Sympathetic Drugs

Sympathetic Drugs
Stress and The Adrenal Glands
Adrenal Medulla:
A Modified Sympathetic Ganglion
Mechanism: Norepinephrine Release
and Recycling
Review of Efferent Pathways: Motor and
Catechalomines: Activity
Stimulates the “fight or fight” reaction
Increased plasma glucose levels
Increased cardiovascular function
Increased metabolic function
Decreased gastrointestinal and genitourinary
Activity of Epinephrine
• Drugs that partially or completely mimic the
actions or norepinephrine (NE) and
epinephrine (Epi).
• Act either - directly on α- and/or βadrenoceptors or indirectly on presynaptic
terminals, usually by causing the release of
• See Below
• β2-Adrenoceptor Agonists – cause bronchial
dilation - used for the treating asthma,
prevent pre-term labor (relaxing uterine
• β1-Adrenoceptor Agonists – (e.g.,
dobutamine) sometimes used to increase the
force of heart contraction in severe lowoutput heart failure.
• α1-Agonists – (e.g., phenylephrine) – used as
mydriatics, decongestants.
• α2-Agonists – (e.g., clonidine, methyldopa) –
centrally acting hypotensive drugs.
• Sympathomimetics act mainly by causing release
of NE (e.g., amphetamine) have the α1/α2
selectivity of NE.
• β-Adrenoceptor antagonists (β-blockers) – used
to treat hypertension, angina, cardiac
arrhythmias, CHF, and glaucoma.
• α-Adrenoceptor antagonists (α-blockers) – limited
clinical application – prazosin (selective α1antagonist – used to treat hypertension.
• Adrenergic neuron blocking drugs – either
deplete the nerve terminals of NE or prevent its
release – used as hypotensive agents.
Metabolism of
Monoamine Oxidase
Catechol-O-methytransferase (COMT)
α1-Adrenoceptors – in several tissues (e.g.,
smooth muscle, salivary glands)  incr IP3 and
[Ca2+]in  vasoconstriction or glandular secretion
• α2-Adrenoceptors – on noradrenergic nerve
terminals. Activation by NE  inhibit AC, decr
cAMP, Ca2+ channels close  decr further nt
• β-Adrenoceptor – stim AC  incr [cAMP]  2nd
messenger intracellular signaling  physiol
Indirectly-Acting Sympathomimetics
• Transported into nerve terminals where they displace
vesicular NE into the cytoplasm. Some is metabolized
by MAO, but the remainder is released by carriermediated transport to activate adrenoceptors.
• Amphetamines – resistant to MAO.
- Peripheral actions - tachycardia, hypertension mainly caused by catecholamine release.
- Dexamfetamine and methylphenidate used for
hyperactive children.
• Cocaine – NE reuptake inhibitor (also dopamine) –
Intense central stimulant  popular drug of abuse.
Acute and chronic
effects of Indirectly
G = Guanethidine
Mechanism of action
of cocaine and reserpine
Directly-Acting Sympathomimetics
• Effects in humans depends on their receptor specificity (α
and/or β) and on the compensatory reflexes they evoke.
• Epi incr bp by stim the rate and force of the heart beat (β1
• Stimulation of vascular α-receptors causes vasoconstriction
(viscera, skin), whereas…,
• Stimulation of vascular β2-receptors vasodilation (skeletal
muscle) …
• And the total peripheral resistance may actually decrease.
• NE has little-to-no effect on the vascular β2-receptors; thus,
the α-mediated vasoconstriction is unopposed.
• The resulting rise in bp reflexively slows the heart, usually
overcoming the direct β1-stimulant action on the heart
β-Receptor-Selective Drugs
• Isoprenaline – stimulates all β-receptors 
incr rate and force of heart beat and 
vasodilation  full diastole and MAP, with
little change in systolic pressure.
• β2-Adrenoceptor Agonists – relatively selective
class of drugs that produce bronchodilation –
used for asthma (resistant to MAO, not
uptaken into neurons).
Adrenoceptor Antagonists
• Decr artiolar and venous tone  decr peripheral
resistance  hypotension.
• Reverse the pressor effects of Epi, because its β2mediated vasodilator effects are unopposed by αmediated vasoconstriction  peripheral
resistance falls (Epi reversal).
• Cause reflex tachycardia – this is greater with
non-selective drugs that also block α2-presynaptic
receptors on the heart, because the augmented
release of NE further stimulates the cardiac βreceptors (e.g., prazosin).
Adrenoceptor Antagonists
• Vary in lipid solubility and cardioselectivity
• All block β1-receptors and decr bp and prevent
• Higher Kow-drugs  more rapid absorption
from GIT, 1st-pass hepatic elimination  more
rapidly eliminated.
• Also more likely to enter CNS and cause
central effects (e.g., nightmares).
• Cardioselectivity diminishes with higher
Adrenoceptor Antagonists
β-Blockers (Cont’d)
• Nevertheless, selective β1-blockade  less
peripheral vasoconstriction (cold hands and feet)
and does not reduce the response to exerciseinduced hypoglycemia (stim of gluconeogenesis
in liver is mediated by β2-receptors).
• Cardioselective drugs may have sufficient β2activity to ppt severe bronchospasms in patients
with asthma – these patients should avoid βblockers .
• Some possess intrinsic sympathomimetic activity
(partial agonists), but this is debatable.
synthesis, storage,
release, and reuptake

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