Transcript Autonomic Nervous System Drugs

Autonomic Nervous System
Drugs
Dr. Felix Hernandez M.D.
Autonomic Drugs
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There are several classes of autonomic
drugs:
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Direct Sympathomimetics
Indirect Sympathomimetics
Mixed Sympathomimetics
Presynaptic Adrenergic Nerve Blockers
Adrenergic Antagonists
Cholinergic Agonists (Cholinomimetics)
Cholinesterase Inhibitors
Muscarinic Antagonists
Local Anesthetics
Direct Sympathomimetics
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Bind to alpha-1, alpha-2, beta-1 and beta 2 receptors
Turn on second messengers which mediate the various
effects associated with each receptor
Drugs include:
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Epinephrine
Norepinephrine
Isoproterenol
Dobutamine
Dopamine
Phenylephrine
Albuterol
Salmeterol
Levalbuterol
Epinephrine (Adrenalin)
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Mechanism of Action:
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Vascular Effects:
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Increased heart rate, increased contractility
Pulmonary Effects:
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Vasoconstriction via a1 and vasodilation via b2
Cardiac Effects:
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Alpha and Beta receptor agonist
Bronchodilation and decreased secretions
Special Characteristics:
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Is injected with local anesthetics to delay distribution
away from the injection site through vasoconstriction.
Norepinephrine (Levophed)
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Mechanism of Action:
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Vascular Effects:
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Reflex slowing of the heart due to vasoconstriction
Pulmonary Effects:
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Intense vasoconstriction via a1 leading to an increase
in MAP
Vasoconstriction is unopposed because it doesn’t bind
to the b2 receptors
Cardiac Effects:
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Alpha>Beta-1>Beta-2 agonist
No b2 effect
Special Characteristics:
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Used in septic shock when intense vasoconstriction is
needed
Isoproterenol (Isuprel)
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Mechanism of Action:
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Vascular Effects:
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Stimulates the heart with greater effect than Epi due
to the vasodilation
Pulmonary Effects:
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Intense vasodilation via b2 with no alpha
Cardiac Effects:
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Only Beta
Is the most potent bronchodilator
Special Characteristics:
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Used to prevent bronchospasm
Dobutamine (Dobutrex)
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Mechanism of Action:
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Vascular Effects:
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Minor change in heart rate but it makes the heart
more efficient
Pulmonary Effects:
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No change in resistance because of low affinity for b2
and a1
Cardiac Effects:
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Beta-1>Beta-2=Alpha
None
Special Characteristics:
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DOC to stimulate the heart
Is a synthetic derivative of dopamine but has no effect
on dopamine receptors
Dopamine (Intropin)
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Mechanism of Action:
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Vascular Effects:
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Increases contractility and increase in systolic BP
Pulmonary Effects:
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Low dose: constricts vessels in sites other than the
kidneys or brain
High Dose: constricts all vessels
Cardiac Effects:
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Dopamine receptors and Beta-1
None
Special Characteristics:
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Used to treat shock related to underperfusion and
reflex vasoconstriction
Phenylephrine (Neo-Synephrine)
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Mechanism of Action:
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Vascular Effects:
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Decreases heart rate due to a reflex reaction to the
increase arterial pressure
Pulmonary Effects:
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Intense vasoconstriction with an increased MAP
Cardiac Effects:
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Alpha
None
Special Characteristics:
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Used to treat SVT
Is included in cold remedies as a decongestant due to
nasal vasoconstriction
Albuterol (Ventolin)
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Mechanism of Action:
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Vascular Effects:
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None but may have reflex tachycardia
Pulmonary Effects:
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Vasodilation
Cardiac Effects:
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Beta-2
bronchodilation
Special Characteristics:
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Used to treat acute asthma exacerbations
Salmeterol (Serevent)
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Mechanism of Action:
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Vascular Effects:
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None but may have reflex tachycardia
Pulmonary Effects:
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Vasodilation
Cardiac Effects:
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Beta-2
Bronchodilation
Special Characteristics:
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Is long acting
Levalbuterol (Xopenex)
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Mechanism of Action:
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Vascular Effects:
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None but may have reflex tachycardia
Pulmonary Effects:
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vasodilation
Cardiac Effects:
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Beta-2
Bronchodilation
Special Characteristics:
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Less cardiac side effects than albuterol
Indirect Sympathomimetics
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Cause norepinephrine release but do not
bind to adrenergic receptors.
