Pharmacology: Katzung Intro to autonomic pharmacology

Question 1

Where do parasympathetic preganglionic fibers originate?

Answer 1

In cranial nerve nuclei III, VII, IX, and X.

Question 2

Where to preganglionic sympathetic fibers originate from?

Answer 2

T1-L5 spinal nerves.

Question 3

What nerve fibers are cholinergic?

Answer 3

All preganglionic fibers, All parasympathetic fibers and most somatic fibers.

Question 4

What are the four aspects of neurotransmitter function?

Answer 4

(1) Synthesis and storage
(2) Release
(3) Termination of action
(4) Effects

Question 5

How is acetylcholine synthesized?

Answer 5

Acetylcholine is synthesized by acetyl-CoA (produced in the mitochondria) and choline (transported via choline acetyl transferase)

Question 6

What is the rate limiting step of ACh synthesis?

Answer 6

The transport of choline via acetyltransferase

Question 7

What drug inhibits choline transport?

Answer 7

Hemicholinium

Question 8

What is vesamicol?

Answer 8

vesamicol is a research drug that blocks the transport of ACh into vesicles by the transporter VAT.

Question 9

How are ACh laden vesicles released?

Answer 9

Calcium influx stimulates vSNARES (VAMPs) to associate with tSNARES (SNAPs). This interaction causes the vesicles to fuse with the terminal cell membrane and release the neurotransmitters into the synaptic cleft.

Question 10

What major toxin can block the fusion of vesicles with the cell membrane?

Answer 10

Botulinum Toxins

Question 11

How is ACh action terminated?

Answer 11

Acetylcholinesterase in the synaptic cleft cleaves acetylcholine into acetate and Choline. Choline may then be reabsorbed by the cell.

Question 12

Why aren’t many drugs targeted at acetylcholine release/production?

Answer 12

Because too many different kinds of nerves use acetylcholine. The action would not be specific enough and there would be adverse effects.

Question 13

What is the primary adrenergic neurotransmitter?

Answer 13

Norpepinephrine.

Question 14

What are some secondary adrenergic neurotransmitters?

Answer 14

Acetylcholine in sweat glands and vasodilatory fibers in skeletal muscle. As well as Dopamine in renal blood vessels.

Question 15

How is norepinephrine synthesized?

Answer 15

Tyrosine –> DOPA –> Dopamine –> Norepinephrine (inside vesicle

Question 16

What is the rate limiting step of Norepinephrine synthesis?

Answer 16

Tyrosine –> DOPA (by tyrosine hydroxylase)

Question 17

What inhibits tyrosine hydroxylase?

Answer 17

Metyrosine

Question 18

What is the action of monoamine oxidase (MAO) in the nerve ending?

Answer 18

MAO on mitochondria inactivates a portion of the Dopamine and the norepinephrine. MAO inhibitors will increase the stores of transmitters in the nerve terminals.

Question 19

What is the mechanism of reserpine?

Answer 19

Reserpine inhibits that transport of norepinephrine into vesicles. This depletes the neurotransmitter stores.

Question 20

How is norepinephrine released from adrenergic nerve terminals?

Answer 20

Calcium influx causes vSNARES to associate with tSNARES. This interaction causes the vesicles to fuse with the membrane and release the neurotransmitters.

Question 21

How is the action of norepinephrine terminated?

Answer 21

Norepinephrine action is terminated by reuptake rather than metabolism

Question 21

How is norepinephrine reabsorbed?

Answer 21

NET or DAT transporters move catecholamines from the cleft into the cells. Inside the cells the catecholamines may be metabolized by MAO or COMT.

Question 22

What drug can block the release of catecholamine filled vesicles?

Answer 22

Guanethidine

Question 22

What are cotransmitters?

Answer 22

Neurotransmitters other than the acetylcholine and norepinephrine that may be released from nerve endings. They typically function in modulation of synaptic interactions.

Question 23

Where are muscarinic receptors found?

