Cardiovascular Autonomic Pharmacology Flashcards
Describe the organisation of the autonomic nervous system in terms of neurones and neurotransmitters
Sympathetics
- Short preganglionic neurone –> ACh –> long postganglionic neurone –> NA
Parasympathetics
- long prehanglionc neurone –> ACh –> short postganglionic neurone –> ACh
What are the 4 cardiovascular effect of sympathetic stimulation?
- increased heart rate and contractility
- vasoconstriction
- some vasodilation
- regulation of renin release for volume control
Which adrenergic receptors are responsible for the following?
- increased heart rate and contractility
- vasoconstriction
- some vasodilation
- regulation of renin release for volume control
- B1
- a1, a2
- B2
- B1
Where are the perivascular nerves found?
Why do large vessels not respond well to sympathetic activity?
In the adventitia of blood vessels
Large vessels don’t respond well as far nerves are far away from target cells
Selective agents with CV relencance:
- a1 agonist
- a2 agonist
- B1 agonist
- B2 agonist
- phenylephrine
- clonidine
- dobutamine
- salbutamol
Selective agents with CV relevance:
- a1 antagonist
- B1 antagonist
- dozazosin
- metoprolol
What are the 4 effects of B-adrenoreceptor activation/
- increase heart rate (positive chronotropic effect)
- increased contractility rate (positive inotropic effect)
- increased automaticity (tendency to reverse owns electrical rhythm, helpful in asystole
- fast relaxation and recovery (lusitropic effect)
Intracellular pathways for B-adrenoreceptor activation
Which four channels are upregulate by beta-1 agonist and how?
What two other effects does it have
B1 agonist binds, Gs, cAMP, PKA
- Ca2+ channels - increased Ca2+ entry
- K+ leak channels for faster repolarisation
- Na+K+ATPase
- If (funny current) - positive chronotropy
- increased ER Ca2+ uptake
- increase Ca2+ sensitivity
What is the most important agonist clinically?
Where does it act?
What are its uses?
Adrenaline B and a adrenoreceptors - asystole, VF - anaphylaxis - local vasoconstriction e.g with local anaesthetics
Give an example of a B1 agonist
What is used for?
Dobutamine
- used to treat carcinogenic shock by providing ‘inotropic support’
What are the classical and alternative pathways for a1 activation in smooth muscle?
Classical pathway - Gq --> PLC --> PIP2--> InsP3 mediated Ca2+ release from SR Alternative pathways - through PKC - through rho-kinase
Give an example of an a1 agonist
What are its effects?
What is it used to treat/
phenylephrine
vasonstriction
used to treat nasal congestion - sudafed
Give an example of an a1 antagonist
What does it do?
What can it treat?
Doxazosin
- causes vasodilation
- hypertension, Raynaud’s
Give examples of betablockers
What are the actions?
What are they used to treat?
propranolol, metoprolol, atenolol
- negative chronotropic actions
- negative inotropic actions
- decrease work done by heart
- used to treat angina, heart failure, cardiac arrythmias, hypertension
Give an example of a mixed a and B antagonist
What does it do?
What is it used in?
carvediol
inhibits a particular cardiac K+ channel (TASK1), leading to class 3 antidysrhythmic action
HEART FAILURE
Why do B-blockers decrease BP?
- decerase CO, esp during exercise/stress - may lead to resting of baroreceptors
- B1 receptors in kidneys lead to renin release
- inhibit the tropic effects of catecholamines in the heart (and hence inhibit cardiac hypertrophy with both hypertension and heart failure)
What re the cardiovascular effects of parasympathetic stimulation on the heart and blood vessels?
Heart
- negative chronotropic effect through action at the SAN
- slow AVN conduction
- little effect on myocardial contractility
Blood vessels
- limited vasodilation, because limited innervation, despite widespread endothelial mAChRs
- complicated by muscarinic receptor-induced release of NO from endothelial cells
What are the two main M2-mediated pathways in the heart?
- Direct G-protein mediated activation of KACh
2. Inhibition of adenylate cyclase - opposing PKA mediated actions on a range of channels
What are the cardiac effects of atropine? Where does it act?
What are its other effects?
What is its key use?
- block cardiac M2 receptors
- decreased secretions. bronchodilation, constripation, urinary retention, pupillary dilation, confusion/hallucinations
- to treat supra ventricular bradycardia, particularly in the presence of low CO
What are the other sympathetic pathways targeted by drugs?
storage
uptake of noradrenaline
release of noradrenaline
metabolism in sympathetic neurones
Which drug affects storage of NAd?
Reserpine:
- enters sympathetic nerve terminals
- inhibits NAd transport into vesicles by inhibiting VMAT, depleting of VMAT
- historically used as an antihypertensive, but depression
Which drugs affect reuptake of NAd?
cocaine and tricyclic antidepressants e.g. imipramine
block neuronal uptake mediated by NAT (NAd transporter)
causes pro-arrythmetic effects
Which drugs affect release of NAD
Indirectly acting sympathomimetic amines
e.g. tyramine, ephedinr, amphetamine
Tyramine is found in many foods, which can cause an increase in blood pressure, particularly in conjunction with MAO inhibitors
- cause of reversal of noradrenaline transport through NET, and so cause release
Which drugs affect metabolism?
MAO
- blocker are the MAOIs e.g. phenelzineu, iproniazid
- catchall o-methyltransferase - blocked by entacapone
