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Pharmacology year 2 > Year 1 sympathetic nervous system > Flashcards

Year 1 sympathetic nervous system Flashcards

1
Q

What is the sympathetic nervous system?

A

“Fight or flight” Blood pressure/heart rate increase, digestive slowing.

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2
Q

describe the pathway of noradrenaline at the adrenergic nerve terminal

A
  1. noradrenaline (NA) vesicle in the presynaptic neurone is stimulated by action potentials to fuse to the membrane and release NA
  2. NA is in the synapse now and one pathway is to bind to the postsynaptic adrenoreceptor on the effector cell and stimulate it
  3. another pathway for NA in the synapse is to be uptaken into the effector cell via OCT3, where NA can be metabolized by COMT
  4. another pathway for NA in the synapse is to be uptaken back into the presynaptic neurone via NA transporter where it can either be metabolised by MAO or put back into vesicles by VMAT2
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3
Q

What are catecholamines?

A

dopamine, noradrenaline, adrenaline
- catechol = 6 C ring with 2 OH groups
- amine = NH2 group

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4
Q

what is the synthesis of catecholamines?

A
  1. tyrosine + tyrosine hydroxylase = L-DOPA
  2. L-DOPA + DOPA decarboxylase = dopamine
  3. dopamine + dopamine beta-hydroxylase = noradrenaline
  4. noradrenaline + phenylethanolamine N-methyl transferase = adrenaline
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5
Q

What are adrenoreceptors?

A

alpha 1, alpha 2, beta 1, beta 2, beta 3
- G coupled receptors

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6
Q

what adrenoreceptors are adrenaline selective for?

A
  • a1, a2, B1, B2
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7
Q

what adrenoreceptors are noradrenaline selective for?

A
  • a1, a2, B1, B3
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8
Q

what adrenoreceptors are isoprenaline (synthetic catecholamine) selective for?

A
  • B1, B2, B3
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9
Q

What do a1 receptors do?

A
  • coupled to Gq = stimulated PLC, which increases IP3/DAG pathway which increases cell Ca = smooth muscle contraction (except GI tract)
  • adrenaline or noradrenaline
    = causes vasoconstriction = increase BP
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10
Q

what do a2 receptors do?

A
  • coupled to Gi = inhibits adenyl cyclase, which decreases cAMP, which reduces Ca influx and thus exocytosis of NA, thus reduces contractions, heart rate, BP…
  • so causes pre-synaptic inhibition by auto (sympathetic nerve terminals) or hetero (nerve terminals of other neurones) receptors
  • they are also post-junctional = e.g. smooth muscle contraction inhibition of insulin release and platelet aggregation
  • adrenaline or noradrenaline
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11
Q

What do B1 receptors do?

A
  • coupled to Gs, which stimulates adenyl cyclase, which increases cAMP:
  • heart = increased cAMP = increased Ca influx which increases rate of action potentials and force of contractions, thus increasing heart rate
  • juxtaglomerular apparatus = increased cAMP = release of renin, which leads to the production of angiotensive 2 which causes vasoconstriction and Na/H2O reabsorption
  • white adipose tissue = increased cAMP = increased lipolysis, so release fatty acids for energy
  • adrenaline or noradrenaline
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12
Q

What do B2 receptors do?

A
  • coupled to Gs, which stimulates adenyl cyclase, which increases CAMP, stimulates smooth muscle relaxation
  • skeletal muscle vasculature = vasodilation, decrease BP
  • bronchial smooth muscle = bronchodilation
  • uterine smooth muscle = relaxation (no labor)
  • pancreas = stimulates insulin release
  • liver = stimulates glycogenolysis
  • skeletal muscle = stimulates glycogenolysis and lactate release
  • white adipocytes = stimulate lipolysis
  • adrenaline only
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13
Q

What do B3 receptors do?

A
  • coupled to Gs or Gi
  • brown adipose tissue = increase lipolysis ad thermogenesis (uncouples fatty acid oxidation from ATP production by having pathways for H+ to escape, thus releasing wasted energy as heat)
  • bladder smooth muscle = relaxation
  • vasculature = vasodilation (nitric oxide release from endothelium)
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14
Q

What does adrenaline do?

A
  • wide range of effects = many receptors
  • effects BP (depends on dose)
  • relaxes bronchiole smooth muscle
  • causes increased breakdown of glycogen into glucose
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15
Q

what are some clinical uses of adrenaline?

A
  • anaphylactic shock =
    systemic histamine release: laryngeal oedema, hypotension, bronchospasm
    i.m adrenaline use (epi-pen): vasoconstriction (a1) reduces laryngeal oedema, increases BP and bronchodilator (B2)
  • cardiac arrest
  • prolongation of action of local anesthetics
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16
Q

gives some examples of a1 agonists

A
  • noradrenaline = circulatory shock, increase BP
  • phenylephrine = nasal decongestants
17
Q

What are ergot alkaloids?

A

These are alpha adrenoreceptor antagonists that are produced by parasitic fungi

18
Q

give some examples of ergot alkaloids

A
  • ergometrine = causes vasocontriction so used to reduce postpartum haemorrhage
  • ergotamine = treat acute migraines
19
Q

give some examples of a2 agonists

A
  • bromonidine = treat glaucoma ( decreases aqueous humour production)
  • demedetomidine = sedative
  • clonidine = old anithypertnesive
20
Q

give an example of a B1 agonist

A

dobutamine = cardiac inotrope (increase cardiac output)

21
Q

give an examples of B2 agonists

A

salbutamol / salmeterol = asthma, premature labour

22
Q

give an example of a B3 agonist

A

mirabegron = treat overactive bladder

23
Q

give some examples of noradrenaline uptake blockers

A
  • prevent presynaptic neurone from uptaking NA via NA transporter
  • so more NA stays in synapse and increases stimulation of adrenoreceptors
  • e.g. cocaine, tricyclic antidepressants, reboxetine
24
Q

What do MAO inhibitors do?

A

block break down of catecholamines, e.g. Noradrenaline
- can be used as antidepressants e.g. phenelzine and moclobemide

25
Q

What is the baroreceptor reflex?

A

Autonomic response to changes in blood pressure detected by baroreceptors in the carotid artery and aortic arch.
- decrease in blood pressure = decreased stimulation of baroreceptors in the aortic arch and carotid sinuses
- this sends signals to the medulla which then increases the activity of vascular and cardiac sympathetic efferents
- this increases vasoconstriction, which increases heart rate and increases blood pressure

26
Q

how does noradrenaline affect pulse rate, blood pressure and blood vessel resistance?

A
  • pulse rate = decrease
  • blood pressure = increase
  • blood vessel resistance = increase (vasoconstriction)
27
Q

how does adrenaline affect pulse rate, blood pressure and blood vessel resistance?

A
  • pulse rate = increase
  • blood pressure = depends on dose (low dose = B = decrease BP, high dose = a = increase BP)
  • blood vessel resistance = decrease (vasodilation)
28
Q

how does isoprenaline affect pulse rate, blood pressure and blood vessel resistance?

A
  • pulse rate = increase
  • blood pressure = slight decrease, but depends on dose
  • blood vessel resistance = decrease (vasodilation)
29
Q

what are the 3 main types of G proteins?

A

Gs, Gi, Gq

30
Q

What does Gi do?

A

inhibits adenyl cyclase, which decreases levels of cAMP in the cell, which can decrease the next molecule amount, e.g. PKA
- overall slows things down e.g. heart rate, blood pressure…

31
Q

What does Gq do?

A

activates phospholipase C, which cleaves a phospholipid from the membrane to PIP2, which is then cleaved into DAG and IP3.
IP3 increase can open calcium channels in the endoplasmic reticulum, increasing calcium levels in the cell = muscle contraction
- overall speeds things up, e.g. contractions, blood pressure, heart rate…

32
Q

What does Gs do?

A

stimulates adenylate cyclase, which increases levels of cAMP in the cell, which can increase the next molecule in the cascade amount e.g. PKA
- overall speed things up e.g. heart rate, blood pressure…

33
Q

What receptors are associated with Gi?

A
  • Beta 2, = decrease heart rate and contractility of atria
  • α2 = decrease sympathetic, decrease insulin release, decrease lipolysis, decrease aqueous humour production, increase platelet aggregation
  • Dopamine 2,3,4 = increases transmitter release in the brain
  • GABA(B) receptor
  • Glutamate mGlu (2-8)
  • Histamine 3,4
  • serotonin 5-HT 1,5
  • opioid
  • prostaglandin
    -somatostatin
34
Q

what receptors are associated with Gq?

A
  • Beta 1,3 = (1) CNS, enteric system (3) increase exocrine secretion, increase gut peristalsis, increase bladder constriction, increase eye muscle contractions
  • a1 = increase smooth muscle contraction (including intestinal + bladder),
  • Histamine 1
  • serotonin 5-HT 2
  • vasopressin 1
  • angiotensin 2
35
Q

what receptors are associated with Gs?

A
  • B1,2,3 = (1) increase heart rate, increase contractility, increase lipolysis, increased renin release, (2) vasodilatation, bronchodilation, increase lipolysis, increase insulin, increase aqueous humor productions (3) increase lipolysis
  • Dopamine 1
  • Histamine 2
  • serotonin 5-HT 4,7
  • vasopressin 2
  • ACTH
  • CRHR
  • FSH
  • GIP
  • glucagon
  • Growth hormone-releasing
  • LH
  • olfactory
  • secretin
  • prostaglandin

Pharmacology year 2 (8 decks)

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