SNS Agonists Flashcards
From which region of the spinal cord do sympathetic fibres originate?
Thoracolumbar
Most sympathetic post-ganglionic neurones release noradrenaline. State 2 exceptions.
Adrenal medulla: A (80%) + NA (20%)
Sweat glands: ACh
How do directly acting sympathomimetics work? Where are they principally used?
Mimic the actions of A + NA by binding to + stimulating adrenoceptors (GPCRs)
Principally used for their actions in the CVS, eyes + lungs
Describe the mechanism of action of the 4 different types of adrenoceptor.
Alpha 1 = PLC -> IP3 + DAG
Alpha 2 = decrease cAMP
Beta 1 + Beta 2 = increase cAMP
State the 2 main actions of beta-1 receptors.
HEART: increase HR + contractility
KIDNEYS: increase renin release -> increase BP
State the 5 main actions of beta-2 receptors.
Bronchodilation HGO: glycogenolysis + gluconeogenesis Vasodilation of vessels to skeletal muscle Relaxation of detrusor Lipolysis
State 2 effects that are mediated by both alpha and beta-receptors.
Exocrine secretions (e.g. salivary gland secretions become thick) GIT motility: decreased muscle motility + tone + contraction of sphincters
What receptors are responsible for the production of aqueous humour by the ciliary body?
Beta receptors
State 7 effects of alpha-1 receptors.
Mydriasis (contraction of radial muscles of the iris- dilation)
Vasoconstriction (skin, mucous, membranes + splanchnic area)
Constriction of trigone + sphincter in bladder
Piloerection
Increased sweating
HGO (glycogenolysis + gluconeogenesis)
Lipolysis
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 NA synthesis + release
State 5 directly acting SNS agonists.
Adrenaline (non-selective) Phenylephrine (alpha-1) Clonidine (alpha-2) Dobutamine (beta-1) Salbutamol (beta-2)
Why is adrenaline used in the treatment of anaphylactic shock?
Causes beta-2 mediated bronchodilation
Stimulates the heart via beta-1 to support BP
Acts on alpha-1 receptors to cause vasoconstriction + an increase in TPR + BP
Slows the release of histamine from mast cells via beta-2.
State 2 pulmonary obstructive conditions in which adrenaline is used therapeutically and explain why.
Asthma
Acute bronchospasm associated with chronic bronchitis or emphysema
It causes beta-2 mediated bronchodilation + suppresses mediator release.
(Selective beta-2 agonists are preferable, though adrenaline is useful in a hypotensive crisis)
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 3 other clinical uses of adrenaline.
Cardiogenic Shock (sudden inability of heart to pump sufficient oxygenated blood)
Beta-1 stimulation has a positive inotropic effect
Spinal Anaesthesia
Anaesthetising through the spine can take away sympathetic output to peripheral resistance vessels
This leads to relaxation of peripheral vasculature, thus patient can’t maintain their BP
Adrenaline with the anaesthetic can constrict blood vessels to maintain BP
Local Anaesthesia
Adrenaline can cause local vasoconstriction, which prevents clearance of anaesthetic from that area due to alpha-1 mediated vasoconstriction
State 3 unwanted actions of adrenaline, what an overdose may cause and what is minimally effected
Secretions are reduced + thickened
CVS: tachycardia, palpitations, arrhythmias, cold extremities, hypertension
Overdose of adrenaline can lead to: cerebral haemorrhage, pulmonary embolism
Skeletal muscle: Tremor
Minimal CNS + GIT effects
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 3 clinical uses of phenylephrine.
Mydriatic Nasal decongestant (reduces white cell infiltration, less fluid exudation + mucous) Vasoconstriction
Describe and explain the effects of clonidine.
Stimulates alpha-2 receptors so has a negative effect on NA synthesis + release.
Decrease in NA release -> less vasoconstriction via alpha-1 action -> fall in TPR + BP
Central action on brainstem: acts on baroreceptors + reduces sympathetic drive from brain.
Reduction in sympathetic activity reduces TPR + reduces amount of NA released at the nerve terminals thus reducing TPR further.
So there are 2 routes of clonidine action in reducing NA release + TPR.
Alpha-2 mediated reduction in NA release in the kidneys will also reduce renin release + hence reduce AII
State 2 clinical uses of clonidine.
Hypertension
Migraine
Describe the susceptibility to breakdown of isoprenaline compared to adrenaline.
Isoprenaline is less susceptible to uptake 1 + MAO breakdown
State 3 clinical uses of isoprenaline.
Cardiogenic Shock
Myocardial Infarction
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 muscles -> reduced venous return, reduced BP
Via the baroreceptors, this triggers a reflex tachycardia
So beta-1 effects are good for patients with heart failure but beta-2 effects are not
State a clinical use of dobutamine.
Cardiogenic shock
It lacks isoprenaline’s reflex tachycardia effect.
Has a short half life, used for its acute effects
Describe the relative resistance of salbutamol to degradation.
Relative resistance to MAO + COMT
State and explain 2 clinical uses of salbutamol.
Asthma
Beta-2 mediated bronchodilation
Inhibition of release of bronchoconstrictor molecules from mast cells
Threatened premature labour
Beta-2 mediated relaxation of uterine smooth muscle
Prevents abortion
State 3 side effects of salbutamol.
Reflex tachycardia
Tremor
Blood glucose dysregulation
How can sympathomimetics be used to treat Glaucoma?
A1 agonist causes vasoconstriction, reduces blood flow to the eye, reduces ability to produce aqueous humour
A2 agonist interferes with B1 function (stops production of aqueous humour)
