Autonomic Nervous System Neuropharmacology

Question 1

What kind of drug is Doxazosin?

Answer 1

Alpha-1 receptor antagonist

Question 2

Antimuscarinic drugs are also called ___________.

Answer 2

parasympatholytics

Question 3

What does the protein CHT do?

Answer 3

Choline transporter – it pumps choline into the presynaptic terminal to be made into acetylcholine

Question 4

What is the rate-limiting step in acetylcholine synthesis?

Answer 4

Presynaptic uptake of choline by CHT

Question 5

CHT is inhibited by ____________.

Answer 5

hemicholinium

Question 6

VAT (vesicle-associated transporter) is inhibited by ___________.

Answer 6

vesamicol

Question 7

What is bethanecol’s bioavailability?

Answer 7

Not good; because it is a similar compound to acetylcholine, it has a permanent charge

Question 8

Nicotine does what to the sympathetic and parasympathetic pathways?

Answer 8

It stimulates them, leading to a mixture of effects: for instance, GI motility can be increased (due to PNS stimulation), while at the same time arousal can result as an effect of stimulating the SNS.

Question 9

There are three main categories of choline esterase inhibitors: reversible, short-acting; reversible, long-acting; and irreversible, long-acting. List some from each category.

Answer 9

RSA: edrophonium
RLA: neostigmine, phyostigmine
ILA: isofluorophate (a nerve gas)

Question 10

What is the main pharmacokinetic difference between neostigmine and phyostigmine?

Answer 10

Phyostigmine is more lipid-soluble and thus has better distribution throughout the body.

Question 11

Atropine has a high specificity for ____________ receptors.

Answer 11

muscarinic

Question 12

Describe the pharmacokinetic distinction between tertiary and quaternary antimuscarinics.

Answer 12

Tertiary compounds can penetrate into the CNS, while quaternary compounds cannot

Question 13

Blocking the ganglionic receptors (nicotinic acetylcholine) leads to differing effects based on which branch of the autonomic nervous system has greater control over the tone of the organ in question. Describe two main differences.

Answer 13

The SNS controls vascular tone, so inhibiting the SNS ganglia leads to vasodilation. The PNS controls the tone of most other organs, so inhibiting PNS ganglia leads to SNS-like stimulation in the gut, for example.

Question 14

Ganglion blockers are _____________ available.

Answer 14

no longer clinically

Question 15

What is DOPA?

Answer 15

Dihydroxyphenylalanine –precursor of both dopamine and norepinephrine

Question 16

What drug inhibits the rate-limiting step in catecholamine synthesis?

Answer 16

Metyrosine, which inhibits the enzyme tyrosine hydroxylase

Question 17

What is the chemical backbone of most adrenergic drugs?

Answer 17

Phenylethylamine

Question 18

“Monoamines” includes both ____________.

Answer 18

catecholamines and 5-hydroxytryptamines (serotonin)

Question 19

What protein removes norepinephrine from the synaptic cleft?

Answer 19

Norepinephrine transporter (NET)

Question 20

What protein moves monoamine precursors into vesicles?

Answer 20

VMAT (vesicle monoamine transporter)

Question 21

Where are MAOs located and why is this important?

Answer 21

Monoamine oxidases are located on mitochondria and degrade monoamines; this is significant because monoamines must be pumped into vesicles to be shielded from MAOs.

Question 22

What does bretylium do?

Answer 22

It inhibits the exocytosis of vesicles containing catecholamines.

Question 23

What drugs block NET?

Answer 23

Cocaine and tricyclic antidepressants

Question 24

How do amphetamines and pseudoephedrine work?

Answer 24

They reverse NET proteins (thus sending NE back out) as they are taken up by neurons

Question 25

Are catecholamines effective orally?

Answer 25

No – there are hepatic enzymes that break them down, namely COMT (catechol-O-methyl transferase)

Question 26

How does reserpine work? What classification does it fall into?

Answer 26

It inhibits the storage of catecholamines, thus ensuring that more catecholamines get metabolized or degraded; it is a sympatholytic.

Question 27

All of the -zocin drugs block __________.

Answer 27

alpha-1 adrenergic receptors

Question 28

What drugs are beta-1 selective antagonists?

Answer 28

Metoprolol and atenolol

Question 29

The most specific neurotransmitter-modifying drugs target ______________.

Answer 29

a specific postsynaptic receptor

Question 30

What type of amino acid facilitates the hydrolysis of acetylcholine?

Answer 30

Serine

Question 31

Describe the pharmacokinetics of atropine and scopalamine and why it is clinically important.

Answer 31

Both distribute easily into the CNS, so they both have undesirable side effects when used at higher doses.

Question 32

Isoproterenol activates what receptors?

Answer 32

Beta-1 and beta-2 (“I SO PROTEct the ßaßies”)

Question 33

Which beta-blockers also block the alpha-1 receptor (and are thus vasodilatory)?

Answer 33

Carvedilol (-dilate) and labetalol (it goes “LABove and beyond”

Question 34

What does stimulation of alpha-2 receptors on the brain stem cause?

Answer 34

Decreased SNS activity (hence clonidine is a depressant)