Intro To Autonomic Pharmacology

Front 1

What are four similarities between the nervous system and the endocrine system?

Back 1

1. both have a high-level integration in the brain
2. both influence function at distant sites
3. Extensive neg feedback in both
4. both use chemicals to transmit info

Front 2

Quick facts about the Somatic nervous system

Back 2

-synapses w/in the cerebrospinal axis result in spinal efferent nerves
-in the periphery it consists of nerves and NMJ
-no ganglia
-interruption of efferents result in paralysis and atrophy

Front 3

Quick facts about the Autonomic nervous system

Back 3

-heart, glands, visceral organs, SM
-spinal efferents form synapses in peripheral ganglia
-some spontaneous activity independent of intact innervation

Front 4

Where do preganglionic sympathetic axon fibers arise from?

Back 4

-the intermediolateral columns of the spinal cord and exit from the CNS through thoracic and lumbar nerves

Front 5

What are the three locations where sympathetic ganglia are found?

Back 5

1. paravertebral - 22 pairs are connected by nerve trunks and form lateral chains
2. prevertebral- located on the ventral surface of the vert column
3. terminal - few, lie near the organ they innervate like the bladder, rectum and cervical ganglia

Front 6

Sympathetic postganglionic fibers

Back 6

-most release NE
-but also some release ACh or DA
-cotransmitters are released along w/ the primary neurotransmitter:
-ATP, NPY, and Substance P

Front 7

Adrenal medulla

Back 7

-modified sympathetic ganglion whose preganglionic symp fibers form synapses on the adrenal chromaffin cells
-these release ACh which binds to nic receptors on surface of chromaffin cells resulting in the secretion of E or NE

Front 8

Preganglionic parasympathetic fibers

Back 8

-arise from the midbrain, medull oblongata and the sacral region of the SC
-most terminate on ganglion cells distributed diffusely or in networks w/in the walls of the innervated organs, or right outside the organ

Front 9

Postganglionic parasympathetic fibers

Back 9

all release ACh which binds to muscarinic receptors on the target organ and elicit a response

Front 10

Cholinergic neurons in the autonomic and somatic nervous systems

Back 10

1. All preganglionic neurons (both para and symp)
2. all somatic motor neurons
3. Postgang parasymp fibers
4. Postgang symp fibers that innervate sweat glands

Front 11

Adrenergic

Back 11

-neurons that release NE or Epi
-MOST SYMPATHETIC POSTGANG NEURONS ARE ADRENERGIC

Front 12

What are the 5 majors steps in the Cholinergic Transmission

Back 12

1. Choline uptake
2. ACh uptake vesicles
3. Vesicle fusion
4. Cholinergic receptors
5. ACh degradation

Front 13

Choline uptake

Back 13

-catalytic action of choline acetyltransferase (ChAT) choline and acetyl-CoA -->ACh
-Acetyl from mito, choline is AT from EC space through Na+ dep carrier
-Hemicholinium can block

Front 14

ACh uptake vesicles

Back 14

-once synthesized it is transported into synaptic vesicles through a vesicular transporter that pumps out protons while loading w/ ACh
-this antiporter can be inhib by Vesamicol--> decrease ACh release

Front 15

Vesicle fusion

Back 15

-AP -->opening of volt gated Ca++ channels-->rise in terminal [Ca++]--> fusion of vesicles w/ the synaptic mem
-requires the action of vesicular associated mem prots (VAMPs) and synaptosome assoc prots (SNAPs)
-BOTOX blocks act, no vesicle fus

Front 16

Autoreceptors

Back 16

-cholinergic receptors in presynaptic cholinergic nerve terminals
-binding of ACh --> decrease in ACh release

Front 17

Heteroreceptors

Back 17

-cholinergic receptors that are present at adrenergic presynaptic nerve terminals
-activation results in a decrease in adrenergic transmitter release

Front 18

ACh degradation

Back 18

-AChE splits ACh into choline and acetate
-choline recycled into the terminal

Front 19

What are the major steps of Adrenergic Transmission?

Back 19

1. Tyrosine uptake
2. Tyrosine hydroxylase
3. Dopamine synthesis
4. Dopamine transport
5. NE synthesis
6. NE release
7. Adrenergic receptors
8. Termination of transmission
9. NE degradation

Front 20

Tyrosine uptake

Back 20

-1st step in adrenergic neurotrans is synthesis of catecholamines
-occurs inside adrenergic terminals and requires uptake of tyrosine from EC space via Na+ dependent carrier protein

Front 21

Tyrosine hydroxylase

Back 21

-1st and rate-lim step in catecholamine synthesis
-hydroxylation of tyrosine to dopa by tyrosine hydroxylase
-can be inhib by tyrosine analog metyrosine, thus no catecholamine synth and no adrenergic neurotrans

Front 22

Dopamine synthesis

Back 22

-dopa is decarboylated to dopamine by dopa decarboxylase

Front 23

Dopamine transport

Back 23

-DA is trans into vesicles by a high affinity catecholamine carrier
-this carrier can also transport NE that has been recycled from previous synaptic activity
-Reserpine and MAO are bad

Front 24

Reserpine

Back 24

-inhibits the high affinity catecholamine carrier
-results in cytoplasmic accum of DA and NE

Front 25

Cytoplasmic Monoamine Oxidase

Back 25

MAO
-rapidly degrades DA and NE that accumulate in the cytoplasm

Front 26

NE synthesis

Back 26

-dopamine is converted to NE w/in the vesicles by dopamine-B-hydroxylase

*in adrenal medulla, NE is further converted to EPI by phenylethanolamine-N-methyltransferase

Front 27

NE release

Back 27

-AP reaches the terminal voltage gated Ca++ channels and then fusion of vesicles w/ plasma membrane--> exocytosis of NE
-betylium and guanethidine can block the fusion

Front 28

Termination of transmission

Back 28

-primarily accomp by reuptake of NT into the nerve terminals
-transport occurs through a specific monoamine transporter that can be blocked by tricyclic antidepressents and cocaine

Front 29

NE degradation

Back 29

-some diffusion away from the synapse
-catecholamines can be degraded by MAO as well as catechol-o-methyltransferase
*minor and not primary mechanism for the termination of synaptic trans

Front 30

Sympathomimetics

Back 30

-agents that cause the same physiological responses as endogenous catecholamines like NE or epi

Front 31

Examples of Sympathomimetics

Back 31

-albuterol--> directly act adr receptors
-tyramine and amphetamine have a similar structure as NE (don't actually directly activate receptors but cause an increase in NE release through non-vesc exocytosis)

Front 32

Major effects of activation of sympathetic nervous system

Back 32

-increase in BP, HR, resp, blood to skeletal muscle, brain, lungs, heart
-pupil and bronchiole dilation
-piloerection
-energy: stim of glycogenolysis, gluconeogenesis,and lipolysis
-reduced blood Q to GI, kidneys

Front 33

Sympathetic and parasympathetic activation of the:

Eye--> Pupillary response

Back 33

Symp: Contracts radial muscle - dilation mydriasis ALPHA 1

Para: contracts circular/sphincter muscle constriction (miosis) M3

Front 34

Sympathetic and parasympathetic activation of the:

Eye--> Lenticular response (accommodation)

Back 34

S: Relaxes ciliary musc - far vision B2

P: contracts ciliary muscle - near vision M3

Front 35

Sympathetic activation of the:

Eye--> Aqueous Humor

Back 35

-incr secretion of aq humor from ciliary epi B2
-increased intraocular pressure B2
-decreased prod of aq humor (presynap inhibition) lowers IOP- A2
-increased outflow of aq humor (lowers IOP) A and B

Front 36

Parasympathetic activation of the:

Eye--> Aqueous Humor

Back 36

-contraction of ciliary muscle increases the P on the trabecular meshwork, opening its pores, increasing the outflow of aq humor into the canal of Schelmm--> decrease in IOP -->(M3)

Front 37

Sympathetic and parasympathetic activation of the:

Heart--> SA node

Back 37

s: accelerates HR (+ly chronotropic)
(B1> B2)

P: decelerates HR (-ly chronotropic) (M2>>M3)

Front 38

Sympathetic and parasympathetic activation of the:

Heart--> Atria

Back 38

s: increase contractility and conduction velocity (B1>B2)

p: decrease contractility and shortened AP duration (M2>>M3)

Front 39

Sympathetic and parasympathetic activation of the:

Heart--> AV node

Back 39

s: increased automaticity and conduction velocity (B1>B2)

p: decreased conduction velocity; AV block (M2>>M3)

Front 40

Sympathetic and parasympathetic activation of the:

Heart--> Ectopic pacemakers

Back 40

s: accelerates HR (B1>B2)

p: no effect

Front 41

Sympathetic and parasympathetic activation of the:

Heart--> Contractility

Back 41

s: increases force of contraction (+ly intropic) (B1>B2)

pL decreases in atria only (M2>>M3)

Front 42

Sympathetic and parasympathetic activation of the:

Blood vessels--> Skin and splanchnic

Back 42

s: contracts (A1)

p: no effect

Front 43

Sympathetic and parasympathetic activation of the:

Blood vessels--> Skeletal M

Back 43

s: relaxes (B2)
-contracts (A1)
-some sympathetic cholinergic fibers lead to dilation

p: no effect

Front 44

Sympathetic and parasympathetic activation of the:

Blood vessels--> Endothelium

Back 44

S: no effect

P: relaxes vasodilation (M3)

Front 45

Release of NO or EDRF (endothelium derived relaxing factor) from endothelium diffuses to muscle where?

