531 - Med Chem I - Exam Ii - Cholinergic System And Drugs

Front 1

Define transmembrane potential.

Back 1

The difference in potential (voltage) between the inside and outside of the cell.

Front 2

What happens to the transmembrane potential of a cell when a depolarizing stimulus is applied? What ion is this usually in response to?

Back 2

The membrane begins to depolarize, aka the membrane potential becomes more positive. This is usually in response to an influx of calcium ions.

Front 3

What must occur for an action potential to happen?

Back 3

A depolarizing stimulus must be applied that reaches the threshold voltage.

Front 4

What is a hyperpolarizing stimulus?

Back 4

A stimulus that make the membrane potential more negative and cannot generate an action potential.

Front 5

What are the two main branches of the nervous system?

Back 5

Central nervous system and peripheral nervous system.

Front 6

What are the two main branches of the peripheral nervous system?

Back 6

Somatic nervous system and autonomic nervous system.

Front 7

What is the main function of the parasympathetic nervous system?

Back 7

The parasympathetic nervous system is responsible for energy conservation and the "rest and digest" state of a person.

Front 8

What is the main function of the sympathetic nervous system?

Back 8

The sympathetic nervous system is responsible for the "fight and flight" state of a person.

Front 9

What are the two main branches of the autonomic nervous system?

Back 9

sympathetic and parasympathetic

Front 10

Where are ganglia located in parasympathetic and sympathetic nervous systems?

Back 10

Parasympathetic system: close to the innervated organs
Sympathetic system: close to the spinal column

Front 11

Which axons are myelinated in the parasympathetic system?

Back 11

Both preganglionic and postganglionic.

Front 12

Which axons are myelinated in the sympathetic system?

Back 12

The preganglionic axons are myelinated and the postganglionic axons are not.

Front 13

What is the ratio of preganglionc:postganglionic axons in both the parasympathetic and sympathetic systems?

Back 13

Parasympathetic= 1:1
Sympathetic= 1:20 (postganlionic unmylinated take up less space)

Front 14

What are the advantages/disadvantages of having myelinated axons?

Back 14

They are much faster, but take up a lot more space/are bulkier.

Front 15

What type of neurotransmitters are used in parasympathetic and sympathetic nervous systems?

Back 15

Parasympathetic: acetylcholine
Sympathetic: acetylcholine for preganglionic axons and norepinephrine for postganglionic axons

Front 16

Where are nicotinic receptors located on neurons?

Back 16

On both the presynaptic and postsynaptic neurons.

Front 17

What are the types and functions of presynaptic muscarinic receptors?

Back 17

M2 and M4; they inhibit Ca2+ entry into presynaptic neuron

Front 18

What is the function of presynaptic nicotinic Ach receptors?

Back 18

They enhance Ca2+ entry into presysnaptic neuron

Front 19

Where are M1 receptors located?

Back 19

Autonomic ganglia, CNS

Front 20

Where are M2 receptors located?

Back 20

Heart: SA node, AV node, atrium, and ventricle.

Front 21

Where are M3 receptors located?

Back 21

Smooth muscle

Front 22

Where are M4 receptors located?

Back 22

CNS

Front 23

Where are M5 receptors located?

Back 23

CNS

Front 24

Where are Nicotinic NM receptors located?

Back 24

Skeletal muscles at neuromuscular junctions

Front 25

Where are Nicotinic NN receptors located?

Back 25

Autonomic ganglia, adrenal medulla, and CNS; these are mainly localized to the CNS.

Front 26

Describe the basic structure of Nicotinic receptors.

Back 26

Composed of five subunits (two of which are alpha) that form a pentamer and span a membrane.

Front 27

Describe the Ach binding sites on Nicotinic receptors.

Back 27

They are located on the alpha subunits and are surround by primarily aromatic amino acids (Tyr, Trp). These amino acids allow for cation-pi interactions with the positively charged Ach.

Front 28

What is the function of M2 domains in Nicotinic receptors?

Back 28

These domains contain five subunits, and each domain is located toward the center of the nicotinic receptor, forming three rings of negatively charged amino acids, which help to "funnel" the positively charged ions through the receptor.

Front 29

Describe the structure of muscarinic agonists' active sites.

Back 29

Typically a negatively charged aspartate stabilizes the positive charge, and an H-bond donor is present to bond with the esther-O.

Front 30

What was the purpose of using steric substitutions on different positions on Ach molecules?

Back 30

To investigate the shape of the receptor binding site. A methyl was substituted at the beta and alpha carbons, and the beta substitution bound tighter to muscarinic receptors and the alpha substitution bound tighter to nicotinic receptors.

Front 31

What happes to the functionality of Ach when a carbamate group is substituted?

Back 31

The molecule is more resistant to hydrolysis because a resonance structure can occur, and the carbonyl group becomes far less electrophilic.

Front 32

How was a selective, orally active muscarinic agonist of Ach receptors achieved?

Back 32

Substitue a carbamate and add an methyl at the beta position; bethanechol.

Front 33

Name the class of drug associated with the following pharmacological responses:

Contraction of smooth muscles
Vasodilation of vascular system
Increased secretion from exocrine glands
Decrease in heart rate and force of contraction
Constriction of pupil

Back 33

Muscarinic agonists

Front 34

Name the class of drug associated with the following pharmacological responses:

Decreased contraction of GI and urinary tract smooth muscles
Dilation of pupils
Reduced gastric secretion
Decreased saliva secretion

Back 34

Muscarinic antagonists.

Front 35

Which type of nicotinic antagonists results in a partially depolarized motor end plate?

Back 35

Depolarizing nicotinic antagonist.

Front 36

What are the two major classes of nicotinic antagonists?

Back 36

Nondepolarizing blockers and depolarizing blockers.

Front 37

Which type of nicotinic antagonist compete with Ach for binding at the neuromuscular junction?

Back 37

Non-depolarizing nicotinic antagonist.

Front 38

What are the two structural analogs used to discover the two main types of Ach receptors?

Back 38

Muscarine (muscarinic)
Nicotine (nicotinic)

Front 39

What is the most stable conformation of Ach found that binds to nicotinic receptors?

Back 39

Antiperiplanar

Front 40

What is the most stable conformation of Ach found that binds to muscarinic receptors?

Back 40

Synclinal or gauche/skew

Front 41

How can you reverse a non-depolarizing blocker?

Back 41

Use a cholinesterase inhibitor to increase concentration of Ach.

Front 42

How can you reverse a depolarizing blocker?

Back 42

You cannot reverse this with increased concentration of Ach; i.e. non-reversible.

Front 43

What are some examples of non-depolarizing blockers?

Back 43

d-tubocurarine, pancuronium, vencuronium, rocuronium

Front 44

What are some examples of depolarizing blockers?

Back 44

decamethonium and succinylcholine

Front 45

What are some examples of physiologic responses when the parasympathetic system is activated?

Back 45

Pupils constrict, heartbeat slows, stomach activity increases, glucose release inhibited

Front 46

What are some examples of physiologic responses when the sympathetic system is activated?

Back 46

Pupils dilated, airways relaxed, glucose is released

Front 47

What is the role of PLP?

Back 47

Decarboxylation

Front 48

What is the role of SAM or Ado-Met?

Back 48

Add a methyl group.

Front 49

What is one of the main differences between agonists and antagonists?

Back 49

In general, antagonists tend to be larger than agonists.

Front 50

What amino acid is the precursor to acetylcholine?

Back 50

Serine!