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

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

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

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Cholinergic Agonist Drugs include: Carbachol Bethanechol Pilocarpine

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

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

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

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

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

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

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: