Pharmacology Ch: 18

· Alpha-2 Receptors are what type of receptor? · They are primarily found in what tissue?

(Are one type of Adrenergic Receptors) o Sometimes called autoreceptors because they modulate the release of NT from the presynaptic terminal § They decrease release of norepinephrine and other chemicals (negative feedback) o Primary location: CNS inhibitory synapses, GI tracts, pancreas, some arterioles § Spinal interneurons: can decrease neuronal excitability and thereby decrease muscle hyperexcitability conditions such as spasticity

· Parasympathetic: 3 areas and name of division?

craniosacral division (midbrain, brainstem, and sacral areas)

What kind of neurons (sympathetic or parasympathetic) innervate the Adrenal medulla?

· Adrenal medulla is innervated by sympathetic neurons.

· Adrenal releases of epinephrine and norepinephrine tend to prolong what effect?

· Adrenal releases of epinephrine and norepinephrine tends to prolong the effect of the sympathetic reaction. o The adrenal medulla serves to augment the sympathetic division.

What are the 2 types of Autonomic Receptors?

· Cholinergic receptors are located at acetylcholine synapses. · Adrenergic receptors are located at norepinephrine synapses.

· Cholinergic receptors are located at _____ synapses. · Adrenergic receptors are located at _____ synapses.

· Cholinergic receptors are located at acetylcholine synapses. · Adrenergic receptors are located at norepinephrine synapses.

The Cortex and limbic system influence autonomic function by interacting with what three structures?

· Cortex and limbic system: also influence autonomic function by interacting with the hypothalamus, brainstem, and spinal cord.

What cranial nerves are part of the Parasympathetic divisions cranial portion?

· Cranial portion: neurons exit the CNS via cranial nerves III, VII, IX, and X

Most sympathetic postganglionic neurons use norepinephrine: and so, are receptors that are adrenergic in nature. What is the exception to this rule? What neurotransmitter is used with the exceptions?

· EXCEPTION: Presence of certain sympathetic postganglionic fibers that use acetylcholine. o These mostly innervate sweat glands and certain blood vessels in the face, neck, and lower extremities.

The Hypothalamus is important in regulating what 4 things, in what portion of the nervous system?

The ANS: body temp, water balance, and energy metabolism.

o What system do some consider this to be a third ANS division?

· Enteric nervous system: GI tract (Other two are Sympathetic / Parasympathetic Divisions)

What is the neurotransmitter at the parasympathetic postganglionic-effector cell synapse?

acetylcholine

What is the transmitter at the sympathetic postganglionic-effector cell?

(usually) norepinephrine

What does stimulation of the sympathetic nervous system do to: - cardiac output, - visceral blood flow, and - cellular metabolism?

- Causes increased cardiac output, - decreased visceral blood flow (to leave more blood for skeletal muscle), and - increased cellular metabolism.

- Enteric nervous system: area? - What types of system "components" does it include? - What is it often considered part of?

- GI tract. - Contains both sympathetic and parasympathetic components. - Some consider this to be a third ANS division. (often considered part of the two primary ANS divisions)

What nonadrenergic, noncholinergic neurotransmitters may also be present in the ANS?

- Purinergic Substances: Adenosine and adenosine triphosphate are possible transmitters in the GI tract, cardiovascular system, and several other organs: --- Neuropeptide Y, vasoactive intestinal polypeptide, calcitonin gene-related peoptide, orexin, cholecystokinin, and angiotensin II may possibly participate in autonomic control (may act as cotransmitters).

Layout of Preganglionic and Postganglionic Neurons of the Somatic nervous system: Where does it synapse?

- Uses one neuron to reach from spinal cord to skeletal muscle. - Does not synapse until it reaches the muscle cell.

o Autonomic reflexes are based on the what 4 step strategy?

1 - A peripheral sensor monitors change. 2 - Information is relayed to the CNS and integrated. 3 - An adjustment is made in the autonomic discharge to the specific organ or tissue. 4 - This alters activity to return physiologic function back to the appropriate level.

What are the 4 sites of synaptic transmission of the autonomic system?

1 o Between preganglionic and postganglionic neurons in the sympathetic division. 2 o Between preganglionic and postganglionic neurons in the parasympathetic division. 3 o Between the sympathetic postganglionic neuron and the effector cell. 4 o Parasympathetic postganglionic-effector cell synapse.

What are the 6 Purinergic Substances which may possibly act as cotransmitters in autonomic control?

1: Neuropeptide Y, 2: vasoactive intestinal polypeptide, 3: calcitonin gene-related peoptide, 4: orexin, 5: cholecystokinin, and 6: angiotensin II.

A muscarinic antagonist that decreases activity in the GI tract may also do what in the lungs and urinary system?

A muscarinic antagonist that decreases activity in the GI tract may also decrease bronchial secretions in the lungs and also cause urinary retention. (No drug is entirely specific for only one receptor subtype.)

What are the two main Autonomic Neurotransmitters?

Acetylcholine and Norepinephrine.

Adrenergic Receptors are located at what synapse? This synapse is between what and what?

Adrenergic Receptors: o Found on the effector cell in the innervated tissue. o Located at the terminal synapse between sympathetic postganglionic adrenergic neurons and the tissue they supply.

What are the five primary types of Adrenergic Receptors?

Adrenergic Receptors: · Alpha-1 Receptors · Alpha-2 Receptors · Beta-1 Receptors · Beta-2 Receptors · Beta-3 Receptors

All _____ neurons and ____ _____ neurons have receptors that are cholinergic in nature.

All preganglionic neurons and parasympathetic postganglionic neurons have receptors that are cholinergic in nature.

All preganglionic neurons and parasympathetic postganglionic neurons have receptors that are ____ in nature.

All preganglionic neurons and parasympathetic postganglionic neurons have receptors that are cholinergic in nature.

· Beta-1 Receptors are what type of receptor? · They are primarily found in what tissue? · They function through the use of what class of drugs?

Are one type of Adrenergic Receptors. Primary location: heart and kidneys. Function through the use of beta-blockers.

The following 4 steps describe what process? 1 - A peripheral sensor monitors change. 2 - Information is relayed to the CNS and integrated. 3 - An adjustment is made in the autonomic discharge to the specific organ or tissue. 4 - This alters activity to return physiologic function back to the appropriate level.

Autonomic reflexes Example of an autonomic reflex: Baroreceptor reflex (Important in the control of BP) Compensatory increase occurs in sympathetic discharge to the heart and peripheral vasculature, and parasympathetic outflow to the heart is decreased Result: increase in cardiac output and an increase in peripheral vascular resistance (brings BP back to appropriate level)

Describe the baroreceptor reflex:

Baroreceptor Reflex: 1 - activated by (momentary) changes in blood pressure detected by baroreceptors (stretch receptors) in aortic arch & carotid sinuses. 2 - increased blood pressure stretches these receptors, increasing action potential to vasomotor & cardiac control centers in medulla. 3 - Compensatory increase occurs in sympathetic discharge to the heart and peripheral vasculature, and parasympathetic outflow to the heart is decreased. Result: increase in cardiac output and an increase in peripheral vascular resistance (brings BP back to appropriate level) (most sensitive to drops in pressure. )

Are Peripheral arterioles innervated by the sympathetic or parasympathetic divisions?

Peripheral arterioles only innervated by sympathetic

Cholinergic Receptors are Subdivided into ____ and ____ .

Cholinergic Receptors are Subdivided into nicotinic and muscarinic.

Adrenergic Receptors are divided into what two types? · Divided into alpha and beta receptors o Found on the effector cell in the innervated tissue o Located at the terminal synapse between sympathetic postganglionic adrenergic neurons and the tissue they supply

Divided into alpha and beta receptors

What type of reflex is the Baroreceptor reflex? Why is this reflex Important?

Example of an autonomic reflex: The Baroreceptor reflex is Important in the control of BP.

What are the five subtypes of Muscarinic cholinergic receptors which are located at all of the synapses between cholinergic postganglionic neurons and the terminal effector cell? Where are they predominantly located? What do they ultimately mediate?

Five subtypes: · M1, M4, and M5: abundant through the CNS. · M2: predominant in the heart. · M3: bladder detrusor muscle and helps control pancreatic insulin release and other peripheral metabolic responses. Ultimately mediate the effect on the tissue itself.

Adrenergic Receptors are Found on the what cells? In what tissue?

Found on the effector cell in the innervated tissue.

What are the relative lengths of the preganglionic, and postganglionic neurons in the Parasympathetic nervous system?

Parasympathetic: long preganglionic, short postganglionic

What portion of the autonomic nervous system has long preganglionic, short postganglionic neurons?

Parasympathetic: long preganglionic, short postganglionic

Where are the two locations of synapses to which the Muscarinic cholinergic receptors belong? What are the two types?

Located at all of the synapses between cholinergic postganglionic neurons and the terminal effector cell. 1. Parasympathetic terminal synapse and 2. Sympathetic postganglionic cholinergic fibers that supply sweat glands and some specialized blood vessels.

Most sympathetic postganglionic neurons use _____ and so, are receptors that are ____ in nature.

Most sympathetic postganglionic neurons use norepinephrine: and so, are receptors that are adrenergic in nature. · EXCEPTION: presence of certain sympathetic postganglionic fibers that use acetylcholine o Innervate sweat glands and certain blood vessels in the face, neck, and lower extremities.

Most ______ postganglionic neurons use norepinephrine: and so, are receptors that are adrenergic in nature.

Most sympathetic postganglionic neurons use norepinephrine: and so, are receptors that are adrenergic in nature. ·EXCEPTION: presence of certain sympathetic postganglionic fibers that use acetylcholine o Innervate sweat glands and certain blood vessels in the face, neck, and lower extremities.

How are the Cranial Portions of the Parasympathetic Division Organized?

Parasympathetic Organization · Cranial portion: neurons exit the CNS via cranial nerves III, VII, IX, and X · Same as sympathetic, preganglionic neurons synapse in the periphery with a postganglionic fiber o Usually takes place in a terminal ganglion that is located directly in the organ or tissue supplied by the postganglionic neuron

Is it correct to say the sympathetic division is always excitatory and the parasympathetic division is always inhibitory? What easy example defends your answer?

No it is NOT correct to say the sympathetic division is ALWAYS excitatory and the parasympathetic division is ALWAYS inhibitory. Ex: GI tract, in which the Parasympathetic stimulates intestinal motility while sympathetic decreases motility.

How do Preganglionic fibers of the Sympathetic division leave the spinal cord? Where do they end?

Preganglionic fibers of the sympathetic division leave spinal cord via the ventral root of the spinal nerve and end in a sympathetic ganglion.

Two divisions of the ANS?

Sympathetic / Parasympathetic Divisions

What are the relative lengths of the preganglionic, and postganglionic neurons in the Sympathetic nervous system?

Sympathetic: short preganglionic, long postganglionic

What portion of the autonomic nervous system has short preganglionic, long postganglionic neurons?

Sympathetic: short preganglionic, long postganglionic

The predominant receptor in the bronchioles is the ______ receptor, but some ______ receptors are also present. So, A pt. using a ______-specific drug such as metaprolol may experience some _____ effects as well.

The predominant receptor in the bronchioles is the beta-2 receptor, but some beta-1 receptors are also present. So, A pt. using a beta-1-specific drug such as metaprolol may experience some respiratory effects as well.

Do drugs that act on the CNS have the potential to alter autonomic function? Why or why not?

Yes, they do this by influencing the Cortex and limbic system, which influences autonomic function by interacting with the hypothalamus, brainstem, and spinal cord.

o ANS:

bodily functions that are largely involuntary or automatic. Ex: BP, digestion, elimination, thermoregulation

o Beta-3 Receptors are what type of receptor? o They are primarily found in what tissue? o What do they increase and inhibit?

o Are one type of Adrenergic Receptors. o Primary location: adipose tissue, heart, and bladder. o Increase lipolysis, and Generally inhibit muscular contraction in these tissues.

· Alpha-1 Receptors are what type of receptor? · They are primarily found in what tissue?

o Are one type of Adrenergic Receptors. o Primary location: smooth muscle. (Peripheral vasculature, intestinal wall, radial muscle of the iris, ureters, urinary sphincter, and spleen capsule)

o Beta-2 Receptors are what type of receptor? o They are primarily found in what tissue? o Especially important in management of what condition? o Responsible for mediating changes in the metabolism of what tissues?

o Are one type of Adrenergic Receptors. o Primary location: bronchiole smooth muscle, smooth muscle of certain vasculatures, gallbladder, and uterus. o Especially important in management of asthma. o Responsible for mediating changes in the metabolism of skeletal muscle and liver cells.

What is the Pharmacological Significance of Autonomic Receptors, in relation to Beta-1 antagonist drugs? What is the main disadvantage of drugs like this in relation to their effect?

o Beta-1 antagonist: slows down heart rate and decrease myocardial activity. o A drug that binds preferentially to one receptor subtype will bind to that receptor at all of its locations.

Where are the majority of the efferent components of the parasympathetic division found?

o CN X (vagus nerve) contains approximately 75% of the efferent component of the entire parasympathetic division

What are the two types of autonomic receptors, divided into two different subtypes each?

o Cholinergic: nicotinic and muscarinic. o Adrenergic: alpha and beta.

o During normal resting conditions, the adrenal medulla secretes what? o During periods of stress how does this change?

o During normal resting conditions, the adrenal medulla secretes small amounts of norepinephrine. o During periods of stress, there is a general increase in sympathetic discharge which causes increased release of epinephrine and norepinephrine.

At what level is the emptying of bowel and bladder integrated?

o Emptying of bowel and bladder: integrated at the level of the sacral spinal cord

Is epinephrine or norepinephrine more effective on cellular metabolism and cardiac function? Why?

o Epinephrine: increases cardiac function and cellular metabolism to a greater extent. - Because it has higher affinity for receptors (binds more readily to the beta subtype adrenergic receptors).

What type of nerve fibers do the pre and post ganglionic neurons of the Autonomic (Sympathetic/Parasympathetic) nervous system have? Where does the synapse occur?

o First neuron: preganglionic § Myelinated type B fibers o Second neuron: postganglionic § Small, unmyelinated type C fibers o Synapse is usually in one of the autonomic ganglia

o Many side effects and beneficial effects of autonomic drugs can be attributed to the interaction of various agents with different ______ .

o Many side effects and beneficial effects of autonomic drugs can be attributed to the interaction of various agents with different receptors.

o ______ ______ receptors: located at all of the synapses between cholinergic postganglionic neurons and the terminal effector cell.

o Muscarinic cholinergic receptors: located at all of the synapses between cholinergic postganglionic neurons and the terminal effector cell. (parasympathetic terminal synapse and sympathetic postganglionic cholinergic fibers that supply sweat glands and some specialized blood vessels)

o Nicotinic cholinergic receptors: located at the ______ in both the sympathetic and parasympathetic pathways.

o Nicotinic cholinergic receptors: located at the junction between preganglionic and postganglionic neurons in both the sympathetic and parasympathetic pathways. Any drug that affects these nicotinic receptors will affect activity in both divisions of the ANS.

o ______ ______ receptors: located at the junction between preganglionic and postganglionic neurons in both the sympathetic and parasympathetic pathways. Any drug that affects these ______ receptors will affect activity in both divisions of the ANS.

o Nicotinic cholinergic receptors: located at the junction between preganglionic and postganglionic neurons in both the sympathetic and parasympathetic pathways. Any drug that affects these nicotinic receptors will affect activity in both divisions of the ANS.

o No drug is entirely ______ for only one receptor subtype. o Organs and tissues in the body do not contain only _______ ______ subtype.

o No drug is entirely specific for only one receptor subtype. o Organs and tissues in the body do not contain only one receptor subtype.

o Parasympathetic discharge does what to the heart and generally brings about changes that encourage what?.

o Parasympathetic discharge slows down the heart and generally brings about changes that encourage inactivity.

The Stimulation of muscarinic receptors on the myocardium will do what to heart rate, smooth muscle contraction in the intestinal wall, and glandular secretion in the intestinal wall?

o Stimulation of muscarinic receptors on the myocardium will: - Decrease the heart rate. - Increases in smooth muscle contraction in intestines. - Increase glandular secretion in the intestinal wall.

o Stimulation of ______ receptors on the myocardium: decrease the heart rate, increases in smooth muscle contraction and glandular secretion in the intestinal wall.

o Stimulation of muscarinic receptors on the myocardium: decrease the heart rate, increases in smooth muscle contraction and glandular secretion in the intestinal wall.

