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ADRENOCEPTOR BLOCKERS
E. TAALA-BAYUBAY, M.D.

Drugs that mimic the actions of epinephrine or nor-epinephrine sympathomimetic drugs know about the physiologic role of the catecholamines

MECHANISM ADRENOCEPTOR ACTIVATING

DIRECT INDIRECT
two different mechanisms:

(1) displacement of stored catecholamines from the adrenergic nerve ending (eg, amphetamine and tyramine) (2) inhibition of reuptake of catecholamines already released (eg, cocaine and tricyclic antidepressants).

SYMPATHETIC NERVOUS SYSTEM

REGULATOR OF ACTIVITIES OF ORGANS SUCH AS THE HEART AND PERIPHERAL VASCULATURE IN RESPONSE TO STRESS MEDIATED BY THE RELEASE OF NOREPINEPHRINE THAT ACTIVATE ADRENOCEPTORS AT POSTSYNAPTIC SITES

Alpha receptors
epinephrine norepinephrine >> isoproterenol.

Beta receptors
isoproterenol > epinephrine norepinephrine.

the adrenal medulla releases epinephrine

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Beta Adrenoceptors
Two subtypes of receptors Beta1 and Beta 2 Receptors Beta 1 receptors have approximately equal affinity for epinephrine and norepinephrine Beta 2 receptors have a higher affinity for epinephrine than for norepinephrine.

Receptor Selectivity
Selectivity means that a drug may preferentially bind to one subgroup of receptors at concentrations too low to interact extensively with another subgroup. Example: norepinephrine preferentially activates 1 receptors as compared with 2 receptors

MOLECULAR MECHANISM
Alpha Adrenoceptors two major groups of receptors
Alpha 1 and Alpha 2.
receptors are coupled by G proteins to the various effector proteins whose activities are regulated by those receptors. G proteins of particular importance for adrenoceptor function include:
Gs, the stimulatory G protein of adenylyl cyclase Gi, the inhibitory G protein of adenylyl cyclase Gq, the protein coupling receptors to phospholipase C.

Alpha 1 subtypes: 1A, 1B, and 1D receptors Alpha 2 subtypes: 2A, 2B, and 2C,

Dopamine Receptors
Brain, splanchnic and renal vasculature five subtypes
D1, D2, D3, D4, and D5 two D1-like receptors (D1 and D5) three D2-like (D2, D3, and D4)

activation of G protein-coupled receptors by catecholamines promotes the dissociation of GDP from the subunit of the appropriate G protein GTP then binds to this G protein, and the subunit dissociates from the unit activated GTP-bound subunit regulates the activity of its effector

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IP3

Effectors of adrenoceptor-activated subunits include:

adenylyl cyclase cGMP phosphodiesterase phospholipase C ion channels

promotes release of sequestered Ca2+ from intracellular stores increases the cytoplasmic concentration of free Ca2+ activation of various calcium-dependent protein kinases increase influx of calcium across the cell's plasma membrane.
activates protein kinase C that modulates activity of many signaling pathways Alpha-1 receptors activate signal transduction pathways peptide growth factor receptors activate tyrosine kinases.

DAG

subunit is inactivated by
hydrolysis of the bound GTP to GDP and Phosphate Result to reassociation of the subunit with the - subunit

Alpha2 inhibit adenylyl cyclase activity cause intracellular cAMP levels to decrease utilize additional signaling pathways regulation of ion channel activities activities of important enzymes involved in signal transduction. Alpha2-receptormediated inhibition of adenylyl cyclase activity Transduced by inhibitory regulatory protein, Gi

ALPHA RECEPTORS

stimulate polyphosphoinositide hydrolysis

formation of inositol 1,4,5trisphosphate (IP3) and diacylglycerol (DAG)

G proteins in the Gq family couple 1 receptors to phospholipase C

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Beta

All three receptor subtypes ( 1, 2, and 3) results in activation of adenylyl cyclase and increased conversion of ATP to cAMP

Receptor Regulation
desensitization occur after exposure to catecholamines and other sympathomimetic drug after a cell or tissue has been exposed for a period of time to an agonist The tissue often becomes less responsive to further stimulation by that agent Other terms: tolerance, refractoriness, and tachyphylaxis

Liver

Inc. cAMP synthesis; activation of glycogen phosphorylase Heart Inc. influx of calcium across the membrane Muscle relaxation

Homologous desensitization refers to loss of responsiveness exclusively of the receptors that have been exposed to repeated or sustained activation by a drug Heterologous desensitization refers to loss of responsiveness of some cell surface receptors that have not been directly activated by the drug.

D1 receptor stimulation of adenylyl cyclase D1-receptor-induced smooth muscle relaxation is presumably due to cAMP accumulation in the smooth muscle of those vascular beds where dopamine is a vasodilator D2 receptor inhibit adenylyl cyclase activity, open potassium channels, and decrease calcium influx.

HOMOLOGOUS

loss of responsiveness exclusively of the receptors that have been exposed to repeated or sustained activation by a drug loss of responsiveness of some cell surface receptors that have not been directly activated by the drug

HETEROLOGOU S

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A major mechanism of desensitization that occurs rapidly involves phosphorylation of receptors by members of the G protein-coupled receptor kinase (GRK) family

This compound consists of a benzene ring with an ethylamine side chain. Substitutions may be made

(1) on the terminal amino group (2) on the benzene ring (3) on the or carbons

KINETICS
Phenylethylamine considered as the parent compound consists of a benzene ring with an ethylamine side chain. chemical structure determines the pharmacokinetic properties

TERMINAL AMINO GROUP

Increasing the size of alkyl substituents on the amino group tends to increase -receptor activity EG. Methyl substitution of NE isopropyl substitution at amino nitrogen (isoproterenol)

BENZENE RING

BENZENE RING

Maximal and activity are found with catecholamines (OH groups at the 3 and 4 positions) absence of one or the other of these groups, particularly the hydroxyl at C3, -reduce the potency of the drugs -Eg. Phenylephrine is less potent than epinephrine -Absence of OH group on the phenyl ring increases bioavailability and prolong duration of action and inc. distribution to CNS -Eg. Ephedrine and amphetamine

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Alpha Carbon

Block oxidation by monoamine oxidase (MAO) and prolong the action of such drugs, particularly the noncatecholamines. Eg. Ephedrine and amphetamine Alpha-methyl compounds also known phenylisopropylamines activate adrenoceptors Beta Carbon important for storage of sympathomimetic amines in neural vesicles

D1 receptors promote vasodilation

renal, splanchnic, coronary, cerebral, and other resistance vessels

D1 receptors in the renal vasculature

play a major role in the natriuresis induced by pharmacologic administration of dopamine

Organ System Effects of Sympathomimetic Drugs

Heart Alpha 1 direct effect Beta increased calcium influx in cardiac cells.
- Pacemaker activity increased positive chronotropic effect - Conduction velocity in the atrioventricular node is increased - refractory period is decreased. Intrinsic contractility is increased positive inotropic effect and relaxation is accelerated

Blood Vessels

Vascular smooth muscle tone Control peripheral vascular resistance and venous capacitance. Alpha receptors increase arterial resistance alpha 2 promote smooth muscle relaxation. constrict in the presence of epinephrine and norepinephrine, as do the splanchnic vessels may constrict or dilate.

