17. Agents Acting On The Biosynthesis, Storage, Release And Elimination Of Catecholamines

Front 1

What is the function of VMAT?

Back 1

VMAT is a transporter protein which transports dopamine into intracellular vesicles.

Front 2

What is the function of norepinephrine transporter (NET)/uptake-1?

Back 2

Uptake-1 recycles noradrenaline in the synaptic cleft by transporting it back into the presynaptic terminal.

Front 3

Which enzymes are involved in the breakdown of catecholamines?

Back 3

Monoamine oxidase (MAO), COMT and aldehyde reductase

Front 4

What are the three possible fates of noradrenaline in the synaptic cleft?

Back 4

- It can bind to postsynaptic noradrenaline receptors

- It can be recycled into the presynaptic nerve terminal by uptake-1

- It can bind to inhibitory α2-adrenergic receptors on the presynaptic nerve terminal

Front 5

Name the drugs which act by influencing catecholamine synthesis

Back 5

Methyldopa, levodopa, carbidopa, methyltyrosine, bensarazide

Front 6

What are the indications for methyltyrosine?

Back 6

Phaeochromocytoma

Front 7

What are the indications for levodopa, carbidopa and benserazide?

Back 7

Parkinson disease

Front 8

What are the indications for methyldopa?

Back 8

Hypertension in pregnancy

Front 9

What is the mechanism of action of methyltyrosine?

Back 9

Methyltyrosine acts as a false substrate for tyrosine hydroxylase, thereby inhibiting the synthesis of noradrenaline and adrenaline

Front 10

What is the mechanism of action of levodopa?

Back 10

Levodopa is L-DOPA, the precursor of dopamine. It can cross the blood brain barrier and increases the synthesis of dopamine in the CNS

Front 11

What is the mechanism of action of carbidopa and benserazide?

Back 11

Carbidopa and benserazide are DOPA decarboxylase inhibitors. DOPA decarboxylase converts L-DOPA into dopamine.

These drugs don't cross the blood brain barrier. When given together with L-DOPA they prevent L-DOPA from being converted in the periphery and increases the amount of L-DOPA which reaches the CNS.

Front 12

What is the mechanism of action of methyldopa?

Back 12

Methyldopa is a false substrate for DOPA decarboxylase. The enzyme converts it into methyldopamine which is further converted into methylnoradrenaline.

Methylnoradrenaline has little activity on α1 receptors but high activity on α2 receptors, thereby increasing the negative feedback.

Because it is a false substrate for DOPA decarboxylase it will also compete with L-DOPA, so it reduces the amount of noradrenaline formed.

Front 13

Name the drugs which influence the storage of noradrenaline

Back 13

Reserpine and tetrabenazine

Front 14

What is the mechanism of action of reserpine and tetrabenazine?

Back 14

They inhibit VMAT, thereby preventing dopamine and noradrenaline from entering the vesicles in the presynaptic nerve terminal. Dopamine and noradrenaline are instead broken down.

Front 15

Name the agents which are indirectly acting sympathomimetics

Back 15

Ephedrine, cocaine, amphetamine and tyramine

Front 16

What are the indications for ephedrine?

Back 16

Nasal congestion, haemorrhoids, hypotension, nocturnal enuresis and to induce mydriasis.

Front 17

What is the mechanism of action of ephedrine?

Back 17

Ephedrine is a β receptor agonist. It is a false substrate for NET and VMAT. It prevents noradrenaline from entering the vesicles, causing it to remain in the cytoplasm. Cytoplasmic noradrenaline is forced out of the cytoplasm into the synaptic cleft through NET.

Front 18

What is the mechanism of action of amphetamine?

Back 18

Amphetamine is a false substrate for NET and VMAT. It prevents noradrenaline from entering the vesicles, causing it to remain in the cytoplasm. Cytoplasmic noradrenaline is forced out of the cytoplasm into the synaptic cleft through NET.

Front 19

What is the mechanism of action of cocaine?

Back 19

Cocaine inhibits NET, preventing noradrenaline from being recycled into the presynaptic nerve terminal from the synaptic cleft.

Front 20

What is the cheese reaction?

Back 20

The cheese reaction is a reaction which occurs when a person who takes MAO-A inhibitor drugs (antidepressants) consumes high amounts of a compounds called tyramine. Tyramine is an indirect sympathomimetic which is found in high amounts in red wine and certain types of cheese.MAO-A normally breaks down ingested tyramine in the GI tract and liver. However, when this enzyme is inhibited tyramine will not be broken down, so it can cause severe hypertension.