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ESA1 - Physiology and Pharmacology > Drugs And The ANS > Flashcards

Drugs And The ANS Flashcards

1
Q

What does the ANS do?

A

Controls all involuntary functions (e.g. Heart rate, blood pressure etc)

Entirely efferent but regulated by afferent inputs

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2
Q

What are the two divisions of the ANS?

A

Sympathetic and parasympathetic

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3
Q

What is the vagus nerve important for?

A

Regulating the heart

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4
Q

Where do parasympathetic nerves originate from?

A

Lateral horn of the medulla and sacral spinal cord

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5
Q

What fibres do parasympathetic nerves have?

A

Long myelinated preganglionic fibres, short unmyelinated postganglionic fibres

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6
Q

Where do sympathetic nerves originate?

A

Lateral horn of the lumbar and thoracic spinal cord

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7
Q

What fibres do sympathetic nerves have?

A

Short myelinated preganglionic fibres, long unmyelinated postganglionic fibres

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8
Q

Where are the ganglia located in sympathetic nerves?

A

Paravertebral chain close to the spinal cord

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9
Q

Where are the ganglia located in parasympathetic nerves?

A

Within the innervated tissues

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10
Q

What are the principal neurotransmitters in the ANS?

A

Acetylcholine and noradrenaline

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11
Q

What are all pre ganglionic neurons?

A

Cholinergic - use ACh as their neurotransmitter

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12
Q

What does parasympathetic and sympathetic pre ganglionic release of ACh result in?

A

Activation of post ganglionic nicotinic ACh receptors

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13
Q

What are parasympathetic post ganglionic neurons?

A

Cholinergic - release ACh which acts on muscarinic ACh receptors in the target effector tissue

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14
Q

What are the 5 mACh receptor subtypes?

A

M1, M2, M3, M4 and M5

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15
Q

What are muscarinic ACh receptors?

A

GPCRs

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16
Q

What are most sympathetic post ganglionic neurons?

A

Noradrenergic - used noradrenaline as principal neurotransmitter

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17
Q

What does noradrenaline interact with?

A

a-adrenoceptors and b-adrenoceptors

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18
Q

Are all adrenoceptors GPCRs?

A

Yes

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19
Q

What are some examples of specialised sympathetic post ganglionic neurons that are cholinergic as opposed to noradrenergic?

A

Those innervating sweat glands and hair follicles

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20
Q

What are other transmitters found in the ANS called?

A

Non Adrenergic, Non Cholinergic transmitters
NANC transmitters

(May be coreleased with NA or ACh)

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21
Q

What are some examples of NANC transmitters?

A

ATP
Nitric Oxide
5-hydroxytryptamine (5HT; serotonin)
Neuropeptides (eg VIP - vasoactive intestinal peptide and substance P)

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22
Q

What does the adrenal medulla release?

A

Adrenaline

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23
Q

Where are chromaffin cells present?

A

Adrenal medulla

24
Q

Why are sympathetic postganglionic neurons in the adrenal glands different?

A

They differentiate to form neurosecretory chromatin cells which can be considered as postganglionic sympathetic neurons that do not project to a target tissue. Instead, on sympathetic stimulation, these cells release adrenaline into the bloodstream

25
Q

What does parasympathetic release of ACh cause in the heart?

A

Bradycardia and reduced cardiac conduction velocity - M2 receptors

26
Q

What does parasympathetic release of ACh cause in smooth muscle?

A

Bronchial contraction
Increased intestinal mobility and secretion

these act on M3 receptors

Bladder contraction (detrusor) and relaxation (trigone/sphincter)Emile erection
Ciliary muscle and iris sphincter contraction

Nitric Oxide generation

27
Q

What does parasympathetic release of ACh cause in glands?

A

Increased sweat/salivary/lacrimal secretion

M1/M3 receptors

28
Q

What does sympathetic release of noradrenaline cause in the heart?

A

Tachycardia and positive inotropy (b1 receptors)

29
Q

What does sympathetic release of noradrenaline cause in smooth muscle?

A

Arteriolar/venous contraction (a1, b2)
Bronchioles/intestine/uterine relaxation (b2)
Bladder sphincter contraction (b2)
Radial muscle contraction in eye (a1)

30
Q

What does sympathetic release of noradrenaline cause in the kidneys?

A

Renin release

31
Q

How is acetylcholine synthesised?

A

AcetylcoA + choline –> acetylcholine + coenzyme A

                       Choline acetyltransferase

Acetyl coA produced from pyruvate by pyruvate dehydrogenase
Choline obtained from diet

32
Q

How is acetylcholine degraded?

A

Acetyl choline —> acetate + choline

By acetylcholinesterase

33
Q

What is trimethaphan used for?

A

Hypertensive emergencies and to produce controlled hypotension during surgery

(Ganglion blocking drug)

34
Q

What is tolterodine and what is it used to treat?

A

mAChR antagonist (M3 receptors in this case)

Used to treat overactive bladder

Side effects include dry mouth

35
Q

What is pyridostigime used to treat?

A

Myasthenia graves - AChE inhibitor so actions of endogenously released ACh can be enhanced

36
Q

What can donepezil be used to treat?

A

Alzheimer’s disease

AChE inhibitor so enhances endogenous release of ACh

37
Q

What often limits the usage of cholinergic drugs?

A

Unwanted side effects - relative lack of selectivity

Eg non selective muscarinic ACh receptor agonist would decrease HR, lead to bronchoconstriction, increase sweating and salivation etc

38
Q

What is the SLUDGE mnemonic?

A

Pathological effects indicative of massive discharge of the parasympathetic nervous system

Salivation
Lacrimation
Urination
Defecation
Gastrointestinal upset
Emesis (vomiting)
39
Q

When is SLUDGE usually encountered?

A

Drug overdose
Ingestion of magic mushrooms
Exposure to organophosphorous insecticides eg parathion
Exposure to nerve gases eg sarin

40
Q

What do parathion and sarin do?

A

Covalently modify acetylcholinesterase to irreversibly deactivate the enzyme and raise acetyl choline levels

41
Q

What are the symptoms of SLUDGE primarily due to?

A

Chronic stimulation of mAChR in organs and muscles innervated by the parasympathetic nervous system

42
Q

How can SLUDGE be treated?

A

Atropine, pralidoxime or other anti cholinergic agents

43
Q

What are some examples of mAChR agonists?

A

Pilocarpine and bethanechol

44
Q

What is pilocarpine used to treat?

A

Glaucoma

45
Q

What is bethanechol used to treat?

A

Urinary retention, stimulates bladder emptying

46
Q

What are some examples of mAChR antagonists?

A

Ipratropium, tiotropium, tolterodine, darifenacin and oxybutynin

47
Q

What are ipratropium and tiotropium used to treat?

A

Asthma and COPD

48
Q

What mAChR antagonists are used to treat overactive bladder?

A

Tolterodine, darifenacin and oxybutynin

49
Q

What do post ganglionic sympathetic neurons generally possess?

A

Highly breaching atonal network with numerous varicosities, each of which is a specialised site for Ca2+ dependent noradrenaline release

50
Q

What enzyme converts noradrenaline to adrenaline in the adrenal medulla?

A

Phenylethanolamine N-methyltransferase

51
Q

Why does noradrenaline only have a limited time in which to influence pre and post synaptic adrenoceptors?

A

It is rapidly removed from the synaptic cleft by noradrenaline transporter proteins

52
Q

How are noradrenaline actions terminated?

A

Uptake 1 - re uptake into pre synaptic terminal by Na+ dependent, high affinity transporter

Uptake 2 - NA not re captured by uptake 1 is taken up by a lower affinity, non neuronal mechanism

53
Q

Which two enzymes is noradrenaline susceptible to metabolism by?

A

Monoamine oxidase (MAO)

Catechol-O-methyltransferase (COMT)

54
Q

What is an example of a b2 selective agonist?

A

Salbutamol, important that it is selective as it limits possible CV side effects

55
Q

What are two examples of adrenoceptor antagonists used in treating hypertension?

A

Doxazosin (a1 adrenoceptor selective antagonist)

Atenolol (b1 adrenoceptor selective antagonist)

ESA1 - Physiology and Pharmacology (11 decks)

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