Sympathetic Nervous System

Front 1

ALPHA 1 (POST SYNAPTIC) RECEPTORS

Back 1

G proteins, activates phospholipase C
-vasoconstriction, mydriasis, relaxation of GI tract, contraction of GI sphincters, contraction of bladder sphincter

Front 2

ALPHA 1 RECEPTOR DRUGS

Back 2

-Neo and methoxyamine
-mimic action of neurotransmitter on postsynaptic receptor

Front 3

ALPHA 2 (PRESYNAPTIC) RECEPTORS

Back 3

-G protein coupled
-inhibits adenylate cyclase, calcium and potassium channels
-Inhibition of norepi release

Front 4

ALPHA 2 RECEPTOR DRUGS

Back 4

-MIMIC ACTION OF NT- clonidine, dexmedetomidine
-INHIBITION OF NT ON POSTSYNAPTIC- yohimbine

Front 5

ALPHA 2 (POSTSYNAPTIC) RECEPTORS

Back 5

-platelet aggregation
-hyperpolarization of cells in the CNS

Front 6

BETA 1 (POSTSYNAPTIC) RECEPTORS

Back 6

G protein coupled
-Stimulates adenylate cyclase and Ca ion channels
-increased conduction velocity, increased automaticity, increased contractility

Front 7

BETA 1 RECEPTOR DRUGS

Back 7

-MIMIC ACTION OF NT- dobutamine
-INHIBITION- metoprolol, esmolol

Front 8

BETA 2 (POSTSYNAPTIC) RECEPTORS

Back 8

G protein, stimulates adenylate cyclase and Ca ion channels
-vasodilation, bronchodilation, GI relaxation, Uterine relaxation, bladder relaxation, glycogenolysis, lipolysis

Front 9

BETA 2 RECEPTOR DRUGS

Back 9

agonist- terbutaline, albuterol
antagonist- (B 1 and B2) propranolol

Front 10

DOPAMINE 1 (POSTSYNAPTIC) RECEPTORS

Back 10

-vasodilation of the splanchnic and renal circulation

Front 11

DOPAMINE 2 (PRESYNAPTIC) RECEPTORS

Back 11

-inhibition of NE release (negative feedback loop)
**also presynaptic alpha

Front 12

ALPHA METHYLDOPA IN THE SNS

Back 12

inhibition of NT synthesis, and is a false transmitter

Front 13

TRICYCLIC ANTIDEPRESSANTS, COCAINE, AND KETAMINE AFFECTS ON SNS

Back 13

Inhibition of uptake of NT

Front 14

AMPHETAMINE EFFECTS ON SNS

Back 14

-displacement of NT from storage sites

Front 15

CARBACHOL EFFECTS ON PNS

Back 15

-displacement of NT from storage sites

Front 16

BRETYLIUM EFFECTS ON THE SNS

Back 16

-prevention of NT release

Front 17

BOTULINUM TOXIN

Back 17

-prevention of NT release in the PNS

Front 18

Norepinephrine (Levophed) (l-isomer)

Back 18

Potent vasoconstrictor and inotropic agent
L-isomer much more potent than d-isomer
More α than β activity
α activity produces increased peripheral vascular resistance, and increased systemic blood pressure and increased coronary artery blood flow
Some β1 activity: in lower doses, β1 cardiac stimulatory effects are seen, but with larger doses, vasoconstrictive effects (α1) are predominate cause of increased BP.
Like other catacholamines, NE increases cAMP in cells via β stimulation, and decreases cAMP via α stimulation.

Front 19

Norepinephrine (Levophed) (l-isomer)

Back 19

Glycogenolysis, inhibition of insulin release and lipolysis is less than seen with EPI.
Reflexive vagal stimulation secondary to increased TPR and BP slows the heart and increases stroke volume.
Blood flow to abdominal organs and skeletal muscle is decreased, while coronary blood flow is increased indirectly due to a stimulation.
Does not increase myocardial O2 consumption.
Normally given only via IV, with rapid onset and short (1 - 2 minute) duration.
Does not cross the BBB.
Use limited, mainly used for shock and severe hypotension.

