1. Demethylated compound

2. Removal of the methyl group (-CH3)

3. Commonly replaced by H+ atom

Nor = without methyl

1. Hydroxylation of tyrosine

2. Rate limiting enzyme = tyrosine hydroxylase

1. MAO (monoamine oxidase) is present in the neuronal mitochondria where it can oxidize Nepi.

• intracellular

2. COMT (catechol O-methyl transferase) is located in the post synaptic cell membrane where it can metabolize Nepi

• extracellular

1. What is the primary mechanism for the termination of the effect of Nepi?

2. What are the other two mechanisms by which these effects may be terminated?

Nepi in the synaptic cleft will:

1. Diffuse away (primary way Nepi is terminated)
   
2. be metabolized by COMT
3. taken back up into presynaptic cells

Alpha-2 receptors main effect is to reduce amount of Nepi entering into synaptic cleft by affecting the presynaptic release.

MAO inside presynaptic nerve cell is capable of metabolizing dopamine, Nepi and Epi. MAO is not located in the storage vesicles. Once inside the vesicles, catecholamines are safe from metabolism.

1. After dopamine is formed but before it enters the vesicles it is suseptible to metabolism

2. Nepi that re-enters cell through reuptake can also be metabolized until it is "safely" inside vesicles.

3. Same applies to dopamine and serotonin that enter cell through reuptake

1. increased glycogenolysis by liver

2. increase release of glucagon

3. decreased release of insulin

1. Anesthetic technique should minimize SNS stimulation or drug induced hypotension.

2. Careful use of anticholinergics and pancuronium bromide ( a muscle relaxant that has antimuscarinic effects)

3. Halothane should be avoided d/t its ability to enhance cardiac dysrhythmic effects of catecholamines

4. Avoid Meperedine d/t anticholinergic properties

5. Avoid indirect acting sympathomimetics d/t unpredictable response

6. If direct acting vasoactive agents are needed (phenylephrine) carefully do so starting with small doses

Ephedrine:

1. indirect acting synthetic catecholamine, stimulates alpha and beta receptors

2. endogenous release of Nepi, has direct stimulant effects on adrenergic receptors

3. resistant to metabolism of MAO in GI allowing unchanged drug to be absorbed after oral administration

4. slow excretion/inactivation d/t prolonged duration of action

5. does not produce marked hyperglycemia

6. increase BP in the presence of SNS blockade produced by regional anesthesia or hypoTN caused by inhaled/injected anesthetics

7. Used to treat chronic bronchial spasms d/t bronchodilating effects (activation of beta-2 receptors)

8. Elevates systemic BP less than Epi but lasts 10 times longer

Pseudoephedrine: similar effects as ephedrine but with less CNS side effects

1. Is isoproterenol a catecholamine?

2. How are isoproterenol, Epi and Nepi structurally similar?

1. Isoproterenol is a direct acting synthetic catecholamine that stimulates both beta-1 and beta-2 receptors.

2. Isoproterenol, Epi and Nepi all contain a catechol ring and are similar except the group on the amine nitrogen

• As the amine nitrogen group gets larger the affinity for beta receptors gets larger

1. What are the roles of alpha-2 receptors?

2. What does the text mean when it states that these receptors may behave as inhibitory autoreceptors?

1. sympathetic adrenergic nerve is stimulated a portion of the release Nepi reacts with alpha-2 receptors on the neuronal membrane causing feedback inhibition of ongoing release of Nepi

2. This inhibitory action decreases further output from the adrenergic neuron and seves as a local modulating system to reduce the sympathetic neurotransmitter output when there is a high sympathetic activity

1. What is COMT?

2. Where is it located?

3. Which vasoactive drugs does it affect?

4. Why does phenylephrine (neosynephrine) last longer than Epi?

1. COMT (catechol O-methyl transferase) is an enzyme involved in the breakdown of neurotransmitters

2. COMT is located in the post synaptic cell membrane

3. Nepi, Epi, isoproterenol, dopamine

4. Phenylephrine lasts longer than Epi b/c it either has a larger volume of distribution or lower clearance. Here it is b/c phenylephrine clearance is less than Epi. (Phenylephrine is not a catecholamine so it is not metabolized by COMT)