Autonomic Nervous Autonomic Nervous System DrugsSystem Drugs

Dr. Felix Hernandez M.D.Dr. Felix Hernandez M.D.

Autonomic DrugsAutonomic Drugs There are several classes of There are several classes of

autonomic drugs:autonomic drugs: Direct SympathomimeticsDirect Sympathomimetics Indirect SympathomimeticsIndirect Sympathomimetics Mixed SympathomimeticsMixed Sympathomimetics Presynaptic Adrenergic Nerve BlockersPresynaptic Adrenergic Nerve Blockers Adrenergic AntagonistsAdrenergic Antagonists Cholinergic Agonists (Cholinomimetics)Cholinergic Agonists (Cholinomimetics) Cholinesterase InhibitorsCholinesterase Inhibitors Muscarinic AntagonistsMuscarinic Antagonists Local AnestheticsLocal Anesthetics

Direct SympathomimeticsDirect Sympathomimetics

Bind to alpha-1, alpha-2, beta-1 and beta 2 Bind to alpha-1, alpha-2, beta-1 and beta 2 receptorsreceptors

Turn on second messengers which mediate the Turn on second messengers which mediate the various effects associated with each receptorvarious effects associated with each receptor

Drugs include:Drugs include: EpinephrineEpinephrine NorepinephrineNorepinephrine IsoproterenolIsoproterenol DobutamineDobutamine DopamineDopamine PhenylephrinePhenylephrine AlbuterolAlbuterol SalmeterolSalmeterol LevalbuterolLevalbuterol

Epinephrine (Adrenalin)Epinephrine (Adrenalin)

Mechanism of Action:Mechanism of Action: Alpha and Beta receptor agonistAlpha and Beta receptor agonist

Vascular Effects:Vascular Effects: Vasoconstriction via a1 and vasodilation via b2Vasoconstriction via a1 and vasodilation via b2

Cardiac Effects:Cardiac Effects: Increased heart rate, increased contractilityIncreased heart rate, increased contractility

Pulmonary Effects:Pulmonary Effects: Bronchodilation and decreased secretionsBronchodilation and decreased secretions

Special Characteristics:Special Characteristics: Is injected with local anesthetics to delay Is injected with local anesthetics to delay

distribution away from the injection site distribution away from the injection site through vasoconstriction.through vasoconstriction.

Norepinephrine (Levophed)Norepinephrine (Levophed) Mechanism of Action:Mechanism of Action:

Alpha>Beta-1>Beta-2 agonistAlpha>Beta-1>Beta-2 agonist Vascular Effects:Vascular Effects:

Intense vasoconstriction via a1 leading to an Intense vasoconstriction via a1 leading to an increase in MAPincrease in MAP

Vasoconstriction is unopposed because it Vasoconstriction is unopposed because it doesn’t bind to the b2 receptorsdoesn’t bind to the b2 receptors

Cardiac Effects:Cardiac Effects: Reflex slowing of the heart due to Reflex slowing of the heart due to

vasoconstrictionvasoconstriction Pulmonary Effects:Pulmonary Effects:

No b2 effectNo b2 effect Special Characteristics:Special Characteristics:

Used in septic shock when intense Used in septic shock when intense vasoconstriction is neededvasoconstriction is needed

Isoproterenol (Isuprel)Isoproterenol (Isuprel)

Mechanism of Action:Mechanism of Action: Only BetaOnly Beta

Vascular Effects:Vascular Effects: Intense vasodilation via b2 with no alphaIntense vasodilation via b2 with no alpha

Cardiac Effects:Cardiac Effects: Stimulates the heart with greater effect than Stimulates the heart with greater effect than

Epi due to the vasodilationEpi due to the vasodilation Pulmonary Effects:Pulmonary Effects:

Is the most potent bronchodilatorIs the most potent bronchodilator Special Characteristics:Special Characteristics:

Used to prevent bronchospasmUsed to prevent bronchospasm

Dobutamine (Dobutrex)Dobutamine (Dobutrex) Mechanism of Action:Mechanism of Action:

Beta-1>Beta-2=AlphaBeta-1>Beta-2=Alpha Vascular Effects:Vascular Effects:

No change in resistance because of low affinity No change in resistance because of low affinity for b2 and a1for b2 and a1

Cardiac Effects:Cardiac Effects: Minor change in heart rate but it makes the Minor change in heart rate but it makes the

heart more efficientheart more efficient Pulmonary Effects:Pulmonary Effects:

NoneNone Special Characteristics:Special Characteristics:

DOC to stimulate the heartDOC to stimulate the heart Is a synthetic derivative of dopamine but has Is a synthetic derivative of dopamine but has

no effect on dopamine receptorsno effect on dopamine receptors

Dopamine (Intropin)Dopamine (Intropin) Mechanism of Action:Mechanism of Action:

Dopamine receptors and Beta-1Dopamine receptors and Beta-1 Vascular Effects:Vascular Effects:

Low dose: constricts vessels in sites other than Low dose: constricts vessels in sites other than the kidneys or brainthe kidneys or brain

High Dose: constricts all vesselsHigh Dose: constricts all vessels Cardiac Effects:Cardiac Effects:

Increases contractility and increase in systolic Increases contractility and increase in systolic BPBP

Pulmonary Effects:Pulmonary Effects: NoneNone

Special Characteristics:Special Characteristics: Used to treat shock related to underperfusion Used to treat shock related to underperfusion

and reflex vasoconstrictionand reflex vasoconstriction

Phenylephrine (Neo-Phenylephrine (Neo-Synephrine)Synephrine)

Mechanism of Action:Mechanism of Action: AlphaAlpha

Vascular Effects:Vascular Effects: Intense vasoconstriction with an increased MAPIntense vasoconstriction with an increased MAP

Cardiac Effects:Cardiac Effects: Decreases heart rate due to a reflex reaction to Decreases heart rate due to a reflex reaction to

the increase arterial pressurethe increase arterial pressure Pulmonary Effects:Pulmonary Effects:

NoneNone Special Characteristics:Special Characteristics:

Used to treat SVTUsed to treat SVT Is included in cold remedies as a decongestant Is included in cold remedies as a decongestant

due to nasal vasoconstrictiondue to nasal vasoconstriction

Albuterol (Ventolin)Albuterol (Ventolin)

Mechanism of Action:Mechanism of Action: Beta-2Beta-2

Vascular Effects:Vascular Effects: VasodilationVasodilation

Cardiac Effects:Cardiac Effects: None but may have reflex tachycardiaNone but may have reflex tachycardia

Pulmonary Effects:Pulmonary Effects: bronchodilationbronchodilation

Special Characteristics:Special Characteristics: Used to treat acute asthma Used to treat acute asthma

exacerbationsexacerbations

Salmeterol (Serevent)Salmeterol (Serevent)

Mechanism of Action:Mechanism of Action: Beta-2Beta-2

Vascular Effects:Vascular Effects: VasodilationVasodilation

Cardiac Effects:Cardiac Effects: None but may have reflex tachycardiaNone but may have reflex tachycardia

Pulmonary Effects:Pulmonary Effects: BronchodilationBronchodilation

Special Characteristics:Special Characteristics: Is long actingIs long acting

Levalbuterol (Xopenex)Levalbuterol (Xopenex)

Mechanism of Action:Mechanism of Action: Beta-2Beta-2

Vascular Effects:Vascular Effects: vasodilationvasodilation

Cardiac Effects:Cardiac Effects: None but may have reflex tachycardiaNone but may have reflex tachycardia

Pulmonary Effects:Pulmonary Effects: BronchodilationBronchodilation

Special Characteristics:Special Characteristics: Less cardiac side effects than albuterolLess cardiac side effects than albuterol

Indirect SympathomimeticsIndirect Sympathomimetics

Cause norepinephrine release but do Cause norepinephrine release but do not bind to adrenergic receptors.not bind to adrenergic receptors.

They enter the presynaptic terminal They enter the presynaptic terminal and displace NE from storage and displace NE from storage vesicles.vesicles.

