SNS Agonists Flashcards
Where do sympathetic nerves originate?
Thoracolumbar region of spinal cord
What do sympathetic post-ganglionic neurones release?
What are the two exceptions?
Noradrenaline
A preganglionic sympathetic neurone drives the release of Adrenaline (80%) and Noradrenaline (20%) from the ADRENAL MEDULLA
ACh is released from the post-ganglionic neurone that innovates the sweat glands
What type of receptors are adrenoceptors?
G-protein coupled
What are the mechanisms of action of the 4 types of adrenoceptors?
Alpha 1 = PLC –> IP3 + DAG
Alpha 2 = DECREASE cAMP
Beta 1 + 2 = INCREASE cAMP
What are directly acting sympathomimetics?
They mimic the actions of Adrenaline and NA by stimulating adrenoceptors
Mainly used for their actions in the CVS, eyes, heart and lungs
Which Adrenoceptors are more selective for Adrenaline and NA?
ALL adrenoceptors can be activated by NA and A
NORADRENALINE is more selective for ALPHA receptors
ADRENALINE is more selective for BETA receptors
How is synthesis and release of Noradrenaline controlled?
by Presynaptic Alpha 2 Receptors
When stimulated, they have a negative effect on synthesis and release
Name five Directly acting SNS agonists and which adrenoceptor they are selective to:
Adrenaline - non-selective
Phenylephrine - Alpha 1
Clonidine - Alpha 2
Dobutamine - Beta 1
Salbutamol - Beta 2
Which factor affects selectivity of a drug the most?
Concentration - at low concentrations the drug will be relatively selective but at high concentrations, the chance of binding to other receptors increases
Why does a Hypersensitivity reaction cause a fall in blood pressure?
Endothelial cells within the membranes of the blood vessels move apart so you get a lot of fluid moving into the tissues
This leads to a fall in circulating fluid volume and hence a fall in blood pressure
What are the symptoms of an Anaphylactic hypersensitivity reaction?
Constriction of Bronchial smooth muscle
Constriction of muscles around the throat
Fall in blood pressure
Vomiting and diarrhoea
Collapse of circulatory system leading to unconsciousness
Why is Adrenaline and not NA given in anaphylactic shock?
ABC - Airway and breathing need to be considered first before circulation
NA would cause vasoconstriction and increase BP, but Adrenaline acts more on beta receptors than NA which will stimulate bronchodilation and relaxation of throat muscles.
What are the effects of Adrenaline when given during anaphylaxis?
Bronchodilation
Relaxation of throat muscles
Tachcardia
Vasoconstriction (via alpha)
Slows release of histamine from mast cells
What processes are mainly controlled by α1 adrenoceptors?
α1+++:
Vasoconstriction
Piloerection
Ejaculation
α1++:
Pupil dilation
Constriction of Trigone and sphinctor
α1+:
Gluconeogenesis, lipolysis
What processes are mainly controlled by β1 adrenoceptors?
β1 ++:
Increased HR and contractility
Increased renin secretion
Lipolysis
What processes are mainly controlled by β2 adrenoceptors?
β2 +++:
Glycogenolysis and Gluconeogenesis
β2 ++:
Vasodilation
β2 +:
Bronchodilation
Relaxes Detrusor
Relaxes Uterus
Name 5 other uses of adrenaline:
Asthma emergencies
Acute bronchospasm
Cardiogenic shock
Spinal Anaesthesia
Local Anaesthesia
Why is adrenaline used to treat an acute bronchospasm?
It causes beta-2 mediated bronchodilation and suppresses mediator release
What is Cardiogenic shock and why is adrenaline used to treat it?
The sudden inability of the heart to pump sufficient oxygen-rich blood (can be from MI or cardiac arrest)
Adrenaline stimulates HR and contractility via Beta-1 positive ionotropic action
How is Adrenaline used in Spinal anaesthesia and why?
During spinal anaesthesia, sympathetic output to the peripheral resistance vessels is removed, so they relax and the patient cannot maintain BP
A little bit of adrenaline at the same time will constrict the blood vessels and Bp can be maintained.
Why is Adrenaline mixed in with Local anaesthetic?
It causes local alpha-1 mediated vasoconstriction which prevents the clearance of the anaesthetic from the area - without it, it would wear off faster
What are the main unwanted actions of adrenaline?
Reduced and thickened secretions
CVS: Tachycardia, palpitations, arrhythmias, cold extremities, hypertension
Tremor (Skeletal muscle)
What can an overdose of adrenaline lead to?
Cerebral haemorrhage
Pulmonary embolism
What is the selectivity of Phenylephrine?
Alpha 1 >> Alpha 2 >>> Beta 1/Beta 2
Phenylephrine is chemically similar to Adrenaline - why is this significant to its metabolism?
It is more resistant to COMT degradation
(But is not resistant to MAO degradation)
What are the clinical uses of Phenylephrine?
Vasoconstriction
Mydriatic
Nasal Decongestant
What is the selectivity of Clonidine?
Alpha 2 >> Alpha 1 >>> Beta 1/Beta 2
What is the main route of action of Clonidine?
What is the second route of action of Clonidine?
It stimulates the presynaptic alpha 2 receptors - negative effect on synthesis and release of NA
Within the brainstem it works on the baroreceptors in this pathway and reduces the sympathetic drive coming out of the brain. The reduction in sympathetic activity reduces the TPR and it also reduces the amount of noradrenaline released at the nerve terminal thus reducing TPR further
What are the clinical uses of Clonidine?
Treatment of Hypertension and Migrane
What is the selectivity of Isoprenaline?
Beta 1 + Beta 2 >>>>>> Alpha 1/Alpha 2
How is Isoprenaline different in terms of metabolism to Adrenaline?
Less susceptible to Uptake-1 and MAO
Has a much longer half-life than adrenaline so better if you need long term beta stimulation
What are the clinical uses of Isoprenaline?
Cardiogenic shock
Acute Heart Failure
Myocardial Infarction
Why is Isoprenaline not good for patients with Heart failure?
It drives Beta-1 receptors to increase HR and Contractility
BUT it will also stimulate Beta-2 in vascular smooth muscle to cause vasodilation in muscles
This gives pooling of blood in the muscles and hence a decreased venous return
Via baroreceptors, you get a reflex tachycardia
Beta-2 stimulation is therefore bad.
What is the selectivity of Dobutamine?
Beta 1 >> Beta 2 >>> Alpha 1/Alpha 2
What is the clinical use for Dobutamine?
Treatment of Cardiogenic shock
How does the difference in selectivity between Dobutamine and Isoprenaline effect the actions of Dobutamine
Because it’s not very Beta-2 selective it doesn’t cause the reflex tachycardia that Isoprenaline does.
What is the selectivity of Salbutamol?
Beta 2 >> Beta 1 >>> Alpha 1/Alpha 2
What is Salbutamol?
(what is it resistant to?)
Synthetic catecholamine derivative with relative resistance to MAO and COMT
What is Salbutamol used to treat and how?
Asthma
Beta-2 mediated relaxation of bronchial smooth muscle
Inhibition of release of bronchoconstrictor substances from mast cells
What is the second clinical use of Salbutamol?
Threatened premature labour:
Beta-2 mediated relaxation of uterine smooth muscle
What are the side effects of Salbutamol?
When is it therefore contraindicated?
Reflex tachycardia
Tremor
Blood sugar dysregulation - Unsuitable for diabetic patients
