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CVS > Autonomic Pharmacology > Flashcards

Autonomic Pharmacology Flashcards

1
Q

List 4 effects of sympathetic stimulation of the cardiovascular system.

Give the receptor that is responsible for each effect.

A

1 - Increased heart rate (beta 1 receptors).

2 - Increased heart contractility (beta 1 receptors).

3 - Vasoconstriction (alpha 1 and 2 receptors).

4 - Vasodilation (beta 2 receptors).

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2
Q

In which layer of a vessel is the innervation found?

A

The tunica adventitia.

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3
Q

Describe the organisation of adrenoceptor subtypes.

A
  • All adrenoreceptors are alpha or beta.
  • There are 2 subtypes of alpha receptors (1 and 2).
  • There are 3 subtypes of beta receptors (1, 2 and 3).
  • There are 3 subtypes of alpha 1 receptors (alpha 1 a, b and d).
  • There are 2 subtypes of alpha 2 receptors (alpha 2 a and b).
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4
Q

Which alpha receptors are found in cardiac tissue?

Which are found in vascular tissue?

A

All alpha receptors are found in vascular tissue only.

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5
Q

Which beta receptors are found in cardiac tissue?

Which are found in vascular tissue?

A
  • Beta 1 receptors are found in cardiac tissue.

- Beta 2 receptors are found in vascular tissue.

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6
Q

List 2 alpha 1 agonists.

A

1 - Phenylephrine.

2 - Midodrine (actually a prodrug).

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7
Q

Give an example of an alpha 1 antagonist.

A

Doxazosin.

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8
Q

List 2 alpha 2 agonists.

A

1 - Clonidine.

2 - Brimonidine.

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9
Q

Give an example of a beta 1 agonist.

A

Dobutamine.

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10
Q

Give an example of a beta 1 antagonist.

A

Metoprolol.

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11
Q

Give an example of a beta 2 agonist.

A

Salbutamol.

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12
Q

List 4 effects of beta adrenoceptor stimulation in the heart.

A

1 - Increased heart rate.

2 - Increased contractility.

3 - Increased automaticity.

4 - Fast relaxation and recovery.

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13
Q

What type of receptors are adrenoceptors?

A

G protein coupled receptors.

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14
Q

Give an example of a non-selective beta agonist.

A

Isoprenaline.

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15
Q

Describe the intracellular pathway that beta receptors use to bring about their effects in the heart.

A

1 - Binding of a beta agonist to a beta receptor triggers the Gs pathway.

2 - PKA opens Ca2+ channels, allowing for faster depolarisation.

3 - PKA opens K+ channels, allowing for faster repolarisation.

4 - cAMP increases Na+/K+ ATPase activity, causing positive chronotropy by increasing the slope of the pacemaker potential.

5 - The Gs pathway also increases sarcoplasmic reticulum Ca2+ uptake by increasing SERCA activity via inhibition of phospholamban.

6 - The Gs pathway also increases Ca2+ sensitivity.

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16
Q

What type of drug is adrenaline?

A

Both a beta and alpha adrenoceptor agonist.

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17
Q

List 4 clinical uses of adrenaline.

A

1 - Used to treat asystole.

2 - Used to treat ventricular fibrillation.

3 - Used to treat anaphylaxis.

4 - When injected locally, causes vasoconstriction, so is commonly used in a mixture with local anaesthetics.

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18
Q

What is dobutamine used to treat?

A

It is used to treat cardiogenic shock by providing inotropic support.

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19
Q

Describe the intracellular pathway that alpha receptors use to bring about their effects in smooth muscle.

A

Classical pathway:

1 - Binding of an alpha agonist to an alpha receptor triggers the Gq pathway.

2 - IP3 acts on the sarcoplasmic reticulum to stimulate Ca2+ release.

Alternative pathway:

3 - PKC phosphorylates CPI-17, which activates myosin light chain kinase.

4 - Myosin light chain kinase phosphorylates the myosin, which facilitates myosin binding to actin and therefore increases contractility.

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20
Q

What is phenylephrine used to treat?

A

Nasal congestion.

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21
Q

What is midodrine used to treat?

How does it work?

A
  • Postural hypotension.

- By causing venoconstriction (it is a prodrug for an alpha 1 agonist).

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22
Q

With which drug might you administer with midodrine to treat postural hypotension?

Why would this work?

A
  • Fludrocortisone.

- Fludrocortisone is a mineralocorticoid that increases circulating volume, which will help treat the hypotension.

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23
Q

What is droxidopa?

A

A prodrug for noradrenaline.

24
Q

What is droxidopa used to treat?

A

Postural hypotension in autonomic failure.

25
Q

What is clonidine used to treat?

How do drugs of its class work?

A
  • Hypertension.

- Alpha 2 agonists work by decreasing sympathetic drive in the CNS.

26
Q

What is brimonidine used to treat?

A

Rosacea.

27
Q

What type of drug is doxazosin?

A

An alpha 1 antagonist.

28
Q

What is doxazosin used to treat?

How do drugs of its class work?

A
  • Hypertension.

- Alpha 1 antagonists cause vasodilation because alpha 1 stimulation causes vasoconstriction.

29
Q

What type of drug is propranolol?

A

A beta 1 and beta 2 antagonist.

30
Q

What type of drug is atenolol?

A

A beta 1 antagonist.

31
Q

List 4 effects of beta antagonists.

A

1 - Negative chronotropic actions.

2 - Negative inotropic actions.

3 - Inhibits automaticity.

4 - Inhibits platelet aggregation.

32
Q

List 4 conditions that can be treated with beta blockers.

A

1 - Angina.

2 - Heart failure.

3 - Cardiac arrhythmias.

4 - Hypertension.

33
Q

What type of drug is carvedilol?

A
  • A mixed beta and alpha adrenoceptor antagonist.

- An inhibitor of a particular cardiac K+ channel.

34
Q

What is carvedilol used to treat?

A

Heart failure.

35
Q

If beta 2 receptors cause vasodilation, why do beta blockers decrease blood pressure? List 3 reasons.

A

1 - Antagonising beta 1 receptors reduces cardiac output, especially during exercise.

2 - Beta 1 receptors in the kidney lead to renin release, which leads to the production of angiotensins, which cause vasoconstriction and fluid retention.

3 - Beta antagonists inhibit the trophic effect of catecholamines in the heart, and hence inhibit cardiac hypertrophy associated with both hypertension and heart failure.

36
Q

Other than antagonising the effects of beta 1 agonists, how might beta antagonists decrease blood pressure in the context of chronic hypertension?

A

By resetting baroreceptors.

37
Q

List 2 effects of parasympathetic stimulation of the heart.

A

1 - Negative chronotropic effect through action at the sinoatrial node.

2 - Reduction of AV node conduction speed.

38
Q

Give an example of an effect of parasympathetic stimulation of vascular tissue.

A

Vasodilation by stimulating nitric oxide release, however the effect is limited due to limited innervation, despite the ubiquity of endothelial mAChRs.

39
Q

List 2 parasympathetic signalling pathways in the heart.

A

1 - Direct G-protein mediated activation of M2 muscarinic potassium channels.

2 - Inhibition of adenylyl cyclase, opposing PKA mediated actions.

40
Q

What type of drug is atropine?

A

A muscarinic antagonist.

41
Q

What type of drug is pilocarpine?

A

A muscarinic agonist.

42
Q

List 6 non-cardiac effects of muscarinic antagonism.

A

1 - Decreased secretions in the mouth, airways and gut.

2 - Bronchodilation.

3 - Constipation.

4 - Urinary retention.

5 - Pupillary dilation.

6 - Confusion / hallucinations.

43
Q

What is atropine used to treat?

A

Supraventricular bradycardia.

44
Q

Describe the intracellular pathway that leads to the release of monoamines into muscles from vascular tissue.

A

1 - Tyrosine is converted into DOPA.

2 - DOPA is converted into dopamine by DOPA decarboxylase.

3 - Dopamine may be converted into noradrenaline or may remain as dopamine to be transported to the muscle.

4 - Some of the monoamine is broken down by monoamine oxidases.

5 - The rest is transported by vesicular monoamine transporter (VMAT) out of the endothelium.

6 - Some of the monoamine diffuses into myocytes.

7 - Some of the monoamine returns to the vasculature. Reuptake of noradrenaline is mediated by noradrenaline transporter (NAT) in a process called ‘uptake 1’.

45
Q

What type of transporter is noradrenaline transporter (NAT)?

A

A secondary active transporter (requiring Na+ and Cl-).

46
Q

List 2 drugs that block noradrenaline transporter (NAT).

A

1 - Cocaine.

2 - Tricyclic antidepressants such as imipramine.

47
Q

Give an example of an effect of noradrenaline transporter (NAT) blockers.

A

Arrhythmias.

48
Q

How do sympathomimetic amines cause positive inotropy?

A

By causing reversal of noradrenaline transport, resulting in release rather than uptake.

49
Q

List 3 sympathomimetic amines.

A

1 - Tyramine.

2 - Ephedrine.

3 - Amphetamine.

50
Q

Give an example of a source of tyramine.

A

Cheese.

51
Q

Why might monoamine oxidase inhibitors result in positive inotropy?

A

Because less monoamine is broken down, so more is released into the circulation.

52
Q

List the subtypes of monoamine oxidases.

A

1 - Monoamine oxidase A.

2 - Monoamine oxidase B.

53
Q

List 3 monoamine oxidase inhibitors.

Which of these exhibits selectivity? For which subtype of monoamine oxidase is the drug selective?

A

1 - Phenelzine.

2 - Iproniazid.

3 - Selegiline - selective for monoamine oxidase B.

54
Q

What is the first line treatment for hypertension in pregnancy?

A

Methyldopa.

55
Q

How does methyldopa work?

A

Two mechanisms:

1 - By inhibiting DOPA decarboxylase, resulting in less peripheral NAd.

2 - Methyldopa is converted into methylnoradrenaline, an alpha 2 agonist.

CVS (18 decks)

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