Autonomic Nervous System Drugs

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: • 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: • 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. AmphetamineMethamphetiamine • 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: • 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: • 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: • 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: • Alpha-1 • Actions: • vasodilation • Clinical Use: • HTN • Side Effects: • Postural hypotension with first dose • Special Features: • None

24. Doxazosin (Cardura) • Receptor: • 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: • 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: • 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: • 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: