropic effects• Alpha 1 receptors (> 10µg/kg/ minute IV) in the
peripheral vasculature resulting in vasoconstriction
• Renal and visceral: • dilates renal and splanchnic
arterioles by activating dopaminergic receptors, thereby increasing blood flow to the kidneys and other viscera• these receptors are not affected
by α- or β-blocking drugs• so, dopamine is clinically useful
in the treatment of shock, in which significant increases in sympathetic activity might compromise renal function
• Ventilation Effects• Infusion of dopamine interferes with the ventilatory
response to arterial hypoxemia, reflecting the role of dopamine as an inhibitory neurotransmitter at the carotid bodies• result is-unexpected depression of ventilation in
patients who are being treated with dopamine to increase myocardial contractility• arterial blood gases have been observed to deteriorate
during infusion of dopamine
• Intraocular Pressure• continuous infusions of dopamine to critically ill
patients are associated with increases in intraocular pressure• this may create a risk in patients with preexisting
glaucoma especially if they are sedated and mechanically ventilated
Therapeutic Uses• the drug of choice for cardiogenic and septic shock• unique among the catecholamines in being able to
simultaneously increase (a)myocardial contractility(b) renal blood flow(c) glomerular filtration rate(d) excretion of sodium(e) urine output
• is given by continuous infusion• It raises blood pressure by stimulating the • β1 receptors on the heart to increase cardiac output • α1 receptors on blood vessels to increase total
peripheral resistance• in addition, it enhances perfusion to the kidney and
splanchnic areas
Adverse effects• produces the same effects as sympathetic
stimulation• is rapidly metabolized by MAO or COMT, and its
adverse effects (nausea, hypertension, and arrhythmias) are, therefore, short-lived
SYNTHETIC CATECHOLAMINES
• two clinically useful synthetic catecholamines are• isoproterenol• dobutamine
Isoproterenol• most potent activator of all the sympathomimetics at
beta 1 and beta 2 receptors• nonselectivity is one of its drawbacks and the reason
why it is rarely used therapeutically• two to three times more potent than epinephrine and at
least 100 times more active than norepinephrine• in clinical doses, isoproterenol is devoid of alpha-agonist
effects
• metabolism-in the liver by COMT is rapid, necessitating a continuous infusion to maintain therapeutic plasma concentrations• uptake of isoproterenol into postganglionic
sympathetic nerve endings is minimal
Effects• intense stimulation of the heart, increasing heart rate,
contractility, and cardiac output• dilates the arterioles of skeletal muscle (β2 effect),
resulting in decreased peripheral resistance• because of its cardiac stimulatory action, it may
increase systolic blood pressure slightly, but it greatly reduces mean arterial and diastolic blood pressures• is a potent bronchodilator (β2 effect)
Clinical Uses• continuous infusion of isoproterenol, 1 to 5 µg/min
is effective in increasing the heart rate in adults in the presence of heart block• provide sustained increases in heart rate before insertion of
a temporary or permanent cardiac pacemaker in the treatment of bradydysrhythmias• the use of isoproterenol as an inotropic drug has decreased
with the availability of dobutamineand phosphodiesterase inhibitors• the use of isoproterenol as a bronchodilator has been
supplanted by availability of specific beta 2 agonists
Dobutamine• synthetic catecholamine that acts as a selective
beta 1 adrenergic agonist• rapid metabolism of dobutamine dictates its
administration as a continuous infusion at 2 to 10µg/kg/minute to maintain therapeutic plasma concentrations• like dopamine, dobutamine should be dissolved in
5% glucose in water for infusion to avoid inactivation of the catecholamine that may occur in an alkaline solution
Clinical Use and Effects• produces potent beta-adrenergic agonist
effects at does < 5µg/kg/minute• dobutamine increases myocardial contractility (beta 1
receptors) • is used to improve cardiac output in patients with
congestive heart failure, particularly if heart rate and systemic vascular resistance are increased• High doses of dobutamine (> 10µg/kg/minute) may
predispose the patient to tachycardia and cardiac dysrhythmias
• increases cardiac output and does not significantly elevate oxygen demands of the myocardium, a major advantage over other sympathomimetic drugs• should be used with caution in atrial fibrillation,
because it increases AV conduction
Summary of the therapeutic uses of adrenergic agonists
BETA-ADRENERGIC RECEPTOR
ANTAGONISTS
• bind selectively to beta-adrenergic receptors and interfere with the ability of catecholamines or other sympathomimetics to provoke beta responses• are competitive antagonists• Nonselective β-blockers act at both β1 and β2 receptors,
whereas cardio-selective β antagonists primarily block β1 receptors• drug-induced beta-adrenergic blockade prevents the
effects of catecholamines and sympathomimetics on the heart and smooth muscles of the airways and blood vessels
• Beta-antagonist therapy should be continued throughout the perioperative period to • maintain desirable drug effects• avoid the risk of sympathetic nervous system
hyperactivity associated with abrupt discontinuation of these drugs
• are derivatives of the beta agonist drug isoproterenol• Substituents on the benzene ring determine whether
the drug acts on beta adrenergic receptors as an antagonist or agonist
Metoprolol• selective beta 1-adrenergic receptor antagonist that
prevents inotropic and chronotropic responses tobeta-adrenergic stimulation• selectivity is dose related, and large doses of
metoprolol are likely to become nonselective, exerting antagonist effects at beta 2 receptors as well as beta 1 receptors
• readily absorbed from the gastro-intestinal tract, but this is offset by substantial hepatic first-pass metabolism such that only about 40% of the drug reaches the systemic circulation
• protein binding is low; it is estimated to account for about 10% of the drug
• elimination half-time of metoprolol is 3 to 4 hours
Esmolol• rapid-onset and short-acting selective beta 1-
adrenergic receptor antagonist that is administered only IV• typical initial dose-0.5 mg/kg IV over about 60 seconds• the full therapeutic effect is evident within 5 minutes• action ceases within 10 to 30 minutes after administration
is discontinued• these characteristics make esmolol a useful drug for
preventing or treating adverse systemic blood pressure and heart rate increases that occur intraoperatively in response to noxious stimulation, as during tracheal intubation
• commercial preparation of esmolol is buffered to pH 4.5 to 5.5, which may be one of the factors responsible for pain on injection• elimination half-time is about 9 minutes• undergoes rapid hydrolysis in the blood by plasma
esterases• Poor lipid solubility limits transfer of esmolol in to the
CNS or across the placenta
Side Effects• side effects of beta-adrenergic antagonists are similar for all
available drugs, although the magnitude may differ depending on their selectivity and the presence or absence of intrinsic sympatho-mimetic activity• exert their most prominent pharmacologic
effects as well as side effects on the cardiovascular system• alter airway resistance, carbohydrate and lipid metabo- lism,
and the distribution of extracellular ions• gastro-intestinal side effects include nausea, vomiting,
and diarrhea
Contraindications• preexisting atrioventricular heart block or cardiac failure• nonselective beta-adrenergic antagonists or high doses
of selective beta adrenergic antagonists are not recommended for administration to patients with chronic obstructive airway disease• in patients with diabetes mellitus, there is the risk that
beta-adrenergic blockade may mask the signs of hyperglycemia and thus delay its clinical recognition
Clinical uses of beta-adrenergicblockers
• Treatment of essential hypertension• Management of angina pectoris• Treatment of acute coronary syndrome• Peri operative beta-adrenergic receptor blockade• Treatment of intraoperative myocardial ischemia
• Suppression of cardiac dysrhythmias• Management of congestive heart failure• Prevention of excessive sympathetic nervous
system activity• Preoperative preparation of hyperthyroid patients• Treatment of migraine headache
Labetalol• is a unique parenteral and oral antihypertensive
drug that exhibits selective alpha 1 and nonselective beta 1 and beta2 adrenergic antagonist effects• presynaptic alpha 2 receptors are spared by labetalol
such that released norepinephrine can continue to inhibit further release of catecholamines
• Metabolism of labetalol is • by conjugation of glucuronic acid• 5% of the drug recovered unchanged in urine
• The elimination half-time is 5 to 8 hours and is prolonged in the presence of liver disease and unchanged by renal dysfunction
• labetalol lowers systemic blood pressure by decreasing systemic vascular resistance (alpha 1 blockade), whereas reflex tachycardia triggered by vasodilation is attenuated by simultaneous beta blockade• Cardiac output remains unchanged• in addition to producing vasodilation by alpha1
blockade, labetalol may cause vasodilation thatis mediated by beta2-adrenergic agonist activity• maximum systemic blood pressure-lowering effect of an
IV dose of labetalol (0.1 to 0.5 mg/kg) ispresent in 5 to 10 minutes
Clinical Uses• safe and effective treatment for hypertensive
emergencies• effective in the treatment of angina pectoris• Labetalol, 0.1 to 0.5 mg/ kg IV, can be administered to
anesthetized patients to attenuate increases in heart rate and blood pressure that are presumed to result from abrupt increases in the level of surgical stimulation
Side Effects• orthostatic hypotension is the most common side
effect of labetalol therapy.• bronchospasm is possible in susceptible patients• other adverse effects associated with beta
adrenergic antagonists (congestive heart failure, bradycardia, heart block) are a potential risk of labetalol therapy, but the Iikely incidence and severity is substantially decreased
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