Autonomic NS 3 Flashcards
Give examples of catecholamines.
Adrenaline, Dopamine, Noradrenaline
How may Tyrosine hydroxylase be inhibited ?
By catecholamines (hence negative feedback)
How may DOPA decarboxylase be targeted ?
Using Methyldopa
Where is Dopamine beta-hydroxylase enzyme located ?
Membrane bound
Where PMNT located ? How is its release induced ?
Mainly located in adrenal medulla
Induced by adrenal cortex hormone
Describe the process of Noradrenaline release.
Release facilitated by Ca2+ (hence ↓Ca2+ influx means ↓NA release)
Is there an equivalent of anticholinesterases for NA ?
No
What process occurs if excessive NA if release in the synapse ?
Binds to α2 adrenoreceptors on pre-synaptic terminal, which goes on to inhibit Calcium intake, thereby reducing NA release
What molecules, besides NA, do vesicles contain during NA release ?
ATP (has its own receptors on post-synaptic terminal)
How much of the NA is recaptured by neurons ?
75%
Which molecules are responsible for NA re-uptake and re-packaging ?
- Norepinephrine transporter (NET)
- Vesicular monoamine transporter (VMAT) (re-packages it)
What are some drugs which can affect noradrenergic neurons ? Give examples for each.
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
Which kind of receptors are Adrenergic receptors ?
Metabotropic (G-protein coupled receptors)
What are the main groups of adrenoreceptors ?
α1, α2
β1, β2, β3
Are there exploitable differences in the selectivity of these receptors (α1, α2, β1, β2, β3) for catecholamines ? Which ones ?
Yes, differences in tissue distribution
Identify the main ANS locations of α1, α2, β1 and β2 adrenoreceptors.
α1
Cardiovascular
GI tract
Genitourinary
α2
Neuronal
β1
Heart
Kidneys
β2
Lungs
Smooth muscle
Skeletal muscle
Identify the functional ANS response of α1, α2, β1 and β2 adrenoreceptors.
α1
Vasoconstriction
Smooth muscle contraction (GI sphincters and genitourinary)
α2
↓transmi tter release
β1
↑ cardiac rate
↑ cardiac force
Renin release
β2
Bronchodilation
Relaxation of visceral smooth muscle
Vasodilation (sk. muscle) Tremor
Which kind of receptor should be targeted when treating nasal congestion ? Why ? Which drugs may used against Nasal Congestion ?
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))
What are some symptoms of asthma ?
Coughing
Wheezing
Shortness of breath
Tightness in the chest
Which kind of receptor should be targeted when treating asthma ? Why ? Which drugs may used against asthma ?
β2 because asthma involves brachoconstriction and β2 stimulation can give rise to brachodilation
SALBUTAMOL, SALMETEROL (all give cause brachodilation)
What are some side effects of salbutamol and salmeterol ? Why ?
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)
What is the main difference between Salbutamol and Salmeterol ?
Short-acting (Short Acting Beta2 Agonist = SABA) = salbutamol
Long-acting (Long Acting Beta2 Agonist = LABA) = salmeterol
What is premature labour defined as ?
Occurring between 24 and 33 weeks of gestation
Which kind of receptor should be targeted when delaying labour ? Why ? Which drugs may be used for this ?
β2 because it stimulates relaxation of visceral smooth muscle (including uterine muscle)
Salbutamol
How does the sympathetic NS control BP ? Mention any important adrenoreceptors involved.
- INCREASES CARDIAC OUTPUT (HEART)
- Increases heart rate
- Increases volume pumped out at each stroke
- β1 receptors mediates both ^ - INCREASES TOTAL PERIPHERAL RESISTANCE (ARTERIES)
- Constricts blood vessels (mainly small arteries/arterioles)
- α1 receptors mediates this
Define Cardiogenic shock.
Damaged heart, unable to supply enough blood to the organs of the body
Which kind of receptor should be targeted in cardiogenic shock ? Why ? Which drugs may be used for this ?
β1 because cardiogenic shock involves insufficient blood supply to the body, and the activation of β1 stimulates increased heart rate and increased force.
Dobutamine
Which kind of receptor should be targeted in Hypertension ? Why ? Which drugs may be used for this ?
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
What are cardiac dysrhthmias ?
Atrial fibrillations, with palpitations, rapid heart rate and inefficient cardiac output
Which kind of receptor should be targeted in dysrhthmias ? Why ? Which drugs may be used for this ?
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
What is a cardiac arrest ?
Cessation of normal cardiac function
Which kind of receptor should be targeted in cardiac arrests ? Why ? Which drugs may be used for this ?
α1 (stimulating it) because α1 causes vasoconstriction
β1 (stimulating it) because β1 causes ↑ cardiac rate ↑ cardiac force
ADRENALINE
Vasoconstriction
↑ cardiac rate ↑ cardiac force
What are the symptoms of anaphylaxis ?
- Narrowing of airways
- Sudden drop in blood pressure
- Red raised itchy skin rash
- Swelling of eyes, lips, hands and feet
Which kind of receptor should be targeted in anaphylaxis ? Why ? Which drugs may be used for this ?
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
What is the main symptom of benign prostatic hyperplasia
Problems with passing urine due to swollen prostate
Which kind of receptor should be targeted in benign prostatic hyperplasia ? Why ? Which drugs may be used for this ?
α1 (blocking it) in order to block smooth muscle contraction
PRAZOSIN
-Relax bladder neck and prostate capsule
TAMSULOSIN
-More prostate-specific
Name all the main adrenoreceptor agonists.
Adrenaline Clonidine Dobutamine Noradrenaline Phenylephrine Salbutamol Salmeterol
Name all the main adrenoreceptor antagonists.
Atenolol Carvedilol Phentolamine Prazosin Propranolol
Describe the synthesis of these different catecholamines, naming the enzymes involved. Which is the RLS?
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)
