14 –Autonomic Nervous System Flashcards
1
Q
NTs: somatic nerves
A
- ACh: nicotinic receptor
2
Q
Receptors in ganglia are always
A
- Nicotinic
3
Q
NTs: preganglionic nerve onto adrenal medulla
A
- ACh: nicotinic receptor
o E+NE released into blood
4
Q
NTs: pre-ganglionic sympathetic nerves
A
- ACh: nicotinic
5
Q
NTs: post-ganglionic sympathetic nerves
A
- NE
o Heart: beta-1
o Smooth muscle : alpha-1,
E from the blood: beta-2
6
Q
NTs: pre-ganglionic parasympathetic nerves
A
- ACh: nicotinic
o Exocrine glands: M3
o Heart: M2
o Smooth muscle : M3
7
Q
NTs: post-ganglionic PS nerves
A
- ACh
8
Q
Sympathetic NS: ‘spinal segments’
A
- Preganglionic nerves exit spin in thoracic and lumbar nerves
- Sympathetic chain ganglion: synapses above and below
o *Responses tend to be ALL OR NONE!
9
Q
Parasympathetic NS: ‘spinal segments’
A
- Cranial and sacral nerves
- Longer pre-ganglionic neuron
- Ganglion may be in the ‘target organ/tissue’
- Discrete activation
o Can get one nerve activated without activated another - *vagus is major player
10
Q
Baroreceptor reflex
A
- Increased arterial pressure=stretch of baroreceptors in aortic arch and carotid artery
- Vasomotor center:
a. Decreased sympathetic impulses on arterioles=vasodilation
b. Increase PS impulses mainly on heart=decrease HR= decrease CO=decrease BP
11
Q
Agonist is
A
- Substance that binds to a receptor and activates it
- Can be an exogenous chemical (drug)
- Mimics actions of an endogenous ligand
12
Q
Antagonist is
A
- Substance that binds to a receptor, but prevents its activation
- Blocks effects of drugs that activate the receptor
- Blocks effects of endogenous activators of a receptor
13
Q
PS vs S
A
- Effects generally oppose each other (physiological systems that antagonise each other)
- One system will have predominant ‘tone’ over the other in a given organ
o Resting: PS should be predominant (exception: arterioles) - Blocking one system often UNMASK activity of opposing system
14
Q
Arterioles
A
- Main controller of BP
- Have no PS innervation!
- Control BP through S innervation degree of activity
15
Q
ACh cholinergic receptors: 2 major subtypes
A
- Muscarinic: M1-M5
- Nicotinic: Nm (skeletal muscle), Nn (neurons: ganglia or adrenal medulla)
16
Q
Muscarinic receptors and drugs
A
- Don’t have any drugs that aren’t toxic
- *’dirty’: hit everything
o Usually many side effects
17
Q
NE and E adrenergic receptors: 2 major subtypes
A
- Alpha-adrenergic: a1, a2
- Beta-adrenergic: b1, b2, b3
18
Q
Beta-3
A
- On many cells
o adipocyte cells! (obesity) - Drugs for anti-obesity?
19
Q
Effects of IV infusion of NE at low to moderate dose
A
- Increase in pulse pressure
- Marked increase in peripheral resistance
- Increase in systolic BP
- increase in diastolic BP
- *no increase in pulse rate as baroreceptor response
20
Q
Beta-1 adrenergic antagonist in a resting animal:
A
- Decrease HR
- Decrease force of contraction in heart
- *vagal stimulation pre-dominates
21
Q
Beta-1 adrenergic antagonist in an agitated animal
A
- Have significant sympathetic stimulation
o *beta-blocker will slow HR and reduce contractility
22
Q
ANS receptor signal transduction
A
- Beta-receptor (M3) activates Gs which stimulates adenyl cyclase=more cAMP=more PKA=effect
- Alpha 2 and M2 receptors (heart)=activate Gi which inhibits adenylyl cyclase=less cAMP=decrease PKA=decreased biological effect
23
Q
How do you turn cAMP ‘off’?
A
- Phosphodiesterase to get AMP
- *if inhibit phosphodiesterase=get more cAMP=more biological effect
- *same with cGMP
24
Q
Vascular endothelium and NO
A
- M3-receptor on endothelium stimulated=activate IP3, DAG=Ca2+ and Ca-calmodulin and get NO
o Short lived
o Some into lumen of artery
o LOTS diffuses into vascular smooth muscle cell - Muscle cell: stimulates guanyly cyclase=get cGMP=relaxation!
- *Viagra prefers to work on this phosphodiesterase=get more dilation
25
Q
Those with disease or lots of oxidated stress: endothelium damage
A
- Endometrium have decreased endothelial cells
o Have M3 receptors on the smooth muscle cells as well (normally don’t see the effect)=activates Gq and get Ca2+ release=contraction - *does not matter for phosphodiesterase (separate, not dependent on NO): can still work when there is endothelial damage
26
Q
Viagar (sildenafil)
A
- Phosphodiesterase inhibitor
- Inhibits degradation of cGMP=greater effect in arteries
- *vasodilate pulmonary arteries in pulmonary hypertension
- No direct effects on cardiac system
- Would slow progression of labour
27
Q
Cholinergic neurotransmission:
A
- Acetate and choline = ACh
- Uptake of ACh into presynaptic terminal vesicles
- Released into synapse and bind N or M receptors
- Continues to activate until acetylcholinesterase breaks it down to choline+acetate (OFF SIGNAL)
28
Q
Botulinum toxin
A
- Blocks exocytosis (release) of ACh
- ANTICHOLINERGIC EFFECT
- *do NOT want to give systemically as it will stop all nerve function (including the diaphragm!)
- Ex. humans; use for excessive sweating
29
Q
Cholinesterase inhibitors
A
- Used to keep the ACh signalling ON
- MASSIVE overflow and activation of N and M receptors
- PROCHOLINERGIC EFFECT
- Ex. insecticides (irreversible inhibitors of acetylcholinesterase)
- Also have reversible=more controllable (to help with muscle function)
30
Q
Acronym to remember effects of cholinesterase inhibitors (high levels of ACh): SLUD
A
- Salivation
- Lacrimation
- Urination
- Defecation
- *also no blood flow
31
Q
Black widow spider venom
A
- Causes ACh release due to leakiness of cholinergic vesicles
- PROCHOLINERGIC toxin
o Milder version of SLUD and muscle twitching + activation compared to acetylcholinesterase inhibitors - *probably more than one spider needed to bit it (or it dies from anaphylaxis)
32
Q
Adrenergic neurotransmission:
A
- Tyrosine to dopa to dopamine into vesicles then inside converted to NE
- Off signal=reuptake by presynaptic nerve
33
Q
Metyrosine
A
- Methylated tyrosine which then forms methyl-NE which will go in the vesicles and be released
- *little to NO ability to activate alpha and beta receptors in tissue
- ANTI-ADRENERGIC EFFECT
o No enough NE to maintain normal tone in blood vessels=get vasodilation and drop in peripheral resistance=drop in BP - *old school: hypotension drug (almost TOO strong)
34
Q
Amphetamine
A
- Causes NE to leak out of vesicles to release NE into nerve terminals
- PRO-ADRENERGIC EFFECT
- Causing activation of alpha and beta receptors (but in an indirect way)
35
Q
Cocaine
A
- Blocks NE reuptake
- More accumulation of NE than amphetamine
- *also effects dopamine reuptake in dopaminergic cells
- *mix of effects that give distinct effects=activate fight or flight
36
Q
Monoamine oxidase (MAO) inhibitors
A
- Old anti-depressants in humans, but used in vet med INHIBIT it
- Promotes more serotonin! (elsewhere)
- Minor role: slightly more NE
- Too many side effects in humans
37
Q
Bretylium
A
- Prevents NE release
- ANTI-ADRENERGIC EFFECT
38
Q
ACh-esterase inhibitors: irreversible vs. reversible
A
- Irreversible: insecticides (toxic)
o If haven’t died: can give anti-muscarinic drugs - Reversible: edrophonium
39
Q
Nicotinic receptors (Nm) on muscle
A
- Opening of Na channel=depolarization=AP to cause muscle contraction
- Off signal=ACh-esterase
40
Q
Antagonists of Nm receptors
A
- Pancuronium
- *can use to Ach-esterase inhibitors to ‘outcompete’ them
- Succinylcholine
41
Q
Pancuronium
A
- competitive antagonist for ACh at Nm receptors
- *used when need flaccid paralysis
o Do NOT want it to paralyze the diaphragm though
42
Q
Succinylcholine
A
- Initially activates Na channels, but then stays on the Nm receptor=PARALYSIS
- Twitching than paralysis
- *common to use when intubating an animal (ex. relax trachea)
