6 Autonomic Pharmacology Flashcards
What are the general effects of sympathetic stimulation on the CVS through different receptors?
B1 - increased heart rate and contractility
regulation of renin release
B2 - some vasodilation
A1 + 2 - vasoconstriction
What does beta adrenoreceptor activation do to the heart?
+ chronotropic
+ inotropic
increased automaticity
lusitropic effect
What is a + chronotropic effect?
increased HR
What is a + inotropic effect?
increased contractility rate
What is the lusitropic effect?
fast relaxation and recovery
What intracellular pathways are associated with B1 activation?
increased Ca2+ entry increased Ca2+ sensitivity increased SR Ca2+ uptake increased I(K) for faster repolarisation increased Na+ / K+ ATPase activity increased I(f)
What is the significance of an increased I(f) during B1 activation?
+ chronotropy
What is the significance of increased SR Ca2+ uptake?
lucitropic effect
Name 2 clinical agonists of B1
Adrenaline
Dobutamine
What is adrenaline used for?
asystole
anaphylaxis
when injected locally, causes vasoconstriction (commonly used with Lidocaine)
What is Dobutamine used for?
used to treat cardiogenic shock
usually only seen in ICU
What is the classical a1 adrenorecptor intracellular pathway?
IP3 mediated Ca2+ from SR
Name 2 a1 agonists used clinically
phenylephrine
midodrine
What is phenylephrine used for?
vasoconstrictant, nasal decongestant
is in Sudafed
What is midodrine used for?
venoconstriction (keeps up total peripheral resistance so blood is shunted centrally)
used for postural hypotension
What is postural hypotension treated with?
midodrine (venoconstriction)
fludocortisone (steroid, increases circulating volume)
What is Droxidopa?
prodrug for NAd
used for short term treatment of postural hypotension in autonomic failure
Name 2 a2 agonists
Clonidine
Brimonidine
What does Clonidine do?
alpha-2 agonist
centrally acting antihypertensives
decreases sympathetic drive
What does Brimonidine do?
direct ranscutaneous vasoconstriction
for Rosacea
Name 5 adrenoreceptor antagonists used clinically
Doxazosin (a1)
Beta Blockers
propranalol (1, 2)
metoprolol (1)
atenolol (1)
Carvedilol (mixed)What does Doxazosin do?
What is it used for?
a1 antagonist
vasodilation
treats hypertension and Raynaud’s syndrome
What is Raynaud’s syndrome?
limits circulation particularly in the hands and feet
What 4 main things do beta blockers do?
- chronotropy
- inotropy
- automaticity
anti-platelet aggregation
What are beta blockers used to treat?
angina
heart failure
cardiac arrhythmias
hypertension
What does Carvedilol do?
mixed B and A antagonist inhibits cardiac K+ chanel, leading to a class III antiarrhythmic action
used for heart failure
What is the implication of using Carvedilol to treat HF?
beat blockers themselves decrease cardiac workload
many with heart failure also have hypertension
so blocking alpha receptors peripherally, can cause BP to decrease
What problem is associated with decreased cadiac output by beta blockers?
may lead to a ‘resetting of baroreceptors’
What are the 3 effects of parasympathetic innervation of the heart?
Vagal rhythm
Negative chronotropy through SAN
Slow AVN conduction
little effect on myocardial contractility
What is the intracellular mechanism associated with M2 receptors?
G(i), inhibits adenyl cyclase
Name a muscarinic antagonist
atropine
What effects does atropine have on the body?
decreased secretions bronchodilation constipation urinary retention pupillary dilation confusion / hallucination
According to the BNF, when is atropine used?
to reverse bradycardia
- following MI w/ hypotension
- XS beta blocker use
- intra-operatively
In what 2 ways can noradrenaline be taken in?
neuronal
non-neuronal
What is neuronal uptake of NAd mediated by?
Noradrenaline Transporter
Name 2 NAT blockers
cocaine tricylic antidepressants (like imipramine)
Name 2 monoamine oxidase inhibitors
phenelzine
iprozinad
What is the MOA of Methyldopa?
DOPA decarboxylase inhibition
converted by dopamine beta hydroxylase to alpha methylnorepinephrine, an a2 agonist, dropping central sympathetic drive
What is methyldopa used for?
treatment of hypertension in pregnancy
Name 3 indirectly acting sympathomimetic amines
tyramine
ephedrine
emphetamine
(substrates for NAd transporter blocker)
Where would you find tyramine?
cheese
