1. Autonomic Nervous System Drugs
Dr. Felix Hernandez M.D.

2. Autonomic Drugs There are several classes of autonomic drugs:
Direct Sympathomimetics
Indirect Sympathomimetics
Mixed Sympathomimetics
Presynaptic Adrenergic Nerve Blockers
Adrenergic Antagonists
Cholinergic Agonists (Cholinomimetics)
Cholinesterase Inhibitors
Muscarinic Antagonists
Local Anesthetics

3. Direct Sympathomimetics
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:
Epinephrine
Norepinephrine
Isoproterenol
Dobutamine
Dopamine
Phenylephrine
Albuterol
Salmeterol
Levalbuterol

4. Epinephrine (Adrenalin)
Mechanism of Action:
Alpha and Beta receptor agonist
Vascular Effects:
Vasoconstriction via a1 and vasodilation via b2
Cardiac Effects:
Increased heart rate, increased contractility
Pulmonary Effects:
Bronchodilation and decreased secretions
Special Characteristics:
Is injected with local anesthetics to delay distribution away from the injection site through vasoconstriction.

5. Norepinephrine (Levophed)
Mechanism of Action:
Alpha>Beta-1>Beta-2 agonist
Vascular Effects:
Intense vasoconstriction via a1 leading to an increase in MAP
Vasoconstriction is unopposed because it doesn’t bind to the b2 receptors
Cardiac Effects:
Reflex slowing of the heart due to vasoconstriction
Pulmonary Effects:
No b2 effect
Special Characteristics:
Used in septic shock when intense vasoconstriction is needed

6. Isoproterenol (Isuprel)
Mechanism of Action:
Only Beta
Vascular Effects:
Intense vasodilation via b2 with no alpha
Cardiac Effects:
Stimulates the heart with greater effect than Epi due to the vasodilation
Pulmonary Effects:
Is the most potent bronchodilator
Special Characteristics:
Used to prevent bronchospasm

7. Dobutamine (Dobutrex)
Mechanism of Action:
Beta-1>Beta-2=Alpha
Vascular Effects:
No change in resistance because of low affinity for b2 and a1
Cardiac Effects:
Minor change in heart rate but it makes the heart more efficient
Pulmonary Effects:
None
Special Characteristics:
DOC to stimulate the heart
Is a synthetic derivative of dopamine but has no effect on dopamine receptors

8. Dopamine (Intropin) Mechanism of Action: Vascular Effects:
Dopamine receptors and Beta-1
Vascular Effects:
Low dose: constricts vessels in sites other than the kidneys or brain
High Dose: constricts all vessels
Cardiac Effects:
Increases contractility and increase in systolic BP
Pulmonary Effects:
None
Special Characteristics:
Used to treat shock related to underperfusion and reflex vasoconstriction

9. Phenylephrine (Neo-Synephrine)
Mechanism of Action:
Alpha
Vascular Effects:
Intense vasoconstriction with an increased MAP
Cardiac Effects:
Decreases heart rate due to a reflex reaction to the increase arterial pressure
Pulmonary Effects:
None
Special Characteristics:
Used to treat SVT
Is included in cold remedies as a decongestant due to nasal vasoconstriction

10. Albuterol (Ventolin) Mechanism of Action: Vascular Effects:
Beta-2
Vascular Effects:
Vasodilation
Cardiac Effects:
None but may have reflex tachycardia
Pulmonary Effects:
bronchodilation
Special Characteristics:
Used to treat acute asthma exacerbations

11. Salmeterol (Serevent)
Mechanism of Action:
Beta-2
Vascular Effects:
Vasodilation
Cardiac Effects:
None but may have reflex tachycardia
Pulmonary Effects:
Bronchodilation
Special Characteristics:
Is long acting

12. Levalbuterol (Xopenex)
Mechanism of Action:
Beta-2
Vascular Effects:
vasodilation
Cardiac Effects:
None but may have reflex tachycardia
Pulmonary Effects:
Bronchodilation
Special Characteristics:
Less cardiac side effects than albuterol

13. Indirect Sympathomimetics
Cause norepinephrine release but do not bind to adrenergic receptors.
They enter the presynaptic terminal and displace NE from storage vesicles.
Drugs include:
Amphetamine
Methamphetamine

14. Amphetamine Methamphetiamine
Mechanism of Action:
Enter presynaptic terminal and displace NE from storage vesicles
Vascular Effects:
vasoconstriction
Cardiac Effects:
Increase in contraction with a reflex bradycardia from increased MAP
CNS Effects:
Wakefulness, euphoria
Unwanted Side Effects:
HTN, cerebral hemorrhage, convulsions, tremor
Special Characteristics:
Used for narcolepsy, ADD, Parkinson’s

15. Mixed Sympathomimetics
Both displace NE from storage vesicles and bind to adrenergic receptors
Drugs Include:
Ephedrine

16. Ephedrine Mechanism of Action: Vascular Effects: Cardiac Effects:
Displaces NE from storage vesicles and binds to adrenergic receptors
Vascular Effects:
Vasoconstriction with an increased MAP via a1
Cardiac Effects:
Similar to EPI but with no change in HR
CNS Effects:
Stimulation
Special Characteristics:
Used to treat narcolepsy
Causes bronchodilation
Used to treat asthma and nasal congestion
Used to dilate pupils

17. Central Adrenergic Nerve Blockers
Bind to alpha-2 receptors on neurons and prevent the release of NE from nerves
Drugs include:
Clonidine
Methyldopa

18. Clonidine (Catapres) Blockade Mechanism: Actions: Side Effects:
Potent alpha-2 agonist
Actions:
Decreases preganglionic sympathetic outflow which results in a decreased BP
Side Effects:
Orthostatic hypotension
Sedation
Rebound hypertension
Clinical Use:
HTN