BLOOD PRESSURE

phenylephrine increases peripheral arterial resistance and decreases venous capacitance. increase stroke volume positive inotropic action Activation results in bronchodilation blood vessels of the upper respiratory tract mucosa contain receptors the decongestant action of adrenoceptor stimulants is clinically useful

RESPIRATORY
Bronchial s. muscle(B2)

skin vessels

Vessels in skeletal muscle

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EYE

Mydriasis effect on radial pupillary dilator muscle of the iris Alpha and beta 2: effects on intraocular pressure
increase outflow of aqueous humor

alpha1 receptor

mediates constriction of the bladder base and prostate

1A receptors play an important role

glaucoma Beta stimulants relax the ciliary muscle

decrease in accommodation

Beta 2 receptor

bladder wall mediate relaxation Ejaculation depends upon normal alpha-receptor (and possibly purinergic receptor) activation in the ductus deferens, seminal vesicles,
and prostate Detumescence of erectile tissue

directly protect neuronal cells in the retina

GIT Relaxation of gastrointestinal smooth

muscle Beta receptors on smooth muscle cells mediate relaxation via hyperpolarization and decreased spike activity in these cells Alph decrease muscle activity indirectly by a2 reducing the release of acetylcholine decrease salt and water flux into the lumen of the intestine

salivary glands

regulate the secretion of amylase and water apocrine on the palms of the hands sweat and a few other areas: glands increased sweat production apocrine nonthermoregulatory glands associated with psychologic stress

GUT
human uterus mediate relaxation may be clinically useful in (B2) pregnancy
bladder base, urethral sphincter, and prostate(alpha)

Beta3 on fat cells Alpha2

increased lipolysis Inhibit lipolysis by decreasing intracellular cAMP Sympathomimetic drugs enhance glycogenolysis in the liver
increased glucose release

mediate contraction and promote urinary continence

high concentration of cathecolamines cause metabolic acidosis.

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Beta 2

promotes the uptake of potassium into cells Blockade of these receptors may accentuate the rise in plasma potassium that occurs during exercise pancreatic islets increase and decrease insulin secretion

Specific Sympathomimetic Drugs

Epinephrine (adrenaline) potent vasoconstrictor and cardiac stimulant. rise in systolic blood pressure positive inotropic and chronotropic actions on the heart B1 vasoconstriction induced in many vascular beds alpha receptors Beta 2 in some vessels leads to dilation

Beta and alpha2

Endocrine Insulin secretion: stimulated by

Beta receptors and inhibited by alpha2 receptors. renin secretion: stimulated by beta1 and inhibited by alpha2 receptors modulate the secretion of parathyroid hormone, calcitonin, thyroxine, and gastrin high concentrations, epinephrine and related agents cause leukocytosis

total peripheral resistance fall fall in diastolic pressure Beta 2 receptors in skeletal muscle contributes to increased blood flow during exercise

CNS

depend on ability to cross the blood-brain barrier Effects: "nervousness" to "a feeling of impending disaster, peripheral effects: tachycardia and tremor

Norepinephrine (levarterenol, noradrenaline) beta1 receptors in the heart and similar potency at alpha receptors little effect on beta 2 receptors increases peripheral resistance and both diastolic and systolic blood pressure Compensatory vagal reflexes tend to overcome the direct positive chronotropic effects

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Isoproterenol (isoprenaline) very potent beta receptor agonist and has little effect on alpha receptors has positive chronotropic and inotropic actions activates beta receptors almost exclusively, it is a potent vasodilator marked increase in cardiac output
fall in diastolic and mean arterial pressure decrease or a slight increase in systolic pressure

Dopamine agonists

central actions are of considerable value for the treatment of Parkinson's disease and prolactinemia

Dopamine immediate metabolic precursor of norepinephrine activates D1 receptors in several vascular beds leads to vasodilation with effect on renal blood flow dopamine activates 1 receptors in the heart.

Dobutamine relatively beta 1-selective synthetic catecholamine. also activates alpha 1 receptors.

Fenoldopam D1 receptor agonist that selectively leads to peripheral vasodilation in some vascular beds IV administered drug for the treatment of severe hypertension

Phenylephrine pure agonist acts directly on the receptors it is not a catechol derivative it is not inactivated by COMT much longer duration of action than the catecholamines effective mydriatic and decongestant and can be used to raise the blood pressure

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Methoxamine like phenylephrine it is predominantly a direct-acting 1-receptor agonist cause a prolonged increase in blood pressure due to vasoconstriction causes a vagally mediated bradycardia for parenteral use

a weak base, accelerate excretion by acidification of the urine ability to activate beta receptors earlier use in asthma. mild CNS stimulant Pseudoephedrine, one of four ephedrine enantiomers, an OTC for decongestant mixtures.

