Pharmacology: Block 2: Neuroeffector Systems 1, Intro To The Nervous System

Front 1

What are the two most general divisions of the nervous system?

Back 1

Peripheral (PNS) and central (CNS)

Front 2

What are the AFFERENT components of the peripheral nervous system?

Back 2

The sensory receptors.

Front 3

What are the two general divisions of the EFFERENT peripheral nervous system?

Back 3

1. The autonomic nervous system

2. The somatic nervous system

Front 4

What are the two divisions of the autonomic nervous system?

Back 4

1. Symapthetic

2. Parasympathetic

Front 5

What is the basic target of the sympathetic nervous system?

Back 5

Smooth muscles.

Front 6

What is the basic target of the parasympathetic nervous system?

Back 6

Glands.

Front 7

What is the basic target of the somatic nervous system?

Back 7

Skeletal muscle.

Front 8

What actions does the somatic nervous system control?

Back 8

1. Consciously controlled functions (movement)

2. Reflexes (e.g. the withdrawl reflex)

Front 9

What is the generalized action of the autonomic nervous system?

Back 9

To control smooth muscle, cardiac muscle, and glands.

To deal with unconsciously controlled visceral functions (e.g. blood flow)

Front 10

Somatic nervous system: neuron organization

Back 10

Originates all along the spinal cord --> single neuron extends to the target --> each neuron branches and innervates many muscle fibers (a "motor unit")

Front 11

Sympathetic nervous system: neuron organization

Back 11

Thoracolumbar spinal cord --> short preganglionic neuron terminates in sympathetic chain --> postganglionic fibers terminate on target organ.

Note that the "crowded" environment of the sympathetic chain ganglia mean that if a neurotransmitter is released in the ganglia, it may end up affecting several different postganglionic neurons. This is responsible for the somewhat diffuse nature of the sympathetic nervous system.

Front 12

Parasympathetic nervous system: neuron organization

Back 12

Originates at craniosacral levels of the CNS --> Long preganglionic neuron --> short postganglionic neuron that synapses in or around target organ.

Front 13

Enteric nervous system: general characteristics

Back 13

Largely independant
Receives sympathetic and parasympathetic imput.

Front 14

Cholenergic neurons release what?

Back 14

Acetylcholine (Miochol-E®)

Front 15

Adrenergic neurons release what?

Back 15

Norepinephrine (Levophed ®)

Front 16

Almost all efferent nerves leaving the CNS are what type of neuron (release what neurotransmitter)?

Back 16

Cholenergic (ACh)

Front 17

What are some examples of cholenergic neurons?

Back 17

1. Somatic
2. Preganglionic sympathetics
3. Postganglionic sympathetics going to sweat glands.
4. Both pre and postganglionic parasympathetic neurons.
5. Preganglionic nerves going to the adrenal medulla.

Front 18

What nerves are adrenergic?

Back 18

Postganglionic sympathetics are adrenergic.

Front 19

Adrenal medulla: innervation and action.

Back 19

Preganglionic sympathetic neurons (cholenergic) --> innervation of catecholamine-secreting cells --> release epinephrine (80%) and norepinephrine (20%)

"The adrenal medulla is similar to a sympathetic ganglion."

Front 20

Special case of sympathetic innervation of renal vascular smooth muscle?

Back 20

There is some evidence that postganglionic sympathetic fibers release dopamine.

Front 21

How is choline transported into a nerve terminal?

What drugs block this process?

Back 21

Choline is transported into the nerve terminal via a sodium dependant transporter.

Can be blocked by hemicholinium drugs

Front 22

Where is acetylCoA generated?

Back 22

In glycolysis in the mitochondria.

Front 23

Where is acetylcholine generated?

Back 23

In the cytoplasm

Front 24

What enzyme transfers an acetyl group from acetylCoA to choline?

Back 24

Choline acetyl transferase (ChAT)

Front 25

What is the action of choline acetyl transferase (ChAT)?

Back 25

Transfers an acetyl group from acetylCoA to choline.

Front 26

What loads acetylcholine into vesicles?

What drug blocks this process?

Back 26

A proton antiporter loads acetylcholine into the vesicles.

Vesamicol blocks this process

Front 27

What causes vesicles to be released at the neuromuscular junction?

What drug blocks this process?

Back 27

Stimulus --> Na into the cell --> Ca release --> fusion of vesicles with membrane mediated by t-SNARES (syntaxin, SNAP-25) and v-SNARES (synaptobrevin, synaptotagmin)

The release of this is blocked by botulinum toxin (Botox®, Myobloc®), which cleaves synaptobrevin.

Front 28

What cleaves ACh?

Back 28

Acetylcholinesterase

Front 29

What are the products of ACh cleavage by acetylcholinesterase?

Back 29

Choline + acetate.

Front 30

What is another enzyme that cleaves ACh more slowly than AChE?