Front 20

Epinephrine (Adrenalin)

Back 20

Potent α and β agonist (non-selective adrenergic agonist).
α1 action leads to arteriolar vasoconstriction. α2 stimulation leads to decreased NE release from neurons.
β1 stimulation leads to increased chronotropic and inotropic activity. β2 stimulation leads to arteriolar vasodilation, bronchial smooth muscle relaxation and increased glycogenolysis.
Major therapeutic effects include: bronchodilation, cardiac stimulation, skeletal muscle vasodilation, and glycogenolysis.
Smooth muscle effects are varied and depend on receptor density and hormonal effects.
Lowers intraocular pressure (wide-angle glaucoma) and causes brief mydriasis.
Topical or local administration constricts blood vessels (hemostasis).

Front 21

Epinephrine (Adrenalin)

Back 21

β2 stimulation also decreases mast cell histamine release.
Systolic pressure usually increased (due to increased inotropy) while diastolic is decreased (vasodilation).
Increases coronary artery vasodilation and stimulates increased myocardial O2 demand which has further local effect (via NO) to increased coronary vasodilation.
Increased risk of arrhythmias due to β1 activity.
At normal doses, some vasoconstriction, some dilation. Mostly constriction at higher doses.

Front 22

Epinephrine (Adrenalin)

Back 22

α stimulation in liver increases gluconeogenesis and inhibits insulin release. β stimulation (β3) in adipose tissue causes catabolism and increased free fatty acids in plasma.
β2 stimulation at skeletal muscle and liver increases glycogenolysis.
Does not cross BBB well.
Duration varies with administrative route: IV – few minutes; IM - 1 - 4 hours; Inhalation - 1 - 3 hours
Uses include acute bronchospasm, anaphylaxis, asthma(??), cardiopulmonary resuscitation, glaucoma, surgical bleeding, ventricular fibrillation and asystole.

Front 23

Isoproterenol (Isuprel)

Back 23

Potent bronchodilator and inotrope.
Synthetic compound similar to EPI.
Potent β agonist (non-selective).
Not used much now due to more selective compounds.
Very little α activity at therapeutic doses.
Increases blood flow (vasodilation) and relaxes GI smooth muscles.
Oral (sublingual), inhalation and IV routes.
Sublingual onset - 30 minutes with 1 - 2 hour duration.
IV very rapid, but less than 1 hour duration.
Inhalational duration is 2 - 4 hours.
Used for acute bronchospasms, bradycardia, asthma, etc.

Front 24

Dobutamine (Dobutrex)

Back 24

Parenteral inotrope.
Selective β1 agonist (minor β2 or α effects).
Stimulates rate and contraction of heart, increasing CO.
Systolic pressure is increased due to increased stroke volume, with little change in diastolic pressure.
Increased coronary blood flow and myocardial O2 demand seen.
Unlike DA, does not increase NE release from sympathetic nerves.
Plasma half-life approximately 2 minutes, so needs to be administered via constant IV infusion.
Uses include cardiac surgery, cardiogenic shock, and heart failure.

Front 25

Dopamine (Intropin)

Back 25

Mimics action of endogenous DA, which is a precursor of EPI and NE.
Works at DA receptors to dilate renal arterioles and increase renal blood flow and GFR.
At low doses, causes much vasodilation in renal, mesenteric, coronary vessels.
At moderate doses, also stimulates β1 receptors, stimulating the heart (while maintaining vasodilation).
At high doses, α receptors also stimulated, increasing TPR.
Does not cross BBB.
Normally given via continuous IV infusion (half-life ~ 2 minutes).
Used for heart failure, shock.

Front 26

Metaproterenol (Alupent)

Back 26

Synthetic compound similar in structure to isoproterenol.
More β2 selective than isoproterenol (but less than Albuterol).
Exclusively used as a bronchodilator.
Use declining due to better β2 agonists.
For COPD, asthma, chronic bronchospasms.

Front 27

Albuterol (Ventolin)

Back 27

Selective β2 agonist.
Indications - bronchospasm in patients with obstructive airway disease, asthma.
Adverse reaction - nervousness, tremor, tachycardia, palpitations.

Front 28

Pirbuterol (Maxair)

Back 28

Relatively selective β2 agonist.
Structurally similar to Albuterol.
Used for asthma and bronchospasms.

Front 29

Salmeterol (Serevent)

Back 29

β2 agonist.
Much more selective for β2 than albuterol.
Note: many β2 receptors now known to be located on the heart. Their function is unclear at present.
For chronic treatment of asthma (BID dosing, due to longer half-life).
Side effects include tachycardia, palpitations, hypersensitivity, tremor, and headaches.

Front 30

Terbutaline (Brethine)

Back 30

β2 agonist.
Used for bronchospasms and asthma, emphysema.
Side effects include tremor, nervousness, tachycardia, palpitations, nausea and vomiting.

Front 31

Clonidine (Catapres)

Back 31

Selective α2 agonist.
More CNS activity than peripheral.
α2 receptor stimulation in the CNS leads to decreased sympathetic outflow, increased parasympathetic outflow.
Indicated for control of hypertension.
Side effects include dry mouth, skin irritation

Front 32

Phenylephrine (Neosynephrine)

Back 32

α agonist.
Used as vasoconstrictor to maintain blood pressure during surgery, decongestant, mydriatic (without cycloplegia).
Contraindicated in narrow angle glaucoma, ventricular tachycardia, aneurisms.
Side effects include bradycardia, decreased CO, arrhythmias, angina, dizziness, CNS excitation.

Front 33

Metaraminol (Aramine)

Back 33

A parenterally administered potent vasoconstrictor (α1).
Used to prevent surgical (spinal anesthesia) hypotension and shock.
Adverse reactions include anxiety, cardiac arrhythmias, and hypertension.

Adrenergic Agonists

Front 34

Methyldopa (Aldomet)

Back 34

Forms α-methyl NE - acts as a false transmitter - less potent than NE.
Used to treat hypertension.
Contraindicated in patients with hepatic disease.
Side effects include angina, congestive heart failure, orthostatic hypotension, bradycardia, many others!

Front 35

Cocaine

Back 35

Inhibits amine re-uptake pump, thus causing increases stimulation. (Indirect effect).
Also has local anesthetic effects - blocks Na+ channels of nerve membranes.
Used for local (topical) anesthesia of mucous membranes in mouth, laryngeal and nasal cavities.
Side effects include vasoconstriction, mydriasis, nervousness, respiratory failure, cardiac arrest, general CNS stimulation.

Front 36

Indirect Adrenergic Agonists
Trigger NE release

Amphetamine (Dexedrine)

Back 36

Stimulates sympathetic neurons to release neurotransmitter.
Also has direct post-synaptic effect (mixed action).
Used for Narcolepsy, ADD, obesity.
Contraindicated in any cardiovascular disease, hypertension, hyperthyroidism.
Adverse reactions include: palpitations, tachycardia, increased blood pressure, psychoses, insomnia, headaches, tremor, general CNS stimulation.

Front 37

Ephedrine
Indirect Adrenergic Agonists

Back 37

Stimulates both α and β receptors
Peripheral actions are due partly to norepinephrine release and partly to direct effect on receptors.
Therapeutic doses of ephedrine produce mainly relaxation of smooth muscle and, if norepinephrine stores are intact, cardiac stimulation and increased systolic and usually increased diastolic blood pressure.
Metabolized to a small extent, with remainder excreted unchanged in urine.
Available in oral and parenteral forms.
Much controversy over use, controlled to block Meth production (as is pseudoephedrine)
Fairly high abuse potential.
Many reported cases of cardiovascular events.