Back 45

-it activates guanylyl cyclase increasing cGMP--> inhib Ca++ release from SR and preventing muscle contraction
-only can be caused by circulating cholinergic agonists

Front 46

Sympathetic and parasympathetic activation of the:

Lung--> Bronchiolar and tracheal SM

Back 46

s: relaxes, bronchodilation (B2)

p: contraction, bronchoconstriction (M3)

Front 47

Sympathetic and parasympathetic activation of the:

Lung--> Bronchial glands

Back 47

s: decreased secretion (A1)
-increased secretion (B2)

p: stimulation (M3, M2)

Front 48

Sympathetic and parasympathetic activation of the:

GI Tract--> SM walls

Back 48

s: relaxation; may be due to presynaptic inhib of ACh release in parasymp terminals (A2,B2)

P: contraction - increased peristalsis (M3)

Front 49

Sympathetic and parasympathetic activation of the:

GI Tract--> SM sphincters

Back 49

S: contraction (A1)


P: Relaxation (M3)

Front 50

Sympathetic and parasympathetic activation of the:

GI Tract--> Secretion

Back 50

s: inhib (A2)

p: increases secretions (M3)

Front 51

Sympathetic and parasympathetic activation of the:

GI Tract--> Myenteric plexus

Back 51

s: no effect

p: potentiates act resulting in further increases in SM tone and contractility (M1)

Front 52

Sympathetic and parasympathetic activation of the:

Genitourinary SM--> Bladder Wall

Back 52

s: relaxation (B2)

p: contraction (M3)

Front 53

Sympathetic and parasympathetic activation of the:

Genitourinary SM--> Sphincter

Back 53

s: contraction (a1)

p: relaxation (M3)

Front 54

Sympathetic and parasympathetic activation of the:

Genitourinary SM--> Uterus

Back 54

S:
relaxes (non-preg this dominates) (B2)
-contracts (only in pregos) (A1)

p: variable effects

Front 55

Sympathetic and parasympathetic activation of the:

Genitourinary SM--> Penis

Back 55

s: ejac (A1)

p: erection (NO release) (M3)

Front 56

Sympathetic and parasympathetic activation of the:

Skin--> Pilomotor SM

Back 56

s: contraction (A1)

p: no effect

Front 57

Sympathetic and parasympathetic activation of the:

Skin--> Eccrine Sweat glands

Back 57

S: increases (M3,M2)

p: no effect

Front 58

Sympathetic and parasympathetic activation of the:

Skin--> Apocrine sweat glands

Back 58

s: increases (a1)

p: no effect

Front 59

Sympathetic and parasympathetic activation of the:

Metabolic functions--> Liver

Back 59

s: stimulates gluconeogenesis and glycogenolysis (B2, a1)

p: no effect

Front 60

Sympathetic and parasympathetic activation of the:

Metabolic functions--> Pancreas

Back 60

s: acini (decreased secretion)(a)
-Islets (B cell) decreased secretion (a2)
-Islets (Bcell) increased secretion (B2)

p: acini (increased secretion) M3, M2

Front 61

Sympathetic and parasympathetic activation of the:

Metabolic functions--> Fat cells

Back 61

s: lipolysis (B3)

p: no effect

Front 62

Sympathetic and parasympathetic activation of the:

Metabolic functions--> kidney

Back 62

s:
-increased renin secretion (B1)
-decreased renin secretion (A1)

Front 63

Sympathetic and parasympathetic activation of the:

Kidney

Back 63

s: dilation of renal blood vessels (D1)

p: no effect

Front 64

Sympathetic and parasympathetic activation of the:

Autonomic nerve endings Presynaptic receptors

Back 64

Symp terms (decrease NE release)
-autoreceptor (a2)
-heteroreceptor (M2, M4)

Parasym terms (dec ACh release)
-autoreceptor (M2,M4)
-heteroreceptor (a2)