SNS agonists

Question 1

what directly acting sympathomimetics?

Answer 1

they mimic the actions of NA/A by binding to and stimulating adrenoceptors (GPCRs)
they are directly acting drugs
they are used principally for their actions in the CVS, eyes and lungs

Question 2

what is the selectivity of noradrenaline?

Answer 2

selectivity – sensitive to alpha:

o a1=a2 > b1=b2.

Question 3

what is the selectivity of adrenaline?

Answer 3

Adrenaline selectivity – sensitive to beta:

o b1=b2 > a1=a2.

Question 4

alpha or beta receptors around the body

Answer 4

see slide

Question 5

where are noradrenaline and adrenaline made?

Answer 5

Noradrenaline remember is made in nerve terminals whereas adrenaline is synthesised in the adrenal medulla.

Question 6

what is the significance of the alpha 2 adrenoceptors?

Answer 6

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

Question 7

below are some directly acting SNS agonists:

which receptor are they more selective for?

Answer 7

1. Adrenaline – non-selective.
2. Phenylephrine - a1-selective.
3. Clonidine - a2-selective.
4. Isoprenaline - b1=b2-selective.
5. Dobutamine - b1-selective.
6. Salbutamol - b2-selective.

Question 8

know noradrenaline metabolism

Answer 8

Noradrenaline metabolism is displayed on the slides

o Tyr à DOPA à DA à NE.

Question 9

what is the significance of the alpha 2 adrenoceptors?

Answer 9

NE binding to prejunctional a2 adrenoceptors (on the presynaptic neurone) negatively feedbacks on NE exocytosis.

Question 10

why can adrenaline be used in anaphylaxis?

Answer 10

ectly Acting SNS Agonists – Adrenaline:
§ Anaphylaxis:
o It is non-selective to adrenoceptors.
o Management of:
§ Airways, Breathing - b2 – bronchodilation.
§ Tachycardia - b1 – reduced chronotropic and ionotropic effect.
§ Peripheral vasodilation - a1 – vasoconstriction.
§ Suppression of mediator release.
o You’ll notice that adrenaline is more important here than noradrenaline as the beta receptors are more important in being triggered.

Question 11

why is adrenaline used in COPD?

Answer 11

o Used in asthma (emergencies via I.M. or S.C.).
o Management of:
§ Airways, Breathing - b2 – bronchodilation.
§ Suppression of mediator release.
o A selective b2-agonist is preferable though.

Question 12

why is adrenaline used in glaucoma?

Answer 12

Increased IOP.
o Vasoconstriction of ocular blood vessels restricts the blood flow and thus the production of aqueous humour (production being derived from blood flow).
o Management of:
§ Intra-ocular Pressure - a1 – vasoconstriction.

Question 13

what are the other uses for adrenaline?

Answer 13

o Cardiogenic shock – use b1 actions.
o Spinal anaesthesia – maintain BP.
o Local anaesthesia – prolong duration of action using a1 action to reduce blood flow and thus removal of anaesthesia drug

Question 14

what are the unwanted effects of SNS agonists (such as adrenaline)?

Answer 14

Unwanted actions: 
§ 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 15

what are the clinical uses of phenylephrine?

what is it resistant to?

Answer 15

Directly Acting SNS Agonists – Phenylephrine:
§ a1»a2»>b1/b2.
§ Molecularly similar to adrenaline but resistant to COMT (but not MAO).
§ Clinical uses include:
o Vasoconstriction.
o Mydriasis – dilation.
o Nasal decongestant (via vasoconstriction).

Question 16

where does clonidine act?

what are the clinical uses of clonidine?

Answer 16

§ a2»a1»>b1/b2.
§ Mainly acts on the prejunctional neuronal a2-receptor to inhibit NA release.
§ Clinical uses include:
o Treatment of hypertension and migraine.
o Reduces sympathetic tone.
§ a2-mediated presynaptic inhibition of NA release.
§ Central brainstem action within baroreceptor pathway to reduce sympathetic outflow.

Question 17

how does isoprenaline differ from adrenaline?

what are the clinical uses of isoprenaline?

Answer 17

§ b1=b2»»a1/a2.
§ Molecularly similar to adrenaline but less susceptible to uptake 1 and MAO breakdown.
§ Fast plasma half-life of 2 hours.
§ Clinical uses:
o 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.

Question 18

what are the clinical uses of dobutamine?

Answer 18

§ b1»b2»>a1/a2.
§ Used to treat cardiogenic shock as lacks isoprenaline’s reflex tachycardia.
§ Administered by IV infusion with a VERY short half-life of 2 minutes – rapidly metabolised by COMT.

Question 19

what is salbutamol resistant to?

what are the clinical uses to salbutamol?

Answer 19

§ b2»b1»>a1/a2.
§ Synthetic catecholamine derivative with resistance to COMT and MAO.
§ Clinical uses:
o Treatment of asthma.
§ b2 relaxation of smooth muscle.
§ Inhibition of release of bronchoconstriction substances.
o Treatment of threatened pre-mature labour.
§ b2 relaxation of smooth muscle.
§ Side effects – reflex tachycardia, tremor, blood sugar dysregulation.