Front 38

Pseudoephedrine (Sudafed)
Indirect Adrenergic Agonists

Back 38

Potent sympathomimetic, they possess direct α1, β1 and β2 activity in addition to triggering the release of catacholamines from the nerve terminal (mixed effects).
Used mainly for asthma, stimulant (OTC) preps.
Contraindicated in CV disease, hypertension.
Side effects include: CNS excitation, tremors, insomnia, nervousness, palpitations, tachycardia, cardiac arrhythmias, headache, sweating.

Front 39

Indirect Adrenergic Agonists
Tyramine (not used clinically)

Back 39

Taken up into nerve terminal and converted to false transmitter that has less activity, leading to decreased sympathetic tone.
Slight direct α activity.
Also triggers release of neurotransmitter from neuron.
Found in some foods (Red wine, chocolate, cheese, etc.) and presents a potential interaction on patients taking monoamine oxidase inhibitors

Front 40

OTHER INDIRECT ADRENERGIC AGONISTS

Back 40

Methamphetamine (Desoxyn)

Methylphenidate ( Ritalin)

Phentermine (Adipex)

Front 41

α1 agonists

Back 41

NE, EPI, DA (higher doses),Phenylephrine, Metaraminol
Effects: Increased arterial tone, increased TPR, increased diastolic pressure, decreased heart rate (reflex), increased venous tone.

Front 42

α2 agonists

Back 42

NE, EPI, Clonidine, α-methyldopa
Effects: Increased tone in large arteries, increased TPR (Post synaptic α2), increased coronary vasodilation.

Front 43

β1 agonists

Back 43

NE, EPI, ISO, DA, Dobutamine
Effects: Increased heart rate, increased O2 consumption, increased automaticity, conduction velocity, increased force of contraction, increased stroke volume and CO, decreased filling volume (in tachycardia), increased coronary vasodilation.

Front 44

β2 agonists

Back 44

Albuterol, Terbutaline, EPI, ISO
Effects: Decreased arterial tone, decreased TPR, decreased diastolic pressure, increased heart rate (reflexive).

Front 45

α2 antagonists

Back 45

block not only post-synaptic receptors, but also the pre-synaptic autoreceptor, and other α2 heteroreceptors on other neurons.

Front 46

Phenoxybenzamine (Dibenzyline)
α - Adrenergic Antagonists

Back 46

α1 and α2 antagonist (‘irreversible’ - covalent binding).
Long lasting effects (at least three days).
Most effective at smooth muscle and exocrine glands.
Used for: pre-op treatment of pheochromocytoma to block potential hypertensive crisis during surgery, sweating and hypertension caused by pheochromocytoma, certain vasospastic disorders, and frostbite therapy.
Side effects include: dizziness, decreased ejaculation ability, fatigue, miosis, orthostatic hypotension, tachycardia.
Half-life is approximately 24 hours, and the drug takes several hours after initial dosing to see effects. Care must be taken with other drugs given even upon cessation of therapy, as blockade may still be present for 7 days after the last dose.
Oral dosing.

Front 47

Phentolamine (Regitine)
α - Adrenergic Antagonists

Back 47

α1 and α2 competitive antagonist.
Shorter duration of action of action than phenoxybenzamine.
Parenteral dosing.
Used for: pheochromocytoma diagnosis, pheochromocytomectomy, MAO induced hypertensive crisis, impotence.
Side effects include: dizziness, decreased ejaculation ability, flushing, hypotension, sinus tachycardia.
Given parenterally - short acting.

Front 48

Prazosin (Minipress)
α - Adrenergic Antagonists

Back 48

Selective α1 antagonist.
For treating hypertension.
Side effects include: dizziness, headaches, drowsiness, palpitations, tachycardia, orthostatic hypotension.
Because it does not block α2 receptors, there is no excessive release of NE from neurons, and less of a risk of reflexive tachycardia seen with other α blockers.
Available as an oral dose form.

