Sympathetic Nervous System Drugs LOs
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Norepinephrine: direct-acting, targets  and 1 receptors.
a. PCK: Action very brief due to rapid metabolism. Administered via IV infusion.
b. Use: Vasoconstrictor, used for vasopressor action to restore systolic blood pressure in
hypotensive states.
c. SE: marked elevations in blood pressure (↑risk of hemorrhage) and increased cardiac
work (severe angina, myocardial infarction, tachycardia, palpitations and serious
ventricular arrhythmias)
Isoproterenol: direct-acting, targets 1 and 2 receptors.
a. PCK: Administered by inhalation in asthma; administered via IV for systemic treatment.
b. Use: bronchodilator in asthma, treatment of cardiogenic shock, acute heart failure, and
some bradyarrhythmias. Largely replaced by other drugs.
c. SE: pronounced cardiac stimulation.
Albuterol: direct-acting, targets 2 receptors
a. PCK: administration via inhalation.
b. Use: bronchodilation in asthma and COPD.
c. SE: tremor, 1 cardiac stimulation possible at high doses.
Phenylephrine: direct-acting, targets 1 receptors
a. PCK: Action very brief due to rapid metabolism. Administered via IV infusion.
b. Use: vasopressor action to restore systolic blood pressure in hypotensive states.
c. SE: marked elevations in blood pressure (↑risk of hemorrhage); CNS stimulation—
anxiety, restlessness, insomnia.
Epinephrine: direct-acting, targets , 1 and 2 receptors.
a. PCK: Action very brief due to rapid metabolism. Administered via IV infusion.
b. Use: vasopressor action to restore systolic blood pressure in hypotensive states, local
vasoconstriction in local anesthetic solution; cardiac stimulation in cardiogenic shock,
acute heart failure, and bradyarrhythmias; smooth muscle relaxation to treat anaphylaxis.
c. SE: marked elevations in blood pressure (↑risk of hemorrhage) and increased cardiac
work (severe angina, myocardial infarction, tachycardia, palpitations and serious
ventricular arrhythmias)
Pseudoephedrine: mixed-acting, targets , 1 and 2 receptors
a. PCK: given orally; indirect effects at low doses via release of NE at 1/1 receptor and
direct effects at high doses via 2 receptor.
b. Use: as a vasoconstrictor for treatment and relief of nasal congestion.
c. SE: generally less potent at producing tachycardia, increased blood pressure and central
stimulation than ephedrine.
Dopamine: mixed-acting, targets  and 1 receptors (and dopamine D1)
a. PCK: Action very brief due to rapid metabolism. Administered via IV infusion. Acts via
DA1 at low doses, 1 at moderate doses, and  at high doses.
b. Use: Low doses improve blood flow to the kidney and abdominal organs, higher doses
have a positive inotropic effect and produce vasoconstriction. Dopamine is also used as a
cardiac stimulant in the management of cardiogenic shock, acute heart failure, and
bradyarrhythmias.
c. SE: dose dependent; marked elevations in blood pressure (↑risk of hemorrhage) and
increased cardiac work (severe angina, myocardial infarction, tachycardia, palpitations
and serious ventricular arrhythmias).
Clonidine: direct-acting, targets 2 receptors; agonist, but targeting of 2 receptors depresses
SNS response.
a. PCK: given orally or transdermally
Use: hypertension, treatment of opiate/alcohol withdrawal symptoms.
SE: dry mount, drowsiness, sedation and fatigue. Abrupt withdrawal may lead to
sympathetic overactivity.
Phentolamine: reversible, targets 1 and 2 receptors.
a. PCK: given parenterally.
b. Use: given as a vasodilator to treat local vasoconstrictor excess (following inadvertent
infiltration of NE, prevents tissue necrosis).
c. SE: postural hypotension and reflex tachycardia, nasal stuffiness, inhibition of
ejaculation, sedation, weakness and sense of fatigue.
Doxazosin: reversible, targets 1 receptors
a. PCK: given orally.
b. Use: as a vasodilator for the treatment of hypertension and vasospastic conditions
including Raynaud’s disease.
c. SE: syncope at onset of treatment, postural hypotension.
Propanolol: reversible, targets 1 and 2 receptors.
a. PCK: given orally.
b. Use: treatment of certain tremors given its ability to block excessive discharge of muscle
spindles.
c. SE: Hypoglycemic episodes—masks early signs of insulin reaction (mediated by
epinephrine release→tachycardia, anxiety, tremor); CNS effects—sedation, sleep
disturbances, and depression.
Atenolol: reversible, targets 1 receptors
a. PCK: given orally.
b. Use: For the treatment of hypertension.
c. SE: depression of myocardial contractility/excitability; can precipitate acute heart failure.
Metoprolol: reversible, targets 1 receptors
a. PCK: given orally.
b. Use: for the treatment of hypertension, angina pectoris and hyperthyroidism.
c. SE: depression of myocardial contractility/excitability; can precipitate acute heart failure.
Carvedilol: reversible, targets 1, 1 and 2 receptors
a. PCK: given orally.
b. Use: management of congestive heart failure.
c. SE: syncope at onset of treatment, postural hypotension; Hypoglycemic episodes—masks
early signs of insulin reaction (mediated by epinephrine release→tachycardia, anxiety,
tremor); CNS effects—sedation, sleepdisturbances, and depression.
Sympatholytic action: interference with adrenergic function in the presynaptic neuron.-Indirect
mechanism of action.
a. Lack of specificity limits clinical utility. Sympatholytic agents listed below.
b. Inhibitors of catecholamine synthetic enzymes: block synthesis of catecholamines.
i. Tyrosine hydroxylase (rate-limiting enzyme in catecholamine synthesis)
1. Metyrosine-used in pheochromocytoma
ii. L-aromatic amino acid (DOPA) decarboxylase
1. -methyldopa-metabolized to alpha-methylnorepinephrine, an agonist
of alpha 2 receptors in. the CNS-antihypertensive agent.
2. Carbidopa-used with levodopa for Parkinson’s to prevent conversion of
levodopa to dopamine.
iii. Dopamine -hydroxylase
1. Disulfiram
c. Inhibitors of catecholamine storage: deplete catecholamine stores.
i. Reserpine
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Inhibitors of catecholamine release: deplete synaptic levels of catecholamines
following increases in presynaptic interneuronal calcium levels.
i. Bretylium
ii. Guanethidine
A.
Direct-acting: The drug itself binds directly to target tissue adrenergic receptors and elicits
the same effects as the endogenous NE. This is the mode of action for most commonly used
therapeutic agents with receptor subtype specific agents allowing selectivity of action.
B.
Indirect-acting: Drug exerts an effect on processing of NE that results in increased
amounts of NE in the synapse, thus indirectly increasing its action at the receptor.
 Most common mechanism of action of indirect-acting agents is to increase storage and
release. The drug is taken up by neuron via norepinephrine transporter and transported
into the storage vesicles [VMAT] where it displaces endogenous stored norepinephrine
into the synapse via reversal of the NET. The released NE then acts on postsynaptic
receptors.
 Inhibition of neurotransmitter reuptake from the synapse, which increases NE levels
at adrenergic synapses, is a common mode of action for antidepressants that act in the
CNS