Download 7th Lecture

Pharmacology 101
Abdelkader Ashour, Ph.D.
7th Lecture
Drugs Acting on the
Sympathetic Nervous
System
Neurohormones at the SNS
 Neurohormones are neurotransmitters that are released at the nerve
endings and facilitate the transmission of nerve impulses
 The two neurohormones (neurotransmitters) of the SNS are epinephrine
and norepinephrine
 Epinephrine is secreted by the adrenal medulla. Norepinephrine is secreted
mainly at nerve endings of sympathetic (also called adrenergic) nerve fibers
Drugs Acting on Adrenergic Receptors
(Sympathetic Drugs)
I. Sympathomimetics:
A. Directly Acting Sympathomimetics, which directly stimulate adrenergic receptors.
They are either:
1. Non-selective a-agonists such as norepinephrine and epinephrine. These drugs
stimulate both a1- and a2-adrenergic receptors
2. Non-selective b-agonists such as isoprenaline and epinephrine. These drugs
stimulate both b1- and b2-adrenergic receptors
3. Selective a1-agonists such as phenylephrine. These drugs are selective for a1adrenergic receptors
4. Selective a2-agonists such as clonidine. These drugs are selective for a2adrenergic receptors (remember that stimulation of a2-adrenergic receptors results
in inhibition of NE release)
5. Selective b1-agonists such as dobutamine. These drugs are selective for b1adrenergic receptors (remember that the cardiac adrenergic receptors are b1)
6. Selective b2-agonists such as salbutamol. These drugs are selective for b2adrenergic receptors (remember that the bronchial adrenergic receptors are b2)
B. Note that:
epinephrine
 all α & all β
norepinephrine
 all α, β1 & β3
isoproterenol (isoprenaline) 
all β
Drugs Acting on Adrenergic Receptors
(Sympathetic Drugs)
I. Sympathomimetics:
B. Indirectly Acting Sympathomimetics are agents that elevate the concentration of
NE at neuroeffector junctions, because they either:
1.
inhibit re-uptake of NE into noradrenergic neurons, e.g., cocaine. Therefore, NE
is not inactivated and has a prolonged action on both a and b receptors
2.
Facilitate NE release. These drugs (e.g., amphetamine) enters noradrenergic
neurons and cause NE release
3.
slow NE breakdown by monoamine oxidase (MAO), such as tranylcypromine
4.
or exert all three of these effects (e.g., amphetamine, methamphetamine)
 The effectiveness of such indirect sympathomimetics diminishes or disappears
(tachyphylaxis) when vesicular stores of NE are depleted.
Drugs Acting on Adrenergic Receptors
(Sympathetic Drugs)
II. Sympathomlytics:
A. Noradrenergic blockers which include
1. Drugs which antagonize the effects produced by a-receptor stimulation.
Examples:
 a1-blockers such as prazosin
 a2-blockers such as yohimbine
2. Drugs which antagonize the effects produced by b-receptor stimulation.
Examples:
 Non-selective b-blockers such as propranolol
 Selective b1-blockers such as atenolol
 Selective b2-blockers. Not in clinical use
B. Drugs that prevent noradrenergic transmission which include:
1. Noradrenergic neuron blockers such as guanethidine which inhibits the
release of noradrenaline from sympathetic nerve terminals.
2. Drugs that deplete NE from noradrenergic neurons such as reserpine.
They prevent the storage of NE in vesicles at noradrenergic nerve
endings, thus NE is immediately inactivated by MAO
3. Drugs that interfere with the synthesis of NE such as methyldopa