SNS Agonists Flashcards
SNS agonists work like sympathetic nervous system so which receptors do they affect?
Adrenergic receptors
What are the classes of adrenergic receptors?
alpha 1/2
beta 1/2
Which reaction cascade do the adrenergic receptors use e.g. cAMP?
alpha 1 - PLC, IP3 and DAG
alpha 2 - decrease cAMP
beta 1 - increase cAMP
beta 2 - increase cAMP
What are some of the effects of the SNS on different organs and what receptors mediate these effects?
eye - dilation of pupil (a1) and aqueous humour production (b)
trachea and bronchioles - dilation (b2)
liver - glycogenolysis and gluconeogenesis (b2 and a1)
adipose - lipolysis (b1 qnd a1)
ureters and bladder - detrussor relaxation (b2) and constriction of trigone and sphincter (a1)
kidney - more renin (b1)
salivary glands - thick viscous secretion (a/b)
skin - piloerection (a1)
heart - increased heart rate and contractility (b1)
GI - reduced motility and tone, sphincter contraction (a/b)
blood vessels (skeletal) - dilation (b2)
blood vessels (other) - constriction (a1)
Where do NA and A predominantly come from?
NA - nerves
A - adrenal glands
What are NA and A more selective for individually?
NA - alpha
A - beta
NA synthesis and metabolism
LEARN
Tyr -> DOPA -> DA -> NA
What do the different adrenergic receptors do?
A1 - Vasoconstriction, relaxation of GIT
A2 – Inhibition of NT release, contraction of VSMC, CNS
B1 – Cardiac stimulation, relaxation of GIT, renin release
B2 – Bronchodilation, vasodilation, relaxation of VSMC, hepatic glycogenolysis
B3 – Lipolysis
Why is adrenaline used to treat anaphylaxis?
ADRENALINE IS NON SELECTIVE EXAMPLE
Treats many sysmptoms caused by histamine e.g. acts on
B2 -bronchodilation
B1 - tachycardia
A1 - vasoconstriction
Can also bind to mast cells and stop histamine release
Which other conditions is adrenaline used for and what receptors will be involved?
B2
- asthma (emergencies)
- acute bronchospasm associated with chronic bronchitis or emphysema
B1
- cardiogenic shock
A1 - to vasoconstrict and maintain BP as anesthetics tend to drop BP and local anesthetic also needs localised effects so constriction reduces blood flow so less chance of spreading
- spinal anesthesia
- local anesthesia
What are the side effects of adrenaline?
- reduced and thickened mucous
- minimal CNS effects
- tachycardia, palpitations, arrhythmias, cold extremities, hypertension, overdose (cerebral hemorrhage of pulmonary oedema)
- minimal GIT effects
- skeletal muscle tremor
Which receptor is phenylephrine selective for?
A1 mainly
What are some of the features of phenylephrine (metabolic)?
chemically related to adrenaline but more resistant to COMT, not to MAO
Why is phenylephrine used as a decongestant?
Inflammation of nasal sinus so plasma leakage
- vasoconstriction needed, less blood flow means less leakage
What else can phenylephrine be used for?
Mydriatic - binds to the alpha 1 receptor on iris and cause pupil dilation (mild)
What does clonidine act on?
A2 - this will be like an antagonist as it reduces NA function
What is glaucoma?
Increased intraocular pressure caused by poor drainage of aqueous humour so production is greater than drainage. Can permanently damage optic nerve and cause blindness if untreated
Which receptors are targetted for glaucoma treatment?
Activate a1 - vasoconstriction of blood vessel so less resources to ciliary epithelium and less aqueous humour made
Activate 2 - decreases aqueous humour production
How do alpha 2 receptors affect NA release?
Have a negative feedback on NE release. NE binding to presynaptic a2 adrenoreceptors causes negative feedback on NA exocytosis
What are the clinical uses of clonidine?
- hypertension and migraine
- anti glaucoma
- can decrease sympathetic tone in the brain by affecting NA release so has systemic affect of reducing sympathetic outflow
What does isprenaline work on?
B1 and B2
Describe how isoprenaline is metabolised
chemically related to adrenaline but more resistant to MAO and uptake 1
What are the clinical uses of isoprenaline?
- cardiogenic shock
- acute heart failure
- MI
What might be an effect of isoprenaline due to its effect on both B1 and B2 receptors?
B2 stimulation in vascular smooth muscle in skeletal muscle results in a fall in venous blood pressure (due to muscle relaxation) which triggers a reflex tachycardia due to stimulation of baroreceptors
Why is dobutamine preferred to isoprenaline?
- has same used as isoprenaline
- lacks the isoprenaline reflex tachycardia as acts on b1
- half life is 2 minutes so short acting, good for emergencies
What does salbutamol act on?
b2 receptors mainly in airway (more cAMP so more relaxation of muscles etc)
What is salbutamol used for?
- treating asthma (b2 relaxation of bronchial smooth muscle and inhibits release of bronchoconstrictors from mast cells
- treatment of premature labour (b2 relaxation of uterine smooth muscle)
What are the side effects of salbutamol?
tremor, blood sugar dysregulation and reflex tachycardia (as does act on some b1 receptors too)
Give examples of some SNS agonists and which receptors they are most selective for
Adrenaline – non-selective.
Phenylephrine - a1-selective
Clonidine - a2-selective
Isoprenaline - b1=b2-selective
Dobutamine - b1-selective
Salbutamol - b2-selective
