SNS Agonist

Question 1

Describe the action of directly acting sympathomimetics

Answer 1

Mimic the action of adrenaline and noradrenaline by binding to and stimulating adrenoreceptors (GPCRs) used principally for their action on eyes, CVS and lungs.

All G protein coupled: Alpha 1: PLC > IP3 and DAG. Alpha 2: decreases cAMP beta 1 and 2 increase cAMP

Question 2

Describe briefly the distribution of adrenoreceptors in body

Answer 2

Look at diagram.

Selectivity for NA: Alpha> beta
Selectivity for A: Beta> alpha

Question 3

Descofbe the metabolism of noradrenaline

Answer 3

1. Tyrosine from the diet is converted to DOPA by tyrosine hydroxylase (rate limiting enzyme)
2. DOPA is converted to dopamine via dopa decarboxylase
3. DOPA converts to NA

Deactivation is via reuptake into the nerve terminal itself or into extra neural tissue

Alpha 2 receptor has a negative effect to control secretion so if NA goes up, decrease of signals

Question 4

Name 5 examples of SNS agonist

Answer 4

1. Adrenaline - non selective
2. Phenylepherrine - alpha 1
3. Clonidine - alpha 2 (works as SNS antagonist because by increasing negative feedback it reduces the effects of SNS used in migraine as antihypertensive)
4. Doubustamine - beta 1
5. Salbutamol - beta 2

Question 5

Describe the clinical uses of adrenaline and unwanted effect

Answer 5

1. Allergic reactions - hypersensitivity due to mast cell, histamine - mediated constriction
2. Asthma - acute bronchospasm associated with chronic bronchitis or emphysema, cardiogenic shock
3. Glaucoma - poor intraocular shock by poor drainage of the aquaeous humour, alpha receptor (blood vessels) and beta (enzymes that make aquaeous humour) so stimulation of alpha means vesse constriction and less aquaeous humour produced and less drainage.

Lots of unwanted side effects: reduced mucus, CVS tachycardia hypertension etc, skeletal tremor.

Question 6

Describe the role of phenylephrine

Answer 6

Selectivity: alpha 1> alpha 2> beta 1> beta 2. Chemically related to adrenaline but more resistant to COMT but not MAO. Used to vasoconstrict blood vessels and in nasal congestion > white cell causes fluid leakage so if less blood = less white cell count.

Used

1. Increase BP via vasoconstriction
2. Mydriasis (pupil dilation)
3. Nasal decongestant (decreased white cell count)

Question 7

Describe the adrenoreceptor agonist role in glaucoma

Answer 7

Alpha 1 vasoconstriction

Alpha 2 humour formation

Question 8

Describe the effect of isoprenaline, dobutamine and salbutamol

Answer 8

Isoprenaline: chemically related to adrenaline but more resistant to MAO and uptake 1 (used in cardiogenic shock and acute heart failure and Mi) but the rapid decrease in BP causes reflexive tachycardia

Dobutamine: cardiogenic shock (B1>b2>a1>a2) lacks the reflexive tachycardia because rapidly metabolised

Salbutamol (ventolin): b2> B1> a1>a2. Used in asthma, broncihial smooth muscle inhibition of release of bronchoconstrictor substances from mast cells and treatment of threatened premature labour