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Pharmacology > Autonomic physiology and pharmacology > Flashcards

Autonomic physiology and pharmacology Flashcards

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1
Q

What is the autonomic nervous system?

A

Part of the nervous system responsible for control of the bodily functions not consciously directed

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2
Q

What are the two divisions of the efferent autonomic nervous system?

A

Sympathetic

Parasympathetic

*enteric nervous system is a third division under the influence of the other two

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3
Q

What are the branches of the sympathetic nervous system?

A

Spinal roots T1-L4 emerging from the spinal cord

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4
Q

What are the branches of the parasympathetic nervous system?

A

Cranial nerves

Spinal roots S2-S4

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5
Q

Describe the symmetry that is seen throughout the ANS

A

The system is constantly controlled by the opposing actions of the sympathetic and parasympathetic branches

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6
Q

Example of a tissue only innervated by one of the two branches of the ANS

A

Vasculature

Only innervated by the sympathetic nervous system

Ciliary muscles of the eye

Only innervated by the parasympathetic nervous system

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7
Q

What is the difference between the afferent and efferent nervous system?

A

The afferent nervous system carries information to the CNS - sensory neurons

The efferent nervous system carries information from the CNS to the peripheral targets - motor neurons

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8
Q

What is the division of the afferent ANS?

A

Not split up into parasympathetic and sympathetic like efferent

Autonomic sensory information is conducted by general visceral afferent fibres

Less is known about this system

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9
Q

What is a consensual response?

A

Reflex observed on one side of the body when the other has been stimulated

For example, if an individual’s right eye is shielded and light shines into the left eye, constriction of the right eye will also occur

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10
Q

What is an autonomic ganglion?

A

Cluster of nerve cell bodies in the autonomic nervous system

Ganglia = where two nerves meet

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11
Q

What determines what type of neurotransmitters are released in the autonomic ganglia?

A

Whether it is the sympathetic or parasympathetic nervous system

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12
Q

Autonomic ganglia are closer to organs in the parasympathetic nervous system

TRUE or FALSE

A

TRUE

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13
Q

Which neurotransmitter is predominantly released in the efferent parasympathetic nervous system ganglia?

A

Acetylcholine

Binds to nicotinic receptors

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14
Q

Which neurotransmitter is predominantly released in the efferent parasympathetic synapse?

A

Acetylcholine

Binds to muscarinic receptors

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15
Q

Which neurotransmitter is predominantly released in the efferent sympathetic nervous system ganglia?

A

Acetylcholine

Binds to nicotinic receptors

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16
Q

Which neurotransmitter is predominantly released in the efferent sympathetic nervous system synapse?

A

Noradrenaline

Binds to alpha or beta adrenergic receptors*

*exception = sweat gland, acetylcholine is released which binds to muscarinic receptors

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17
Q

Which was the first discovered neurotransmitter?

A

Acetylcholine

Otto Loewi

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18
Q

Describe how the first neurotransmitter was discovered

A

Lowei wasn’t convinced that the action of nerves at the NMJ was electrical

He placed two hearts in water connected through a tube

The stimulation of one heart through the vagus nerve caused the same response in the heart in the separate beaker

Concluded that the chemical produced had travelled through the water and affected the other heart

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19
Q

How were the two receptors ACh acts through discovered?

A

Dale extracted the ACh

When placed on targets, it was discovered these two NT cause similar reactions as nicotine and muscarine

Concluded that acetylcholine acts on two different receptors - muscarinic and nicotinic

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20
Q

How did scientists conclude that adrenaline and noradrenaline acted on different receptors?

A

Ahlquist knew they were different structurally

Same molar concentrations of adrenaline had more of an effect on the heart than noradrenaline

Isoprenaline was artificially produced, and had strong effects on the heart without any effect on the vasculature

Concluded this was because adrenaline and noradrenaline works on different receptors

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21
Q

What are the two receptors of the sympathetic nervous system?

A

Alpha

Beta

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22
Q

What are the subtypes of alpha and beta receptors?

