6 Autonomic Pharmacology

Question 1

What are the general effects of sympathetic stimulation on the CVS through different receptors?

Answer 1

B1 - increased heart rate and contractility
regulation of renin release
B2 - some vasodilation
A1 + 2 - vasoconstriction

Question 2

What does beta adrenoreceptor activation do to the heart?

Answer 2

+ chronotropic
+ inotropic
increased automaticity
lusitropic effect

Question 3

What is a + chronotropic effect?

Answer 3

increased HR

Question 4

What is a + inotropic effect?

Answer 4

increased contractility rate

Question 5

What is the lusitropic effect?

Answer 5

fast relaxation and recovery

Question 6

What intracellular pathways are associated with B1 activation?

Answer 6

increased Ca2+ entry
increased Ca2+ sensitivity
increased SR Ca2+ uptake
increased I(K) for faster repolarisation
increased Na+ / K+ ATPase activity
increased I(f)

Question 7

What is the significance of an increased I(f) during B1 activation?

Answer 7

+ chronotropy

Question 8

What is the significance of increased SR Ca2+ uptake?

Answer 8

lucitropic effect

Question 9

Name 2 clinical agonists of B1

Answer 9

Adrenaline

Dobutamine

Question 10

What is adrenaline used for?

Answer 10

asystole
anaphylaxis

when injected locally, causes vasoconstriction (commonly used with Lidocaine)

Question 11

What is Dobutamine used for?

Answer 11

used to treat cardiogenic shock

usually only seen in ICU

Question 12

What is the classical a1 adrenorecptor intracellular pathway?

Answer 12

IP3 mediated Ca2+ from SR

Question 13

Name 2 a1 agonists used clinically

Answer 13

phenylephrine

midodrine

Question 14

What is phenylephrine used for?

Answer 14

vasoconstrictant, nasal decongestant

is in Sudafed

Question 15

What is midodrine used for?

Answer 15

venoconstriction (keeps up total peripheral resistance so blood is shunted centrally)

used for postural hypotension

Question 16

What is postural hypotension treated with?

Answer 16

midodrine (venoconstriction)

fludocortisone (steroid, increases circulating volume)

Question 17

What is Droxidopa?

Answer 17

prodrug for NAd

used for short term treatment of postural hypotension in autonomic failure

Question 18

Name 2 a2 agonists

Answer 18

Clonidine

Brimonidine

Question 19

What does Clonidine do?

Answer 19

alpha-2 agonist

centrally acting antihypertensives
decreases sympathetic drive

Question 20

What does Brimonidine do?

Answer 20

direct ranscutaneous vasoconstriction

for Rosacea

Question 21

Name 5 adrenoreceptor antagonists used clinically

Answer 21

Doxazosin (a1)
Beta Blockers
     propranalol (1, 2)
     metoprolol (1)
     atenolol (1)
Carvedilol (mixed)

Question 22

What does Doxazosin do?

What is it used for?

Answer 22

a1 antagonist
vasodilation

treats hypertension and Raynaud’s syndrome

Question 23

What is Raynaud’s syndrome?

Answer 23

limits circulation particularly in the hands and feet

Question 24

What 4 main things do beta blockers do?

Answer 24

• chronotropy
• inotropy
• automaticity

anti-platelet aggregation

Question 25

What are beta blockers used to treat?

Answer 25

angina heart failure cardiac arrhythmias hypertension

Question 26

What does Carvedilol do?

Answer 26

``` mixed B and A antagonist inhibits cardiac K+ chanel, leading to a class III antiarrhythmic action ``` used for heart failure

Question 27

What is the implication of using Carvedilol to treat HF?

Answer 27

beat blockers themselves decrease cardiac workload many with heart failure also have hypertension so blocking alpha receptors peripherally, can cause BP to decrease

Question 28

What problem is associated with decreased cadiac output by beta blockers?

Answer 28

may lead to a 'resetting of baroreceptors'

Question 29

What are the 3 effects of parasympathetic innervation of the heart?

Answer 29

Vagal rhythm Negative chronotropy through SAN Slow AVN conduction little effect on myocardial contractility

Question 30

What is the intracellular mechanism associated with M2 receptors?

Answer 30

G(i), inhibits adenyl cyclase

Question 31

Name a muscarinic antagonist

Answer 31

atropine

Question 32

What effects does atropine have on the body?

Answer 32

``` decreased secretions bronchodilation constipation urinary retention pupillary dilation confusion / hallucination ```

Question 33

According to the BNF, when is atropine used?

Answer 33

to reverse bradycardia - following MI w/ hypotension - XS beta blocker use - intra-operatively

Question 34

In what 2 ways can noradrenaline be taken in?

Answer 34

neuronal | non-neuronal

Question 35

What is neuronal uptake of NAd mediated by?

Answer 35

Noradrenaline Transporter

Question 36

Name 2 NAT blockers

Answer 36

``` cocaine tricylic antidepressants (like imipramine) ```

Question 37

Name 2 monoamine oxidase inhibitors

Answer 37

phenelzine | iprozinad

Question 38

What is the MOA of Methyldopa?

Answer 38

DOPA decarboxylase inhibition converted by dopamine beta hydroxylase to alpha methylnorepinephrine, an a2 agonist, dropping central sympathetic drive

Question 39

What is methyldopa used for?

Answer 39

treatment of hypertension in pregnancy

Question 40

Name 3 indirectly acting sympathomimetic amines

Answer 40

tyramine ephedrine emphetamine (substrates for NAd transporter blocker)

Question 41

Where would you find tyramine?

Answer 41

cheese