Test 1- Sympathetic NS

Question 1

Recall that in the SNS short preganglionic neurons emerge from

Answer 1

Recall that in the SNS short preganglionic neurons emerge from the thoracolumbar spine to synapse on ganglia. At those ganglionic synapses acetylcholine is the neurotransmitter and the dominant receptor type is nicotinic (remember that drugs and toxins that work on nicotinic receptors in the neuromuscular junction may not have the same degree of effect at the ganglionic nicotinic receptors). The post- ganglionic neuron continues on to the target or effector organ and at the terminal synapse Norepinephrine (NE) is the primary neurotransmitter.

Question 2

Monoamine Oxidase (MAO)

Answer 2

NE is synthesized, stored in lysosomes and then released when an impulse travels down the neuron. Once in the synaptic cleft the NE interacts with receptors (pre or post-synaptic) and initiates a second messenger response. The NE then dissociates from the receptor and most of it is taken back up by the presynaptic neuron and recycled, some of the neurotransmitter is broken down by Monoamine Oxidase (MAO) and catechol-O-methyltransferase (COMT). A small amount is metabolized in the liver or taken up by the post-synaptic neuron.

Question 3

Sites of drug action:

Answer 3

Most of the drugs that we use will interact directly with sympathetic receptors (alpha or beta, pre or post- synaptic). Other mechanisms that can indirectly increase or decrease the sympathetic response include actions on:

Question 4

Sites of drug action: Synthesis:

Answer 4

Synthesis: (eg. methyldopa which acts as a false transmitter, diverting NE production to cause reduced NE and also production of a different substance that causes sympathetic inhibition).

Question 5

Sites of drug action: Storage:

Answer 5

Storage: (eg. reserpine which is sometimes used as a sedative in equines, it blocks NE uptake into vesicles so when the stored reserves are used there is no more NE (depletion of mediator)).

Question 6

Sites of drug action:Release:

Answer 6

Release: (eg. bretylium is an antiarrhythmic drug that blocks release of NE from nerve terminals, thereby reducing the amount available in the synapse).

Question 7

Sites of drug action:Uptake/Reuptake:

Answer 7

Uptake/Reuptake: (eg imipramine (a tricyclic antidepressant) inhibits re-uptake of NE causing it to remain in the synapse longer).

Question 8

Receptor:

Answer 8

Many of the drugs that we will discuss work at the adrenergic receptors and these are all considered direct-acting agents. These drugs have variable affinity and action at different receptor types. It is important to know 1) where the receptors are (eg. what organ) and what they do (normal activity) as well as 2) which receptor(s) a particular drug interacts with predominately and 3) whether the drug is an agonist (does the same thing the endogenous ligand would do) or antagonist (blocks the receptor).

Question 9

Clinically these drugs are often used for:

Answer 9

Agonists: - Cardiac disease (epinephrine, beta-1 agonists) - Anaphylactic/anaphylactoid reactions (epinephrine) - Obstructive airway disease (beta-2 agonists) - Sedation/analgesia (alpha-2 agonists) Antagonists: - To treat tachyarrhythmias (beta-1 blockers) - Vasodilation (alpha-1 blockers) - Reversal of alpha-2 sedation (alpha-2 blockers)