Answer 23

(1) Heart (2) vascular endothelium (3) Smooth muscle (4) Presynaptic nerve terminals (5) Exocrine glands

Question 23

Where are nicotinic receptors located?

Answer 23

Nicotinic receptors are located on ion channels in ganglia and skeletal muscle end plates.

Question 24

Where are alpha adrenergic receptors found?

Answer 24

(1) vascular smooth muscle (2) Presynaptic nerve terminals (3) blood platelets (4) Lipocytes (5) Neurons.

Question 25

Where are beta adrenergic receptors found?

Answer 25

(1) Most smooth muscle (2) Cardiac muscle (3) some presynaptic nerve terminals (4) Lipocytes (5) Brain

Question 26

What is the specific location, mechanism and function of M1 (muscarinic) receptors?

Answer 26

M1 receptors are found in Nerve endings. They are Gq coupled which increases IP3 and starts a DAG cascade.

Question 27

What is the specific location, mechanism and function of M2 receptors?

Answer 27

M2 receptors are found in the heart and some nerve endings. They Gi coupled and decrease cAMP thus activating K+ channels.

Question 28

What is the specific location, mechanism and function of M3 receptors?

Answer 28

M3 receptors are found on effector cells in smooth muscle, glands, and endothelium. They are Gq coupled and increase IP3 which starts a DAG cascade.

Question 29

Where are Nn receptors located and how do they function?

Answer 29

Nn receptors are found in ANS ganglia and they function by opening ion channels and evoking action potentials.

Question 30

Where are Nm receptors located and how do they function?

Answer 30

Nm receptors are found in neuromuscular end plates. They open ion channels and evoke action potentials.

Question 31

Where are alpha1 receptors located and how do they function?

Answer 31

alpha1 receptors are found in effector tissues such as smooth muscle and glands. They are Gq mediated and cause an increase in intracellular Ca leading to contraction or secretion.

Question 32

Where are alpha 2 receptors located and how do they function?

Answer 32

Alpha 2 receptors are found in nerve endings and some smooth muscle. They are Gi mediated therefore they decrease cAMP. They function to decrease transmitter release in nerves or cause contraction in smooth muscle.

Question 33

Where are beta 1 receptors located and how do they function?

Answer 33

beta 1 receptors are located in the juxtaglomerular apparatus, and cardiac muscle. They are Gs mediated (increase cAMP) and they increase HR, contraction force, and renin release.

Question 34

Where are beta 2 receptors located and how do they function?

Answer 34

Beta 2 receptors are located in smooth muscle, liver, and heart. They are Gs mediated and they relax smooth muscle, increase glycogenolysis, and increase HR and contraction force.

Question 35

Where are beta 3 receptors located and how do they function?

Answer 35

Beta 3 receptors are located in adipose cells and are Gs mediated. They increase lipolysis.

Question 36

Where are most dopamine receptors located?

Answer 36

In the CNS.

Question 37

Where are D1 receptors located and what is their function?

Answer 37

D1 receptors are located in smooth muscle. They are Gs mediated and they relax renal vascular smooth muscle.

Question 38

Where are beta 3 receptors located and how do they function?

Answer 38

Beta 3 receptors are located in adipose cells and are Gs mediated. They increase lipolysis.

Question 39

Where are most dopamine receptors located?

Answer 39

In the CNS.

Question 40

Where are D1 receptors located and what is their function?

Answer 40

D1 receptors are located in smooth muscle. They are Gs mediated and they relax renal vascular smooth muscle.

Question 41

Which branch of the ANS is dominant in the eye? or in the heart?

Answer 41

The parasympathetic nervous system is the dominant input in both the heart and the eye.

Question 42

How doe local feedback work in nerve terminals?

Answer 42

Nerve terminals often have autoreceptors that bind neurotransmitter released from that same cell. These receptors then either stimulate or inhibit the further release of neurotransmitter from that terminal.