SNS agonists Flashcards
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 SNS agonists
DIRECT = binds to the adrenoceptor and mimic the action of adrenaline and noradrenaline
INDIRECT = 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 𝛼1 = via PLC, IP3, DAG 𝛼2 = decreases cAMP (inhibitory) β1 = increases cAMP β2 = increases cAMP
State the main effector functions mediated by β1 receptors
HEART – increase heart rate + increase contractility
KIDNEYS – increase renin release => increase blood pressure
Lipolysis
State the main effector functions mediated by β2 receptors
LUNGS - Bronchodilation
LIVER - Hepatic glucose output (glycogenolysis + gluconeogenesis)
BLOOD VESSELS - Vasodilation of vessels supplying skeletal muscle
URETERS and BLADDER - relaxes detrusor
UTERUS - relaxation of uterine smooth muscle
State some effector functions that are mediated by both 𝛼 and β receptors
SALIVARY GLANDS - thick viscous secretion
GASTROINTESTINAL - decreased motility and tone, sphincter contraction
What receptors are responsible for the increased and decreased production of aqueous humour by the ciliary body?
β receptors - control the enzyme that makes the aqueous humour
𝛼1 receptors are involved in vasoconstriction of the vessels in the ciliary body = reduced blood flow within the ciliary body
𝛼2 receptors also decrease humour production
State the main effector functions mediated by 𝛼1 receptors
EYE - pupil dilation/mydriasis (contraction of radial muscles of the iris)
URETERS and BLADDER - constriction of trigone and sphincter
SKIN - piloerection
BLOOD VESSELS - vasoconstriction of vessels supplying skin, mucous membranes and splanchnic area
Glycogenolysis, gluconeogenesis and lipolysis
Describe the action of pre-synaptic alpha-2 receptors
Have a negative influence on noradrenaline synthesis and release
Describe the relative receptor selectivity of adrenaline and noradrenaline.
Noradrenaline is more selective for ALPHA-receptors
Adrenaline is more selective for BETA-receptors
Summarise the biosynthesis pathway of noradrenaline
Tyrosine => DOPA; catalysed by tyrosine hydroxylase
DOPA => Dopamine; catalysed by DOPA decarboxylase
Uptake of Dopamine into vesicle
Dopamine => Noradrenaline; catalysed by dopamine β-hydroxylase
Vesicle exocytosis and noradrenaline release.
Uptake 1 (neuronal re-uptake): converted to metabolites by Monoamine oxidase A (MAO-A) in mitochondria
Uptake 2 (extra neuronal uptake): degradation by COMT
𝛼2 receptors are located at the nerve terminal and inhibit vesicle exocytosis (when bound to noradrenaline)
List five directly acting SNS agonists
Phenylephrine (a1>a2) Clonidine (a2>a1) Dobutamine (b1>b2) Salbutamol (b2>b1) Isoprenaline (b1=b2)
What are the symptoms of anaphylaxis, and why is adrenaline used in the treatment?
In anaphylaxis:
- IgE-coated mast cell degranulation and systemic release of inflammatory mediators
- Increase in capillary permeability => increased movement of fluid into the tissues => depleted circulating fluid volume => drop in blood pressure
- Contraction of bronchial smooth muscle and constriction of muscles around the throat => respiratory distress
- Constriction of GI smooth muscle => vomiting and diarrhoea
Adrenaline causes β2 mediated bronchodilation, β1 mediated tachycardia and 𝛼1 mediated vasoconstriction
What are some other clinical uses of adrenaline?
- In asthma emergencies (i.m., s.c.)
- Acute bronchospasm associated with chronic bronchitis
or emphysema - Cardiogenic shock (sudden inability of heart to pump sufficient oxygen-rich blood)
- Used in spinal anaesthesia to maintain BP (peripheral vasculature relaxed due to sympathetic block of anaesthetic)
- Used in local anaesthesia to cause vasoconstriction prolonging action (prevent clearance)
List and categorise the unwanted effects of adrenaline
Secretions are reduced and thick
CVS:
- tachycardia, palpitations, arrhythmias, cold extremities, hypertension
- Overdose of adrenaline => cerebral haemorrhage, pulmonary embolism
CNS: minimal
GIT: minimal
Skeletal muscle: tremor
How does phenylephrine differ from adrenaline chemically?
Selectivity: a1»a2»>b1/b2
Chemically related to adrenaline but more resistant to COMT (not MAO)
List the clinical uses of phenylephrine
- Vasoconstriction
- Mydriasis
- Nasal decongestant
Describe the selectivity of clonidine
Selectivity: a2»a1»>b1/2
List and explain the clinical uses of clonidine
Treatment of hypertension and migraine
- It reduces sympathetic tone by 𝛼2 adrenoceptor mediated
presynaptic inhibition of NA release - It has a central action in brainstem within
baroreceptor pathway to reduce
sympathetic outflow
How does isoprenaline differ from adrenaline chemically?
Selectivity: ß1=ß2»»α1/𝛼2
Chemically related to adrenaline but more resistant to MAO and uptake 1
List the clinical uses of isoprenaline
- Cardiogenic shock
- Acute heart failure
- Myocardial infarction
State the caution related to β2 stimulation by isoprenaline
β2-stimulation in vascular smooth muscle supplying skeletal muscle => fall in venous blood pressure which triggers a reflex tachycardia via the stimulation of baroreceptors.
State the selectivity of dobutamine and its clinical use? Why might it be better than isoprenaline?
Selectivity: β1»β2»>α1/α2
Clinical use = Cardiogenic shock
- Lacks isoprenaline’s reflex tachycardia
- Plasma half life 2 minutes (rapidly metabolised by COMT)
State the selectivity of salbutamol (Ventolin). What is it resistant to?
Selectivity: b2»b1»>a1/2
It is a synthetic catecholamine derivative with relative resistance to MAO and COMT
Explain the clinical uses of salbutamol
Treatment of Asthma:
- β2 mediated relaxation of bronchial smooth muscle
- Inhibition of release of bronchoconstrictor substances from mast cells
Treatment of threatened premature labour:
- β2 mediated relaxation of uterine smooth muscle
What are the side effects associated with salbutamol?
Reflex tachycardia
Tremor
Blood sugar dysregulation
Which adrenoceptor mediates the enhancement of lipolysis in adipose tissue?
β3 adrenoreceptor