Drugs include:Drugs include: AmphetamineAmphetamine MethamphetamineMethamphetamine

AmphetamineAmphetamineMethamphetiamineMethamphetiamine

Mechanism of Action:Mechanism of Action: Enter presynaptic terminal and displace NE from storage Enter presynaptic terminal and displace NE from storage

vesiclesvesicles Vascular Effects:Vascular Effects:

vasoconstrictionvasoconstriction Cardiac Effects:Cardiac Effects:

Increase in contraction with a reflex bradycardia from Increase in contraction with a reflex bradycardia from increased MAPincreased MAP

CNS Effects:CNS Effects: Wakefulness, euphoriaWakefulness, euphoria

Unwanted Side Effects:Unwanted Side Effects: HTN, cerebral hemorrhage, convulsions, tremorHTN, cerebral hemorrhage, convulsions, tremor

Special Characteristics:Special Characteristics: Used for narcolepsy, ADD, Parkinson’sUsed for narcolepsy, ADD, Parkinson’s

Mixed SympathomimeticsMixed Sympathomimetics

Both displace NE from storage Both displace NE from storage vesicles and bind to adrenergic vesicles and bind to adrenergic receptorsreceptors

Drugs Include:Drugs Include: EphedrineEphedrine

EphedrineEphedrine Mechanism of Action:Mechanism of Action:

Displaces NE from storage vesicles and binds to Displaces NE from storage vesicles and binds to adrenergic receptorsadrenergic receptors

Vascular Effects:Vascular Effects: Vasoconstriction with an increased MAP via a1Vasoconstriction with an increased MAP via a1

Cardiac Effects:Cardiac Effects: Similar to EPI but with no change in HRSimilar to EPI but with no change in HR

CNS Effects:CNS Effects: StimulationStimulation

Special Characteristics:Special Characteristics: Used to treat narcolepsyUsed to treat narcolepsy Causes bronchodilationCauses bronchodilation Used to treat asthma and nasal congestionUsed to treat asthma and nasal congestion Used to dilate pupilsUsed to dilate pupils

Central Adrenergic Nerve Central Adrenergic Nerve BlockersBlockers

Bind to alpha-2 receptors on neurons Bind to alpha-2 receptors on neurons and prevent the release of NE from and prevent the release of NE from nervesnerves

Drugs include:Drugs include: ClonidineClonidine MethyldopaMethyldopa

Clonidine (Catapres)Clonidine (Catapres)

Blockade Mechanism:Blockade Mechanism: Potent alpha-2 agonistPotent alpha-2 agonist

Actions:Actions: Decreases preganglionic sympathetic outflow Decreases preganglionic sympathetic outflow

which results in a decreased BPwhich results in a decreased BP Side Effects:Side Effects:

Orthostatic hypotensionOrthostatic hypotension SedationSedation Rebound hypertensionRebound hypertension

Clinical Use:Clinical Use: HTNHTN

Methyldopa (Aldomet)Methyldopa (Aldomet)

Blockade Mechanism:Blockade Mechanism: Metabolized to alpha-Metabolized to alpha-

methylnorepinephrine which is a potent methylnorepinephrine which is a potent alpha-2 agonistalpha-2 agonist

Actions:Actions: Decreases sympathetic outflow causing a Decreases sympathetic outflow causing a

rapid decrease in BPrapid decrease in BP Side Effects:Side Effects:

Sedation, mild orthostatic hypotension, Sedation, mild orthostatic hypotension, coombs positive RBC, rebound HTNcoombs positive RBC, rebound HTN

Clinical Use:Clinical Use: HTNHTN

Adrenergic AntagonistAdrenergic Antagonist

Block NE from binding to the postsynaptic Block NE from binding to the postsynaptic adrenergic receptorsadrenergic receptors

Drugs include:Drugs include: PhenoxybenzaminePhenoxybenzamine PhentolaminePhentolamine PrazosinPrazosin DoxazosinDoxazosin LabetalolLabetalol PropranololPropranolol TimilolTimilol MetoprololMetoprolol

Phenoxybenzamine Phenoxybenzamine (Dibenzyline)(Dibenzyline)

Receptor:Receptor: Alpha-1 and alpha-2Alpha-1 and alpha-2

Actions:Actions: Vasodilation, blocks sympathetic outflow from Vasodilation, blocks sympathetic outflow from

the brainthe brain Clinical Use:Clinical Use:

PheochromocytomaPheochromocytoma Controls HTNControls HTN

Side Effects:Side Effects: Postural hypotension, reflex tachy, sexual Postural hypotension, reflex tachy, sexual

dysfunctiondysfunction Special Features:Special Features:

nonenone

Phentolamine (Regitine)Phentolamine (Regitine)

Receptor:Receptor: Alpha-1, alpha-2Alpha-1, alpha-2

Actions:Actions: VasodilationVasodilation

Clinical Use:Clinical Use: PheochromocytomaPheochromocytoma

To control HTN and is the pharmacological testTo control HTN and is the pharmacological test

Side Effects:Side Effects: Tachycardia, arrhythmias, hypotensive Tachycardia, arrhythmias, hypotensive

episodesepisodes Special Features:Special Features:

nonenone

Prazosin (Minipress)Prazosin (Minipress)

Receptor:Receptor: Alpha-1Alpha-1

Actions:Actions: vasodilationvasodilation

Clinical Use:Clinical Use: HTNHTN

Side Effects:Side Effects: Postural hypotension with first dosePostural hypotension with first dose

Special Features:Special Features: NoneNone

Doxazosin (Cardura)Doxazosin (Cardura)

Receptor:Receptor: Alpha-1Alpha-1

Actions:Actions: vasodilationvasodilation

Clinical Use:Clinical Use: HTN, BPHHTN, BPH

Relaxes smooth muscle in the bladder neckRelaxes smooth muscle in the bladder neck

Side Effects:Side Effects: Postural hypotension with first dosePostural hypotension with first dose

Special Features:Special Features: NoneNone

Labetalol (Normodyne)Labetalol (Normodyne)

Receptor:Receptor: Alpha-1, Beta-1, Beta-2Alpha-1, Beta-1, Beta-2

Actions:Actions: Decreases BP from alpha blockade without a reflex Decreases BP from alpha blockade without a reflex

tachycardia from b1 blockadetachycardia from b1 blockade Clinical Use:Clinical Use:

HTNHTN Side Effects:Side Effects:

Suppresses a failing heart, impotence, orthostatic Suppresses a failing heart, impotence, orthostatic HTNHTN

Special Features:Special Features: Contraindicated in patients with asthma or Contraindicated in patients with asthma or

bradycardiabradycardia

Propranolol (Inderal)Propranolol (Inderal) Receptor:Receptor:

Beta-1 and Beta-2Beta-1 and Beta-2 Actions:Actions:

Decreases inotropy and chronotropy and O2 Decreases inotropy and chronotropy and O2 demand, decreased release of renindemand, decreased release of renin

Clinical Use:Clinical Use: HTN, angina pectoris, SVT, ventricular HTN, angina pectoris, SVT, ventricular

arrhythmias, MI, Migraine prophylaxisarrhythmias, MI, Migraine prophylaxis Side Effects:Side Effects:

Suppression of a failing heart, CNS sedation Suppression of a failing heart, CNS sedation and depression, rebound HTN, impotenceand depression, rebound HTN, impotence

Special Features:Special Features: Contraindicated in patients asthmaContraindicated in patients asthma

Timilol (Blocadren)Timilol (Blocadren) Receptor:Receptor:

Beta-1 and Beta-2Beta-1 and Beta-2 Actions:Actions:

Decreases inotropy and chronotropy and O2 Decreases inotropy and chronotropy and O2 demand, decreased release of renindemand, decreased release of renin

Clinical Use:Clinical Use: HTN, MI, migraine prophylaxis, decrease HTN, MI, migraine prophylaxis, decrease

intraocular pressureintraocular pressure Side Effects:Side Effects:

Suppression of a failing heart, CNS sedation Suppression of a failing heart, CNS sedation and depression, rebound HTN, impotenceand depression, rebound HTN, impotence

Special Features:Special Features: Contraindicated in patients with asthmaContraindicated in patients with asthma

Metoprolol (Lopressor)Metoprolol (Lopressor)

Receptor:Receptor: Beta-1Beta-1

Actions:Actions: Same as propranolol but with less Same as propranolol but with less

bronchospasm in asthmaticsbronchospasm in asthmatics Clinical Use:Clinical Use:

HTN, angina pectoris, MIHTN, angina pectoris, MI Side Effects:Side Effects:

Lower toxicity than propranololLower toxicity than propranolol Special Features:Special Features:

NoneNone

Cholinergic AgonistCholinergic Agonist

Drugs include:Drugs include: CarbacholCarbachol BethanecholBethanechol PilocarpinePilocarpine

Carbachol (Miostat or Isopto)Carbachol (Miostat or Isopto)

Receptor:Receptor: M1, M2, M3, NicotinicM1, M2, M3, Nicotinic

Clinical Uses:Clinical Uses: Glaucoma, miosis for surgeryGlaucoma, miosis for surgery

Contraindications:Contraindications: Where constriction is undesirableWhere constriction is undesirable

Bethanecol (Urecholine)Bethanecol (Urecholine)

Receptor:Receptor: M1, M2 M3, NicotinicM1, M2 M3, Nicotinic

Clinical Uses:Clinical Uses: Induce evacuation of a non-obstructed Induce evacuation of a non-obstructed

bladderbladder Increase GI motility after surgeryIncrease GI motility after surgery

Contraindications:Contraindications: Bradycardia, parkinsonism, epilepsy, Bradycardia, parkinsonism, epilepsy,

hypo/hyper tensionhypo/hyper tension

Pilocarpine (Isopto-Carpine)Pilocarpine (Isopto-Carpine)

Receptor:Receptor: M1, M2, M3M1, M2, M3

Clinical Uses:Clinical Uses: Cystic fibrosis sweat test, glaucoma Cystic fibrosis sweat test, glaucoma

(miosis/constriction), xerostomia (dry (miosis/constriction), xerostomia (dry mouth)mouth)

Contraindications:Contraindications: Bradycardia, parkinsonism, epilepsy, Bradycardia, parkinsonism, epilepsy,

hypo/hyper tensionhypo/hyper tension

Cholinergic AntagonistsCholinergic Antagonists

Drugs include:Drugs include: AtropineAtropine ScopolamineScopolamine OxybutyninOxybutynin Side effects are Red, Hot, Dry, MadSide effects are Red, Hot, Dry, Mad

Red as a beet, hot as an oven, dry as a Red as a beet, hot as an oven, dry as a bone, mad as a hatterbone, mad as a hatter

AtropineAtropine Action at Organ:Action at Organ:

Low dose: bradycardiaLow dose: bradycardia High Dose: TachycardiaHigh Dose: Tachycardia Bronchodilation and decreased secretionsBronchodilation and decreased secretions Decreased GI motilityDecreased GI motility Decreased salivation and sweatingDecreased salivation and sweating MydriasisMydriasis

Clinical Uses:Clinical Uses: Preanesthetic to prevent respiratory secretions, low dose Preanesthetic to prevent respiratory secretions, low dose

for tachycardia, high dose for bradycardiafor tachycardia, high dose for bradycardia Side Effects:Side Effects:

Dry mouth, urinary retention, tachycardiaDry mouth, urinary retention, tachycardia Special Notes:Special Notes:

Contraindicated in glaucoma, BPH, obstructive bowel Contraindicated in glaucoma, BPH, obstructive bowel disease and asthma patientsdisease and asthma patients

ScopolamineScopolamine

Action at Organ:Action at Organ: More potent at eye, and glands than More potent at eye, and glands than

atropine but less potent in the heart, atropine but less potent in the heart, lungs and GIlungs and GI

Clinical Uses:Clinical Uses: Prevention of motion sicknessPrevention of motion sickness

Side Effects:Side Effects: CNS depression in low dosesCNS depression in low doses Like atropine in high dosesLike atropine in high doses

Special Notes:Special Notes: Contraindication if hypersensitive to Contraindication if hypersensitive to

belladonna (plant) or barbituratesbelladonna (plant) or barbiturates

Oxybutynin (Ditropan)Oxybutynin (Ditropan)

Action at Organ:Action at Organ: Direct antispasmodic effect on smooth Direct antispasmodic effect on smooth

musclemuscle Clinical Uses:Clinical Uses:

Relief of bladder spasms that result in Relief of bladder spasms that result in urinary leakage and incontinenceurinary leakage and incontinence

Side Effects:Side Effects: Decreased sweating, rash, decreased Decreased sweating, rash, decreased

lacrimation, mydriasislacrimation, mydriasis Special Notes:Special Notes: