Flashcards in SNS Agonists Deck (34)
Most sympathetic post-ganglionic neurones release noradrenaline. State two exceptions.
Adrenal medulla – adrenaline (80%) and noradrenaline (20%)
Sweat glands – acetylcholine
State the difference between directly and indirectly acting sympathomimetics.
Directly acting – binds to the adrenoceptor and mimic the action of adrenaline and noradrenaline by stimulating the receptors
Indirectly acting – inhibits the uptake and breakdown systems leading to the accumulation of neurotransmitter in the synaptic cleft
Describe the mechanism of action of the four different types of adrenoceptor.
ALL adrenoceptors are G-protein coupled
Alpha 1 = PLC -> IP3 + DAG
Alpha 2 = decrease cAMP
Beta 1 + Beta 2 = increase cAMP
State the main actions of beta-1 receptors.
HEART – increase heart rate + increase contractility
KIDNEYS – increase renin release -> increase blood pressure
State the main actions of beta-2 receptors.
Hepatic glucose output – glycogenolysis + gluconeogenesis
Vasodilation of vessels to skeletal muscle
Relaxation of the uterus (in women)
State some effects that are mediated by both alpha and beta-receptors.
Exocrine secretions (e.g. salivary gland secretions become thick)
GIT motility – decreased muscle motility and tone + contraction of sphincters
What receptors are responsible for the production of aqueoushumour by the ciliary body?
State some effects of alpha-1 receptors.
Mydriasis (contraction of radial muscles of the iris)
Constriction of trigone and sphincter in the bladder
Increased motility and tone of the ureters
Stimulates ejaculation (in males)
Contraction of pilomotor muscle + increased localised secretion of sweat glands e.g. palm of hands
Hepatic glucose output (glycogenolysis and gluconeogenesis)
What is the principle action of beta-blockers?
KIDNEYS – it inhibits the beta-1 mediated increase in renin secretion
It also decreases heart rate and contractility but its main action in reducing blood pressure is through the kidneys
Describe the relative selectivity of adrenaline and noradrenaline.
Noradrenaline is more selective for ALPHA-receptors
Adrenaline is more selective for BETA-receptors
Describe the action of pre-synaptic alpha-2 receptors.
Pre-synaptic alpha-2 receptors have a negative influence on noradrenaline synthesis and release
State five directly acting SNS agonists.
Phenylephrine – alpha-1
Clonidine – alpha-2
Dobutamine – beta-1
Salbutamol – beta-2
Isoprenaline – beta 1+ beta 2
Why is adrenaline more effective than noradrenaline in dealing with hypersensitivity?
During the hypersensitivity reaction, the most important problem to deal with is BREATHING.
Adrenaline is more selective for beta receptors than noradrenaline so is better at causing beta-2 mediated bronchodilation, thus opening up the airways.
Adrenaline also stimulates the heart via beta-1 to support blood pressure.
Adrenaline also acts on the alpha-1 receptors to cause vasoconstriction and an increase in TPR and blood pressure. Adrenaline can also slow down the release of histamine from mast cells via beta-2.
State two pulmonary obstructive conditions in which adrenaline is used therapeutically and explain why.
Acute bronchospasm associated with chronic bronchitis or emphysema
It causes beta-2 mediated bronchodilation and it suppressors mediator release.
Which receptors are involved in the generation of aqueous humour in the eye?
Alpha-1 involved in vasoconstriction of the vessels in the ciliary body
Beta-receptors control the enzyme that makes the aqueous humour
Why is adrenaline used as a treatment for glaucoma?
Adrenaline can stimulate the alpha-1 receptors to cause vasoconstriction of the vessels in the ciliary body thus reducing the blood flow within the ciliary body -> reduced production of aqueous humour
State and explain three other clinical uses of adrenaline.
Cardiogenic Shock (the sudden inability of the heart to pump sufficientoxygenated blood)
Beta-1 stimulation has a positive inotropic effect
Cardiogenic shock can happen in MI or cardiac arrest
Anaesthetising through the spine can take away the sympathetic output to the peripheral resistance vessels
This leads to relaxation of the peripheral vasculature so the patient can’t maintain their blood pressure
Giving a little adrenaline with the anaesthetic can constrict the blood vessels to maintain blood pressure
Giving adrenaline with the LA can cause local vasoconstriction, which prevents clearance of the anaesthetic from that area
This is due to alpha-1 mediated vasoconstriction
State some unwanted actions of adrenaline.
Secretions are reduced and thick
CVS – tachycardia, palpitations, arrhythmias, cold extremities, hypertension
Describe the resistance to degradation of phenylephrine.
Phenylephrine is MORE resistant to COMT degradation than adrenaline but it is NOT resistant to MAO degradation
State some clinical uses of phenylephrine.
It causes vasoconstriction
Describe and explain the effects of clonidine.
Clonidine stimulates alpha-2 receptors so has a negative effect on NA synthesis and release.
Decrease in NA release -> less vasoconstriction via alpha-1 action -> fall in TPR and blood pressure
Clonidine also has a central action on the brainstem – acts on baroreceptors and reduces the sympathetic drive coming out of the brain.
Reduction in sympathetic activity reduces TPR and reduces the amount of NA released at the nerve terminals thus reducing TPR further.
So there are two routes of clonidine action in reducing NA release and TPR.
Alpha-2 mediated reduction in NA release in the kidneys will also reduce renin release and hence reduce angiotensin II.
State some clinical uses of clonidine.
It is used to treat hypertension and migraine.
Describe the susceptibility to breakdown of isoprenaline compared to adrenaline.
Isoprenaline is less susceptible to uptake 1 and MAO breakdown
State three clinical uses of isoprenaline.
Acute Heart Failure
What is a big problem with isoprenaline with regards to its action on beta 2 receptors?
Isoprenaline brings about positive effects via Beta-1 stimulation
However, stimulation of Beta-2 leads to vasodilation of blood vessels in the muscles -> pooling of blood within the muscles -> reduced venous return
Via the baroreceptors, you get a reflex tachycardia
So the beta-1 effects are good for patients with heart failure but the beta-2 effects are not
State a clinical use of dobutamine.
It lacks isoprenaline’s reflex tachycardia effect
Administration via IV infusion (half-life = 2 mins)
Describe the relative resistance of salbutamol to degradation.
Relative resistance to MAO and COMT
State and explain two clinical uses of salbutamol.
Beta-2 mediated relaxation of bronchial smooth muscle (bronchodilation)
Inhibition of release of bronchoconstrictor molecules from mast cells
Threatened premature labour
Beta-2 mediated relaxation of uterine smooth muscle
This will prevent abortion
State some side effects of salbutamol.
Blood glucose dysregulation