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Introduction to medicine (Year 1) > Physiology + pharmacology Sympathetic > Flashcards

Physiology + pharmacology Sympathetic Flashcards

- Outline the effects of the fear-fight-flight response on the body - Describe the effect of stimulating the sympathetic nervous system and different adrenoceptors involved in the heart, blood vessels, kidney, metabolism, GI tract, eye, lungs, and sweat glands - Describe adrenergic neurotransmission, and how drugs may alter release and termination of noradrenaline - Outline different adrenoreceptor subtypes and their associated intracellular pathways, and the effects of adrenoreceptor agonists a

1
Q

Where are the pre-ganglionic sympathetic neurones located?

A
  • Thoracolumbar region
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2
Q

What are the biological effects of the sympathetic nervous system on the body?

A

Initiates fear-fight-flight response
- Increased heart rate + contractility
- Increased cardiac output
- Increased vasoconstriction
- Increased blood pressure
- Increased air into lungs
- Increased oxygen uptake/carbon dioxide removal
- Dilation of pupils, increased light into eyes, better vision
- Increased fuel to muscles: breakdown glycogen/lipids
- Increased sweating: temperature regulation
- Decrease non-essential functions (decreased GI tract activity etc) - limits energy use

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3
Q

What organs does the sympathetic nervous system act on?

A
  • Heart
  • Blood vessels (arteries, veins etc)
  • Kidney
  • Metabolism
  • Lungs
  • Eye
  • Sweat gland
  • GI tract
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4
Q

Which receptor does noradrenaline and adrenaline act on in the heart?

A

Beta 1 adrenoceptors

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5
Q

Which receptor does noradrenaline and adrenaline act on in blood vessels?

A

Alpha 1 adrenoceptors

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6
Q

What is the effect of stimulation of the sympathetic nervous system on the heart?

A
  • Noradrenaline and adrenaline act at B1 adrenoceptors on heart
  • On SAN- increases generation of electrical acuity which increases heart rate- chronotropic effect
  • On cardiac muscle cells- increases force of contraction of atria and ventricles, increases stroke volume
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7
Q

Define stroke volume

A

Volume of O2 pumped by heart’s left ventricle

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8
Q

How do you calculate cardiac output?

A

Stroke volume X heart rate

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9
Q

What is the effect of stimulation of the sympathetic nervous system on blood vessels?

A
  • Noradrenaline and adrenaline act at alpha 1 -adrenoceptors on blood vessels
  • Vasoconstriction (constriction of arterioles) - Increases blood vessel resistance (TPR - total peripheral resistance)
  • Venoconstriction - constriction of veins, increases returns of blood to heart, increasing cardiac output
  • Overall, all of this combines, then leads to an increase in blood pressure
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10
Q

How do you calculate blood pressure?

A

CO X TPR

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11
Q

What is the effect of stimulation of the sympathetic nervous system on the kidneys?

A
  • Noradrenaline acts at B1- adrenoceptors (on afferent arterioles) to release renin from prorenin
  • Renin causes production of angiotensin II (Ang II) from angiotensinogen
  • Ang II increases blood pressure
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12
Q

What is the effect of the sympathetic nervous system on liver and skeletal muscle (metabolism)?

A
  • Stimulation of alpha/beta adrenoceptors
  • Breaks down glycogen into glucose (glycogenolysis)
  • Promotes glucose synthesis (gluconeogenesis)
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13
Q

What is the effect of the sympathetic nervous system on the pancreas (metabolism)?

A
  • Stimulation of alpha/beta adrenoceptors
  • Decreased insulin response, which normally ‘stores glucose’
  • Increased glucagon due to increased conversion of glycogen stores into free glucose
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14
Q

What is the effect of the sympathetic nervous system on Adipose tissue (metabolism)?

A
  • Stimulation of Beta 3 adrenoceptors
  • Increased lipolysis: triglycerides broken down into free fatty acids + glycerol
  • Both increase ATP levels for energy
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15
Q

What is the effect of the sympathetic nervous system on GI tract?

A
  • Stimulation of alpha and B2 adrenoceptors
  • Activation of alpha 1 adrenoceptors evokes contraction of bladder shincter
  • B2 adrenoceptors induces relaxation of smooth muscle allowing filling
  • Bowel/bladder function non-essential during ‘fear-fight-flight’
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16
Q

What is the effect of the sympathetic nervous system on the lungs?

