Pharm Test 2 Lecture 5

Front 1

What are the naturally occuring catecholamines?

Back 1

(1) Dopamine
(2) NE
(3) Epi

Front 2

Draw catecol or the other derivative of catecholamines...phenylethylamine.

Back 2

:)

Front 3

What is the first step of the synthesis of catecholamines?

Back 3

The first step is when Tyrosine is converted to DOPA via the enzyme Tyrosine Hydroxylase. This is the rate limiting step.

Front 4

What is DOPA converted to and where does this reaction occur?

Back 4

DOPA is then converted to dopamine via the enzym dopa decarboxylase. This reaction takes place in the axoplasm.

Front 5

After dopamine is made what is dopamine converted to?

Back 5

Dopamine is transported from the axoplasm into adrenergic storage vesicles where it is converted to NE by te enzyme DBetaH.

Front 6

What is Norepinephrine then converted to?

Back 6

Norepinephrine is then converted to Epinephrine via the enzyme PNMT. This occurs in the adrenal medulla and some neurons in the brain.

Front 7

T/F: NE is not stored in vesicles.

Back 7

False: NE is stored in nerve terminals in small, membrane-bound vesicles along with ATP and soluble proteins include DBetaH.

Front 8

T/F: Catecholamine storage in the adrenal medulla is in smaller vesicles.

Back 8

FALSE: Catecholamine storage in the adrenal medulla is in larger vesicles called chroaffin granules. The ratio of EPI to NE in chromaffin vesicles of humans is 85%:15%.

Front 9

T/F: Catecholamines are very strong molecules - resisting degradation.

Back 9

FALSE: Catecholamines are very labile compounds. Sequetration within storage vesicles protects these amines from degradation.

Front 10

T/F: Vesicular storage provides a mechanism through which catecholamines can be released slower.

Back 10

FALSE: Vesicular storage provides a mechanism through which catecholamines can be released rapidly upon demand and rapidly removed when demand ceases.

Front 11

When do storage vesicles come into play?

Back 11

Once synthesized, dopamine is transported into storage vesicles, by a vesicular uptake system. This active amine pump also transports NE into vesicles after its reentry into the nerve terminal.

Front 12

When is NE released?

Back 12

Synchronous release of the contents of many storage vesicles into the synaptic space occurs when an action potential reaches the end terminals of a postganglionic sympathetic nerve.

Front 13

The NE response is terminated by an active reuptake of the NE. What are the three reuptake pumps?

Back 13

(1) Uptake 1 - active transporter on the post-synaptic terminal.
(2) Vesicular Uptake Pump - the one that takes the NE back into the storage vesicle.
(3) Uptake 2 - found in the non-terminal tissue (liver, glial cells)

Front 14

What are the two enzymes for catecholamine degradation?

Back 14

(1) catechol-o-methyl transferase which is present in the periphery and methylates the three - hydroxyl group.
(2) Monoamine Oxidase - found on the outside membrane of mitochondria in the cytoplasm. This will remove the amino group or whatever substitution group on the O group.

Front 15

Differentiate between MAO-A and MAO-B.

Back 15

MAO-A metabolizes NE and serotonin and MAO-B metabolizes dopamine.

Front 16

Alpha-methyl-p-tyrosine: What is the mechanism of this drug? When is this drug used?

Back 16

Alpha-methyl-p-tyrosine acts on the tyrosine hydroxylase and thereby inhibits the formation of Epi and NE. It is a drug used to treat pheochrmocytomas - a tumor that produces excessive amounts of EPI and NE which results in hypertension, tachycardia, ect.

Front 17

Alpha-methyldopa: What is the mechanism of action for this drug?

Back 17

Alpha-methyl dopa is simply a mehtylated form of dopa. As synthesis continues a methylated form of NE exists and is stored in storage vesicles. This methylated form does not cause a reaction, instead it takes up space that NE would normally take, thereby reducing the amount of NE reacted. This is called a false transmitter.

Front 18

What are two drugs that inhibit reuptake of NE by acting on pumps?

Back 18

(1) Cocaine
(2) Reserpine

Front 19

Cocaine: What is the mechanism for action for this drug? When will you see this effect?

Back 19

Cocain acts by inhibiting the reuptake of NE and by doing so we prolong and increase the signal of the released NE. Will notice the effect right away.

Front 20

Reserpin: What is the mechaism for action for this drug? When will you see htis effect? what has it been used for?

Back 20

Reserpin inhibits the uptake of dopamine and NE into storage vesicles. You will notice this effect in 24 hours. It has been used to depress the action of CNS. Reserpin causes people to get very sleepy and depressed and so on.

Front 21

Tyramine: Where is tyramine found? What is the drug's mechanism? Are there any risks for toxicities? If so, who is at risk?

Back 21

(1) Tyramine is found in fermented cheeses, wines, and pickled heron.
(2) Tyramine can be taken into storage vesicles, where they displace the stored NE. This NE diffuses from the nerve terminal and causes an acute sympathomimetic effet. MAO in the liver and gut normally breaks down the tyramine before they can gain access to the bloodstream but patients treated with MAO inhibitors (such as phenylzine) can develop hypertensive crises due to injestion of foods high in tyramine.

Front 22

What is Selegiline? What is it treated for?

Back 22

Selegiline is a drug given to patient's who have Parkinson's disease. This helps to increase the dopamine release.

Front 23

Relate ENTECAPONE and TALCAPONE to SELEGILINE.

Back 23

Entecapone and Talcapone are inhibitors of catechol-o-methyl transferase. These drugs are given additionally to DOPA in patients who have Parkinson's disease. This prevents the metabolism of DOPA and improves the effect.