Front 49

Terazosin (Hytrin)
α - Adrenergic Antagonists

Back 49

Selective α1 antagonist.
Closely related to prazosin, but less potent.
More water soluble and higher bioavailability that prazosin, and also has a longer t1/2 (12 hrs), and can be used qD.
Used mainly for treatment of hypertension and benign prostatic hyperplasia (BPH).
Available as an oral dose form.

Front 50

Doxazosin (Cardura)
α - Adrenergic Antagonists

Back 50

Selective α1 antagonist.
Also closely related to prazosin.
Similar bioavailability as prazosin, but has a longer t1/2 (20 hrs), and can be used qD.
Used mainly for treatment of hypertension and benign prostatic hyperplasia (BPH).
Available as an oral dose form

Front 51

Alfuzosin (Uroxatral)
α - Adrenergic Antagonists

Back 51

Selective α1 antagonist.
Also closely related to prazosin.
Similar bioavailability as prazosin, but with a slightly longer t1/2 (3-5 hrs).
Used mainly for treatment of benign prostatic hyperplasia (BPH)- relaxes smooth muscle in bladder neck and prostate.
Available as an extended release oral dose form.

Front 52

Tamsulosin (Flomax)
α - Adrenergic Antagonists

Back 52

Selective α1A antagonist (but limited α1B activity, which controls vascular smooth muscle).
Therefore, somewhat more selective at treating BPH, with little effect on blood pressure.
t1/2 of 5-10 hrs.
Metabolized mainly by P-450 system.
Available as an oral dose form.

Front 53

Yohimbine (Yocon
α - Adrenergic Antagonists

Back 53

Selective competitive α2 antagonist.
Blocks central α2 receptors leading to increased blood pressure and heart rate (decreased parasympathetic outflow, and increased sympathetic outflow), possible aphrodisiac properties, due to peripheral α2 blockade and parasympathetic override.
Side effects include: antidiuretic effects, CNS excitation, hypertension, tachycardia, increased motor activity, nervousness, irritability, nausea and vomiting.
Local injections into penile shaft to increase erections.

Front 54

Propranolol (Inderal)
β - Adrenergic Antagonists

Back 54

Prototype β blocker.
Non-selective (blocks both β1 and β2 receptors).
Used for hypertension, ‘speakers’ nerves, angina, arrhythmias, migraines, pheochromocytoma.
Has membrane stabilizing effect (local anesthetic), which enhances its anti-arrhythmic effects (most b blockers share this property).
Contraindicated in shock, bradycardia, asthma, congestive heart failure.
Side effects include: bradycardia, congestive heart failure, hypotension, heart block, insomnia, hallucinations, bronchospasms.

Front 55

Nadolol (Corgard)
β - Adrenergic Antagonists

Back 55

Non-selective β antagonist.
For treating angina, hypertension.
Contraindicated in bradycardia, bronchial asthma, shock, heart block, myocardial infarction.
Side effects include: bradycardia, cardiac failure, conduction disturbances, arrhythmias, dizziness, bronchospasm, diarrhea, impotence, decreased libido, blurred vision.

Front 56

Timolol (Timoptic)
β - Adrenergic Antagonists

Back 56

Non-selective β antagonist.
For treating hypertension, ocular hypertension (wide angle glaucoma).
Contraindications include asthma, COPD, bradycardia, heart failure.
Side effects include fatigue, bradycardia, dizziness, cold hands and feet.

Front 57

Pindolol (Visken)
β - Adrenergic Antagonists

Back 57

Non-selective β antagonist with some sympathetic agonist activity.
A vasodilatory β blocker (due to strong β2 agonist activity).
Also not as much bronchoconstriction as with other β2 blockers.
Used to treat hypertension.
Contraindications: bradycardia, COPD, heart failure.
Side effects include fatigue, dizziness, diarrhea, cardiac failure.

