1. Pharmacology 101 Abdelkader Ashour, Ph.D. 7 th Lecture

2. Drugs Acting on the Sympathetic Nervous System

3. 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

4. Drugs Acting on Adrenergic Receptors (Sympathetic Drugs) I.Sympathomimetics: A.Directly Acting Sympathomimetics, which directly stimulate adrenergic receptors. They are either: 1.Non-selective  -agonists such as norepinephrine and epinephrine. These drugs stimulate both  1 - and  2 -adrenergic receptors 2.Non-selective  -agonists such as isoprenaline and epinephrine. These drugs stimulate both  1 - and  2 -adrenergic receptors 3.Selective   -agonists such as phenylephrine. These drugs are selective for  1 - adrenergic receptors 4.Selective   -agonists such as clonidine. These drugs are selective for   - adrenergic receptors (remember that stimulation of   -adrenergic receptors results in inhibition of NE release) 5.Selective   -agonists such as dobutamine. These drugs are selective for   - adrenergic receptors (remember that the cardiac adrenergic receptors are    6.Selective  2 -agonists such as salbutamol. These drugs are selective for  2 - adrenergic receptors (remember that the bronchial adrenergic receptors are  2  B.Note that: epinephrine  all α & all β norepinephrine  all α, β 1 & β 3 isoproterenol (isoprenaline)  all β

5. 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  and  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.

6. Drugs Acting on Adrenergic Receptors (Sympathetic Drugs) II.Sympathomlytics: A.Noradrenergic blockers which include 1.Drugs which antagonize the effects produced by  -receptor stimulation. Examples:    -blockers such as prazosin    -blockers such as yohimbine 2.Drugs which antagonize the effects produced by  -receptor stimulation. Examples:  Non-selective  -blockers such as propranolol  Selective   -blockers such as atenolol  Selective   -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