adrenoceptor agents [compatibility mode]

8/6/2019 Adrenoceptor Agents [Compatibility Mode]

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E. TAALA-BAYUBAY, M.D.

ADRENOCEPTOR

BLOCKERS

ADRENOCEPTORACTIVATING

SYMPATHETIC NERVOUS SYSTEM

REGULATOR OF ACTIVITIES OF ORGANSSUCH AS THE HEART AND PERIPHERALVASCULATURE IN RESPONSE TOSTRESS

MEDIATED BY THE RELEASE OFNOREPINEPHRINE THAT ACTIVATEADRENOCEPTORS AT POSTSYNAPTICSITES

the adrenal medulla releasesepinephrine

Drugs that mimic the actions of

epinephrine or nor-epinephrinesympathomimetic drugs

know about the physiologic role ofthe catecholamines

MECHANISM

DIRECT

INDIRECT

two different mechanisms:

(1) displacement of stored catecholaminesfrom the adrenergic nerve ending (eg,amphetamine and tyramine)

(2) inhibition of reuptake of catecholaminesalready released (eg, cocaine and tricyclic

antidepressants).

Alpha receptors

epinephrine norepinephrine >>isoproterenol.

Beta receptors

isoproterenol > epinephrine

norepinephrine.


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Beta Adrenoceptors

Two subtypesof receptors

Beta1 and Beta 2 Receptors

Beta 1 receptors have approximately equalaffinity for epinephrine and norepinephrine

Beta 2 receptors have a higher affinity forepinephrine than for norepinephrine.

Alpha Adrenoceptors

two major groups of receptors

Alpha 1 and Alpha 2.

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)

Receptor Selectivity

Selectivity means that a drug may preferentially

bind to one subgroup of receptors atconcentrations too low to interact extensivelywith another subgroup.

Example: norepinephrine preferentiallyactivates 1 receptors as compared with 2receptors

MOLECULAR MECHANISM

receptors are coupled by G proteins to thevarious effector proteins whose activities areregulated by those receptors.

G proteins of particular importance foradrenoceptor 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.

activation of G protein-coupled receptors bycatecholamines promotes the dissociation of

GDP from the subunit of the appropriate Gprotein

GTP then binds to this G protein, and thesubunit dissociates from the unit

activated GTP-bound subunit regulates theactivity of its effector


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Effectors of adrenoceptor-activated subunitsinclude:

adenylyl cyclase

cGMP phosphodiesterase

phospholipase C

ion channels

subunit is inactivated by

hydrolysis of the bound GTP to

GDP and Phosphate

Result to reassociation of thesubunit with the - subunit

ALPHA RECEPTORSstimulate

polyphosphoinositide

hydrolysisformation of inositol 1,4,5-

trisphosphate (IP3) anddiacylglycerol (DAG)

G proteins in the Gq family

couple 1 receptors tophospholipase C

IP3 promotes release of sequestered Ca2+ from

intracellular stores

increases the cytoplasmic concentration of free Ca2+

activation of various calcium-dependent protein

kinasesincrease influx of calcium across the cell's plasma

membrane.

DAG activates protein kinase C that modulates activity of many signalingpathwaysAlpha-1 receptors activate signal transduction pathways peptide growth

factor receptorsactivate tyrosine kinases.

Alpha2 inhibit adenylyl cyclase activitycause intracellular cAMP levels todecreaseutilize additional signaling pathways

regulation of ion channel activitiesactivities of important enzymesinvolved in signal transduction.

Alpha2-receptormediated inhibition ofadenylyl cyclase activityTransduced by inhibitory regulatoryprotein, Gi


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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 cAMPLiver Inc. cAMP synthesis; activation of

glycogen phosphorylase

Heart Inc. influx of calcium across themembrane

Muscle relaxation

D1 receptor stimulation of adenylyl cyclaseD1-receptor-induced smoothmuscle relaxation is presumablydue to cAMP accumulation in

the smooth muscle of thosevascular beds where dopamineis a vasodilator

D2 receptor inhibit adenylyl cyclase activity,open potassium channels, anddecrease calcium influx.

Receptor Regulation

desensitization occur after exposure tocatecholamines and other sympathomimetic

drug after a cell or tissue has been exposed fora period of time to an agonist

The tissue often becomes less responsive tofurther stimulation by that agent

Other terms: tolerance, refractoriness, andtachyphylaxis

Homologousdesensitization refers to loss ofresponsiveness exclusively of the receptors

that have been exposed to repeated orsustained activation by a drug

Heterologousdesensitization refers to loss ofresponsiveness of some cell surface receptorsthat have not been directly activated by thedrug.

HOMOLOGOUS loss of responsiveness

exclusively of the receptors

that have been exposed to

repeated or sustained

activation by a drugHETEROLOGOU

Sloss of responsiveness ofsome cell surface receptors

that have not been directlyactivated by the drug


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A major mechanism of desensitization

that occurs rapidly involves

phosphorylation of receptors bymembers of the G protein-coupled

receptor kinase (GRK) family

KINETICS

Phenylethylamine considered as the

parent compound

consists of a benzene ring with anethylamine side chain.

chemical structure determines the

pharmacokinetic properties

BENZENE RING

This compound consists of a benzene ringwith an ethylamine side chain.

Substitutions may be made

(1) on the terminal amino group

(2) on the benzene ring

(3) on the or carbons

TERMINAL

AMINO

GROUP

Increasing the size of

alkyl substituents on the

amino group tends toincrease -receptor activity

EG. Methyl substitution of

NE isopropyl substitutionat amino nitrogen

(isoproterenol)

BENZENERING

Maximal and activity are found with catecholamines (OHgroups at the 3 and 4 positions)

absence of one or the other of these groups, particularly thehydroxyl at C3,-reduce the potency of the drugs-Eg. Phenylephrine is less potent than epinephrine

-Absence of OH group o n the phenyl ring increasesbioavailability and prolong duration of action and inc.

distribution to CNS-Eg. Ephedrine and amphetamine


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AlphaCarbon

Block oxidation by monoamineoxidase (MAO) and prolong the actionof such drugs, particularly thenoncatecholamines.Eg. Ephedrine and amphetamine

Alpha-methyl compounds also knownphenylisopropylamines

BetaCarbon

activate adrenoceptorsimportant for storage ofsympathomimetic amines in neuralvesicles

Organ System Effectsof Sympathomimetic

Drugs

Blood Vessels Vascular smooth muscle toneControl peripheral vascular resistanceand venous capacitance.Alpha receptors increase arterial

resistance

alpha 2 promote smooth musclerelaxation.

skin vessels

Vessels inskeletalmuscle

constrict in the presence ofepinephrine and norepinephrine, as dothe splanchnic vessels

may constrict or dilate.

D1 receptors promote

vasodilation renal, splanchnic,

coronary, cerebral, and

other resistance vessels

D1 receptors in therenal vasculature play a major role in the

natriuresis induced by

pharmacologicadministration of dopamine

HeartAlpha 1

Beta

direct effect

increased calcium influx incardiac cells.

- Pacemaker activity increasedpositive chronotropic effect- Conduction velocity in theatrioventricular node is increased- refractory period is decreased.Intrinsic contractility is increased -positive inotropic effect and

relaxation is accelerated

BLOODPRESSURE phenylephrine increases peripheral

arterial resistance and decreasesvenous capacitance.increase stroke volumepositive inotropic action

RESPIRATORYBronchial s.muscle(B2)

Activation results in bronchodilationblood vessels of the upperrespiratory tract mucosa containreceptors the decongestant actionof adrenoceptor stimulants isclinically useful


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EYE Mydriasis effect on radial pupillarydilator muscle of the irisAlpha and beta 2: effects on intraocularpressure

increase outflow of aqueous humor

glaucomaBeta stimulants relax the ciliary muscle

decrease in accommodation

directly protect neuronal cells in theretina

GIT

Beta

Alph

a 2

Relaxation of gastrointestinal smooth

muscle

receptors on smooth muscle cells

mediate relaxation viahyperpolarization and decreased

spike activity in these cells

decrease muscle activity indirectlyby

reducing the release of acetylcholinedecrease salt and water flux into the

lumen of the intestine

GUThuman uterus(B2)

bladder base,urethralsphincter, andprostate(alpha)

mediate relaxation may be

clinically useful in

pregnancy

mediate contraction andpromote urinary continence

alpha1receptor

mediates constriction of the bladderbase and prostate

1A receptors play an important role

Beta 2receptor

bladder wall mediate relaxation

Ejaculation depends upon normalalpha-receptor (and possiblypurinergic receptor) activation in theductus deferens, seminal vesicles,and prostateDetumescence of erectile tissue

salivaryglands

regulate the secretion of

amylase and water

apocrinesweat

glands

on the palms of the hands

and a few other areas:increased sweat productionapocrine

nonthermoregulatory glands

associated with psychologic

stress

Beta3 onfat cells

Alpha2

increased lipolysis

Inhibit lipolysis by decreasingintracellular cAMP

Sympathomimetic drugs enhanceglycogenolysis in the liver

increased glucose release

high concentration ofcathecolamines cause metabolicacidosis.


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Beta 2

Beta andalpha2

promotes the uptake of potassiuminto cellsBlockade of these receptors mayaccentuate the rise in plasma

potassium that occurs duringexercise

pancreatic islets increase anddecrease insulin secretion

Endocrine Insulin secretion: stimulated byBeta receptors and inhibited byalpha2 receptors.renin secretion: stimulated bybeta1 and inhibited by alpha2receptorsmodulate the secretion ofparathyroid hormone, calcitonin,thyroxine, and gastrinhigh concentrations, epinephrineand related agents causeleukocytosis

CNS depend on ability to crossthe blood-brain barrierEffects: "nervousness" to "a

feeling of impendingdisaster,

peripheral effects:tachycardia and tremor

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

total peripheral resistance fall fall indiastolic pressure

Beta 2 receptors in skeletal muscle

contributes to increased blood flow during

exercise

Norepinephrine (levarterenol, noradrenaline)

beta1 receptors in the heart and similar potency

at alpha receptors little effect on beta 2 receptors

increases peripheral resistance and bothdiastolic and systolic blood pressure

Compensatory vagal reflexes tend to overcomethe direct positive chronotropic effects


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Isoproterenol (isoprenaline)

very potent beta receptor agonist and has littleeffect 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

immediate metabolic precursor ofnorepinephrine

activates D1 receptors in several vascularbeds

leads to vasodilation with effect on renalblood flow dopamine activates 1 receptorsin the heart.

Fenoldopam

D1 receptor agonist that selectively leads

to peripheral vasodilation in somevascular beds

IV administered drug for the treatment of

severe hypertension

Dopamine agonists

central actions are of considerable

value for the treatment of Parkinson'sdisease and prolactinemia

Dobutamine

relatively beta 1-selective synthetic

catecholamine.

also activates alpha 1 receptors.

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 thecatecholamines

effective mydriatic and decongestant and can be usedto 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

Midodrine

a prodrug that is enzymatically hydrolyzed todesglymidodrine, an alpha 1receptor selectiveagonist

peak concentration: 1 hour after midodrineadministration

for postural hypotension

cause hypertension in supine position.

Ephedrine

first orally active sympathomimetic drug

found in Ma-huang

noncatechol phenylisopropylamine

has high bioavailability and a relativelylong duration of action

phenylisopropylamines, fraction of thedrug is excreted unchanged in the urine

a weak base, accelerate excretion byacidification of the urine

ability to activate beta receptors earlier use inasthma.

mild CNS stimulant

Pseudoephedrine, one of four ephedrineenantiomers, an OTC for decongestantmixtures.

Xylometazoline and oxymetazoline

direct-acting agonists

used as topical decongestants

promote constriction of the nasal mucosa.

in large doses, oxymetazoline may causehypotension

oxymetazoline has significant affinity for alpha2A receptors

Amphetamine

a phenylisopropylamine that is important chiefly

because of its use and misuse as a centralnervous system stimulant

pharmacokinetics are similar to those ofephedrine

readily enters the central nervous system

stimulant effects on mood and alertness and adepressant effect on appetite

release of catecholamines.


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Methamphetamine (N-

methylamphetamine)

is very similar to amphetamine

With even higher ratio of central to

peripheral actions.

Methylphenidate and pemoline areamphetamine variants

major pharmacologic effects and abusepotential are similar to those of amphetamine

appear to have efficacy in some children withattention deficit hyperactivity disorder

Pemoline life-threatening hepatic failure.

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

Phenylpropanolamine (PPA)

is a sympathomimetic drug

an over-the-counter agent in numerous weightreduction and cold medications

withdrawn from over-the-counter use in theUSA regarding an association with hemorrhagicstroke.

Receptor-SelectiveSympathomimetic Drugs

Dexmedetomidine

centrally acting alpha2-selective agonist

indicated for sedation of initially intubated andmechanically ventilated patients

Beta-selective agonists

very important because of the separation

of beta1 and beta2 effects

reduce adverse effects in several clinicalapplications.


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Cocaine

is a local anesthetic with a peripheralsympathomimetic action

results from inhibition of transmitter reuptake at

noradrenergic synapses readily enters the central nervous system andproduces an amphetamine-like effect

inhibit dopamine reuptake into neurons in the"pleasure centers" of the brain

smoked, "snorted" into the nose, or injected for rapidonset of effect have made it a heavily abused drug

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 therelease of stored catecholamines

patients treated with MAO inhibitors

particularly inhibitors of the MAO-A

isoformthis effect of tyramine may begreatly intensified, leading to markedincreases in blood pressure

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

Hypotension

Shock / cardiogenic shock

Heart failure

Asthma

Anaphylactic shock

Mydriatic agent

Glaucoma

Premature labor

ADHD

ADRENOCEPTOR

BLOCKERS


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Alpha 1

Inc. rate of heart contraction

Vasoconstriction incr. Blood pressure

Mydriasis

Decrease secretion of salivary glands

Increase contraction of bladder andprostate capsule

Inc. ejaculation

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

Beta 2

Dilates the bronchioles

Promotes gastrointestinal and uterine

relaxation Promote increase blood sugar through

glycogenolysis in the liver

Increase blood flow in the skeletal muscles


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ALPHA BLOCKING DRUGS

IRREVERSIBLE, Long acting Covalently bind with the receptors

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

Alpha 2 selective Yohimbine


PHENTOLAMINE

Imidazole derivative

Potent competetive antagonist at both alpha 1 andalpha 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 H2receptors


Oral: Limited absorption

Peak concentration: 1 hour after intake

Half life: 5 to 7 hours Adverse effects after IV administration:

Tachycardia

Arrythmias

Myocardial ischemia

Adverse effects after oral administration:

Tachycardia, nasal congestion and headache


PHENOXYBENZAMINE

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


Attenuates catecholamine induced vasoconstriction

Causes li ttle fall in BP in supine position

Reduces BP in upright posture or if blood volume isreduced

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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Clinical use: treatment of

pheochromocytoma

Adverse effects:

Fatigue, sedation and nausea

Cause tumors in animals


TOLAZOLINE

Obsolete agent similar to phentolamine

PRAZOSIN

Piperazilyn quinazoline

Effective in the management of hypertension

Highly selective for alpha 1 receptors

Relaxation of both arterial and venous vascularsmooth muscle and prostate smooth muscle

Bioavailability: 50%; half-life: 3 hours


TERAZOSIN

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 metabolizedin the liver

Excreted in the urine

Half life: 9 to 12 hours


DOXAZOSIN (cardura)

Efficacious in the treatment of hypertension and

BPH Half life: 22 hours

Extensively metabolized

Moderate bioavailability

Excreted in the urine or feces


TAMSULOSIN

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 versusvascular smooth muscle

Effective in BPH


ALFUZOSIN

Alpha 1 selective quinazoline derivative

Approved for use in BPH Bioavailability: 60%

Half life: 5 hours

INDORAMIN

Alpha 1 selective

antihypertensive


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URAPIDIL Alpha 1 antagonist,Weak alpha 2 agonist,5-HT 1A agonist

action,Weak Beta 1 agonist Antihypertensive and BPH

LABETALOL

Alpha selective and beta antagonistic effect

Trazodone

Can block alpha 1

Neuroleptic drugs: potent dopamine antagonist


YOHIMBINE

Indole alkaloid, alpha 2 selective antagonist

Useful in autonomic insufficiency

Promote neurotransmitter release by blockade ofpresynaptic alpha 2 receptors

Improves male sexual function

Can abruptly reverse the antihypertensive effect ofalpha 2 adrenoceptor agonist such as clonidine

CLINICAL USE

1. PHEOCHROMOCYTOMA

SYMPTOMS: nintermittent orsustained hypertension, headaches,

palpitations, and increased sweating

Diagnosis: chemical assay of bloodand urine

Presence of catecholamines

Plasma metanephrine

CT and MRI

CLINICAL USE

Non selective alpha blockers

Presurgical management ofpheochromocytoma

Patients with severe hypertension andreduced blood volume ( needed to becorrected prior to surgery)

Phenoxybenzamine is usually used duringpreparatory phase

10-20mg/d

For at least 1 to 3 weeks before surgery

CLINICAL USE

chronic treatment of inoperable

pheochromocytoma

May also respond to alpha 1selective antagonist

Metyrosine

Useful in symptomatic patients withinoperable and metastaticpheochromocytoma

CLINICAL USE

HYPERTENSIVE EMERGENCIES

In pheochromocytoma, overdosage ofsymphatomimetics and clonidinewithdrawal

Phentolamine and labetalol

RAYNAUDS PHENOMENON

Phentolamine, prazosin andphenoxybenzamine


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CLINICAL USE

Local vasoconstrictor excess

Phentolamine has been used to reversethe intense local vasoconstriction

caused by inadvertent infiltration ofalpha agonist into subQ tissue

Local infiltration to ischemic tissue

CLINICAL USE

Urinary Obstruction Prazosin, doxazosin and terazosin are

efficacious

Useful also in hypertensive patients

Erectile dysfunction Combination of phentolamine with nonspecific

smooth muscle relaxant papaverine

Injected directly into the penis

Fibrotic reaction may occur

Orthostatic hypotension may occur

BETA-BLOCKING DRUGS

Competetive pharmacologic antagonist

Propranolol is the prototype drug

Drugs in this group are usually classifiedinto subgroups Receptor selectivity

Partial agonist activity

Local anesthetic action

Lipid solubility

Receptor Selectivity

Beta1 receptor selectivity

Acebutolol, atenolol, esmolol, metoprolol

For patients with asthma

Beta 2 receptor selectivityButoxamine

Used only in research

Nonselective beta blockers

Nadolol, propranolol and timolol

Combined alpha and beta blocking action

Labetalol, carvadilol

Partial Agonists activity

Intrinsic sympathomimetic activity

Use in patients with asthma can cause somebronchodilation

Pindolol and acebutolol

Local anesthetic activity

Membrane stabilizing activity

Disadvantage when used topically in the eye

Decreases protective reflexes

Increase risk of corneal ulceration

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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TOXICITY

Bradycardia

Atrioventricular blockade

Congestive heart failure

Patients with airway dse - may suffer severe asthmaattacks

Premonitory symptoms of hypoglycemia from insulinover dosage (tachycardia, tremor and anxiety) maybe masked

Mobilization of glucose from the liver may be

impaired

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 hoursand esmolol = 10 mins)

Metabolized in the liver

Excreted unchanged in the urine

PROPRANOLOL Prototypical B blocker

Long acting form is available

Prolonged absorption: 24 hours

May block some serotoninreceptors

No detectable partial agonistaction

METOPROLOL

ATENOLOL

Beta 1 selective group

Safer in patients withbronchoconstriction in response topropranolol

Preferred for patients withdiabetes or peripheral vasculardisease

NADOLOL Very long duration of action

Spectrum of action is similar totimolol

TIMOLOL Non selective agent

Has excellent ocular hypotensive

effectAdministered topically in the eye

Levobunolol (nonselective

Betaxolol(beta 1selective)

Used for topical ophthalmicapplication in glaucoma

Betaxolol may less likely causebronchoconstriction

Careteolol Non selective beta antagonist

PINDOLOLACEBUTOLOLCARTEOLOLBOPINDOLOLOXPRENOLOLCELIPROLOLPENBUTOLOL

Partial Beta agonist activity

Effective in hypertension andangina

Less likely to cause bradycardiaand abnormalities in plasma lipids

Pindolol may potentiate the actionof antidepressant medication

Celiprolol is beta 1 selective andactivate beta 2 ; have lessbronchoconstrictor effect

Acebutolol is beta 1 selectiveantagonist

LABETALOL Reversible adrenoceptoranagonist; Racemic mixture of twopairs of chiral isomers

Alpha 1 selective

Induces hypotensionwith less

tachycardiaCARVEDILOL

MEDROXALOL

BUCINDOLOL

Non selective beta receptorantagonist

With some capacity to block alpha1 adrenergic receptors


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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

ESMOLOL 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

HYPERTENSION BETA BLOCKERS ARE WELL TOLERATEDAND EFFECTIVE IN HYPERTENSION

ISHCEMIC HEARTDISEASE

Reduce anginal episode

Improves exercise tolerance

Block cardiac beta receptors

Decrease cardiac work andoxygen demand

Timolol, propranolo andmetropolol prolongs survival inMI

CLINICAL USES

CARDIACARRYTHMIAS

Supraventricular and ventricular

arrythmias

Slows ventricular reponse rate in

atrial flutter and fibrillationReduce ventricular ectopic beats

SOTALOL has antiarrythmic effect

involving ion channel blockade

HEART FAILURE Metoprolol, bisoprolol andcarvedilol are effective intreating chronic heart failure

CLINICAL USES

Glaucoma Reduced production of aqueoushumor by ciliary body

Timolol are suitable for local

use (1 mg)

Betaxolol, carteolol,levobunolol, and metipranolol

HYPERTHYROIDISM Blockade of adrenoceptors

Inhibition of peripheralconversion of T3 and T4

Propranolol in thyroid storm

CLINICAL USES

Neurologic disease migraine headache

Propranolol

Preventive effect: metroprolol,atenolol, timolol, and nadolol

Skeletal muscle tremor:Propranolol

Alcohol withdrawal : propranolol

HYPERTHYROIDISM Blockade of adrenoceptors

Inhibition of peripheral conversion of

T3 and T4Propranolol in thyroid storm

CLINICAL USES

DRUG LIPID

SOLUBILITY

T1/2 BIOAVAILABILITY LOCAL

ANESTHETIC

METOPROLO

L

MOD 3-4

HRS

50 Y

PROPRANOL

OL

HIGH 3.5-6

HRS

90 Y

BISOPROLOL LOW 9-2

HRS

80 N

ESMOLOL LOW 10 MIN 40 N

SOTALOL LOW 12

HRS

90 N

ATENOLOL LOW 6-9 40 N

adrenoceptor agents [compatibility mode]

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