Midodrine a prodrug that is enzymatically hydrolyzed to desglymidodrine, an alpha 1receptor selective agonist peak concentration: 1 hour after midodrine administration for postural hypotension cause hypertension in supine position.

Xylometazoline and oxymetazoline direct-acting agonists used as topical decongestants promote constriction of the nasal mucosa. in large doses, oxymetazoline may cause hypotension oxymetazoline has significant affinity for alpha 2A receptors

Ephedrine first orally active sympathomimetic drug found in Ma-huang noncatechol phenylisopropylamine has high bioavailability and a relatively long duration of action phenylisopropylamines, fraction of the drug is excreted unchanged in the urine

Amphetamine a phenylisopropylamine that is important chiefly because of its use and misuse as a central nervous system stimulant pharmacokinetics are similar to those of ephedrine readily enters the central nervous system stimulant effects on mood and alertness and a depressant effect on appetite release of catecholamines.

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Methamphetamine (Nmethylamphetamine) is very similar to amphetamine With even higher ratio of central to peripheral actions.

Phenylpropanolamine (PPA) is a sympathomimetic drug an over-the-counter agent in numerous weight reduction and cold medications withdrawn from over-the-counter use in the USA regarding an association with hemorrhagic stroke.

Receptor-Selective Sympathomimetic Drugs

Methylphenidate and pemoline are amphetamine variants major pharmacologic effects and abuse potential are similar to those of amphetamine appear to have efficacy in some children with attention deficit hyperactivity disorder Pemoline life-threatening hepatic failure. Dexmedetomidine centrally acting alpha2-selective agonist indicated for sedation of initially intubated and mechanically ventilated patients

Modafinil a new drug with both similarities to and differences from amphetamine significant effects on central ALPHA1B receptors appears to affect GABAergic, glutaminergic, and serotonergic synapses

Beta-selective agonists very important because of the separation of beta1 and beta2 effects reduce adverse effects in several clinical applications.

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Cocaine is a local anesthetic with a peripheral sympathomimetic action results from inhibition of transmitter reuptake at noradrenergic synapses readily enters the central nervous system and produces an amphetamine-like effect inhibit dopamine reuptake into neurons in the "pleasure centers" of the brain smoked, "snorted" into the nose, or injected for rapid onset of effect have made it a heavily abused drug

Food Tyramine Content of an Average Serving Beer (No data) Broad beans, fava beans Negligible (but contains dopamine) Cheese, natural or aged Nil to 130 mg (Cheddar, Gruyre, and Stilton especially high) Chicken liver Nil to 9 mg Chocolate Negligible (but contains phenylethylamine) Sausage, fermented (eg, salami, pepperoni, summer sausage)Nil to 74 mg Smoked or pickled fish (eg, pickled herring) Nil to 198 mg Snails (No data) Wine (red) Nil to 3 mg Yeast (eg, dietary brewer's yeast supplements) 268 mg

Clinical application
Tyramine normal by-product of tyrosine metabolism in the body also found in high concentrations in fermented foods such as cheese readily metabolized by MAO in the liver inactive when taken orally With indirect sympathomimetic action caused by the release of stored catecholamines Hypotension Shock / cardiogenic shock Heart failure Asthma Anaphylactic shock Mydriatic agent Glaucoma Premature labor ADHD

patients treated with MAO inhibitors particularly inhibitors of the MAO-A isoformthis effect of tyramine may be greatly intensified, leading to marked increases in blood pressure

ADRENOCEPTOR BLOCKERS

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Alpha 1

Beta 2

Inc. rate of heart contraction Vasoconstriction incr. Blood pressure Mydriasis Decrease secretion of salivary glands Increase contraction of bladder and prostate capsule Inc. ejaculation

Dilates the bronchioles Promotes gastrointestinal and uterine relaxation Promote increase blood sugar through glycogenolysis in the liver Increase blood flow in the skeletal muscles

Alpha 2

Inhibit release of norepinephrine Dilates blood vessels Produces hypotension Decrease gastrointestinal motility and tone

Beta 1

Increase heart rate and force of contraction Increase renin secretion which increases blood pressure

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ALPHA BLOCKING DRUGS

Oral: Limited absorption Peak concentration: 1 hour after intake Half life: 5 to 7 hours Adverse effects after IV administration:

Tachycardia Arrythmias Myocardial ischemia Tachycardia, nasal congestion and headache

Adverse effects after oral administration:

ALPHA BLOCKING DRUGS

ALPHA BLOCKING DRUGS

IRREVERSIBLE, Long acting

Covalently bind with the receptors

PHENOXYBENZAMINE

Phenoxybenzamine binds covalently to alpha receptors Causes irreversible blockade Competetive pharmacologic antagonist

REVERSIBLE, shorter acting

Dissociate from receptors

Phentolamine and prazosin

Alpha 1 selective

Doxazosin and Terazosin Yohimbine

Binds covalently to alpha receptors Causes irreversible blockade Duration of action: 14 to 48 hours Less alpha selective than prazosin Inhibit reuptake of NE Blocks histamine, acetylcholine, and serotonin Antagonism of alpha mediated events

Alpha 2 selective

ALPHA BLOCKING DRUGS

ALPHA BLOCKING DRUGS

PHENTOLAMINE

Imidazole derivative Potent competetive antagonist at both alpha 1 and alpha 2 Decrease peripheral resistance : Blocks alpha 1 Effects of vascular smooth muscle on alpha 2 Minor inhibitory effects on serotonin receptors Agonist effect at muscarinic and H1 and H2 receptors

Attenuates catecholamine induced vasoconstriction Causes little fall in BP in supine position Reduces BP in upright posture or if blood volume is reduced Cardiac output is increased as a reflex effect Kinetics

Absorbed orally Bioavailability is low Dose: 10-20 mg/d and progressively increased

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ALPHA BLOCKING DRUGS

Clinical use: treatment of pheochromocytoma Adverse effects:

ALPHA BLOCKING DRUGS

DOXAZOSIN (cardura)
Efficacious in the treatment of hypertension and BPH Half life: 22 hours Extensively metabolized Moderate bioavailability Excreted in the urine or feces

Fatigue, sedation and nausea Cause tumors in animals

ALPHA BLOCKING DRUGS

ALPHA BLOCKING DRUGS

TOLAZOLINE

TAMSULOSIN

Obsolete agent similar to phentolamine Piperazilyn quinazoline Effective in the management of hypertension Highly selective for alpha 1 receptors Relaxation of both arterial and venous vascular smooth muscle and prostate smooth muscle Bioavailability: 50%; half-life: 3 hours

PRAZOSIN

Competetive alpha 1 antagonist High bioavailability Half life: 9 to 15 hours Metabolized extensively in the liver High affinity for alpha 1A and 1D Inhibit contraction in prostate smooth muscle versus vascular smooth muscle Effective in BPH

ALPHA BLOCKING DRUGS

ALPHA BLOCKING DRUGS

TERAZOSIN

ALFUZOSIN

Reversible alpha 1 selective antagonist Effective in hypertension Approved for use in men with urinary symptoms due to benign prostatic hyperplasia With high bioavailability but extensively metabolized in the liver Excreted in the urine Half life: 9 to 12 hours

Alpha 1 selective quinazoline derivative Approved for use in BPH Bioavailability: 60% Half life: 5 hours Alpha 1 selective antihypertensive

