Rabin's Lecture 1

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Rabin's Lecture 1
2010-09-18 13:25:32
Cardio Svetik

Cardio Drugs and mechanisms
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  1. Cholinergic receptors: Nicotinic nAchR
    • Receptor-operated channel (ROC)
    • Depolarize by increase Na and K conductance
    • ANS ganglia
    • Adrenal medulla
  2. Cholinergic receptors: Muscarinic mAchR
    M1, M3, M5
    • G protein-coupled receptor (GPCR)
    • Phospholipase C [increased PKC and increased IP3 and Ca]
    • M3 smooth muscle and glands
  3. Cholinergic receptors
    Muscarinic mAchR, M2, M4
    • G protein coupled receptor (GPCR)
    • Hyperpolarize by opening GIRK
    • Decrease Adenylyl cyclase
    • M2 heart (SA, atrium, AV node)
  4. Parasympathetic cardiac response
    • PNS via vagus - SA and AV node
    • - Hyperpolarization decreases HR and decreases AV conduction
    • - Dominant cardiac influence of vagus is at SA node

    Decrease force of atrial contraction - reduced refractory period and shortens action potential

    Very sparse PNS innervation of ventricular myocardium and low sensitivity to mAchR agonists
  5. PNS Vascular response
    • insignificant contribution to overall vascular resistance
    • few vascular beds innervated by PNS
    • Erectile tissue is exception.

    Stimulation M3Ach receptors on endothelial cells causes increase in NO secretion to diffuse and relax vascular smooth muscle
  6. Response to stress: SNS
    Blood FAs
    Blood glucose
    • Increased lypolysis
    • Increased glycogenolysis and gluconeogenesys
  7. Response to stress SNS
    decreased insulin secretion
  8. SNS
    • increase HR
    • increase AV conduction
    • increase stroke volume
    • increase CO
  9. SNS
    bronchodilation, increase O2
  10. SNS
    • Vasodilitation (skeletal)
    • Vasoconstriction (e.g. GI)
  11. SNS
    increased renin release
  12. SNS
    Lymphoid organs/immune cells
    • eye - mydriasis - pupil dilation
    • skin - sweating (Ach)
    • GI - increased sphincter tone, decreased peristalsis
    • Bladder - increased sphincter tone, relax smooth muscle
    • Lymphoid organs, immune cells - modulate immune response
  13. Heart SNS response

    SA node
    atrial muscle
    AV node
    ventricular muscle
    • SA node - increased HR
    • atrial muscle - increased contraction force
    • AV node - increased conduction
    • ventricular muscle - significantly increased contraction force, increased SV, increased CO
  14. Vasculature and kidney SNS response
    • Vasculature dilation or constriction
    • Kidney - increased renin release
  15. Heart PNS response
    SA node
    atrial muscle
    AV node
    ventricular muscle
    • SA node - decrease heart rate significantly
    • atrial muscle - decreased force of contraction
    • AV node - decreased conduction
    • ventricular muscle - none
  16. Vasculature and kidney PNS response
    • Vasculature - minimal influence - dilate erectile tissue
    • kidney - none
  17. SNS Mediators - endogenous Catecholamines
    • NE - primary NT from MOST postganglionic sympathetic nerves
    • Epi - primary neurohumor release by adrenal medulla
    • Dopamine - NT in CNS but also in various vascular beds (e.g.) renal, mesenteric
  18. Heart receptors
    Heart is mostly Beta 1 and some Beta 2 receptors
  19. Alpha 1:
    1A, 1B, 1D
    • Epi > NE
    • increased phospholipase C
    • Increased Ca
    • Increased PKC
    • Postsynaptic only
  20. Alpha 2:
    2A, 2B, 2C
    • Epi >/= NE
    • decreased adenylyl cyclase
    • increased K conductance
    • postsynaptic in CNS
  21. Beta 1:
    Epi >/= NE

    • Found post-synaptically
    • Regulated by neuronal NE
    • Gs
    • increase adenylyl cyclase

    Heart, Kidney
  22. Beta 2:
    Epi >> NE

    • Typically non-innervated
    • Regulated by circulating Epinephrine
    • Gs
    • Increases adenylyl cyclase

    Lung, skeletal muscle, vasculature
  23. Beta 3:
    Iso > NE > Epi

    • Gs and Gi/o
    • Adenylyl cyclase
    • Increased MAPK
    • Increased NO & cGMP

    Fat, heart, GI
  24. Heart:
    Primary Receptor
    SNS Response
    • Beta-1
    • Increased HR
    • Increased SV
    • Increased AV conduction
    • Increased CO
  25. Vasculature:
    Primary Receptor
    SNS Response
    • dilation - Beta-2
    • constriction - Alpha-1
  26. Lung:
    Primary Receptor
    SNS Response
    • Beta-2
    • bronchodilation
  27. Kidney:
    Primary Receptor
    SNS Response
    • Beta-1
    • Increased renin release
  28. GI:
    Primary Receptor
    SNS Response
    • Alpha-1 : Increased sphincter tone
    • Alpha / Beta : decreased peristalsis
  29. Bladder:
    Primary Receptor
    SNS Response
    • Alpha / Beta : relax xmooth muscle
    • Alpha-1: increased sphincter tone
  30. Uterus:
    Primary Receptor
    SNS Response
    • Alpha-1: contraction
    • Beta-2: relaxation
  31. Eye:
    Primary Receptor
    SNS Response
    • Alpha-1
    • Mydriasis
  32. Metabolic:
    Primary Receptor
    SNS Response
    • Alpha / Beta
    • Increased lipolysis
    • Increased glyconeogenesis
    • Increased glycogenolysis
  33. Skin:
    Primary Receptor
    SNS Response
    • mAch
    • Sweat
  34. Immune Cells:
    Primary Receptor
    SNS Response
    • Beta-2
    • modulate immunity
  35. Isolated Denervated Heart
    • +'ve chronotropic
    • +'ve inotropic
    • increased CO
    • decreased efficiency
  36. Isolated Denervated heart
    • +'ve chronotropic:
    • Increased HR
    • SA node: SNS increases rate of phase 4 depolarization

    • +'ve inotropic:
    • Increased SV
    • Increased force of ventricular contraction
    • Increased dP/dt
    • Increased rate of relaxation
    • Shorten duration of contraction

    Increased CO

    Decreased efficiency: Increased work / Increased oxygen consumption
  37. Catecholamine Induced Arrhythmias
    High concentration of catecholamines can result from:
    - Pheochromocytoma
    - Severe anxiety
    - Cocaine overdose
    • Heart sensitized to carecholamine-induced arrhythmias by:
    • - General anesthetic
    • - Myocardial infarction

    Normally, 95 % of NE gets reabsorbed, but cocaine will make this transporter function in the opposite derection, causing very increased levels of NE in the synaptic clefts.
  38. Baroreceptor reflex in response to High and Low BP
    • High BP: decreased sympathetic activity, increased parasympathetic activity
    • Low BP: increased sympathetic activity, decreased parasympathetic activity
  39. Blood pressure response to exogenous catecholamines depends upon the change in
    CO and TPR
  40. Vascular response:
    Beta-2 adrenergic receptors
    Alpha adrenergic receptors
    • Beta-2 - vasodilation
    • Alpha - vasoconstriction
  41. The specific vascular response to a compound depends on:
    • Relative affinity of the compound for beta-1 vs. alpha adrenergic receptors
    • AND
    • Relative density of beta-2 vs. alpha adrenergic receptors in tissue
  42. CV response to Norepinephrine (NE)
    Affinity Alpha1~Alpha-2 > Beta-1 >> Beta-2

    • Alpha-AR mediated vasoconstriction leads to:
    • Increase in TPR and therefore to Increased B.P.
    • Causes Vagal mediated reflex to DECREASE HR
    • Increased stroke volume via ventricular B-1 AR
    • Slight increase in CO at best
  43. CV response to Epinephrine (Epi)
    • Affinity: B-1~B2 > a-1~a-2
    • Effects:
    • +'ve Inotropic
    • +'ve chronotropic
    • Increased CO
    • Decreased TPR
    • Minimal effect (slight increase) mean BP at therapeutic levels.
  44. CV response to Isoproterenol
    • Affinity: B-1~B-2 >>> a
    • Effects:
    • +'ve inotropic
    • +'ve chronotropic
    • Increases CO
    • Decreases TPR
    • Decreases BP
  45. In familial dysautonomia, how would the absense of the baroreceptor reflex affect the response to ISO?
    • HR would be lower than in a normal person
    • BP would be lower than normal
    • SV - would be lower than in a normal person?!
  46. CV response to Dopamine
    • Affinity: D-receptor >> Beta-1 AR >> Alpha-1 AR
    • Vasodilation via D-1 receptor in:
    • Renal
    • Mesenteric
    • Intracerebral
    • Coronary beds

    At higher doses +'ve inotropic effect with increased CO via Beta-1 AR with less effects on HR
  47. Dobutamine
    • "Beta-1 agonist"
    • Affinity: B-1 > B-2 > a
    • increased CO due to increased myocardial contractility
    • Modest increase in HR
    • Not much change in TPR

    Used short-term after surgery to increase CO
  48. Other actions of catecholamines:
    Immune cells
    • Other actions of catecholamines:
    • GI - decreased peristalsis (a/B) and increased sphincter tone (a-1)
    • Lung bronchodilation (B-2)
    • Eye - mydriasis (a-1)
    • Bladder relaxation of detrusor (B-2) and contraction of sphincter (a-1)
    • Uterus Decreased frequency, duration and intensity of contraction (B-2)
    • Immune cells - modulate magnitude of response (B-2)
    • Metabolic - Increase blood glucose increased glycogenolysis and glyconeogenesis, decreased insulin release]; increased blood fatty acids [increased lypolysis]
  49. Sympathomimetic: Amphetamine
    Uses Uptake I to facilitate release of catecholamines (NE periphery; NE and DA centrally) fron CYTOSOLIC pool

    • NOT exocytotic release of storage granules
    • Inhibits re-uptake of extracellular catecholamines
    • Alpha-AR mediated vasoconstriction -> increase in BP and vagal-mediated reflex bradycardia

    • Analeptic
    • decreased appetite
    • Contracture of urinary sphincter
    • D-isomer more potent in CNS
    • L-isomer more potent in CV
  50. Sympathomymetic: Ephedrine
    • Also uses Uptake I, but CAN also stimulate A and B-AR
    • Increased blood pressure: Alpha-AR mediated vasoconstriction
    • BUT increased heart rate (don't see the reflex bradycardia) - reflex sloweing is balanced by direct stimulation of myocardium
    • Relaxation of bronchial smooth muscle
    • Mydriasis w/o affecting accommodation - from local administration
  51. Direct-Acting Sympathomymetics
    • Alpha agonists: Phenylephrine, Methoxamine
    • Increase TPR, increase HR, Reflex bradycardya

    "Selective" Beta-2 Agonists: Albuterol, terbutaline, metaproterenol
  52. Adrenergic Amines: Uses
    • Decongestant (phenylephrine, ephedrine):
    • alpha-AR mediated vasoconstriction to reduce blood flow to mucous membranes

    • Combination with local anesthetic (Epi):
    • increases frequency of successful nerve block(localizes anesthetic), prolongs duration and decreases systemic toxicity

    • Local tissue hemostats (Epi):
    • alpha-AR mediated vasoconstriction; possible "rebound effect"

    • Hypotension (IF inadequate perfusion):
    • Ephedrine to offset hypotension with spinal anesthetic, increases HR a little bit

    • Shock: except for anaphylactic shock, or life threatening hypotension, sympathomimetics used when treatment of etiology unsatisfactory
    • shock usually activates sympathetics with increased vasoconstriction ( with spinal cord inury, might not get the sympathetic activation)
    • Dopamine

    Mild-moderate HF: Dobutamine (Beta-1 > Beta-2 >> Alpha) for short-term therapy to increase CO after cardiac or major vascular surgery

    Cardiac Arrest: Epi if external cardiac compression and defibrillation fail

    Bronchial asthma: Beta-2 selective (Albuterol) agonists; epi, iso for bronchodilation)

    • Severe allergic reaction: Epi
    • Decreases edema, maintains BP, Relaxes bronchial smooth muscle, suppresses histamine and leukotriene release from mast cells

    Preterm Labor: Uterus relaxation

    • Opthamology:
    • Mydriasis - topical Phenylephrine
    • Wide-Angle Glaucoma - stimulation of alpha-AR reduce production of aqueous humor
  53. Drugs that alter Cenral Regulation of Sympathetic Activity
    Clonidine, Methyl-dopa
  54. Drugs that deplete NE from Nerve Terminal
    Guanethedine, Reserpine
  55. Alpha-AR antagonists:
    • Phenoxybenzamine
    • Phentolamine
    • Prazosin
  56. Beta-AR antagonists
    • Pindolol
    • Carvedilol
    • Labetalol
    • Nebivolol
    • Atenolol
    • Labetalol
    • Exmolol
    • Sotalol
  57. Clonidine
    • In CNS: stimulates POSTSYNAPTIC alpha-2AR and imidazoline I-1 receptors
    • - reduction in sympathetic outflow - reduces tonic sympathoexcitatory tone
  58. Effects of Clonidine
    • Decreased TPR: from decreased sympathetic vascular tone and decreased Beta-1AR stimulation of renin release
    • Decreased HR
    • Decreased CO
    • Decreased BP: Supine - mainly decreased HR and decreased SV; Upright - decreased HR, decreased SV and decreased vascular resistance

    Sympathetic reflexes minimally affected
  59. Adverse effects of Clonidine
    • Secation
    • Xerostomia
    • Sexual Dysfunction
    • Abrupt withdrawal associated with rebound sympathetic tone:
    • -Rebound HTN
    • -Tachycardia
    • -Sweating
    • -Abdominal pain
    • -Headache
    • -Nervousness
  60. Methyl Dopa
    • methyl dopa -> Alpha-methyl DA -> alpha-methyl NE
    • Alpha-methyl NE is a potent and selective against at alpha-2AR
    • In CNS Alpha-methyl NE interacts with postsynaptic alpha-2 AR to: decrease sympathetic outflow from medullar centers (no affinity for beta-1, beta-1 nor alpha-1)
  61. Effects of Methyl Dopa
    • Younger pts: Decreased BP, due to Decreased TPR; not much change in CO
    • Older pts: Decreased BP, due to Decreased TPS AND Decreased CO due to Decreased HR and Decreased stroke volume secondary to relaxation of veins and reduction in preload

    NOT 1st line anti-HTN, but may be preferred in pregnancy - because effective and safe to fetus and mother and maintains uretine perfusion, not teratogenic
  62. Adverse side effects of Methyl Dopa
    • Sedation
    • Sexual Dysfunction
    • Abrupt withdrawal -> rebound HTN
    • Hepatitis
    • Anemia
  63. Guanethedine
    • Transported into neurons by Uptake I and disrupts storage granule
    • Reduction in neuronal NE stores
  64. Effects of Guanethedine
    • Decreases neuronal NE stores -> decreases NE amt releasec by action potential
    • Decreases BOTH alpha-AR and beta-AR mediated responses:
    • Decreases BP
    • Decreases CO and HR
    • Decreases sympathetic reflexes
    • Decreased response indirect acting sympathomimetics
  65. Adverse effects of Guanethedine
    • Orthostatic hypotension
    • GI cramping, pain, diarrhea
    • Fluid retention: Decreased CO -> Decreased GFR
    • Chronic admin - supersensitivity to exogenous adrenergic amines
    • Muscle weakness
    • Sexual dysfunction
  66. Reserpine
    • blocks vesicular transporter for NE, DA, 5-HT
    • Reduction in neuronal monoamine stores
    • Rate of depletion proportional to neuronal activity
  67. Effects of Reserpine
    • Decreased alpha-AR and beta-AR mediated responses:
    • Decreased BP
    • Decreased CO and HR

    Decreased response to indirect ating sympathomimetics
  68. Adverse effects of reserpine
    • CNS effects: Depression, nightmares
    • GI cramping, pain, diarrhea
    • Chronic Admin: Supersensitivity to exogenous adrenergic amines
    • Sexual dysfunction
  69. Phenoxybenzamine
    • Alpha-AR antagonist: Irreversible, insurmountable, noncompetitive
    • Blockade is slow-developing, but long-lasting (3-4 days)
    • Does NOT block Beta-AR
    • No intrinsic activity
    • Degree of Antagonism is directly proportional to alpha-adrenergic tone - greater effect in "upright" patients
    • -Decreases BP if supported by sympathetic activity of sympathomimetics
  70. Phentolamine
    • Competetive, reversible antagonismm of Alpha-AR
    • Does NOT block Beta-AR
    • No intrinsic activity
    • Response proportional to level of alpha-AR tone
    • Most effective antagonizing effects circulating carecholamines
  71. CV effects when:
    NE administered in addition to phentolamine?
    NE alone: Alpha-AR vasoconstriction - increase in TPR and increase in BP AND reflex bradycardia

    NE+Phentolamine: Increased HR, Increased CO
  72. Prazosin
    • Selective Alpha-1-AR antagonist
    • No effect on alpha-2 AR or Beta-AR

    • Decreases TPR therefore Decreases BP without significant tachycardia
    • Block alpha-1 AR in CNS involved with baroreceptor reflex
    • presynaptic alpha-1 AR autoreceptors not blocked
    • Faborable changes in blood lipid chemistry: Decreased total cholesterol and TG and Increased HDL-cholesterol

    "First Dose Effect": postural hypotension and syncope with 1st dose or increase in dosing
  73. Alpha-AR Antagonists: USES
    • Acute HTNive crisis (e.g. phentolamine):
    • OD aphetamine or alpha-AR agonist
    • Combo with beta-AR blocker for abrupt clonidine withdrawal

    • Essential HTN (e.g. prazosin):
    • Adjunct rather than monotherapy
    • Reported increased risk cardiac failure with doxazosin

    Raynaud's Syndrome:

    Combined with Beta-AR blocker for pre- and operative management of pheochromocytoma ( so have increased circulating catecholamines - to protect give Alpha and Beta blocker, Beta blocker 1st)
  74. Benign prostatic hyperplasia (BPH):
    • increased size of prostate with change in composition, functioning and sympatheti control
    • May cause lower urinary tract symptomes
    • Treat with Alpha-1 selective antagonists: Tamsulosin - Affinity Alpha1-A >~Alpha1-D > Alpha1-B / Alfuzosin - nonselective alpha-1 AR antagonist BUT "clinically uroselective"
    • Mainly Alpha-1AR in prostate smooth muscle, proximal urethra and neck of bladder
  75. Beta-AR antagonists
    • Competetive antagonists
    • Effects proportional to Beta-adrenergic tone
    • Increased tone during exercise and myocardial inadequacy
  76. Beta-AR antagonists
    • Some have weak intrinsic activity (e.g. pindolol):
    • Manifestation inversely related to beta-adrenergic tone
    • Less decrease in HR, CO and exercise tolerance
    • Less likely to increase serum TG and decrease HDL-colesterol
    • Maybe preferred in diabetic and possibly in patients with bradycardia
    • NOT for angina, after MI, or in heart failure

    Some have membrane-stabilizing effect-as antiarrhythmics - block Ca current into cell - (e.g. propranolol, acebutolol)

    Fatigue and "Sexual dysfunction"
  77. Newer generation beta blockers, additional properties
    • Carvedilol, Labetalol: Vasodilation due to alpha-AR blockade
    • Nebivolol: Vasodilation via generation of NO

    • Drug profules of beta blockers may differ due to differences in physiochemical and pharmacologic properties
    • "Heterogeneous drug class"
  78. Effects of Beta-AR antagonists
    • Decrease: HR, SV, CO, AV conduction - Beta-1 blockade
    • Block Beta-2 vasodilation supported by ISO and EPI
    • Block Beta-2 bronchodilation: increase resistance to airflow; precipitate asthmatic attack in individuals with asthma or with chronic obstructive bronchiole disorders
    • Inhibit increase in blood glucose & FFA by sympathomimetics: slow recovery from insulin-induced hypoglycemia
    • Chronic administration of non-selective beta-blockers associated with increased serum TG, and decreased HDL-cholesterol: Beta-1 selective blockers improve lipid profile
  79. Adverse effects/contraindications of Beta-AR blockers
    • Heart Block: decreased AV conduction may convert partial to complete block
    • Severe Bradycardia:
    • Asthma and active obstructive airway disease: because they increase airflow resistance
    • Raynaud's syndrome: Exacerbate alpha-AR vasoconstriction
    • Withdrawal syndrome with abrupt discontinuation:
    • Rebound HTN
    • Exacerbate anginal attacks
    • Supersensitivity to exogenous Beta-AR agonists
  80. Uses of Beta-AR blockers
    • Arrhythmias
    • Angina pectoris
    • Essential HTN
    • Post-MI
    • Hyperthyroidism
    • Migraine prophylaxix
    • Benign essential tremor
    • Peri-operative
    • Congestive Heart Failure
    • Adverse myocardial remodeling
    • Toxix effects of catecholamines on myocardium primarily via Beta-AR
  81. Uses of Beta-AR blockers
    • Decreases HR, and Decreases Ca2+ overload and inhibits delayed afterdepolarization:
    • Increases AV conduction time and prolongs SV refracoriness:
    • Controlling ventricular response to atrial tachy, fibrillation, or flutter
    • Terminate reentrant arrhythmias involving AV node:
    • because increases refractory period so arrhythmia comes around and hits tissue in refractory period