19. Methyldopa (Aldomet) Blockade Mechanism: Actions: Side Effects:
Metabolized to alpha-methylnorepinephrine which is a potent alpha-2 agonist
Actions:
Decreases sympathetic outflow causing a rapid decrease in BP
Side Effects:
Sedation, mild orthostatic hypotension, coombs positive RBC, rebound HTN
Clinical Use:
HTN

20. Adrenergic Antagonist
Block NE from binding to the postsynaptic adrenergic receptors
Drugs include:
Phenoxybenzamine
Phentolamine
Prazosin
Doxazosin
Labetalol
Propranolol
Timilol
Metoprolol

21. Phenoxybenzamine (Dibenzyline)
Receptor:
Alpha-1 and alpha-2
Actions:
Vasodilation, blocks sympathetic outflow from the brain
Clinical Use:
Pheochromocytoma
Controls HTN
Side Effects:
Postural hypotension, reflex tachy, sexual dysfunction
Special Features:
none

22. Phentolamine (Regitine)
Receptor:
Alpha-1, alpha-2
Actions:
Vasodilation
Clinical Use:
Pheochromocytoma
To control HTN and is the pharmacological test
Side Effects:
Tachycardia, arrhythmias, hypotensive episodes
Special Features:
none

23. Prazosin (Minipress) Receptor: Actions: Clinical Use: Side Effects:
Alpha-1
Actions:
vasodilation
Clinical Use:
HTN
Side Effects:
Postural hypotension with first dose
Special Features:
None

24. Doxazosin (Cardura) Receptor: Actions: Clinical Use: Side Effects:
Alpha-1
Actions:
vasodilation
Clinical Use:
HTN, BPH
Relaxes smooth muscle in the bladder neck
Side Effects:
Postural hypotension with first dose
Special Features:
None

25. Labetalol (Normodyne)
Receptor:
Alpha-1, Beta-1, Beta-2
Actions:
Decreases BP from alpha blockade without a reflex tachycardia from b1 blockade
Clinical Use:
HTN
Side Effects:
Suppresses a failing heart, impotence, orthostatic HTN
Special Features:
Contraindicated in patients with asthma or bradycardia

26. Propranolol (Inderal)
Receptor:
Beta-1 and Beta-2
Actions:
Decreases inotropy and chronotropy and O2 demand, decreased release of renin
Clinical Use:
HTN, angina pectoris, SVT, ventricular arrhythmias, MI, Migraine prophylaxis
Side Effects:
Suppression of a failing heart, CNS sedation and depression, rebound HTN, impotence
Special Features:
Contraindicated in patients asthma

27. Timilol (Blocadren) Receptor: Actions: Clinical Use: Side Effects:
Beta-1 and Beta-2
Actions:
Decreases inotropy and chronotropy and O2 demand, decreased release of renin
Clinical Use:
HTN, MI, migraine prophylaxis, decrease intraocular pressure
Side Effects:
Suppression of a failing heart, CNS sedation and depression, rebound HTN, impotence
Special Features:
Contraindicated in patients with asthma

28. Metoprolol (Lopressor)
Receptor:
Beta-1
Actions:
Same as propranolol but with less bronchospasm in asthmatics
Clinical Use:
HTN, angina pectoris, MI
Side Effects:
Lower toxicity than propranolol
Special Features:
None

29. Cholinergic Agonist
Drugs include:
Carbachol
Bethanechol
Pilocarpine

30. Carbachol (Miostat or Isopto)
Receptor:
M1, M2, M3, Nicotinic
Clinical Uses:
Glaucoma, miosis for surgery
Contraindications:
Where constriction is undesirable

31. Bethanecol (Urecholine)
Receptor:
M1, M2 M3, Nicotinic
Clinical Uses:
Induce evacuation of a non-obstructed bladder
Increase GI motility after surgery
Contraindications:
Bradycardia, parkinsonism, epilepsy, hypo/hyper tension

32. Pilocarpine (Isopto-Carpine)
Receptor:
M1, M2, M3
Clinical Uses:
Cystic fibrosis sweat test, glaucoma (miosis/constriction), xerostomia (dry mouth)
Contraindications:
Bradycardia, parkinsonism, epilepsy, hypo/hyper tension

33. Cholinergic Antagonists
Drugs include:
Atropine
Scopolamine
Oxybutynin
Side effects are Red, Hot, Dry, Mad
Red as a beet, hot as an oven, dry as a bone, mad as a hatter

34. Atropine Action at Organ: Clinical Uses: Side Effects: Special Notes:
Low dose: bradycardia
High Dose: Tachycardia
Bronchodilation and decreased secretions
Decreased GI motility
Decreased salivation and sweating
Mydriasis
Clinical Uses:
Preanesthetic to prevent respiratory secretions, low dose for tachycardia, high dose for bradycardia
Side Effects:
Dry mouth, urinary retention, tachycardia
Special Notes:
Contraindicated in glaucoma, BPH, obstructive bowel disease and asthma patients

35. Scopolamine Action at Organ: Clinical Uses: Side Effects:
More potent at eye, and glands than atropine but less potent in the heart, lungs and GI
Clinical Uses:
Prevention of motion sickness
Side Effects:
CNS depression in low doses
Like atropine in high doses
Special Notes:
Contraindication if hypersensitive to belladonna (plant) or barbiturates

36. Oxybutynin (Ditropan)
Action at Organ:
Direct antispasmodic effect on smooth muscle
Clinical Uses:
Relief of bladder spasms that result in urinary leakage and incontinence
Side Effects:
Decreased sweating, rash, decreased lacrimation, mydriasis
Special Notes: