Autonomic Nervous System Flashcards
(92 cards)
1
Q
ANS Pharmacology
A
The study of drugs that act on receptors and neurotransmitters in the ANS to alter nervous system function.
2
Q
Drugs acting on the ANS are important in the treatment of which diseases?
A
- eye
- cardiovascular system
- respiratory tract
- GI and urinary tract
3
Q
What are the 2 branches of the Nervous System?
A
- Central (brain and spinal cord)
2. Peripheral (Somatic and autonomic)
4
Q
Describe the Peripheral Nervous System.
A
Efferent Neurons (Motor) and Afferent Neurons (Sensory) -Efferent Nervous system divided into somatic (conscious) and autonomic (unconscious)
5
Q
What are the 3 divisions of the ANS?
A
- parasympathetic
- sympathetic
- enteric- collection of neurons that regulates the GI tract
6
Q
How do ANS fibers interact with their target neurons (3 steps)?
A
- cell body of the first neuron resides in brain/spinal cord (pre-ganglionic neuron)
- pre-ganglionic neuron synapses w/ post ganglionic neuron in a ganglia (autonomic ganglion)
- ganglionic neuron innervates the target organ (cardiac muscles, smooth muscles, exocrine glands)
7
Q
In what 3 ways do the PNS and SNS differ in their organization?
A
- Preganglionics in different regions of CNS
- Different location of ganglia
- Different lengths of preganglionic fibres
8
Q
SNS v PNS: From what region of the CNS do the preganglionics originate?
A
PNS-cranial and sacral SC region
SNS-thoracic and lumbar SC region
9
Q
SNS v PNS: Where is the ganglia located?
A
PNS-close to target tissue
SNS-close to spinal cord in a chain
10
Q
SNS v PNS:What length is the pre-ganglionic fibre?
A
PNS-long
SNS-short
11
Q
How do SNS and PNS affect the heart?
A
SNS= increased rate and contractility
PNS=decreased rate
12
Q
How do SNS and PNS affect the intestine?
A
SNS=decreased motility
PNS=increased motility
13
Q
How do SNS and PNS affect the pupil?
A
SNS=dilate
PNS=constrict
14
Q
How do SNS and PNS affect the respiratory system?
A
SNS=bronchodilation
PNS=bronchoconstriction
15
Q
How do SNS and PNS affect the LUTS?
A
SNS= stimulates ejaculation/voiding
PNS=stimulates erection/voiding
16
Q
Explain PNS neurotransmission?
A
- Releases Ach at autonomic ganglion, neuronal nicotinic R
- releases Ach at post ganglionic neuron, muscarinic R
- affects cardiac and smooth muscle, gland cells, nerve terminals
17
Q
Draw out diagram of SNS transmission-include neurotransmitters and receptors.
A
See ANSI lecture
18
Q
Explain ANS regulation in the eye
A
PNS: Ach causes sphinctor pupillae to contract-Miosis
SNS: Noradrenaline cause dilator pupillae to contract-Mydriasis
19
Q
Explain organ level integration of the ANS.
A
See ANSII
20
Q
Cholinergic Agonists
A
-drugs that mimic the action of Ach at cholinergic R and increase PNS responses
21
Q
Cholinergic Antagonists
A
-drugs that inhibit the action of Ach at cholinergic R and decreases PNS response
22
Q
Cholinergic Receptors (2)
A
- muscarinic-high affinity for muscarine, low affinity for nicotine
- nicotinic-high affinity for nicotine, low for muscarine
23
Q
Acetyl cholinesterase
A
-breaks down Ach in the synaptic cleft, choline is recycle back to axon terminal
24
Q
Draw the pathway for cholinergic neurotransmission.
A
See ANSII
25
Vesamicol
Inhibits Ach uptake into synaptic vesicles
26
Botulinum toxin
Inhibits vesicular release of Ach
27
Describe the Muscarinic Receptor Subtypes (3)
M1: CNS, ANS
M2: acts on heart, decreased heart rate
M3: smooth muscle contraction, exocrine gland-increased secretion
28
Describe the Nicotinic R Subtypes (2)
```
Nn:
Autonomic ganglia- stimulate both SNS and PNS
Adrenal Medulla-releases Adr/NA
Nm:
skeletal muscle contraction
```
29
Muscarinic Agonists
-activate muscarinic R directly
30
What is a non-selective muscarinic agonist?
ACh
| -dont see long duration of action due to ACh esterase
31
What is a selective muscarinic agonist (2)?
- muscarine
| - pilocarpine
32
What is a synthetic analogue of Ach?
-bethanechol
33
What are uses of direct muscarinic antagonists?
1. stimulate tone in bladder after surgery
2. increase gut motility
3. glaucoma
34
How do muscarinic agonists work in the treatment of glaucoma?
Activate M3 receptors on the ciliary muscle to cause contraction and increase fluid drainage
35
What are the side effects of muscarinic agonists (5)?
1. stimulate all muscarinic R
2. GI disturbances (eg nausea and vomiting)
3. miosis
4. effects on heart rate (bradycardia)
5. salivation and bronchoconstriction
* overstimulation of the PNS
36
Muscarinic Antagonists
-bind to muscarinic R preventing Ach from binding
37
Give 2 examples of muscarinic antagonists.
Atropine-naturally occurring alkaloid
| Ipratropium bromide-synthetic analogue
38
3 Uses of Atropine
1. Dilate eye pupil for ophthalmic exam
2. treat bradycardia
3. to reduce secretion during surgery
39
What is the effect of muscarinic agonist on the eye?
- ciliary muscles contract
- refractive power of the lens increases, able to focus on near
- miosis
40
What is the effect of muscarinic antagonist on the eye?
- block the PNS
- make the lens thinner for far vision
- mydriasis
41
Uses of ipratropium bromide (Atrovent)
- to reduce cholinergic bronchoconstriction
- non-selective for all muscarinic subtypes (i.e. M1-M3)
- used to treat asthma and COPD
42
Name 2 nicotinic agonists?
Nicotine-selective
| Non-selective-Ach
43
What are the uses of nicotinic agonists?
- to treat nicotine addiction
| - patch, gum aerosol
44
What are the side effects of nicotinic agonists?
- CNS
| - tremor, convulsions, coma
45
Ganglionic Blockers
- nicotinic R antagonist
- block nicotinic nerve R at autonomic ganglia
- not used
46
Neuromuscular Blockers
-block nicotinic muscle receptors at the neuromuscular junction on skeletal muscles
47
What are the 2 classes of neuromuscular blockers?
1. Non-depolarizing (competitive) antagonists
| 2. Depolarizing (non-competitive) antagonists
48
Non-depolarizing (competitive) nicotinic antagonists
- binds in the place of Ach, doesn't cause sodium influx
| - can overcome blockade using acetylcholine esterase inhibitor
49
Curare
- Non-depolarizing (competitive) nicotinic antagonist
- used to produce skeletal muscle paralysis during surgery and in ICU
- side effects = paralysis
- selective at the neuromuscular junction, doesn't bind at the ganglion due to differences in structure
50
Depolarizing (non-competitve) nicotinic antagonists
- binds in the place of Ach and remains bounds
- causes depolarization
- receptor becomes desensitized
51
Succinylcholine
- Depolarizing (non-competitve) nicotinic antagonist
- used to produce skeletal muscle paralysis during surgery and in ICU
- takes time to wear off
52
Cholinesterase Inhibitors
Enhance duration of action of Ach by prevent its metabolism in the synapse
53
Reversible cholinesterase inhibitors
- weakly bind Ach esterase
| - neostigmine and physostigmine
54
Uses of Reversible cholinesterase inhibitors (3)
1. loss of tone in bladder and gut (increases gut and bladder motility)
2. glaucoma (same as muscarinic agonists)
3. myasthenia gravis
55
What are side effects of reversible cholinesterase inhibitors?
- same as for direct muscarinic agonists
| - salivation, miosis, bronchocontriction, bradycardia
56
Irreversible Cholinesterase Inhibitors
-covalent bond w/ Ach esterase
57
Pralidoxime
-compound that can break down covalent bond of irreversible cholinesterase inhibitors
58
Treatment for irreversible cholinesterase inhibitors
- support respiration
- decontamination
- use muscarinic antagonist (atropine)
- use pralidoxime
59
Examples of irreversible cholinesterase inhibitors (2)
- insecticides (parathion and malathion)
| - nerve gases (sarin)
60
Effects of irreversible cholinesterase inhibitors
- effects at both muscarinic and nicotinic R
- initial signs are muscarinic (bronchoconstriction, salivation, GI symptoms)
- followed by central and peripheral nicotinic signs (e.g. persistent activation of skeletal muscle, paralysis)
61
Adrenergic Agonists (sympathomimetics, adrenergics)
Mimic the action of epinephrine and norepinephrine at adrenergic R, increases SNS responses
62
Adrenergic Antagonists (sympatholytics, antiadrenergics)
Inhibit the action of NA at adrenergic receptors and decrease SNS responses
63
Localization of Adrenergic R
- alpha1 and beta2 on smooth muscle
- beta1 in heart
- alpha1 and beta2 on blood platelets, adipose, endocrine tissue
- alpha2 on presynaptic terminal of sympathetic neuron
64
Draw the pathway for adrenergic neurotransmission
ANS III
65
Cocaine
Inhibits NE reuptake
66
Amphetamine
Stimulates release of NE
67
What are the 3 ways that adrenergic agonists mimic the actions of NE?
1. Direct acting
2. Selective
3. Indirect acting
68
Direct Acting Adrenergic Agonists
```
Non-selective
-bind to pre or post synaptic adrenergic Rs
eg NE (alpha1, alpha2, beta1)
```
69
Phenylephrine
-direct adrenergic alpha1 agonist
70
What is phenylephrine used to treat (3)?
1. Nasal congestion
- constricts blood vessels in nasal mucosa
2. to dilate pupils
- activates alpha1 R on iris radial muscle
3. combine w/ local anaesthetic
- to constrict blood vessels and prolong nerve block
71
What is a side effect of phenylephrine?
-can increase bp due to vasoconstriction
72
SNS regulation of Vascular tone
NE acts on alpha1, causes vasoconstriction
- circulating epinephrine for adrenal medulla causes vasodilation mediated by beta2R
- ANSIII diagram
73
Direct Alpha2 agonists
- alpha2 R (autoreceptor) on pre-synaptic nerve terminal
| - decreased NE release via inhibition of adenylate cyclase and cAMP signalling
74
clonidine
- direct alpha2 agonist
- has CNS actions
- used to treat hypertension by reducing SNS outflow from the brain to the periphery
- side effects are sedation
75
Direct beta1 agonists
- acts in the heart
- increased Ca influx
- increased force of contraction cardiac muscle
- dobutamine
76
Direct beta2 agonists
- beta2 in airway smooth muscle
- decreased contraction of smooth muscle (bronchodilation)
- salbutamol
77
Direct Adrenergic Agonists (at multiple subtypes)
-adrenaline
78
What is adrenaline used to treat? How?
- anaphylaxis
- activates alpha1 R in vascular smooth muscle and beta1 R in cardiac muscle to increase cardiac output, leading to increased BP
- reduces mucous membrane congestion by activating alpha1
- activates B2 in smooth muscle of respiratory system
79
What are the 2 mechanisms of indirect adrenergic agonists?
1. inhibition of reuptake (cocaine)
| 2. cause release of NE (amphetamine)
80
Cocaine
- indirect adrenergic agonist
- blocks reuptake
- useful as local anaesthetic in nasopharyngeal surgery (blocks sodium channels in nerves)
81
What are the side effects of cocaine?
- powerful CNS stimulant
- increased HR, bp, force of contraction
- arrhymias due to Ca influx into tissue
82
Amphetamine/Ephedrine
- indirect adrenergic agonist
| - causes release of noradrenaline from sympathetic nerve terminals
83
What is the mechanism of action of amphetamine?
- amphetamine and NE taken up by same transporter
- increases presence of cytosolic NE in the pre-synaptic nerve terminal, NE can't be stored
- Monoamine transporter works in reverse and moves NE into synapse
84
What is amphetamine used to treat?
- narcolepsy, ADHD
| - appetite suppressant
85
Tyramine and the Cheese Reaction
- by product of tyrosine metabolism can be produced in protein rich foods
- metabolized by MAO in liver
- indirect agonist causing release of stored NE
- inhibition of MAO produces increased tyramine levels and release of NE
- patients taking MAO inhibitors (depression) must avoid tyramine rich food to prevent high bp
86
Phentolamine
- alpha adrenergic antagonist
- non selective for alpha1 and 2
- increased heart rate b/c NE can still act on beta2
87
Prazosin
- alpha adrenergic antagonist
- selective for alpha1
- used to treat high bp b/c doesn't block alpha2 so NE can still feedback
88
Propanolol
- direct beta antagonist
| - non selective
89
Metropolol
- direct beta antagonist
| - cardioselective, beta1
90
What are the uses of metropolol and propanolol?
- high bp, angina, arrhythmias
| - glaucoma, decrease aqueous humour secretion in the eye
91
What are the side effects of metropolol and propanolol?
- exercise tolerance
| - asthma
92
Beta AR blockers and glaucoma
- aqueous humour is secreted by the ciliary epithelium
- beta AR blockers act at Beta AR receptors on the epithelium and decrease aqueous humour secretion leading to a decreased pressure in the eye
- used topically so non selectivity is ok