Front 58

Labetalol (Normodyne)
β - Adrenergic Antagonists

Back 58

α1, β1 and β2 antagonist (non-selective).
Partial agonist at some β2 receptors.
For treating hypertension.
Contraindications: asthma, cardiac failure, severe bradycardia.
Side effects include postural hypotension, sweating, dizziness, nausea and vomiting, nasal stuffiness, bradycardia, impotence.

Front 59

Carvedilol (Coreg)
β - Adrenergic Antagonis

Back 59

α1, β1 and β2 antagonist.
Higher β:α blockade than labetolol (and longer duration).
Indications: angina, heart failure (NYHA type II and III), hypertension.
Contraindications: bronchospasm, emphysema, COPD, asthma, bradycardia, diabetes mellitus, heart failure (NYHA type IV), liver disease, pheochromocytoma.
Adverse reactions: Bronchospasm, diarrhea, dyspnea, fatigue, headaches, hypotension, peripheral edema, bradycardia, syncope.

Front 60

Metoprolol (Lopressor)
β - Adrenergic Antagonists

Back 60

β1 antagonist.
Used to treat hypertension and angina pectoris.
Contraindications: bradycardia, heartblock, shock, myocardial infarction.
Side effects include dizziness, bradycardia, nightmares, congestive heart failure, peripheral edema, bronchospasms, nausea, diarrhea.

Front 61

Acebutolol (Sectral)
β - Adrenergic Antagonists

Back 61

Mostly β1 blockade, but is also a partial sympathetic agonist (non-selective).
Low lipid solubility, so little CNS side effects.
Membrane stabilizing effect on the action potential is present, but less than propranolol.
Used in the reduction of hypertension and to control ventricular arrhythmias.
Does not cause as much bronchoconstriction as non-selective β blockers.
Less likely to cause bradycardia than other β1 blockers, due to its intrinsic sympathomimetic activity.
Side effects include: alopecia, dizziness, angina, fatigue, heart failure.

Front 62

Atenolol (Tenormin)
β - Adrenergic Antagonists

Back 62

Blocks β1 mostly.
Used to treat hypertension, acute myocardial infarction, angina pectoris.
Contraindicated in bradycardia, heart block, shock, cardiac failure.
Adverse reactions include bradycardia, dizziness, fatigue.

Front 63

Esmolol (Brevibloc)
β - Adrenergic Antagonists

Back 63

β1 antagonist.
Given by IV infusion.
Used for atrial fibrillation or flutter, paroxysmal supraventricular tachycardia.
Contraindications: bronchospasms, bradycardia, shock.
Side effects: AV block, cardiac arrest, hypotension, bradycardia.
Half-life of only a few minutes (very short duration).

Front 64

Metyrosine (Demser)
Misc. Adrenergic Agents

Back 64

Inhibitor of tyrosine hydroxylase.
Used for pheochromocytoma.
Contraindicated in hepatic disease, Parkinson's disease.
Adverse reactions include anxiety, confusion, crystalluria, depression, Parkinsonism, salivation.

Front 65

6-hydroxydopamine (experimental)
Misc. Adrenergic Agents

Back 65

Taken up into adrenergic nerve terminals and destroys the cells.
Stimulates free radical production in cells, leading to cell death.
Therefore, removes adrenergic neurons (chemical sympathectomy).

Front 66

Bretylium (Bretylol)
Misc. Adrenergic Agents

Back 66

Blocks catecholamine release from nerve terminal.
Used for ventricular tachycardia, prophylaxis of ventricular fibrillation.
Adverse reactions: hypotension, bradycardia.

Front 67

Reserpine (Serpalan)
Misc. Adrenergic Agents

Back 67

Inhibits storage of catecholamines (and serotonin) in granules, leading to depletion.
Initial effects may cause transient release.
Used for hypertension, schizophrenia.
Contraindications include: mental depression, peptic ulcer, ulcerative colitis.
Side effects: vomiting, diarrhea, dry mouth, syncope, angina, many more.