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Pharmacology > Autonomic physiology and pharmacology > Flashcards

Autonomic physiology and pharmacology Flashcards

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
Q

Describe the branches of the nervous system

A

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

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26
Q

Describe the adrenergic system in the brain

A

The locus coeruleus uses adrenaline and noradrenaline

Important in controlling mood and synchronization of physiological responses to stress and pain

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27
Q

Describe the cholinergic system in the brain

A

Acetylcholine is involved in memory formation and higher cognitive functions

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28
Q

Why is it complicated to use adrenergic or cholinergic agonists/antagonists to modulate the autonomic system?

A

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
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29
Q

List drugs used to modulate the autonomic nervous system

A

Reserpine

Physostigmine

Atropine

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30
Q

Describe the action of Reserpine

A

Used to treat hypertension

Irreversibly blocks the monoamine transporter, depleting the vesicles of adrenergic NTs by blocking vesicular transport mechanisms

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31
Q

Why is Reserpine not used more widely?

A

Serious side-effects = suicide

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32
Q

Describe the action of Physostigmine

A

Natural Acetylcholinesterase inhibitor

Causes a build up of acetylcholine

Potentiates the effect of ACh

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33
Q

What have been the uses of Acetylcholinesterase inhibitors?

A

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

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34
Q

How must Acetylcholinesterase inhibitors be given in order to be used as treatment?

A

Low doses

Be reversible

Due to potentially dangerous effects

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35
Q

What is the main NT of the parasympathetic nervous system?

A

ACh

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36
Q

What is the main NT of the sympathetic nervous system?

A

Noradrenaline and Adrenaline

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37
Q

Describe the advantage of Atropine compared to Reserpine and Physostagmine

A

It is selective antagonist of muscarinic receptors

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38
Q

What are the medical applications of atropine?

A

Treatment of poisoning by nerve agent

Cardiac arrest

Decrease salivary secretion during anaesthesia

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39
Q

What are the three beta receptors?

A

Beta 1: heart muscle - positive ionotropic and chronotropic agent

Beta 2: bronchial smooth muscle, skeletal smooth muscle vasculature

Beta 3: adipose tissue

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40
Q

How have beta 1 receptors been targeted for therapy?

A

Treatment of hypertension

Safer for asthma sufferers with hypertension

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41
Q

How have beta 2 receptors been targeted for therapy?

A

Selective agonists for asthma sufferers

Bronchodilator

Salbutamol

Little effect on the heart - poisitve

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42
Q

What are the different types of alpha receptors?

A

Alpha 1

Alpha 2

43
Q

Where are alpha 1 receptors expressed?

A

Vascular smooth muscle cells

Causes vasoconstriction in all the blood vessels but those expressed in the cardiac vasculature and skeletal muscle vasculature

44
Q

Where are alpha 2 receptors expressed?

A

Presynaptic autoreceptor

Modulates the release of neurotransmitters

45
Q

How have alpha 2 receptors been targeted for therapy?

A

Alpha 2 receptor agonists inhibit the release of norepinephrine

Used to decrease blood pressure

Acts as an antihypertensive drug

46
Q

What are other neurotransmitters than NA, A and ACh called?

A

NANC (non-adrenergic, non-cholinergic neurotransmitters)

47
Q

List NANC neurotransmitters

A

Nitric oxide

Serotonin

ATP

Neuropeptide Y

Substance P

Vasoactive intestinal polypeptide

48
Q

How were NANC NT discovered?

A

Upon the continued smooth muscle contraction despite the blockade of both adrenergic and cholinergic synapses

49
Q

What did the discovery of NANC NT reveal?

A

Neurons can release more than one neurotransmitter at a time

50
Q

What percentage of hypertension cases is caused by secondary conditions?

A

5%

Conditions like pheochromocytoma

51
Q

What is allostasis?

A

The process of achieving homesostasis through physiological change

52
Q

Why do alpha-1 antagonists and alpha-2 antagonists have differing effects on blood pressure?

A

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
Q

Which alpha receptor antagonist causes an increase in blood pressure?

A

Alpha 1 antagonist

Receptor binding to noradrenaline causes vasodilation

If this is blocked, the vasculature undergoes decreased vasodilation

54
Q

Why have many different types of antihypertensive drugs been developed?

A

The heterogeneous presentation of patients upon the use of drugs

The unknown cause of the disease

Many side effects

55
Q

What are 4 classes of drugs used to treat hypertension?

A

ACE inhibitors

Angiotensin II blockers

Calcium channel blockers

Potassium channel openeners

56
Q

How do ACE inhibitors alleviate hypertension?

A

Targets the renin-angiotensin system

Causes a blockage of active compounds further down the pathway

57
Q

What is the major side effect of ACE inhibitors?

A

Importance of ACE in the modulation of bradykinin action

Causes a chronic cough

58
Q

How do Angiotensin II blockers alleviate hypertension?

A

Inhibits the action of angiotensin II in the vasculature, leading to vasodilation

More specific than ACE inhibitors, and do not cause cough

59
Q

Which patient population is advised against Angiotensin II blockers?

A

Pregnant women

Angiotensin II is involved in the genesis of the kidney in the embryo

60
Q

How do calcium channel blockers alleviate hypertension?

A

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
Q

Which patient population is advised against calcium channel blockers?

A

Patients with congestive heart failure who have experienced a heart attack

More difficult for their heart muscle to start pumping again

62
Q

How do potassium channel openers alleviate hypertension?

A

Cause the release of potassium

Hyperpolarising the membrane

Makes it more difficult for the smooth muscles to contract

63
Q

What is the major complication of potassium channel openers?

A

Potassium channel openers influence insulin release from the pancreas

Induces periodic diabetes

64
Q

What is mydriasis?

A

Pupil dilation

65
Q

What is miosis?

A

Pupil constriction

66
Q

What is the best way to examine the autonomic nervous system?

A

Pupils

You can stimulate miosis and mydriasis through altering the muscarinic or adrenergic receptors

67
Q

How do you stimulate mydriasis?

A

a-adrenergic agonists

Muscarinic blockers

68
Q

What is the role of the muscarinic blockers when stimulating mydriasis?

A

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
Q

Describe the actions of the ANS

A

Regulates smooth muscle tone

Regulates cardiac function

Actions on exocrine and endocrine secretions

Actions on intermediate metabolism

70
Q

Only efferent autonomic pathways are targets for drug action

TRUE or FALSE

A

TRUE

71
Q

What are the two neurons that make up the efferent autonomic pathways?

A

Preganglionic fibres

Postganglionic fibres

72
Q

Describe the enteric nervous system

A

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
Q

Where is acetylcholine released from?

A

Postganglionic parasympathetic neurons

Preganglionic neurons

Motor nerves

74
Q

Where is noradrenaline released from?

A

Postganglionic sympathetic neurons

75
Q

What is the function of NANC?

A

Primary transmitters in the enteric and sensory neurons

Co-transmitters with NA and ACh in autonomic nerves

76
Q

What are co-transmitters?

A

Released together with neurotransmitters

Commonly have different response speeds to neurotransmitters

77
Q

Which co-transmitter is released with ACh?

A

ATP

78
Q

Which co-transmitter is released with NO?

A

NA

79
Q

Which co-transmitter is released with VIP?

A

NPY

80
Q

Where do sympathetic ganglia lie?

A

Far away from target site

81
Q

Where do parasympathetic ganglia lie?

A

Close to target organs

82
Q

Compare the responses evoked from sympathetic and parasympathetic nerves

A

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
Q

Describe the storage and release of noradrenaline

A

Stored in dense-core storage vesicles

Released by calcium-mediated exocytosis

84
Q

What is another name for adrenaline?

A

Epinephrine

85
Q

What is another name for noradrenaline?

A

Norepinephrine

86
Q

Alpha receptors are specific for NA, and do not react to adrenaline

TRUE or FALSE

A

FALSE

These receptors act to both, but to different extents

87
Q

What type of receptors are alpha receptors?

A

G-protein coupled

a1 = Gq 
a2 = Gi
88
Q

What type of receptors are beta receptors?

A

G-protein coupled

All Gs

89
Q

How do a1 receptors carry out their function upon binding to their agonist?

A

G-protein mediated

Second messengers IP3 and DAG generate

Increase Ca2+

Activates the contractile mechanisms in smooth muscle cells

90
Q

How do a2 receptors carry out their function upon binding to their agonist?

A

Inhibit adenylate cyclase

Reduces cAMP

Inhibits opening of Ca2+

Promote opening of K+ channels

91
Q

What is the main antagonist used clinically?

A

a1-selective antagonists

92
Q

What is the effect of a1-selective antagonists?

A

Fall in blood pressure

Rise in heart rate

Decreased tone of the smooth muscle at the bladder neck

93
Q

What are the unwanted effects of a1-selective antagonists?

A

Extension of their pharmacological effects

Increased heart rate
Postural hypotension
Congestion of the nasal blood vessels

94
Q

What is the effect of beta-1 agonists?

A

Increase in heart rate/force

95
Q

What is the effect of beta-2 agonists?

A

Dilation of bronchioles and arterioles

Relaxation of bladder muscle

Glycogenolysis

96
Q

What is the effect of beta-3 agonists?

A

Lipolysis

97
Q

Describe the mechanism of function of beta receptors

A

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
Q

What are the main effects of b-antagonists?

A

Antihypertensive effect

Antianginal effect

Limited action in normal individual, main action seen in pathological conditions

99
Q

How do b-antagonists cause antihypertensive effects?

A

Reduces cardiac output

Decreases release of renin

Central decrease in sympathetic action

100
Q

How do b-antagonists cause antianginal effects?

A

Slowing of the heart muscle

Decreased metabolic demand

101
Q

How are uptake 1 inhibitors used ?

A

Increase the effects of NA through interfering with the main method of terminating NA action

102
Q

How do sympathomimetic amines work?

A

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
Q

What is carbidopa used for clinically?

A

Reduces the peripheral sympathetic activity when used as an adjunct with levodopa

104
Q

How does methyldopa work as an antihypertensive?

A

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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