A
  • Receive sympathetic innervation
  • Bronchioles contain Beta 2 adrenoceptors which are activated by circulating adrenaline released from adrenal glands to produce bronchodilation
  • Facilitates breathing
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17
Q

What is the effect of the sympathetic nervous system on the eyes?

A
  • Stimulation of alpha1 adrenoceptors on dilator papillae (radial muscle of iris) dilates pupil- increase light on retina- more acute sight
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18
Q

What is the effect of the sympathetic nervous system on the sweat glands?

A
  • Release of ACh and this binds to Mus receptors, induces sweating- temperature control
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19
Q

What is adrenergic transmission?

A
  • Transmission of noradrenaline at a synapse or neuroeffector junction (post ganglionic synaptic terminals and CNS)
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20
Q

What type of receptors are adrenergic receptors?

A

GPCRs

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21
Q

What are the different types of adrenergic receptors and where are they?

A
  • Alpha 1 - Pupils, GI tract, skin, glands, urinary tract, blood vessels
  • Alpha 2 - regulate release of catecholamines (adrenaline, noradrenaline)
  • Beta 1 - Heart, urinary tract
  • Beta 2 - lungs, skeletal muscle, blood vessels, coronary blood vessels
  • Beta 3 - bladder, fat cells
22
Q

Describe what happens at the adrenergic synapse

A
  • Where drug therapy can be applied
  • At pre-synaptic terminal, NA synthesised, packaged into vesicle
  • Vesicle moves toward nerve end terminal, fuse with pre-synaptic membrane, release contents via exocytosis into synaptic cleft
  • Post- synaptic membrane (heart, blood vessels) acts at different receptors (alpha 1, beta 1, beta 2)
  • After NA produced its effects, it can be taken back into the pre-synaptic terminal by an uptake transporter- this is how response is terminated and this is the alpha 2 receptor
  • When it has been taken back up, it can be recycled back into the vesicle (by uptake transporters) OR can be broken down by the enzyme monoamine oxidase (MAO)
23
Q

What is the negative feedback system at the
adrenergic synapse?

A
  • If lots of NA released, they acts at alpha 2 adrenoceptors that are at the presynaptic terminal
  • When the alpha 2 adrenoceptors are stimulated, the release of the neurotransmitter at the pre-synaptic terminal is switched off, which will decrease the noradrenaline released, because it inhibits the motility of the vesicle to the pre-synaptic membrane
24
Q

What happens if the neurotransmitter binds to alpha 1 receptors?

A

Vasoconstriction increases as alpha 1 receptors are present on blood vessels

25
Q

What happens if the neurotransmitter binds to Beta 1 receptors ?

A

Increased cardiac contraction, as Beta 1 receptors are present at the heart

26
Q

What happens if the neurotransmitter binds to Beta 2 receptors ?

A
  • Increased bronchodilation as Beta 2 receptors line the airways
27
Q

How are noradrenaline and adrenaline synthesised?

A
  • Tyrosine is converted to DOPA via tyrosine hydroxylase in the cytoplasm
  • DOPA is converted to dopamine via DOPA decarboxylase
  • Dopamine is converted to noradrenaline via dopamine hydroxylase
  • Noradrenaline is converted into adrenaline via phenylethanolamine- N- methyl transferase (PNMT). This enzyme is found in the adrenal medulla
  • The adrenal medulla, which is the main site for adrenaline release
28
Q

What is ephedrine?

A
  • An adrenaline drug
29
Q

How can drugs facilitate the release of noradrenaline?

A
  • Amphetamine/ ephedrine- Inhibit reuptake transporters, increasing levels of NO (and DA) in synaptic cleft. They can also act as a CNS stimulant
30
Q

How can drugs inhibit the release of noradrenaline?

A
  • Guanethidine- Competes with NA for inclusion into vesicles/NA release/distribution, reducing NA release
  • Clonidine- alpha 2 agonist, specifically stimulates pre-synaptic alpha 2 receptors in brain, reducing NA release by preventing motility of vesicle to fuse with pre-synaptic membrane

These drugs may be used in hypertensive emergencies to reduce sympathetic activity, e.g. reduce peripheral resistance in blood vessels, reduce heart rate, reduce blood pressure

31
Q

How can drugs terminate the inhibition of noradrenaline?

A
  • Monoamine oxidase (MOA) can break down NT
  • Drugs like cocaine inhibit reuptake transporters, stopping reuptake of NA, so NA (and DA- dopamine) in synaptic cleft, increases sympathetic responses
  • Cocaine acts like this due to its high affinity for the reuptake transporters on the pre-synaptic membrane, preventing the binding of NT, hence inducing the increase of sympathetic responses
32
Q

How to most drugs that modulate the sympathetic nervous system work?

A
  • Via activating (agonists) or blocking (antagonists) adrenergic receptors
33
Q

What type of receptors pathways are involved when drugs modulate the sympathetic nervous system?

A

All of the G-protein receptor pathways , Gq, Gi, Gs

34
Q

What type of G protein is the alpha 1 receptor?

A
  • Gq, increases PLC which converts Pip2 into IP3 + DAG.
  • This increases release of Ca2+ and increases PKC leading to smooth muscle contraction (blood vessels, bladder, eyes)
35
Q

What type of G protein is the alpha 2 receptor?

A
  • Gi, decreases AC, leading to a decrease in cAMP
  • This decreases PKA leading to inhibition of sympathetic activity and reduced NA release
36
Q

What type of G protein are the beta 1, 2 and 3 receptors?

A
  • Gs, increases AC, increases cAMP
  • Increases PKA, leading to inhibition of smooth muscle contraction.
  • Beta 1 = heart/renal actions
  • Beta 2 = airways, blood vessels
  • Beta 3 = bladder, fat cells
37
Q

How do adrenergic receptor agonists prolong anaesthetic effect?

A
  • Adrenaline acts at alpha 1, leading to vasoconstriction, preventing loss of local anaesthetic
38
Q

What adrenergic receptor agonist has anti-obesity effects and what receptor does it act at?

A
  • BRL37344
  • Acts at Beta 3 receptor
39
Q

What adrenergic receptor agonist reduces and overactive and what receptor does it act at?

A
  • Mirabegron drug
  • Acts at beta 3 receptor, relaxes detrusor muscle
40
Q

What adrenergic receptor agonist is used in premature labour and what receptor does it act at?

A
  • Salbutamol
  • Acts at Beta 2
  • Relax myometrium (smooth muscle)
41
Q

What adrenergic receptor agonist is used for nasal decongestion and what receptor does it act at?

A
  • Phenylepherine
  • Acts at alpha 1
  • Leads to vasoconstriction of nasal vessels
42
Q

What adrenergic receptor agonist is used in asthma inhalers and what receptor does it acts act?

A
  • Salbutamol
  • Acts at beta 2
  • Relaxes airway smooth muscle, leads to bronchodilation
43
Q

What adrenergic receptor agonists act as a cardiac stimulant and what receptor does it act at?

A
  • Adrenaline/dobutamine
  • Acts at beta 1
  • Increases heart rate and contractility/stroke volume
44
Q

What adrenergic receptor agonist can be used in acute anaphylaxis and what receptors does it act at?

A

-Adenaline
- Acts at alpha 1, beta 1, beta 2
- Alpha 1 = vasoconstriction
- Beta 1 = Increase heart rate/ contractility
- Beta 3 = bronchodilation

45
Q

What adrenergic receptor antagonist has an anti-hypertensive effect and what receptor does it act at?

A
  • Prazosin
  • Acts at alpha 1, will increase vasodilation, decreasing blood pressure
46
Q

What adrenergic receptor antagonist can be used for adrenal gland tumours and what receptor does it act at?

A
  • Phenoxybenzamine
  • Acts at alpha 1
  • Prevent excess vasoconstriction due to high adrenaline levels, decreases BP
47
Q

What adrenergic receptor antagonist can be used for an underactive bladder and what receptor does it act at?

A
  • Tamsulosin
  • Acts at alpha 1
  • Relax internal sphincter muscle
48
Q

What adrenergic receptor antagonist can be used for glaucoma and what receptor does it act at?

A
  • Timolol
  • Acts at beta 2
  • Reduces secretion
  • Reduces intraocular pressure
49
Q

What adrenergic receptor antagonists can be used for angina, heart failure and arrhythmia and what receptor do they act at?

A
  • Atenlol
  • Bisoprolol
  • Act at beta 1
  • Decrease heart rate, conduction and contractility, reduce oxygen demand
50
Q

What adrenergic receptor antagonists can be used for hypertension and what receptor do they act at?

A
  • Atenlol
  • Bisoprolol
  • Act as beta 1
  • Reduce renin release
  • Decrease RAAS

Introduction to medicine (Year 1) (55 decks)

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