SNS agonist

Question 1

What do the different adrenergic receptors do?

Answer 1

a1 - coupled with PLC -> IP3 +DAG

a2 - decreases cAMP

b1 + b2 - increase cAMP

Question 2

What are some effects mediated by each receptor?

Answer 2

dilation of pupil - a1

liver’s capacity to liberate glucose - b2

increased HR and contractility - b1

dilation of blood vessels - b2

constriction of blood vessels - a1

Question 3

Which receptors are noradrenaline and adrenaline more selective of?

Answer 3

NA - alpha

A - beta

Question 4

How is noradrenaline produced and metabolised?

Answer 4

tyrosine-> (tyrosine hydroxylase) DOPA-> (DOPA decarboxylase) dopamine -> (dopamine b-hydroxylase) NA -> diffuses into blood/ postjuntional receptor/ extraneuronal uptake/ metabolized/neuronal uptake/ prejunctional receptor

** NE binding to prejunctional a2 adrenoceptors negatively feedbacks on NE exocytosis

Question 5

What are some directly acting SNS agonists?

Answer 5

Adrenaline – non-selective.

Phenylephrine - a1-selective

Clonidine - a2-selective

Isoprenaline - b1=b2-selective

Dobutamine - b1-selective

Salbutamol - b2-selective

Question 6

Why is adrenaline a good treatment for anaphylaxis?

Answer 6

it’s non-selective

Management of:
- Airways, Breathing - b2 – bronchodilation.

• Tachycardia - b1 – reduced chronotropic and ionotropic effect.
• Peripheral vasodilation - a1 – vasoconstriction.
• Suppression of mediator release.

adrenaline is more important here than noradrenaline as the beta receptors are more important in being triggered

Question 7

What are other clinical uses of adrenaline?

Answer 7

• asthma (emergency) (b2 -> bronchiodilation)
• cardiogenic shock (mainatin BP) (b1 -> inotropic effects)
• acute bronchospasm (b2)
• spinal and local anaesthetic (a1-> spinal - maintains BP, LA - vasoconstriction - prolongs action)

Question 8

How can adrenaline be used to treat glaucoma?

Answer 8

Increased IOP

Vasoconstriction of ocular blood vessels restricts the blood flow and thus the production of aqueous humour (production being derived from blood flow)

Management of:
- Intra-ocular Pressure - a1 – vasoconstriction.

Question 9

What are some unwanted effects of adrenaline?

Answer 9

• Secretions – reduced and thickened.
• CNS – minimal.
• CVS – tachycardia/palpitations/arrhythmia, hypertension/cold-extremities, overdose; cerebral haemorrhage and pulmonary oedema.
• GIT – minimal.
• Skeletal muscle – tremor

Question 10

What is phenylepherine?

Answer 10

a1 - selective

molecularly similar to adrenaline but resistant to COMT (not MAO)

clinical uses:
vasoconstriction
mydriasis (pupil dilation)
nasal decongestant (via vasoconstriction)

Question 11

What is clonidine?

Answer 11

Mainly acts on the prejunctional neuronal a2-receptor to inhibit NA release.

Clinical uses include:

• Treatment of hypertension and migraine.
• Reduces sympathetic tone.
  > a2-mediated presynaptic inhibition of NA release.
  > Central brainstem action within baroreceptor pathway to reduce sympathetic outflow

Question 12

What is isoprenaline?

Answer 12

equally selective for b1 and b2

Molecularly similar to adrenaline but less susceptible to uptake 1 and MAO breakdown.

Fast plasma half-life of 2 hours.

Clinical uses:

• Cardiogenic shock
• acute heart failure
• MI

> CAUTION - b2-stimulation in VSM in skeletal muscle triggers a fall in venous BP triggering a reflex tachycardia via stimulation of BR