SNS agonists Flashcards

1
Q

Most sympathetic post-ganglionic neurones release noradrenaline. State two exceptions.

A

Adrenal medulla – adrenaline (80%) and noradrenaline (20%)

Sweat glands – acetylcholine

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2
Q

State the difference between directly and indirectly acting SNS agonists

A

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

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3
Q

Describe the mechanism of action of the four different types of adrenoceptor.

A
ALL adrenoceptors are G-protein coupled 
𝛼1 = via PLC, IP3, DAG
𝛼2 = decreases cAMP (inhibitory)
β1 = increases cAMP
β2 = increases cAMP
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4
Q

State the main effector functions mediated by β1 receptors

A

HEART – increase heart rate + increase contractility

KIDNEYS – increase renin release => increase blood pressure

Lipolysis

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5
Q

State the main effector functions mediated by β2 receptors

A

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

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6
Q

State some effector functions that are mediated by both 𝛼 and β receptors

A

SALIVARY GLANDS - thick viscous secretion

GASTROINTESTINAL - decreased motility and tone, sphincter contraction

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7
Q

What receptors are responsible for the increased and decreased production of aqueous humour by the ciliary body?

A

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

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8
Q

State the main effector functions mediated by 𝛼1 receptors

A

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

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9
Q

Describe the action of pre-synaptic alpha-2 receptors

A

Have a negative influence on noradrenaline synthesis and release

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10
Q

Describe the relative receptor selectivity of adrenaline and noradrenaline.

A

Noradrenaline is more selective for ALPHA-receptors

Adrenaline is more selective for BETA-receptors

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11
Q

Summarise the biosynthesis pathway of noradrenaline

A

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)

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12
Q

List five directly acting SNS agonists

A
Phenylephrine (a1>a2)
Clonidine (a2>a1)
Dobutamine (b1>b2) 
Salbutamol (b2>b1)
 Isoprenaline (b1=b2)
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13
Q

What are the symptoms of anaphylaxis, and why is adrenaline used in the treatment?

A

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

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14
Q

What are some other clinical uses of adrenaline?

A
  • 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)
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15
Q

List and categorise the unwanted effects of adrenaline

A

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

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16
Q

How does phenylephrine differ from adrenaline chemically?

A

Selectivity: a1»a2»>b1/b2

Chemically related to adrenaline but more resistant to COMT (not MAO)

17
Q

List the clinical uses of phenylephrine

A
  • Vasoconstriction
  • Mydriasis
  • Nasal decongestant
18
Q

Describe the selectivity of clonidine

A

Selectivity: a2»a1»>b1/2

19
Q

List and explain the clinical uses of clonidine

A

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
20
Q

How does isoprenaline differ from adrenaline chemically?

A

Selectivity: ß1=ß2»»α1/𝛼2

Chemically related to adrenaline but more resistant to MAO and uptake 1

21
Q

List the clinical uses of isoprenaline

A
  • Cardiogenic shock
  • Acute heart failure
  • Myocardial infarction
22
Q

State the caution related to β2 stimulation by isoprenaline

A

β2-stimulation in vascular smooth muscle supplying skeletal muscle => fall in venous blood pressure which triggers a reflex tachycardia via the stimulation of baroreceptors.

23
Q

State the selectivity of dobutamine and its clinical use? Why might it be better than isoprenaline?

A

Selectivity: β1»β2»>α1/α2

Clinical use = Cardiogenic shock

  • Lacks isoprenaline’s reflex tachycardia
  • Plasma half life 2 minutes (rapidly metabolised by COMT)
24
Q

State the selectivity of salbutamol (Ventolin). What is it resistant to?

A

Selectivity: b2»b1»>a1/2

It is a synthetic catecholamine derivative with relative resistance to MAO and COMT

25
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
26
What are the side effects associated with salbutamol?
Reflex tachycardia Tremor Blood sugar dysregulation
27
Which adrenoceptor mediates the enhancement of lipolysis in adipose tissue?
β3 adrenoreceptor