INDORAMIN

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ALPHA BLOCKING DRUGS

URAPIDIL

Alpha 1 antagonist,Weak alpha 2 agonist,5-HT 1A agonist action,Weak Beta 1 agonist Antihypertensive and BPH Alpha selective and beta antagonistic effect

CLINICAL USE Non selective alpha blockers Presurgical management of pheochromocytoma

LABETALOL

Trazodone

Patients with severe hypertension and reduced blood volume ( needed to be corrected prior to surgery) Phenoxybenzamine is usually used during preparatory phase

Can block alpha 1

Neuroleptic drugs: potent dopamine antagonist

10-20mg/d For at least 1 to 3 weeks before surgery

ALPHA BLOCKING DRUGS

YOHIMBINE

Indole alkaloid, alpha 2 selective antagonist Useful in autonomic insufficiency Promote neurotransmitter release by blockade of presynaptic alpha 2 receptors Improves male sexual function Can abruptly reverse the antihypertensive effect of alpha 2 adrenoceptor agonist such as clonidine

CLINICAL USE chronic treatment of inoperable pheochromocytoma May also respond to alpha 1 selective antagonist Metyrosine
Useful in symptomatic patients with inoperable and metastatic pheochromocytoma

CLINICAL USE
1.

PHEOCHROMOCYTOMA

CLINICAL USE HYPERTENSIVE EMERGENCIES

SYMPTOMS: nintermittent or sustained hypertension, headaches, palpitations, and increased sweating Diagnosis: chemical assay of blood and urine

In pheochromocytoma, overdosage of symphatomimetics and clonidine withdrawal Phentolamine and labetalol Phentolamine, prazosin and phenoxybenzamine

Presence of catecholamines Plasma metanephrine CT and MRI

RAYNAUDS PHENOMENON

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CLINICAL USE Local vasoconstrictor excess

Receptor Selectivity
Beta1 receptor selectivity
Acebutolol, atenolol, esmolol, metoprolol For patients with asthma

Phentolamine has been used to reverse the intense local vasoconstriction caused by inadvertent infiltration of alpha agonist into subQ tissue Local infiltration to ischemic tissue

Beta 2 receptor selectivity

Butoxamine Used only in research

Nonselective beta blockers

Nadolol, propranolol and timolol

Combined alpha and beta blocking action

Labetalol, carvadilol

CLINICAL USE
Urinary Obstruction

Partial Agonists activity

Intrinsic sympathomimetic activity Use in patients with asthma can cause some bronchodilation Pindolol and acebutolol

Prazosin, doxazosin and terazosin are efficacious Useful also in hypertensive patients Combination of phentolamine with nonspecific smooth muscle relaxant papaverine Injected directly into the penis Fibrotic reaction may occur Orthostatic hypotension may occur

Erectile dysfunction

Local anesthetic activity

Membrane stabilizing activity Disadvantage when used topically in the eye
Decreases protective reflexes Increase risk of corneal ulceration

BETA-BLOCKING DRUGS
Competetive pharmacologic antagonist Propranolol is the prototype drug Drugs in this group are usually classified into subgroups
Receptor selectivity Partial agonist activity Local anesthetic action Lipid solubility

Lipid solubility
Acebutolol and atenolol are less lipid soluble

EFFECTS AND CLINICAL USE Treatment of open angle glaucoma Cardiovascular applications: hypertension, angina and arrythmias Chronic congestive heart failure
Lavetalol and carvedilol may be beneficial if used in low dosage and titrated carefully

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NADOLOL TOXICITY Bradycardia Atrioventricular blockade Congestive heart failure Patients with airway dse - may suffer severe asthma attacks Premonitory symptoms of hypoglycemia from insulin over dosage (tachycardia, tremor and anxiety) may be masked Mobilization of glucose from the liver may be impaired

TIMOLOL

Levobunolol (non selective Betaxolol(beta 1 selective) Careteolol

Very long duration of action Spectrum of action is similar to timolol Non selective agent Has excellent ocular hypotensive effect Administered topically in the eye Used for topical ophthalmic application in glaucoma Betaxolol may less likely cause bronchoconstriction Non selective beta antagonist

CNS adverse effects

Sedation Fatigue Sleep alterations Less lipid soluble have less CNS action

Well absorbed after oral administration Peak concentration occur at 1 to 3 hours Half-life: 3 to 10 hours ( except nadolol = 24 hours and esmolol = 10 mins) Metabolized in the liver Excreted unchanged in the urine

PINDOLOL ACEBUTOLOL CARTEOLOL BOPINDOLOL OXPRENOLOL CELIPROLOL PENBUTOLOL

Partial Beta agonist activity Effective in hypertension and angina Less likely to cause bradycardia and abnormalities in plasma lipids Pindolol may potentiate the action of antidepressant medication Celiprolol is beta 1 selective and activate beta 2 ; have less bronchoconstrictor effect Acebutolol is beta 1 selective antagonist

PROPRANOLOL Prototypical B blocker Long acting form is available Prolonged absorption: 24 hours May block some serotonin receptors No detectable partial agonist action METOPROLOL Beta 1 selective group ATENOLOL Safer in patients with bronchoconstriction in response to propranolol Preferred for patients with diabetes or peripheral vascular disease

LABETALOL

Reversible adrenoceptor anagonist; Racemic mixture of two pairs of chiral isomers Alpha 1 selective Induces hypotensionwith less tachycardia Non selective beta receptor antagonist With some capacity to block alpha 1 adrenergic receptors

CARVEDILOL MEDROXALOL BUCINDOLOL

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CARVEDILOL

antagonizes action of catecholamines Half-life: 6-8 hours Extensively metabolized in the liver Stereoselective metabolism of its two isomers( R isomer: CYP2D6) Drug interaction may occur Clinical benefits in chronic heart failure Ultra short acting beta 1 selective Esterase in RBC rapidly metabolize esmolol Steady state is achieved quickly Safer to use Use in supraventricular arrythmia, arrythmia due to thyrotoxicosis, perioperative hypertension, and MI in acutely ill patients

CLINICAL USES
Glaucoma Reduced production of aqueous humor by ciliary body Timolol are suitable for local use (1 mg) Betaxolol, carteolol, levobunolol, and metipranolol HYPERTHYROIDISM Blockade of adrenoceptors Inhibition of peripheral conversion of T3 and T4 Propranolol in thyroid storm

ESMOLOL

CLINICAL USES
HYPERTENSION ISHCEMIC HEART DISEASE
BETA BLOCKERS ARE WELL TOLERATED AND EFFECTIVE IN HYPERTENSION

CLINICAL USES
Neurologic disease migraine headache Propranolol Preventive effect: metroprolol, atenolol, timolol, and nadolol Skeletal muscle tremor: Propranolol Alcohol withdrawal : propranolol
Inhibition of peripheral conversion of T3 and T4 Propranolol in thyroid storm

Reduce anginal episode Improves exercise tolerance Block cardiac beta receptors Decrease cardiac work and oxygen demand Timolol, propranolo and metropolol prolongs survival in MI

HYPERTHYROIDISM Blockade of adrenoceptors

DRUG

CLINICAL USES
CARDIAC ARRYTHMIAS
Supraventricular and ventricular arrythmias Slows ventricular reponse rate in atrial flutter and fibrillation Reduce ventricular ectopic beats SOTALOL has antiarrythmic effect involving ion channel blockade
METOPROLO L PROPRANOL OL

LIPID SOLUBILITY MOD

T1/2

BIOAVAILABILITY

LOCAL ANESTHETIC Y

3-4 HRS 3.5-6 HRS 9-2 HRS

50

HIGH

90

BISOPROLOL LOW

80

ESMOLOL SOTALOL

LOW LOW

10 MIN 40 12 HRS 6-9 90

N N

HEART FAILURE

Metoprolol, bisoprolol and carvedilol are effective in treating chronic heart failure

ATENOLOL

LOW

40

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