How disbursed among tissues are the effects of Parasympathetic discharge typically?

o Tends to be fairly discrete and affect only one organ or tissue.

o Parasympathetic discharge does what to intestinal digestion and absorption?

o Tends to increase intestinal digestion and absorption (store energy for future).

The adrenal medulla serves to augment what division?

o The adrenal medulla serves to augment the sympathetic division. · Adrenal releases of epinephrine and norepinephrine tends to prolong the effect of the sympathetic reaction.

o Body temperature is monitored by what receptors? o Where are these receptors? o What body structure makes the appropriate adjustments to temperature?

o Thermoreceptors, o The receptors are in the skin, viscera, and hypothalamus. o Hypothalamus makes the appropriate adjustments (such as sweating being increased or decreased and blood flow being redistributed)

o Somatic:

voluntary function (skeletal muscle)

Two parts of the nervous system?

somatic and autonomic

· Sympathetic Nervous System: 2 Areas and name of division?

thoracolumbar division (thoracic/upper lumbar)

Layout of the Autonomic (Sympathetic/Parasympathetic) Preganglionic and Postganglionic Neurons: Where does it synapse?

use two neurons in sequence to reach from CNS to the peripheral organ being supplied. o Synapse is usually in one of the autonomic ganglia.

Is the heart innervated by the Sympathetic or Parasympathetic divisions of the nervous system? What significance does this have?

· Heart: innervated by both divisions o If innervated by both, a physiological antagonism usually exists (one division increases, while the other decreases function) (Other tissues may be supplied by only one division)

· Most of the autonomic control is manifested through....

· Most of the autonomic control is manifested through autonomic reflexes.

At what point would a sympathetic neuron carrying a signal split that signal to many neurons? What happens to the many neurons the signal has been split to?

· One sympathetic preganglionic neuron may synapse with many postganglionic fibers. o The postganglionic fiber then leaves the ganglion to travel to the effector tissue it supplies.

Stimulation of the Parasympathetic division tends to do what to body energy?

· Parasympathetic division tends to conserve energy and store it.

What does the Sympathetic division tend to do to body energy? What situational stimulus increases sympathetic discharge?

· Sympathetic division tends to mobilize body energy. o Sympathetic discharge is increased with stressful situations. o Causes increased cardiac output, decreased visceral blood flow (leaves more blood for skeletal muscle), increased cellular metabolism, etc. o Results in more massive and diffuse reaction Effects are commonly observed on many tissues throughout the body

· Sympathetic ganglia located in what 3 areas:

· Sympathetic ganglia located in 3 areas: o Paired paravertebral: lie bilaterally on either side of the vertebral column. o Unpaired prevertebral: lie anterior to the aorta. o Terminal ganglia: lie directly in the tissue that is innervated.

What are the three types of sympathetic ganglia?

· Sympathetic ganglia types are divided into 3 locations: o Paired paravertebral: lie bilaterally on either side of the vertebral column. o Unpaired prevertebral: lie anterior to the aorta. o Terminal ganglia: lie directly in the tissue that is innervated.

What are the main 2 products made by the Adrenal Medulla? How widely are these dispersed and how quickly are they removed from body tissues?

· Synthesizes and secretes norepinephrine and epinephrine. o They tend to circulate extensively throughout the body because they are released into the bloodstream and are removed more slowly than locally produced

What are the ratios of the substances produced by the adrenal medulla?

· Synthesizes and secretes norepinephrine and epinephrine: o 20% norepinephrine and 80% epinephrine.

What is the Transmitter at the preganglionic-postganglionic synapse in both divisions?

· Transmitter at the preganglionic-postganglionic synapse in both divisions: acetylcholine. (Also the neurotransmitter at the parasympathetic postganglionic-effector cell synapse).

What tissues of the body are innervated by the ANS?

· Virtually all tissues in the body are in some way innervated by the ANS, except skeletal muscle.