Pharmacodynamics and Autonomic Pharmacology I

Question 1

Potency

Answer 1

Question 2

Partial agonists

Answer 2

give a partial effect, even at saturating concentrations.

Question 3

Neutral agonists

Answer 3

Does nothing to the activity of the target even though it binds

Question 4

Inverse agonists

Answer 4

Suppress the basal level of signaling of a biomolecule.

Question 5

The autonomic nervous system is activated mainly by centers located in the. . .

Answer 5

spinal cord, brain stem, and hypothalamus.

Portions of the cerebral cortex may also send signals down to these three regions to regulate their activity.

Question 6

Characteristics of sympathetic activation

Answer 6

• Activation of the reticular system (alertness)
• Feeling of energy and euphoria and ignorance of pain (endorphin release)
• Increased heart rate, breathing rate, deepness of breath (mediated by pons and medulla oblongata)
• Elevation of muscle tone
• Activation of sweat glands
• Mobilization of glycogen and triglyceride energy stores (glucagon secretion)

Question 7

Characteristics of parasympathetic activation

Answer 7

• Constriction of the pupils
• Secretion by digestive glands
• Secretion of insulin and anabolism
• Changes in blood flow associated with sexual arousal
• Increased gut peristalsis
• Loosening of rectal and internal urinary sphinctres
• Constriction of respiratory passages
• Reduction in heart rate and contraction force

Question 8

Origin of a somatic motor signal

Answer 8

Question 9

Origin of an autonomic motor signal

Answer 9

Question 10

Sympathetic motor neurons synapse in ____. Parasympathetic motor neurons synapse in ____.

Answer 10

Sympathetic motor neurons synapse in sympathetic chain ganglia. Parasympathetic motor neurons synapse in ganglia in the vicinity of the tissues they innervate.

Question 11

In the somatic motor system, muscle relies on innervation for ____.

In the autonomic motor system, muscle relies on innervation for ____.

Answer 11

In the somatic motor system, muscle relies on innervation for all activity.

In the autonomic motor system, muscle relies on innervation for tuning activity up or down.

Question 12

The one exception to the sympathetic = adrenergic rule

Answer 12

Sweat glands are innervated by sympathetic cholinergic neurons and utilize the muscarinic receptor.

Question 13

Thoracolumbar system

Answer 13

Aka the sympathetic chain, associated ganglia, and innervated organs

So named because it arises in T1 and goes until L2/L3.

Question 14

Craniosacral system

Answer 14

Aka the parasympathetics of the brain stem (CN III, VII, IX, X) and sacral vertebrae, associated ganglia, and innervated organs.

Question 15

Cranial nerve X

Answer 15

Better known as the vagus nerve.

Provides parasympathetic innervation to the major organs in the chest and abdomen, including the heart, tracheobronchial tree, kidneys, and GI system down to the proximal colon.

Parasympathetic nerves originating in the sacral region of the spinal cord innervate the remainder of the colon, urinary bladder, and genitalia.

Question 16

Catecholamine biosynthesis pathway

Answer 16

Question 17

Adrenergic neuron diagram

Answer 17

Question 18

Cocaine

Answer 18

Norepinephrine transporter blocker

Prevents norepinephrine reuptake

Question 19

Reserpine

Answer 19

Blocks re-loading of catecholaminergic granules in adrenergic neurons via the VMAT (Vesicular monoamine transporter) channel.

This prevents only re-loading of granules, reuptake is not affected.

Question 20

α₁ receptors

Answer 20

Expressed in:

Smooth muscle, heart, liver

Effects:

Contraction of vacsular and genitourinary smooth muscle, relaxation of intestinal smooth muscle. Increased cardiac inotropy (contraction force), glycogenolysis and gluconeogenesis in liver.

Mediators:

G_q/G_i/G_o

Question 21

β₁ receptors

Answer 21

Expressed in:

Heart, renal juxtaglomerular cells

Effects:

Tachycardia, increased cardiac inotropy, increased atrioventricular node conduction velocity, renin secretion in juxtaglomerular cells.

Mediators:

G_s

Question 22

α₂ receptors

Answer 22

Expressed in:

Pancreatic β cells, platelets, nerves, vascular smooth muscle

Effects:

Decreased insulin secretion, aggregation of platelets, decreased norepinephrine release in adrenergic neurons, contraction of vascular smooth muscle

Mediators:

G_i/G_o

Question 23

β₂ receptors

Answer 23

Expressed in:

Smooth muscle, liver, skeletal muscle

Effects:

Smooth muscle relaxation, glycogenolysis and gluconeogenesis in liver, glyogenolysis and K⁺ uptake in skeletal muscle.

Mediators:

G_s

Question 24

β₃ receptors

Answer 24

Expressed in:

Adipose tissue

Effects:

Lipolysis

Mediators:

G_s

Question 25

Adrenergic receptor agonists

Answer 25

Question 26

Calcium-induced calcium release

Answer 26

Question 27

Systole is mediated by ____, while diastole is mediated by ____.

Answer 27

Systole is mediated by rapid rise in cardiac myocyte calcium levels, while diastole is mediated by ATP-dependent calcium pumps which remove calcium from cardiac myocytes.

Question 28

Phospholamban

Answer 28

Binds to and inhibits the SERCA pump in cardiac myocytes.

Part of the system that regulates the tuning of cardiac contractions by the autonomic nervous system.

Question 29

Activation of β₁ cardiac receptors in cardiac myoctes leads to. . .

Answer 29

Activation of adenylyl cyclase and Protein Kinase A (PKA). Downstream, this causes phosphorylation of L-type calcium channels, NCX channels, RyR2 receptors, and phospholamban.

The phosphorylation of these proteins leads to a higher level of calcium in the cytoplasm, which causes a greater degree of contraction during systole.

The phosphorylation of phospholamban blocks its ability to inhibit SERCA, allowing SERCA to move calcium faster and counterbalancing the greater systolic pressure with a greater diastolic pressure.

Question 30

Sympathetic stimulation induces ___ in the GI tract.

Answer 30

Sympathetic stimulation induces muscle relaxation in the GI tract.

Question 31

Where does muscle relaxation require ATP?

Answer 31

Powering the Calcium ATPase to pump calcium back outside of the cell or into the SR.

ATP is sequestered by the tropomyosin relaxation, but is not consumed.