ANS Pharmacology

Question 1

neuropeptidergic

Answer 1

ANS neurotransmission pathways important physiologically but not so much clinically/pharmacologically

calcitonin gene-related peptide
vascular intestinal polypeptide
nitric oxide
tachykinins

Question 2

differences between cholinergic and adrenergic neurotransmission

Answer 2

cholinergic
- neurons produce, secrete, and/or respond to acetylcholine

adrenergic
- neurons produce, secrete, and/or respond to norepinephrine or epinephrine

Question 3

alpha 1 neurotransmitters

Answer 3

norepinephrine
- at physiologic levels

epinephrine

• during fight/flight rxn
• after high dose administration

Question 4

alpha 2 neurotransmitters

Answer 4

norepinephrine and epinephrine

- both only at high doses (fight/flight, or administration)

Question 5

beta 1 NTs

Answer 5

norepinephrine
- at physiologic levels

epinephrine
- at physiologic levels

isoproterenol
- beta specific

Question 6

beta 2 NTs

Answer 6

norepinephrine
- at high levels

epinephrine
- at physiologic levels

isoproterenol
- beta specific

Question 7

beta 3 NTs

Answer 7

norepinephrine

epinephrine

isoproterenol

Question 8

alpha 1 mechanism

Answer 8

metabotropic

• increase intracellular Ca
• produce IP3 and DAG

Question 9

alpha 2 mechanism

Answer 9

metabotropic

• inhibition of adenylyl cyclase
• decrease cAMP

Question 10

beta mechanism

Answer 10

metabotropic

• stimulate adenylyl cyclase
• increase cAMP

Question 11

nicotinic mechanism

Answer 11

ionotropic

• influx of cations
• depolarization

Question 12

muscarinic mechanism

Answer 12

M1/M3/M5

• coupled with Gq
• stimulate phospholipase C
• IP3 and DAG

M2/M4

• coupled with Gi
• inhibit adenylyl cyclase
• decrease cAMP

Question 13

where are alpha 1 receptors found and what actions do they stimulate

Answer 13

primarily on the post-synaptic membrane

vascular smooth muscle
- contraction

pupillary dilator muscle
- contraction

heart
- increase force of contraction

Question 14

where are alpha 2 receptors found and what actions do they stimulate

Answer 14

pre-synaptic membrane
- auto-inhibition, dec. NT release

platelets
- aggregation

some vascular smooth muscle

• *non-synaptic**
• contraction

fat cells
- inhibit lipolysis

Question 15

where are beta 1 receptor found and what actions do they stimulate

Answer 15

heart
- increase rate and force of contraction

juxtoglomerular cells
- increase renin release

Question 16

where are beta 2 receptors found and what actions do they stimulate

Answer 16

respiratory, uterine, and vascular smooth muscle
- relaxation

non-synaptic

Question 17

where are beta 3 receptors found and what actions do they stimulate

Answer 17

adipocytes

- lipolysis

Question 18

where are Nn receptors found and what actions do they stimulate

Answer 18

post-ganglionic ANS neurons

- excitatory

Question 19

where are Nm receptors found and what actions do they stimulate

Answer 19

skeletal muscle

- contraction

Question 20

what actions do muscarinic receptors stimulate

Answer 20

decrease the rate and force of cardiac contraction

facilitate smooth muscle contraction
- except in blood vessels muscarinic receptors cause dilation of BV (via NO stimulation effect on endothelial cells)

Question 21

describe blood vessels under physiologic NE release

Answer 21

1. NE released from sympathetic nerves
2. only innervates alpha 1 receptors (beta 2 are non-synaptic)
3. alpha 1 stimulation causes contraction
4. increase blood pressure

Question 22

describe blood vessels under fight/flight conditions

Answer 22

1. epinephrine released in addition to physiologic NE
2. binds beta 1 and beta 2 (only bind alpha at very high levels)
3. skeletal muscle vessels (alpha and beta 2) will be slightly more dilated than the subcutaneous muscle vessels (only have alpha)

Question 23

predominant tone?

arterioles

Answer 23

sympathetic

Question 24

predominant tone?

heart

Answer 24

parasympathetic

Question 25

predominant tone? bronchial smooth muscle

Answer 25

parasympathetic

Question 26

predominant tone? GI and urinary tracts

Answer 26

parasympathetic

Question 27

predominant tone? sweat glands

Answer 27

sympathetic

Question 28

predominant tone? pilomotor muscles

Answer 28

sympathetic

Question 29

describe cross-talk between sympathetic and parasympathetic neurons

Answer 29

sympathetic nerve terminal - alpha 2 receptors for auto-inhibition - M2 receptors for inhibition by parasympathetic Ach release parasympathetic nerve terminal - M2 receptors for auto-inhibition - alpha 2 or beta 2 receptors for inhibition by sympathetic NE release * *beta 2 effect varies (excitatory or inhibitory) between spp.

Question 30

miosis control

Answer 30

contraction of sphincter muscles | - stimulated by parasympathetic muscarinic receptors

Question 31

mydriasis control

Answer 31

contraction of radial muscles | - stimulated by sympathetic a1 receptors

Question 32

identify 3 major differences between a1 and B2 control of blood vessel diameter

Answer 32

a1 - vasoconstriction - basically all vascular smooth muscle - synaptic B2 - vasodilation - smooth muscle of skeletal muscle vasculature - non-synaptic

Question 33

antagonist mechanisms

Answer 33

1. prevent synthesis 2. prevent vesicle formation 3. prevent "docking" of the vesicle 4. stimulate auto-inhibitor receptors (i.e. a2) 5. accelerate breakdown of NT in cleft 6. increase uptake of NT from cleft 7. block post-synaptic receptors - competitive inhibition = direct antagonism

Question 34

agonist mechanisms

Answer 34

1. increase 2nd messenger action 2. decrease NT degradation (i.e. inhibit AchE) 3. block reuptake of NT (cocaine, dopamine) 4. stimulate release of NT (black widow venom) 5. increase synthesis (i.e. L-dopa = precursor to dopamine) 6. stimulate post-synaptic receptors (direct agonist)

Question 35

sympathomimetics

Answer 35

direct agonists of a1, B1, B2, a2 (post-synaptic) direct antagonists of pre-synpatic a2 indirect agonists

Question 36

sympatholytics

Answer 36

direct antagonists of a1, B1, B2, a2 (post-synaptic) direct agonists of pre-synpatic a2 indirect antagonists

Question 37

parasympathomimetics

Answer 37

direct agonists of Nn, Nm, or M direct antagonists of M2 (pre-synaptic) indirect agonists

Question 38

NE synthetic pathway

Answer 38

tyrosine - tyrosine hydroxylase L-dopa dopamine - dopamine-beta-hydroxylase norepinephrine - phenylethanolamine N-methyltransferase epinephrine

Question 39

how to AchE inhibitors vary

Answer 39

duration of action

Question 40

why use sympathomimetics (7)

Answer 40

1. hypotension 2. anaphylaxis 3. urinary incontinence 4. nasal congestion 5. bradycardia 6. congestive heart failure / cardiac arrest 7. asthma

Question 41

why use sympatholytics (3)

Answer 41

1. hypertension 2. glaucoma 3. congestive heart failure / cardiac arrest

Question 42

if the heart fails because it has been working to hard, how do you treat

Answer 42

sympatholytics

Question 43

why use parasympathomimetics (3)

Answer 43

1. glaucoma 2. GI stasis and urinary retention (in the absence of obstruction) 3. myasthenia gravis

Question 44

why use parasympatholytics (6)

Answer 44

1. produce mydriasis *** 2. pre-anesthetic 3. GI hypermotility, GI spasms, urinary tract 4. antiemetic 5. urinary incontinence 6. OP toxicity Tx