    Sotalol: Nonselective Beta blocker that also blocks K+ channels
  82. Uses of Beta-AR blockers
    Angina pectoris:
    • Effective in stress-induced where have decreased O2 demand:
    • Combo therapy to counter adverse effects of nitrates:
    • --Beta blockers decrease reflex tachycardia and (+) inotropic effects of nitrates
    • --Nitrates alleviate increased coronary vascular resistance with Beta blockers and attenuate the increase in left ventricular end diastolic volume associated with beta blockers by increasing venous compliance
  83. Uses of Beta-AR blockers
    Essential HTN:
    • Beta-1 AR selective, nonselective Beta blockers, and newer generation Beta-blockers:
    • --slow developing antihypertensive action (weeks) for traditional Beta-blockers (i.e. Beta-1 selective and non-selective)
    • --Delay not observed with vasodilaroty Beta blockers (labetalol, carvedilol, nebivolol)
    • Some recent question regarding exact role in HTN therapy:
    • --meta-analysis suggest compared with other antihypertensives, Beta-blockers may increase risk adverse CV outcomes, especially in elderly
  84. Uses of Beta-AR blockers
    • Decreases mortality: with administration of drugs during early MI and continued long-term
    • Mechanism:
    • Decreased O2 demand and therefore decreases ischemia
    • Redistribution of myocardial blood flow
    • Anti-arrhythmic action
  85. Uses of Beta-AR blockers
    Management of peripheral symptoms: tachycardia, tremor
  86. Uses of Beta-AR Blockers
    Migraine prophylaxis:
    Benign Essential tremor:
    • Uses of Beta-AR Blockers
    • Migraine prophylaxis: decreases frequemcy which may lead to suppression
    • Benign Essential tremor:
    • Perioperative:
    • Adverse cardiac outcome in 1-5% patients undergoing noncardiac surgery;
    • Initiation peri-ip Beta-Blockers found to decrease incidence of non-fatal MI but increased incidence of non-fatal stroke + significant hypotension and bradycardia
    • Peri-operative Beta-blockers for patient already on Beta-blocker therapy
  87. Uses of Beta-AR blocker
    Congestive Heart Failure:
    • Activation of sympathetic and renin-angiotensin aldosterone systems are compensatory for acure myocardial inadequacy:
    • Direct action on hear to increase CO
    • Vasoconstriction to maintain BP and allow organ perfusion
    • Venous constriction to increase venous return and increased cardiac filling
    • Volume expansion due to H2O and Na+ retention
  88. Uses of Beta-AR blocker
    Congestive Heart Failure:
    • BUT chronic activation Contributes to downward spiral of:
    • -excessive vasoconstriction
    • -volume expansion
    • -progressive left ventricular dysfunction
    • Chronic excessive sympathetic activation causes vasoconstriction of coronary arteries with thichen ventricular wall -> myocardial ischemia
    • Long-term exposure to excessive EPI and NE leads to pathological remodeling:
  89. Uses of Beta-AR blockers: CHF and prolonged exposure to excessive catecholamines:
    • Adverse myocardial remodeling:
    • Increased apoptosis: increased Ca++ leads to Ca++ overload which uncouples mitochondrial oxidative phosphorylation with decreased ATP

    Hypertrophy of myocytes and fibroblast growth --- increase the risk of ischemia

    • Fetal gene expression:
    • Remodeling also leads to electrophysiological heterogeneity which can promote re-entry arrhythmias
    • Desensitization of Beta-1 and Beta-1 BUT not Beta-3
  90. Uses of Beta-AR blockers: CHF
    • Toxic effects of catecholamines on myocardium promarily via Beta-AR but also involve alpha-AR
    • Carvedilol: (Beta-1, Beta-2, Alpha-1 antagonist + antioxidant)
    • Alter natural history and slow progression:
    • Prevent and reverse catecholamine-mediated myocardial dysfunction and remodeling:
    • Slow developing efficacy (months):
    • Decreases sudden cardiac death:
    • Allow Beta-AR to resensitize:
  91. Proprandolol
    nonselective Beta-1 and Beta-2 blocker
  92. Metoprolol
    "selective" beta-1 blocker
  93. Atenolol
    selective Beta-1 blocker; limited CNS penetration - ADVANTAGE
  94. Carvedilol
    Beta-1, Beta-2, Alpha-1 blocker and antioxidant
  95. Labetalol:
    Beta-1, Beta-2, Alpha-1 blocker --> so without delay
  96. Esmolol:
    very short-acting Beta-1 blocker (T1/2 ~9mins)
  97. Sotalol:
    Nonselective Beta-1 and Beta2 blocker + blocks K+ channel
  98. Nebivolol:
    Beta-1 selective blocker + NO generator