A

Alpha 1 and alpha 2

Beta 1, beta 2, beta 3

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23
Q

Describe the action of the parasympathetic nervous system

A

Pupil constriction

Decreased heart rate

Bronchoconstriction

Increased motility and secretion of the GI tract

Smooth muscle contraction

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24
Q

Describe the effect of the sympathetic nervous system

A

Pupil dilation

Heart

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25
Describe the branches of the nervous system
The NS is split up into the CNS and PNS Within the PNS you have the ANS and the somatic NS Within the CNS you have the Brain and the Spinal Cord
26
Describe the adrenergic system in the brain
The locus coeruleus uses adrenaline and noradrenaline Important in controlling mood and synchronization of physiological responses to stress and pain
27
Describe the cholinergic system in the brain
Acetylcholine is involved in memory formation and higher cognitive functions
28
Why is it complicated to use adrenergic or cholinergic agonists/antagonists to modulate the autonomic system?
These transmitters are not specific to the ANS and are used in other non-autonomic systems - Motor system uses Ach in the NMJ - ACh and NA are involved in CNS functions
29
List drugs used to modulate the autonomic nervous system
Reserpine Physostigmine Atropine
30
Describe the action of Reserpine
Used to treat hypertension Irreversibly blocks the monoamine transporter, depleting the vesicles of adrenergic NTs by blocking vesicular transport mechanisms
31
Why is Reserpine not used more widely?
Serious side-effects = suicide
32
Describe the action of Physostigmine
Natural Acetylcholinesterase inhibitor Causes a build up of acetylcholine Potentiates the effect of ACh
33
What have been the uses of Acetylcholinesterase inhibitors?
Irreversible inhibitors have been used as pesticides and chemical warfare due to their effect on the ANS Reversible inhibitors have been used for treatment of myasthenia gravis, Alzheimer's and control of bladder in stroke patients
34
How must Acetylcholinesterase inhibitors be given in order to be used as treatment?
Low doses Be reversible Due to potentially dangerous effects
35
What is the main NT of the parasympathetic nervous system?
ACh
36
What is the main NT of the sympathetic nervous system?
Noradrenaline and Adrenaline
37
Describe the advantage of Atropine compared to Reserpine and Physostagmine
It is selective antagonist of muscarinic receptors
38
What are the medical applications of atropine?
Treatment of poisoning by nerve agent Cardiac arrest Decrease salivary secretion during anaesthesia
39
What are the three beta receptors?
Beta 1: heart muscle - positive ionotropic and chronotropic agent Beta 2: bronchial smooth muscle, skeletal smooth muscle vasculature Beta 3: adipose tissue
40
How have beta 1 receptors been targeted for therapy?
Treatment of hypertension Safer for asthma sufferers with hypertension
41
How have beta 2 receptors been targeted for therapy?
Selective agonists for asthma sufferers Bronchodilator Salbutamol Little effect on the heart - poisitve
42
What are the different types of alpha receptors?
Alpha 1 Alpha 2
43
Where are alpha 1 receptors expressed?
Vascular smooth muscle cells Causes vasoconstriction in all the blood vessels but those expressed in the cardiac vasculature and skeletal muscle vasculature
44
Where are alpha 2 receptors expressed?
Presynaptic autoreceptor Modulates the release of neurotransmitters
45
How have alpha 2 receptors been targeted for therapy?
Alpha 2 receptor agonists inhibit the release of norepinephrine Used to decrease blood pressure Acts as an antihypertensive drug
46
What are other neurotransmitters than NA, A and ACh called?
NANC (non-adrenergic, non-cholinergic neurotransmitters)
47
List NANC neurotransmitters
Nitric oxide Serotonin ATP Neuropeptide Y Substance P Vasoactive intestinal polypeptide
48
How were NANC NT discovered?
Upon the continued smooth muscle contraction despite the blockade of both adrenergic and cholinergic synapses
49
What did the discovery of NANC NT reveal?
Neurons can release more than one neurotransmitter at a time
50
What percentage of hypertension cases is caused by secondary conditions?
5% Conditions like pheochromocytoma
51
What is allostasis?
The process of achieving homesostasis through physiological change
52
Why do alpha-1 antagonists and alpha-2 antagonists have differing effects on blood pressure?
Because alpha 2 receptors are found in the presynaptic membrane Decreases the release of noradrenaline when the concentration has reached a certain threshold in the synaptic cleft Blocking this causes the increased release of NA and therefore more vasodilation, leading to decreased blood pressure
53
Which alpha receptor antagonist causes an increase in blood pressure?
Alpha 1 antagonist Receptor binding to noradrenaline causes vasodilation If this is blocked, the vasculature undergoes decreased vasodilation
54
Why have many different types of antihypertensive drugs been developed?
The heterogeneous presentation of patients upon the use of drugs The unknown cause of the disease Many side effects
55
What are 4 classes of drugs used to treat hypertension?
ACE inhibitors Angiotensin II blockers Calcium channel blockers Potassium channel openeners
56
How do ACE inhibitors alleviate hypertension?
Targets the renin-angiotensin system Causes a blockage of active compounds further down the pathway
57
What is the major side effect of ACE inhibitors?
Importance of ACE in the modulation of bradykinin action Causes a chronic cough
58
How do Angiotensin II blockers alleviate hypertension?
Inhibits the action of angiotensin II in the vasculature, leading to vasodilation More specific than ACE inhibitors, and do not cause cough
59
Which patient population is advised against Angiotensin II blockers?
Pregnant women Angiotensin II is involved in the genesis of the kidney in the embryo
60
How do calcium channel blockers alleviate hypertension?
