8: SNS agonists

Question 1

Where are a1 adrenoreceptors located?

What is their second messenger mechanism and prinicpal effect?

Answer 1

Alpha 1 receptors:

• Eye (contraction of iris dilator muscle)
• vasoconstriction (SM constriction)
• excretion of nose
• contraction of ureter–> holding urine

–> Exitory via

PLC into IP3 and DAG

Question 2

Where are alpha 2 adrenorecpetors commonly found?

What is their secound messenger system and principal effect?

Answer 2

Usually inhibitory –> decerease of cAMP

• regulation in CNS
• reduction of aqueous humor production in ciliary body

Question 3

Where are ß1 receptors located?

What is their secound messenger system?

Answer 3

Heart –> icrease heart rate + force of contraction

Kideny–> increase renin –> increase reabsorbtion

Messenger System: increase in cAMP

Question 4

Where are ß2 adrenoreceptors located?

What is their 2nd messenger system

Answer 4

Bronchios/Airway

Vessels –> causing vasodilation

uterine smooth muscle

increase in cAMP

Question 5

How would you medically treat an anaphylactic shock?

What are the (desired) effects?

Answer 5

Adrenaline (non-selective adrenoreceptor agonist) e.g. in Epipen

It counteracts the problems associated with too much histamine release:

• ß2–> Bronchiodilation
• ß1 –> tachycardia
• a1 –> vasoconstriction
• Might bind to ß receptors on mast cells and supresses the release of mediator cells

–> to increase BP and maintain breathing

Question 6

What do you use adrenaline for? (as drug)

Answer 6

1. Anaphylactic shock
2. Emergency Astmah + acute bronchspasm (ß2)
3. Cardiogenic shock (ß1)
4. Maintaining BP during spinal anestehsia (a1)
5. Prolonging effect during local anesthesia (a1)

Question 7

What are the side effects of Adrenaline use?

When might this be problematic?

Answer 7

• Reduces and thickened secretions
• Tremor (skeletal muslce)
• CVS effects
  
  • tachycardia, palpitation, arrythmias
  • vasoconstriction (cold extremities)+ high BP
  • at overdose: cerebral haemorrhage and pulmonary oedema
• (Minimal CNS and GI effects)

Overall: not too severe, only in elderly patients of with underyling condition (e.g. heart problems)

Question 8

What are COMT and MAO?

Where are they situated

Answer 8

Both enzymes that break down Adrenaline/Noradrenaline

Catechol-O-Methyltransferase –> More peripheral

MAO –>Monoaminooxidase = More in CNS

Question 9

Which drug is a a1 selective agonist?

Answer 9

More or less selective:

Phenylephrine

Question 10

What is the mechanism of action and the clinical use of Phenylephrine?

Answer 10

It is a (more or less) a1 selective adreno agonist

It is more resistant than Adrenlaine to COMT –> longer there than Adrealine itself

• vasoconstriction
• Mydriasis
• Nasal decongestant (abschwellendes Mittel)
  
  • vasoconstriction –> less fluid production

Question 11

Which drug is used as a a2 adrenergic agonist?

Answer 11

Clonidine

–> a2 receptors are inhibitory!

• Glaucoma (decrease of humous production due to stimmulation of a2 receptor)
• Treatment in hypertension and migrane
• Reduction of sympathetic tone (by reducing sympathetic outflow via binding to a2 receptors in brainstem that then reduce signaling –< presynaptic inhibition of Noradrenline release)

Question 12

What are the clinical uses for Clonidine?

Answer 12

More or less selective a2 adrenoreceptor agonist

a2 receptors are inhibitory!

• Treatment of Glaucoma (decrease of humous production due to stimmulation of a2 receptor)
• Treatment in hypertension and migrane
• Reduction of sympathetic tone (by reducing sympathetic outflow via binding to a2 receptors in brainstem that then reduce signaling –< presynaptic inhibition of Noradrenline release)

Question 13

Which adrenorecepors controll vascular tone in the brain?

Answer 13

ß2 receptors–> would not want vasoconstriction to the brain

Question 14

What is an example of a adrenergic ß receptor selective drug?

Answer 14

Isoprenaline

• more resistant to break down by MAO (central effects) and uptake 1 than Adrenaline

Question 15

When would you use Isoprenaline as medication?

What is the problem with the use of isoprnaline?

Answer 15

It is a adrenergic ß receptor selective agonsit (ß1=ß2)

Used in:

• Cardiogenic shock
• Acute heart failure
• MI

Can be problematic: (especially in e.g. Astmah medication when patients would always get refelx tachycardia)

• stimmulation of ß2 receptors causes vasodilation
• –> drop in BP
• Causing reflex tachycardia (via Baroreceptors)

Question 16

What is a adrenergic ß1 receptor selective drug?

Answer 16

Dobutamine

Question 17

What is the clinical use and characteristics of Dobutamine?

Answer 17

Used in

• cardiogenic shock
• (because of short half life of 2 min)

–> but does not have refelx tachycardia (like isoprenaline

Question 18

Name a adrenergic ß2 receptor selective drug?

Answer 18

Salbutamol

Question 19

What is the clinicl use of Salbutamol?

Explain the mechanism of action and unwanted effects

Answer 19

Salbutamol –> increase in cAMP –> increase in PKA

• Main use in astmah
• side effects
  
  • Cardiac–> increase in BP, tachycardia, arrythmias
  • hyperglycaemia
  • tremor, restlessness