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NAS > Overview of the Pharmacology of the Autonomic Nervous System > Flashcards

Overview of the Pharmacology of the Autonomic Nervous System Flashcards

1
Q

What are the breakdown products of acetylcholine by acetylcholinesterase?

A

Choline and acetate.

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2
Q

Give an example of an anticholinesterase. What could this be used to treat?

A

Neostigmine.

Myasthenia Gravis.

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3
Q

What is hexamethonium?

A

An antagonist for nicotinic receptors.

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4
Q

How many transmembrane segments comprise muscarinic receptors?

A

7

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5
Q

How many subtypes of muscarinic receptors are there?

A

5 (M1, M2, M3, M4, M5)

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6
Q

What are parasympathomimetic drugs?

A

Drugs that mimic the effects of parasympathetic stimulation.

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7
Q

What is glaucoma and how can it be treated?

A

An eye condition where the optic nerve is damaged by high pressure of fluid in the eye.

Treat using pilocarpine or timolol.

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8
Q

What is the mechanism of action of pilocarpine for treating glaucoma?

A

Pilocarpine is an agonist for M3 muscarinic receptors on the ciliary muscle of the eye.

This improves drainage of aqueous humour (similar to plasma but lower protein concentrations).

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9
Q

Where can M1 muscarinic receptors be found?

A

In the stomach.

In salivary glands.

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10
Q

Where can M2 muscarinic receptors be found?

A

In cardiac tissue.

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11
Q

Where can M3 muscarinic receptors be found?

A

In smooth muscle tissue.

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12
Q

List 5 muscarinic antagonists.

A

IATTH: Ibrahim Ali tortures the homeless.

Ipratropium
Atropine
Tropicamide
Tolterodine
Hyoscine
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13
Q

What is ipratropium used for?

A

Treating asthma.

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14
Q

List 2 uses of atropine.

A

Treating bradycardia.

Decreasing secretions during operations.

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15
Q

What is tropicamide used for?

A

Dilating the pupils.

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16
Q

What is tolterodine used for?

A

Treating urinary incontinence.

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17
Q

What is hyoscine used for?

A

Treating motion sickness.

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18
Q

How many subtypes of adrenoceptors are there?

A

5:

a1, a2, b1, b2, b3

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19
Q

What are the effect(s) of stimulating a1 adrenoceptors?

A

Smooth muscle contraction (e.g. vasoconstriction and GIT smooth muscle constriction).

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20
Q

What are the effect(s) of stimulating a2 adrenoceptors?

A

Presynaptic inhibition of sympathetic outflow by inhibiting the release of noradrenaline (a negative feedback mechanism).

21
Q

What are the effect(s) of stimulating b1 adrenoceptors?

A

Increase heart rate and contractility.

22
Q

What are the effect(s) of stimulating b2 adrenoceptors?

A

Smooth muscle relaxation (i.e. vasodilation and bronchodilation).

23
Q

What are the effect(s) of stimulating b3 adrenoceptors?

A

Smooth muscle relaxation in the bladder wall.

Stimulates lipolysis.

24
Q

List 4 clinical uses of a-adrenoceptor agonists.

Give an example of a drug for each use.

Give the name of the alpha adrenoceptor subtype targeted by each drug.

A

To treat anaphylactic shock. (α/β)
-Adrenaline and noradrenaline.

To treat hypertension (α2)
-Clonidine

Nasal decongestants. (α1)
-Phenylephrine.

To treat erythema (redness of skin due to hyperemia / increased blood flow) in rosacea. (α2)
-Brimonidine

25
Q

What type of receptors are adrenoceptors?

A

G-protein coupled receptors.

26
Q

What type of alpha subunit are a1-adrenoceptors associated with?

A

Gq:

Activates phospholipase C -> DAG -> IP3 + PKC.

27
Q

What type of alpha subunit are a2-adrenoceptors associated with?

A

Gs:

Activates adenylyl cyclase, ATP -> cAMP -> PKA.

28
Q

What type of alpha subunit are all b-adrenoceptors associated with?

A

Gs:

Activates adenylyl cyclase, ATP -> cAMP -> PKA.

29
Q

What type of alpha subunit are M1, M2 and M3 muscarinic receptors associated with?

A

M1 and M3 are Gq:

Activates phospholipase C -> IP3 + DAG etc.

M2 are Gs:

Activates adenylyl cyclase, ATP -> cAMP -> PKA.

30
Q

List 2 clinical uses of a-adrenoceptor antagonists.

Give an example of a drug for each use.

Name the subtype of alpha adrenoceptor targeted by each drug.

A

To treat hypertension. (a1)
-Doxazosin

To treat benign prostatic hyperplasia. (a1)
-Tamsulosin

31
Q

List 5 clinical uses of b-adrenoceptor agonists.

Give an example of a drug for each use.

Name the subtype of beta adrenoceptor for each drug.

A

1 - To treat cardiogenic shock. (β1)
– adrenaline, dobutamine

2 - To treat anaphylactic shock. (α/β)
– adrenaline

3 - To treat asthma. (β2)
and
4 - To delay premature labour. (β2)
- salbutamol

5 - To treat bradycardia. (β1)
- dobutamine

32
Q

List 6 clinical uses of b-adrenoceptor antagonists.

A

Metropolol:

  • To treat angina. (β1)
  • To treat cardiac arrhythmias. (β1)
  • To treat hypertension. (β1)
  • To treat anxiety. (β1)
  • To treat chronic heart failure. (β1)

Timolol:

•To treat glaucoma. (β1 and β2)

33
Q

Starting from tyrosine, what are the intermediates in NAd synthesis?

A

Tyrosine -> DOPA -> Dopamine -> NAd

34
Q

What is the name of the transporter that is responsible for NAd exocytosis?

A

VMAT (vesicular monoamine transporter)

35
Q

What is the name of the transporter that is responsible for NAd uptake to the adrenal medulla?

A

NAT (Noradrenaline transporter)

36
Q

What are the 3 main catecholamines?

A

Dopamine

Adrenaline

Noradrenaline

  • Catecholamines are basically all of the monoamines except serotonin.
37
Q

List 4 monoamine neurotransmitters.

A

Dopamine

Serotonin

Adrenaline

Noradrenaline

38
Q

What is the main mechanism for terminating the actions of NAd at the synapse?

A

Uptake of NAd by NAT transporter.

39
Q

What type of transporter is NAT?

A

A secondary active transporter (cotransporter).

40
Q

What is cotransported with catecholamines at NAT cotransporters?

A

Na+ and Cl-

41
Q

List 2 agents that inhibit catecholamine reuptake.

A

Cocaine

Tricyclic antidepressants

42
Q

What is desipramine?

What are its adverse effects?

A

A tricyclic antidepressant.

Adverse effects:

  • Tachycardia
  • Dysrhythmia
43
Q

List 4 effects of cocaine.

A
  • Euphoria.
  • Tachycardia.
  • Increased peripheral BP.
  • Local anaesthesia.
44
Q

What are MAOIs used to treat?

How do they work?

List 5 adverse effects.

A

Used as antidepressants.

Work by blocking MAO, usually irreversibly. This increases levels of monoamines (adrenaline, noradrenaline, dopamine and serotonin).

Adverse effects:

  • Postural hypotension (low BP after standing up, due to some MAOIs preventing the release of noradrenaline from sympathetic nerve endings)
  • Weight gain
  • Restlessness
  • Insomnia
  • Cheese reaction!!!
45
Q

List 4 examples of mono-amine oxidase inhibitors.

A

Phenelzine

Tranylcypromine

Iproniazid

Moclobemide (reversible)

46
Q

List 3 examples of indirectly acting sympathetic amines.

A

Amphetamine

Ephedrine

Tyramine

47
Q

How do indirectly acting sympathetic amines work?

A
  • Transported into nerve terminals and into vesicles.
  • Displace noradrenaline, which leaks out via NAT (reverse transport).
  • Similar effect on dopamine and serotonin in CNS (this underlies their use as substances of abuse).
  • Long lasting effects.
48
Q

What do monoamine oxidases do?

A

Metabolise cytoplasmic monoamines, reducing their concentration.

NAS (16 decks)

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