Autonomic nervous system 3 Flashcards
What are the catecholamines?
Dopamine, Adrenaline, Noradrenaline
What determines what kind of catecholamine receptor there will be?
The enzymes present, because they are all derived form the same pathway
What is the rate limiting step in the synthesis of the catecholamines?
- Tyrosine to DOPA
* Tyrosine hydroxylase
What are the enzymes present in the catecholamine pathway?
- Tyrosine hydroxylase
- DOPA decarboxylase
- Dopamine beta-hydroxylase (DBH) (membrane bound)
- PNMT
Where is PMNT located?
Mainly in the adrenal medulla
What induces PMNT?
Adrenal cortex hormones
What can inhibit tyrosine hydroxylase?
Catecholamines
Which catecholamine pathway enzyme is targeted in treating the hypertension in pregnancy?
DOPA decarboxylase
Targets the production of noradrenaline
What is methydopa?
Inhibits DOPA decarboxylase- treatment of Parkinson’s
What is noradrenaline release facilitated by?
Calcium ions
What receptors are present of the presynaptic terminal?
α2 adrenoreceptors
What is the role of α2 adrenoreceptors
- Binding of noradrenaline signals that there is enough noradrenaline
- Decreases the Ca 2+ influx
- Therefore decreases noradrenaline release
What happens to noradrenaline in the synaptic cleft?
- ~75% recaptured by neurones
- Norepinephrine transporter (back into the neurone) (NET)
- Repackaged by vesicular monoamine transporter
What is noradrenaline uptake and degradation affected by?
- Sympathomimetic drugs
- Monoamine oxidase inhibitors
- Uptake inhibitors
How do monoamine oxidase inhibitors work?
Dopinergic transmission stops the internal degradation of dopamine/noradrenaline so there is more to release - important in the treatment of mental disorders
How do uptake inhibitors work?
Prevents the uptake, prolonging the duration of effect at the junction
How do amphetamines act as a drug of abuse?
- Hijacks the transport system and displaces the noradrenaline
- NET transporter in reverse: takes amphetamine up and forces noradrenaline out meaning it is released (also from vesicles and amphetamine causes vesicles to be released)
Which drugs affect catecholamine synthesis?
Methyldopa
Which drugs affect catecholamine release?
- Drugs that act on the α2 adrenoreceptors e.g. clonidine
* Drugs that are indirectly acting sympathomimetics e.g. amphetamines
Which drugs are inhibitors of catecholamine uptake?
• NET inhibitors e.g. cocaine, tricyclic antidepressants
Which drugs inhibit catecholamine metabolic degradation?
Monoamine oxidase inhibitors used in depression
What class of receptors are adrenergic receptors?
Metabotropic receptors
What are the two main groups of adrenoreceptors?
α(1 and 2)
β (1,2 and 3)
β3
Adipocytes very little drugs target it
Where is the main location of the α1 receptor?
- Cardiovascular
- GI tract
- Genitourinary
What is the cellular response from the α1 receptor?
- Increased IP3
* Increased DAG
What is the functional ANS response of the α1 receptor?
- Vasoconstriction
* Smooth muscle contraction (GI sphincters and genitourinary)
Where is the main location of the α2 receptor?
Neuronal
What is the cellular response of the α2 receptor?
Decreases cAMP
What is the functional ANS response of the α2 receptor?
Decreased transmitter release
Where is the main location of the β1 receptor?
- Heart
* Kidneys
What is the functional response of the β1 receptor?
Increases cAMP
What is the functional ANS response of the β1 receptor?
- Increased cardiac rate
- Increased cardiac force
- Renin release
Where is the main location of the β2 receptor?
- Lungs
- Smooth muscle
- Skeletal muscle
What is the cellular response of the β2 receptor?
Increases cAMP
What is the functional ANS response of the β2 receptor?
- Bronchodilation
- Relaxation of visceral smooth muscle
- Vasodilation (Skeletal muscle)
- Tremor
What drugs target upper respiratory tract infection and how?
- Phenylephrine
- Constricts the airway blood vessels
- Alpha 1 agonists
What drugs target asthma and how?
• Salbutamol • Salmeterol (• Potentially Terbutaline) • inhaler so directing it to the correct tissue • Cause bronchodilation • β2 receptor
What are the side effect of Salbutamol and Salmeterol?
- Muscle tremor
* Cardiac arrhythmias
What is the difference between Salbutamol and salmeterol?
- Short acting: Salbutamol
* Long acting: Salmeterol
What can Salbutamol be used to treat that salmeterol can’t?
- Premature labour between 24 and 33 weeks of gestation
- Need to delay delivery to prepare treatment or transfer
- Causes relaxation of uterine Smoot muscles (B2)
- stop giving it and effects wear off quickly
How can you calculate mean arterial blood pressure?
Cardiac output x Total peripheral resistance
How does the symapthetic nervous system increase cardiac output?
- Increases heart rate
- Increases volume on each stroke
- Mediated by the β1 receptor
How does the sympathetic nervous system increase total peripheral resistance?
- Constriction of blood vessels (mainly small arteries and arterioles)
- Mediated by a1 recpetors
What is cardiogenic shock?
Damaged heart, unable to supply enough blood to the organs
What drug can be used to treat cardiogenic shock?
- Dobutamine
- Increases heart rate and force
- Agonist for the B1 receptor
Which drugs can decrease blood pressure and how?
- Prazosin - antagonist for a1
- Propranolol - decreases heart rate and force by blocking B1 receptors and decreases renin release by kidneys B1
- Antenolol - decreases heart rate and force by blocking B1 and decreases renin release B1
- Clonidine- stimulation of pre-synaptic alpha 2 receptors, decreases noradrenaline release, central effect
What is the difference between propranolol and atenolol?
- Receptor selectivity
- Atenolo binds beta 1
- Propanolol binds to beta 1 and 2
Which groups of people would you not want to give propananol to and why?
- Asthmatics
* Blocks Beta 2 receptor - less bronchorestriction
What drugs can be used to treat cardiac dysrhthmias?
- Propranolol: decreases heart rate and force by blocking B1 receptors, renin release
- Atenolol, decreases heart rate and force by blocking B1 receptors, renin release by kidneys
Which agonist is appropriate for cardiac arrest? Why?
- Adrenaline
- Vasoconstriction a1
- Increases heart rate B1
What is the appropriate drug to treat anaphylaxis?
- Adrenaline
- Vasoconstriction a1
- Decrease of histamine release by mast cells causing bonchodilation B2
- Increases heart rate and force B1
What is benign prostatic hyperplasia?
Swollen prostate causing problems with passing urine
What is used to treat bening prostatic hyperplasia?
• Prazosin
- relaxes bladder neck and prostate capsule by blocking a1 receptors
• Tamsulosin
- more prostate specific
What are the agonists for the alpha 1 receptor?
- Noradrenaline
- Adrenaline
- Phenylephrine
What are the agonists for the alpha 2 receptor?
- Noradrenaline
- Adrenaline
- Clonidine
What are the agonists for the beta 2 receptor?
- Adrenalin
- Noradrenaline
- Salbutamol
- Salmeterol
What are the agonists for the Beta 2 receptor?
- Adrenaline
- Noradrenaline
- Salbutamol
- Salmeterol
- Dobutamine
What are the antagonists for the alpha 1 receptor?
- Phenotalamine +++
- Prazosin +++
- Carvediol +
What are the antagonists for the alpha 2 receptor?
- Phentolamine +++
- Prazosin +
- Carvediol +
What are the antagonists for the beta 1 receptor?
- Propranolol +++
- Atenolol +++
- Carvediol ++
What are the antagonists for the B2 receptor?
- Propranolol +++
- Atenolol +
- Carvediol ++