They enter the presynaptic terminal and
displace NE from storage vesicles.
Drugs include:
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Amphetamine
Methamphetamine
Amphetamine
Methamphetiamine
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Mechanism of Action:
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Vascular Effects:
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Wakefulness, euphoria
Unwanted Side Effects:
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Increase in contraction with a reflex bradycardia from increased
MAP
CNS Effects:
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vasoconstriction
Cardiac Effects:
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Enter presynaptic terminal and displace NE from storage vesicles
HTN, cerebral hemorrhage, convulsions, tremor
Special Characteristics:
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Used for narcolepsy, ADD, Parkinson’s
Mixed Sympathomimetics
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Both displace NE from storage vesicles
and bind to adrenergic receptors
Drugs Include:
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Ephedrine
Ephedrine
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Mechanism of Action:
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Vascular Effects:
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Similar to EPI but with no change in HR
CNS Effects:
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Vasoconstriction with an increased MAP via a1
Cardiac Effects:
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Displaces NE from storage vesicles and binds to adrenergic
receptors
Stimulation
Special Characteristics:
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Used to treat narcolepsy
Causes bronchodilation
Used to treat asthma and nasal congestion
Used to dilate pupils
Central Adrenergic Nerve Blockers
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Bind to alpha-2 receptors on neurons and
prevent the release of NE from nerves
Drugs include:
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Clonidine
Methyldopa
Clonidine (Catapres)
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Blockade Mechanism:
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Actions:
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Decreases preganglionic sympathetic outflow which
results in a decreased BP
Side Effects:
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Potent alpha-2 agonist
Orthostatic hypotension
Sedation
Rebound hypertension
Clinical Use:
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HTN
Methyldopa (Aldomet)
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Blockade Mechanism:
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Actions:
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Decreases sympathetic outflow causing a rapid
decrease in BP
Side Effects:
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Metabolized to alpha-methylnorepinephrine
which is a potent alpha-2 agonist
Sedation, mild orthostatic hypotension,
coombs positive RBC, rebound HTN
Clinical Use:
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HTN
Adrenergic Antagonist
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Block NE from binding to the postsynaptic adrenergic
receptors
Drugs include:
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Phenoxybenzamine
Phentolamine
Prazosin
Doxazosin
Labetalol
Propranolol
Timilol
Metoprolol
Phenoxybenzamine (Dibenzyline)
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Receptor:
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Actions:
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Alpha-1 and alpha-2
Vasodilation, blocks sympathetic outflow from the
brain
Clinical Use:
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Pheochromocytoma
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Side Effects:
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Controls HTN
Postural hypotension, reflex tachy, sexual dysfunction
Special Features:
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none
Phentolamine (Regitine)
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Receptor:
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Actions:
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Alpha-1, alpha-2
Vasodilation
Clinical Use:
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Pheochromocytoma
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Side Effects:
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To control HTN and is the pharmacological test
Tachycardia, arrhythmias, hypotensive episodes
Special Features:
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none
Prazosin (Minipress)
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Receptor:
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Actions:
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HTN
Side Effects:
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vasodilation
Clinical Use:
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Alpha-1
Postural hypotension with first dose
Special Features:
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None
Doxazosin (Cardura)
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Receptor:
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Actions:
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Alpha-1
vasodilation
Clinical Use:
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HTN, BPH
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Side Effects:
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Relaxes smooth muscle in the bladder neck
Postural hypotension with first dose
Special Features:
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None
Labetalol (Normodyne)
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Receptor:
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Actions:
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HTN
Side Effects:
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Decreases BP from alpha blockade without a reflex
tachycardia from b1 blockade
Clinical Use:
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Alpha-1, Beta-1, Beta-2
Suppresses a failing heart, impotence, orthostatic HTN
Special Features:
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Contraindicated in patients with asthma or bradycardia
Propranolol (Inderal)
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Receptor:
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Actions:
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HTN, angina pectoris, SVT, ventricular arrhythmias,
MI, Migraine prophylaxis
Side Effects:
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Decreases inotropy and chronotropy and O2 demand,
decreased release of renin
Clinical Use:
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Beta-1 and Beta-2
Suppression of a failing heart, CNS sedation and
depression, rebound HTN, impotence
Special Features:
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Contraindicated in patients asthma
Timilol (Blocadren)
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Receptor:
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Actions:
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HTN, MI, migraine prophylaxis, decrease intraocular
pressure
Side Effects:
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Decreases inotropy and chronotropy and O2 demand,
decreased release of renin
Clinical Use:
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Beta-1 and Beta-2
Suppression of a failing heart, CNS sedation and
depression, rebound HTN, impotence
Special Features:
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Contraindicated in patients with asthma
Metoprolol (Lopressor)
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Receptor:
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Actions:
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HTN, angina pectoris, MI
Side Effects:
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Same as propranolol but with less bronchospasm in
asthmatics
Clinical Use:
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Beta-1
Lower toxicity than propranolol
Special Features:
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None
Cholinergic Agonist
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Drugs include:
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Carbachol
Bethanechol
Pilocarpine
Carbachol (Miostat or Isopto)
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Receptor:
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Clinical Uses:
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M1, M2, M3, Nicotinic
Glaucoma, miosis for surgery
Contraindications:
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Where constriction is undesirable
Bethanecol (Urecholine)
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Receptor:
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Clinical Uses:
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M1, M2 M3, Nicotinic
Induce evacuation of a non-obstructed bladder
Increase GI motility after surgery
Contraindications:
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Bradycardia, parkinsonism, epilepsy,
hypo/hyper tension
Pilocarpine (Isopto-Carpine)
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Receptor:
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Clinical Uses:
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M1, M2, M3
Cystic fibrosis sweat test, glaucoma
(miosis/constriction), xerostomia (dry mouth)
Contraindications:
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Bradycardia, parkinsonism, epilepsy,
hypo/hyper tension
Cholinergic Antagonists
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Drugs include:
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Atropine
Scopolamine
Oxybutynin
Side effects are Red, Hot, Dry, Mad
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Red as a beet, hot as an oven, dry as a bone,
mad as a hatter
Atropine
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Action at Organ:
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Clinical Uses:
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Preanesthetic to prevent respiratory secretions, low dose for
tachycardia, high dose for bradycardia
Side Effects:
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Low dose: bradycardia
High Dose: Tachycardia
Bronchodilation and decreased secretions
Decreased GI motility
Decreased salivation and sweating
Mydriasis
Dry mouth, urinary retention, tachycardia
Special Notes:
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Contraindicated in glaucoma, BPH, obstructive bowel disease and
asthma patients
Scopolamine
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Action at Organ:
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Clinical Uses:
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Prevention of motion sickness
Side Effects:
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More potent at eye, and glands than atropine
but less potent in the heart, lungs and GI
CNS depression in low doses
Like atropine in high doses
Special Notes:
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Contraindication if hypersensitive to
belladonna (plant) or barbiturates
Oxybutynin (Ditropan)
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Action at Organ:
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Clinical Uses:
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Relief of bladder spasms that result in urinary
leakage and incontinence
Side Effects:
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Direct antispasmodic effect on smooth muscle
Decreased sweating, rash, decreased
lacrimation, mydriasis
Special Notes: