Autonomic NS 3

Question 1

Give examples of catecholamines.

Answer 1

Adrenaline, Dopamine, Noradrenaline

Question 2

How may Tyrosine hydroxylase be inhibited ?

Answer 2

By catecholamines (hence negative feedback)

Question 3

How may DOPA decarboxylase be targeted ?

Answer 3

Using Methyldopa

Question 4

Where is Dopamine beta-hydroxylase enzyme located ?

Answer 4

Membrane bound

Question 5

Where PMNT located ? How is its release induced ?

Answer 5

Question 6

Describe the process of Noradrenaline release.

Answer 6

Release facilitated by Ca2+ (hence ↓Ca2+ influx means ↓NA release)

Question 7

Is there an equivalent of anticholinesterases for NA ?

Answer 7

No

Question 8

What process occurs if excessive NA if release in the synapse ?

Answer 8

Binds to α2 adrenoreceptors on pre-synaptic terminal, which goes on to inhibit Calcium intake, thereby reducing NA release

Question 9

What molecules, besides NA, do vesicles contain during NA release ?

Answer 9

ATP (has its own receptors on post-synaptic terminal)

Question 10

How much of the NA is recaptured by neurons ?

Answer 10

75%

Question 11

Which molecules are responsible for NA re-uptake and re-packaging ?

Answer 11

Question 12

What are some drugs which can affect noradrenergic neurons ? Give examples for each.

Answer 12

DRUGS AFFECTING CATECHOLAMINE SYNTHESIS
– e.g. methyldopa

DRUGS AFFECTING CATECHOLAMINE RELEASE
– Indirectly acting sympathomimetics (e.g. amphetamines)
– By acting on α2 adrenoreceptors (e.g. clonidine)

INHIBITORS OF CATECHOLAMINE UPTAKE
– NET inhibitors (e.g. cocaine, tricylic antidepressants)

INHIBITORS OF CATECHOLAMINE METABOLIC DEGRADATION
– Monoamine oxidase inhibitors used in depression

Question 13

Which kind of receptors are Adrenergic receptors ?

Answer 13

Metabotropic (G-protein coupled receptors)

Question 14

What are the main groups of adrenoreceptors ?

Answer 14

Question 15

Are there exploitable differences in the selectivity of these receptors (α1, α2, β1, β2, β3) for catecholamines ? Which ones ?

Answer 15

Yes, differences in tissue distribution that allow for some specificty of drug action

Question 16

Identify the main ANS locations of α1, α2, β1 and β2 adrenoreceptors.

Answer 16

Question 17

Identify the functional ANS response of α1, α2, β1 and β2 adrenoreceptors.

Answer 17

Question 18

Which kind of receptor should be targeted when treating nasal congestion ? Why ? Which drugs may used against Nasal Congestion ?

Answer 18

α1 because nasal congestion is mainly due to vasodilation in nasal mucosa and α1 stimulation can give rise to vasoconstriction

PHENYLEPHRINE (Constriction of airway blood vessels (α1))
This vasoconstriction helps to reduce blood flow to the nasal mucosa and decreases sweeling of the nasal tissue

Question 19

What are some symptoms of asthma ?

Answer 19

Coughing
Wheezing
Shortness of breath
Tightness in the chest

Question 20

Which kind of receptor should be targeted when treating asthma ? Why ? Which drugs may used against asthma ?

Answer 20

β2 because asthma involves brachoconstriction and β2 stimulation can give rise to brachodilation

SALBUTAMOL (short acting), SALMETEROL (long acting) - all give cause brachodilation

Question 21

What are some side effects of salbutamol and salmeterol ? Why ?

Answer 21

Muscle tremor and Cardiac arrhythmias
Because tremors are linked to β2 which is stimulated here, whilst arrhythmias are due to the fact that they have a little affinity for β1 leading to some β1 functional response (i.e. ↑ cardiac rate ↑ cardiac force)

Question 22

What is the main difference between Salbutamol and Salmeterol ?

Answer 22

Short-acting (Short Acting Beta2 Agonist = SABA) = salbutamol

Long-acting (Long Acting Beta2 Agonist = LABA) = salmeterol

Question 23

What is premature labour defined as ?

Answer 23

Occurring between 24 and 33 weeks of gestation

Question 24

Which kind of receptor should be targeted when delaying labour ? Why ? Which drugs may be used for this ?

Answer 24

β2 because it stimulates relaxation of visceral smooth muscle (including uterine muscle)

Salbutamol

Also terbutaline

Question 25

How does the sympathetic NS control BP ? Mention any important adrenoreceptors involved.

Answer 25

1. INCREASES CARDIAC OUTPUT (HEART) - Increases heart rate - Increases volume pumped out at each stroke - β1 receptors mediates both ^ 2. INCREASES TOTAL PERIPHERAL RESISTANCE (ARTERIES) - Constricts blood vessels (mainly small arteries/arterioles) - α1 receptors mediates this

Question 26

Define Cardiogenic shock.

Answer 26

Damaged heart, unable to supply enough blood to the organs of the body

Question 27

Which kind of receptor should be targeted in cardiogenic shock ? Why ? Which drugs may be used for this ?

Answer 27

β1 because cardiogenic shock involves insufficient blood supply to the body, and the activation of β1 stimulates increased heart rate and increased force. Dobutamine | See lecture online

Question 28

Which kind of receptor should be targeted in Hypertension ? Why ? Which drugs may be used for this ?

Answer 28

α1 (inhibiting it) because α1 causes vasoconstriction β1 (inhibiting it) because β1 causes ↑ cardiac rate ↑ cardiac force and ↑ renin release by kidneys α2 (stimulating it) because α2 causes ↓ NA release PRAZOSIN (blocks α1 receptors) Vasodilation PROPRANOLOL (blocks β1 receptors) ↓ heart rate and force ↓ renin release by kidneys ATENOLOL (blocks β1 receptors) ↓ heart rate and force ↓renin release by kidneys CLONIDINE (stimulates pre-synaptic α2 receptors) ↓ NA release Central effect

Question 29

What are cardiac dysrhthmias ?

Answer 29

Atrial fibrillations, with palpitations, rapid heart rate and inefficient cardiac output

Question 30

Which kind of receptor should be targeted in dysrhthmias ? Why ? Which drugs may be used for this ?

Answer 30

β1 (inhibiting it) because β1 causes ↑ cardiac rate ↑ cardiac force and ↑ renin release by kidneys PROPRANOLOL (blocks β1 receptors) ↓ heart rate and force ↓ renin release by kidneys ATENOLOL (blocks β1 receptors) ↓ heart rate and force ↓renin release by kidneys

Question 31

What is a cardiac arrest ?

Answer 31

Cardiac arrest occurs when the heart suddenly and unexpectedly stops pumping

Question 32

Which kind of receptor should be targeted in cardiac arrests ? Why ? Which drugs may be used for this ?

Answer 32

α1 (stimulating it) because α1 causes vasoconstriction β1 (stimulating it) because β1 causes ↑ cardiac rate ↑ cardiac force ADRENALINE Vasoconstriction ↑ cardiac rate ↑ cardiac force

Question 33

What are the symptoms of anaphylaxis ?

Answer 33

- Narrowing of airways - Sudden drop in blood pressure - Red raised itchy skin rash - Swelling of eyes, lips, hands and feet

Question 34

Which kind of receptor should be targeted in anaphylaxis ? Why ? Which drugs may be used for this ?

Answer 34

α1 (stimulating it) because α1 causes vasoconstriction β1 (stimulating it) because β1 causes ↑ cardiac rate ↑ cardiac force β2 (stimulating it) because β2 causes bronchodilation and ↓ histamine release by mast cells ADRENALINE Vasoconstriction ↑ heart rate and force Bronchodilation ↓ histamine release by mast cells

Question 35

What is the main symptom of benign prostatic hyperplasia

Answer 35

Problems with passing urine due to swollen prostate

Question 36

Which kind of receptor should be targeted in benign prostatic hyperplasia ? Why ? Which drugs may be used for this ?

Answer 36

α1 (blocking it) in order to block smooth muscle contraction PRAZOSIN -Relax bladder neck and prostate capsule TAMSULOSIN -More prostate-specific

Question 37

Name all the main adrenoreceptor agonists.

Answer 37

Question 38

Name all the main adrenoreceptor antagonists.

Answer 38

Question 39

Describe the synthesis of these different catecholamines, naming the enzymes involved. Which is the RLS?

Answer 39

Tyrosine (enzyme: Tyrosine hydroxylase) --> DOPA (enzyme: DOPA decarboxylase) --> Dopamine (enzyme: Dopamine β-hydroxylase (DBH)) --> Noradrenaline (enzyme: PNMT) --> Adrenaline The RLS is the initial state (conversion of Tyrosine into DOPA)