Back 30

Pseudocholinesterase.

(Butyrylcholinesterase, synthesized in the liver)

Front 31

What is the precursor to L-DOPA?

Back 31

Tyrosine

Front 32

How does tyrosine get into the neuron?

Back 32

Via a sodium dependant carrier

Front 33

What converts tyrosine to L-DOPA?

What drug blocks this process?

Back 33

Tyrosine hydroxylase.

Blocked by Metyrosine

Front 34

What converts DOPA to dopamine?

Back 34

DOPA decarboxylase.

Front 35

What facilitates the transport of dopamine into vesicles?

What drug blocks this process?

Back 35

VMAT (vesicular monoamine transporter)

Blocked by Reserpine

Front 36

What converts dopamine to norepinephrine in vesicles?

Back 36

Dopamine beta hydroxylase

Front 37

What is a receptor on the pre-synaptic membrane that binds a product of that neuron called?

Back 37

An autoreceptor

Front 38

What is the main way that NE transmission is terminated?

What drugs can block this process?

Back 38

1. Uptake by the PRE-synaptic neuron by a norepinephrine transporter (NET).

This process can be blocked by cocaine and tricyclic antidepressants.

Front 39

What are some drugs besides NE that NET transports?

Back 39

Amphetamine
Ephedrine

Front 40

What are two minor ways that NE transmission is terminated?

Back 40

1. Uptake by the POST-synaptic cell

2. Inactivation by MAO (monoamine oxidase) and COMT (catechol-O-methyl transferase)

Front 41

(extra credit)

What is the enzyme that converts norepinephrine to epinephrine?

Back 41

Phenylethanolamine-N-methyltransferase

Front 42

What is the only difference between NE and E?

Back 42

E has an extra methyl group.

Front 43

Where is the majority of E synthesized?

Back 43

In the adrenal medulla.

Front 44

What two ions does the nicotinic receptor control the flow of?

Back 44

Na (influx) and K (efflux)

Front 45

What are the two subtypes of nicotinic receptor?

What is the clinical significance of this?

Back 45

1. Receptor at the neuromuscular junction (pentamer α, β, γ, δ)

2. Receptor in autonomic ganglia (only α, β chains)

The significance of this is that different drugs can target different receptors.

Front 46

What chain of the nicotinic receptor does ACh bind?

Back 46

To the α chain.

Front 47

(extra credit)

In adult nicotinic receptors, what chain is replaced by what?

Back 47

The γ chain is replaced by the δ chain.

Front 48

What are the basic characteristics of the muscarinic receptor?

Back 48

It is a seven transmembrane domain monomer.

Front 49

When ACh binds the muscarinic receptor, what two things get activated?

Back 49

Gq, Gi

Front 50

What does Gq activate?

Back 50

Receptor --Gq--> PLC (phospholipase C) --> Makes PIP2 from lipids --> IP3 and DAG.

IP3 releases Ca from the SR
DAG activates PKC

Front 51

What does Gi activate?

Back 51

Gi opens K channels (only with M2 receptors) and inhibits adenyl cyclase.

Front 52

What does PLC do?

Back 52

Hydrolyzes PIP2 --> DAG + IP3

Front 53

What does IP3 do?

Back 53

Mediates the release of Ca from intracellular stores (e.g. ER)

Front 54

What does DAG do?

Back 54

Activates PKC (protein kinase C), which modulates various ion channels.

Front 55

What are the main muscarinic subtypes?

Back 55

M1, M2, M3

Front 56

What G protein is associated with M1?

Back 56

Gq

Front 57

What G protein is associated with M2?

Back 57

Gi

Front 58

What G protein is associated with M3?

Back 58

Gq

Front 59

Gq activates which muscarinic subtypes?

Back 59

M1, M3

Front 60

Gi activates which muscarinic and adrenergic subtypes?

Back 60

M2 and α2 and D2

(First-aid: MAD 2's)

Front 61

What is the second messenger of the M1 receptor?

Back 61

IP3, DAG

Front 62

What is the second messenger of the M3 receptor?

Back 62

IP3, DAG

Front 63

What is the action of Gi?

Back 63

Inhibits adenyl cyclase
Opens K channels in muscarinic receptors

Does NOT open K channels with adrenergic alpha-1 receptors.

Front 64

In what tissues are M1 receptors located?

Back 64

Autonomic ganglia
Some presynaptic sites
CNS

Front 65

In what tissues are M2 receptors located?

Back 65

Heart
Smooth muscle
Some presynaptic sites

Front 66

In what tissues are M3 receptors located?

Back 66

Most target organs
Glands
Smooth muscle
Endothelium

Front 67

Prototypical muscarinic antagonist.

Back 67

Atropine (Atropen®)

"Atropine blocks the muscarinic receptor"

Front 68

Prototypical muscarinic agonist.

Back 68

Bethanechol (Urecholine®)(Muscarine)

"Bethanechol activates muscarinic receptors"

Front 69

Prototypical GANGLION nicotinic antagonist.

Back 69

Trimethaphan (Arfonad®)

Front 70

Prototypical GANGLION nicotinic agonist.

Back 70

(DMPP) Dimethylphenylpoperazinium

Front 71

Prototypical NEUROMUSCULAR nicotinic antagonist.

Back 71

Tubocurarine

Front 72

Prototypical NEUROMUSCULAR nicotinic agonist.

Back 72

Succinylcholine (Quelicin ®, Anectine ®)

Actually is such a good "activator" of the nicotinic receptor that it opens the channels wide - eventually no signal is produced.

Front 73

What is the order of sensitivity of α receptors to

Epinephrine
Norepinephrine
Isoproterenol

What about β receptors?

Back 73

α = epinephrine ≥ norepinephrine ≫ isoproterenol

β = isoproterenol > epinephrine ≥ norepinephrine

Front 74

What are the four basic types of adrenergic receptors?

Back 74

α1, α2, β1, β2

Front 75

What G-protein is associated with α1 receptors?

Back 75

Gq

Front 76

What G-protein is associated with α2 receptors?

Back 76

Gi

Front 77

What G-protein is associated with β1 receptors?

Back 77

Gs --> adenyl cyclase up --> cAMP up --> PKA up.

Front 78

What G-protein is associated with β2 receptors?

Back 78

Gs --> adenyl cyclase up --> cAMP up --> PKA up.

Front 79

What is the second messenger system involved with α1 receptors?

Back 79

IP3, DAG

Front 80

What is the second messenger system involved with α2 receptors?

Back 80

Gi --> AC down

Note that Gi here doesn't affect K transport

Front 81

What is the second messenger system involved with β1 receptors?

Back 81

AC up

Front 82

What is the second messenger system involved with β2 receptors?

Back 82

Stimulates adenyl cyclase.

Front 83

What is the predominant location of α1 receptors?

Major function?

Back 83

Smooth muscles in the peripheral vasculature.

Vasoconstriction.

Front 84

What is the predominant location of α2 receptors?

Back 84

Presynaptic sites
Platelets
Fat cells

Front 85

What is the predominant location of β2 receptors?

Back 85

Smooth muscle
Cardiac muscle

Simple way to think about it: lungs and skeletal muscle.

Vasodilation, bronchodilation, HR up, contractility up, lipolysis up, glucagon release up.

Front 86

β1 antagonist

Back 86

Metoprolol (Toprol®, Lopressor®)

Front 87

β1 agonist

Back 87

Dobutamine (Dobutrex®)

Front 88

α1 antagonist

Back 88

Prasozin (Minipress®)

Front 89

α1 agonist

Back 89

Phenylephrine (Neosynephrine®)

Front 90

α2 antagonist

Back 90

Yohimbe (Yocon®)

Front 91

α2 agonist

Back 91

Clonidine (Catapres®, Dixarit®)

Front 92

β2 antagonist

Back 92

Butoxamine

Front 93

β2 agonist

Back 93

Albuterol (Ventolin®, Preventil®)

Front 94

True or false: epinephrine activates all four adrenergic receptors?

Back 94

True

Front 95

What adrenergic receptor does E bind better than NE?

Back 95

β2 receptors

Front 96

β2 receptors in the bronchioles respond mainly to _______ ________.

Back 96

β2 receptors in the bronchioles respond mainly to CIRCULATING EPINEPHRINE.

Front 97

What is the main way by which junctional transmission is modulated?

Back 97

By prejunctional receptors

Front 98

Prejunctional M1 receptor: reduces or stimulates neurotransmitter release?

Back 98

Stimulates

Front 99

Prejunctional M2 receptor: reduces or stimulates neurotransmitter release?

Back 99

Reduces

Front 100

Prejunctional neuromuscular receptor: reduces or stimulates neurotransmitter release?

Back 100

Stimulates

Front 101

Prejunctional α2 receptor: reduces or stimulates neurotransmitter release?

Back 101

Reduces

Front 102

Prejunctional β2 receptor: reduces or stimulates neurotransmitter release?

Back 102

Stimulates

Front 103

What is a way to remember which prejunctional receptors do what?

Back 103

Write it out, it alternates

M1 - stim
M2 - red
M2 - red
NM - stim
α2 - red
α2 - red
β2 - stim
β2 - stim

Front 104

What is denervation supersensitivity?

Back 104

A dramatic increase in the amount of receptors following denervation.

This is an example of POSTsynaptic regulation

Front 105

What are two examples of POSTsynaptic signal modulation?

Back 105

1. Modulation of receptor number or sensitivity (e.g. denervation sensitivity)

2. Activation of several different postsynaptic receptors (which can be excitatory (EPSP) or inhibitory (IPSP))