What does the chemical prefix nor signify

nor:without morphine

the prefix nor is most often used to indicated a demethylated compount...demethylation is the chemical process resulting in the removal of a methyl group

(-CH3) from a molecule.

What is the rate-limiting step of catecholamine biosynthesis?

What is the primary mechanism for the termination of the effect of norepinephrine?

Norepinephrine in the synaptic cleft either:

1)Diffuses away-the primary way.

2)Is metabolized by COMT (catechol O-methyl  

    transferase).

3)Is taken back up into the presynaptic cell.

Yes it is a direct acting synthetic catecholamine that stimulates both beta1 and beta2 adrenergic receptors.

They all contain the catechol ring and are very similar in structure with the difference being the group on the amine nitrogen.

What are the roles of the alpha-2 receptors?

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

When the sympathetic adrenergic nerve is stimulated a portion of norepinephrine reacts with lpha-2 receptors on the neuronal membrane causing feedback inhibition of the ongoing release of norepinephrine from the neuron.

The above mechanism decreases further output and serves as a local modulating system to reduce (inhibit) the sympathetic neurotransmitter output when there is increased sympathetic activity.

What is COMT? Where is it located? Which vasoactive drugs does it affect? Why does phenylephrine?

Catechol O methyltransferase (COMT) is an enzyme involved in the breakdown on neurotransmitters.

COMT is located in the postsynaptic cell membrane.

Because Norepinephrine, Epinephrine, Isoproterenol, and Dopamine all have a catechol hydroxyl group they can be inactivated by COMT.

Phenylephrine lasts longer than Epinephrine because it either has a larger volume of distribution or lower clearance. In this case it is because phenylephrine clearance is less than Epinephrine because it is not a catecholamine and is not broken down by COMT and is a poor substrate for MAO.

How does MAO differ from COMT (compare where these enzymes are located and contrast their action.)

MAO=intracellular oxidizes norepinephrine

COMT=extracellular intersynaptic space

          metabolizes (methylate) norepinephrine

Norepinephrine is stored in postganglionic neurons. What keeps all this stored norepinephrine from being metabolized before it is released into the synaptic cleft?

There is MAO inside the presynaptic nerve cell that is capable of metabolizing Dopamine, Norepinephrine, and Epinephrine however it is not located in the storage vesicles. Therefore when inside the vesicles, catecholamines are safe from metabolism. After Dopamine is formed, but before it is in vesicles it is susceptable to metabolism. Norepinephrine that enters the cell through reuptake can also be metabolized until it is safe in the vesicles. The same thing applies to Dopamine and other biogenic amines like seratonin that are released into the synapse and then enter the cell through reuptake.

Catecholamine administration may produce hyperglycemia. What is the mechanism by which this applies?

Increased glycogenolysis in the liver.

Increased release of glucagon with a decreased release of insulin.

You Should be extremely careful with anticholinergics and pancuronium bromide (a muscle relaxant that has antimuscarinic effects).

Avoid halothane  because of its ability to enhance the cardiac dysrhythmic effects of catecholamines. 

Avoid meperidine because it also has anticholinergic properties

Avoid indirect acting sympathomimetics (because of unpredictable response).

If direct-acting vasoactive agents are needed (eg, phenylephrine) should carefully begin with small doses of these medications.

Ephedrine- an indirect acting synthetic noncatecholamine that stimulates alpha and beta receptors.

The pharmacologic effects of ephedrine are due in part to endogenous release of norepinephrine (indirect acting) but the drug also has direct stimulant effects on adrenergic receptors (direct acting) Resistant to metabolism by MAO in the GI tract, permits unchanged drug to be absorbed following oral admin. IM injection is also acceptable because the drug induced local vasoconstriction is insufficient to greatly delay systemic absorption.The slow inactivation and excretion are responsible for the prolonged duration of action. Does not produce marked hyperglycemia. Clinical uses: used to increase BP in the presence of sympathetic nervous system blockade produced by regional anesthesia or hypotension caused by inhaled or injected anesthetics. Can be used as a chronic oral med to treat bronchial asthma because of the bronchodilating effects by activation of beta2 receptors, onset is slow compared with epi. Has a decongestant and antiemetic effect. Systemic BP elevating response is less intense than epi and lasts 10 times longer.

Pseudoephedrine is similar to ephedrine but has fewer CNS side effects.

For the test be able to recognise the structure of epinephrine.