Block the entry of calcium, which is used for muscle contraction Decreases blood pressure by decreasing the contractility of cardiac and vascular smooth muscle cells Does not affect skeletal muscle, since their calcium channels are different that those targeted by this blocker
61
Which patient population is advised against calcium channel blockers?
Patients with congestive heart failure who have experienced a heart attack More difficult for their heart muscle to start pumping again
62
How do potassium channel openers alleviate hypertension?
Cause the release of potassium Hyperpolarising the membrane Makes it more difficult for the smooth muscles to contract
63
What is the major complication of potassium channel openers?
Potassium channel openers influence insulin release from the pancreas Induces periodic diabetes
64
What is mydriasis?
Pupil dilation
65
What is miosis?
Pupil constriction
66
What is the best way to examine the autonomic nervous system?
Pupils You can stimulate miosis and mydriasis through altering the muscarinic or adrenergic receptors
67
How do you stimulate mydriasis?
a-adrenergic agonists Muscarinic blockers
68
What is the role of the muscarinic blockers when stimulating mydriasis?
Cilliary muscles change the lense shape upon contraction No innervation from the sympathetic nervous system, but muscarinic receptors are present Blocking these allows us to dilate the pupil
69
Describe the actions of the ANS
Regulates smooth muscle tone Regulates cardiac function Actions on exocrine and endocrine secretions Actions on intermediate metabolism
70
Only efferent autonomic pathways are targets for drug action TRUE or FALSE
TRUE
71
What are the two neurons that make up the efferent autonomic pathways?
Preganglionic fibres Postganglionic fibres
72
Describe the enteric nervous system
Neurons with cell bodies in the plexuses of the intestinal wall Autonomic nerves terminate on these cells System can operate autonomously in the control of peristalsis and secretion
73
Where is acetylcholine released from?
Postganglionic parasympathetic neurons Preganglionic neurons Motor nerves
74
Where is noradrenaline released from?
Postganglionic sympathetic neurons
75
What is the function of NANC?
Primary transmitters in the enteric and sensory neurons Co-transmitters with NA and ACh in autonomic nerves
76
What are co-transmitters?
Released together with neurotransmitters Commonly have different response speeds to neurotransmitters
77
Which co-transmitter is released with ACh?
ATP
78
Which co-transmitter is released with NO?
NA
79
Which co-transmitter is released with VIP?
NPY
80
Where do sympathetic ganglia lie?
Far away from target site
81
Where do parasympathetic ganglia lie?
Close to target organs
82
Compare the responses evoked from sympathetic and parasympathetic nerves
Sympathetic responses are more diffuse Preganglionic fibres branch and synapse with postganglionic neurons in several segments above and below their origin in the spinal cord Also release of catecholamines from the adrenal medulla increases the effect radius Parasympathetic responses are more localised Connect with only a few postganglionic fibres
83
Describe the storage and release of noradrenaline
Stored in dense-core storage vesicles Released by calcium-mediated exocytosis
84
What is another name for adrenaline?
Epinephrine
85
What is another name for noradrenaline?
Norepinephrine
86
Alpha receptors are specific for NA, and do not react to adrenaline TRUE or FALSE
FALSE These receptors act to both, but to different extents
87
What type of receptors are alpha receptors?
G-protein coupled ``` a1 = Gq a2 = Gi ```
88
What type of receptors are beta receptors?
G-protein coupled All Gs
89
How do a1 receptors carry out their function upon binding to their agonist?
G-protein mediated Second messengers IP3 and DAG generate Increase Ca2+ Activates the contractile mechanisms in smooth muscle cells
90
How do a2 receptors carry out their function upon binding to their agonist?
Inhibit adenylate cyclase Reduces cAMP Inhibits opening of Ca2+ Promote opening of K+ channels
91
What is the main antagonist used clinically?
a1-selective antagonists
92
What is the effect of a1-selective antagonists?
Fall in blood pressure Rise in heart rate Decreased tone of the smooth muscle at the bladder neck
93
What are the unwanted effects of a1-selective antagonists?
Extension of their pharmacological effects Increased heart rate Postural hypotension Congestion of the nasal blood vessels
94
What is the effect of beta-1 agonists?
Increase in heart rate/force
95
What is the effect of beta-2 agonists?
Dilation of bronchioles and arterioles Relaxation of bladder muscle Glycogenolysis
96
What is the effect of beta-3 agonists?
Lipolysis
97
Describe the mechanism of function of beta receptors
G proteins Activate adenylate cyclase Increase cAMP Activates protein kinase A PKA inactivates the myosin light chain kinase, reducing the contraction In heart, PKA phosphorylates Ca2+ channels, increasing he inward Ca2+ current and the force of contraction
98
What are the main effects of b-antagonists?
Antihypertensive effect Antianginal effect Limited action in normal individual, main action seen in pathological conditions
99
How do b-antagonists cause antihypertensive effects?
Reduces cardiac output Decreases release of renin Central decrease in sympathetic action
100
How do b-antagonists cause antianginal effects?
Slowing of the heart muscle Decreased metabolic demand
101
How are uptake 1 inhibitors used ?
Increase the effects of NA through interfering with the main method of terminating NA action
102
How do sympathomimetic amines work?
Taken by uptake 1 and into vesicles Exchange with NA NA is released from the neuron as a response Increases alertness and decreases appetite
103
What is carbidopa used for clinically?
Reduces the peripheral sympathetic activity when used as an adjunct with levodopa
104
How does methyldopa work as an antihypertensive?
Taken up by amino acid transporter NA-producing enzymes transforms it into methylnoradrenaline Acts on a2-adrenoreceptors to reduce the release of NA Antihypertensive

Pharmacology (13 decks)

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