18. Adrenergic receptor agonists

Last updated on October 17, 2019 at 18:46

Catecholamines Selective α-receptor agonists Selective β-receptor agonists
Non-subtype selective α1 selective α2 selective Non-subtype selective β2 selective
Dobutamine Oxymetazoline Clonidine Ephedrine Formoterol
Dopamine Phenylephrine Methyl-DOPA Salbutamol/albuterol
Epinephrine Xylometazoline Salmeterol
Isoprenaline Terbutaline
Norepinephrine

In the previous topic we saw some indirectly acting sympathomimetics. Now we’re going to look at some directly acting ones.

Adrenergic receptors

Adrenergic receptors, or adrenoceptors are the receptors that catecholamines can bind to. Seven types are important: α1, α2, β1, β2, β3, D1 and D2.

They’re all G-protein coupled receptors. Recall that depending on the type of G-protein on the inside of the cell will the activity of the receptor be different. Gs-type G-protein activates adenylyl cyclase, Gi type inhibits it and Gq type activates phospholipase C.

α1 receptor has a Gq type G-protein, meaning that when an agonist binds to it will phospholipase C be activated. The result will be activation of protein kinase C.

α2 receptor has Gi type G-protein, meaning it reduces the activity of adenylyl cyclase and therefore reduces the level of cAMP in the cell and inhibits protein kinase A. Recall from the previous topic that α2 receptor is part of the negative feedback, so it makes sense that it is inhibitory.

All β receptors are Gs coupled, meaning that they activate adenylyl cyclase and therefore increase the level of cAMP and activates protein kinase A.

Hint: An easy way to remember the G-proteins of α and β receptors is to remember the mnemonic “qiss”, which sounds almost like “kiss”. α1 has Gq, α2 has Gi, β1 has Gs and β2 has Gs. 

D1 and D2 are the receptors for dopamine. D1 is Gs coupled as well and therefore activates protein kinase A. D2 is Gi coupled and therefore inactivates protein kinase A. D1 activates vasodilation of renal, splanchnic, coronary and cerebral vessels.

Not written in the table is the fact that β1 receptors stimulate renin release.

Catecholamines in clinical practice

Indications:

Noradrenaline is used for severe hypotension.

Adrenaline is used in cardiac arrest and anaphylactic shock. It can also be added to local anaesthetic solutions to increase their effect and topically to stop bleeding.

Dopamine is used to treat shock.

Dobutamine is used in cardiogenic shock.

Isoprenaline is used in bradycardia and heart block.

Mechanism of action:

Adrenaline has more effect on β than α adrenergic receptors. However, in high doses the α effects predominate.

Noradrenaline has mainly α1 and β1 receptor effects.

Dobutamine is a synthetic (not endogenous) catecholamine that has most activity on β1-receptors. It is used when increased cardiac output is acutely needed.

Isoprenaline is also a synthetic catecholamine. It only has activity on β receptors.

Dosing:

The dose of adrenaline in anaphylactic shock is 0.25 – 1 mg, while for local anaesthetic action the dose is only 10 – 20 µg.

Selective alpha 1 receptor agonists
  • Phenylephrine
  • Oxymetazoline
  • Xylometazoline

Indications:

Phenylephrine is used as a nasal decongestant and to treat hypotension.

Oxymetazoline and xylometazoline are used as nasal decongestants.

Mechanism of action:

These drugs are α1-selective agonists. They increase blood pressure by causing vasoconstriction. This vasoconstriction also decreases the swelling in the nasal mucous membrane.

Phenylephrine has some alpha 2 agonist effect as well.

Selective alpha 2 receptor agonists
  • Methyldopa
  • Clonidine

Indications:

Methyldopa is used to treat hypertension in pregnancy.

Clonidine is used to treat ADHD and hypertension.

Mechanism of action:

All α2-selective agonists decrease blood pressure by acting on α2-receptors in the vasomotor centre in the medulla oblongata.

Methyldopa itself isn’t an alpha 2 agonist, but its metabolite methylnoradrenaline is.

Selective beta 1 receptor agonists
  • Ephedrine
  • Dobutamine

Dobutamine was described with the catecholamines above.

Indications:

Ephedrine is used to treat nasal congestion, haemorrhoids, hypotension, nocturnal enuresis and to produce mydriasis.

Mechanism of action:

Recall from the previous topic that ephedrine is an indirectly acting sympathomimetic, however it has some direct effects on β receptors as well.

Selective beta 2 receptor agonists
  • Salbutamol/albuterol
  • Formeterol
  • Salmeterol
  • Terbutaline

Indications:

The selective β2 agonists are mainly used as inhalations to treat asthma.

They, especially terbutaline, can also relax the uterus. By relaxing the uterus can they prevent premature labour.

Mechanism of action:

Beta 2 agonists induce bronchodilation and dilation of the uterus.

Pharmacokinetics:

The beta 2 selective agonists are separated into the short-acting ones and long-acting ones:

  • Short-acting beta 2 agonists (SABA)
    • Salbutamol/albuterol
    • Terbutaline
  • Long-acting beta 2 agonists (LABA)
    • Formoterol
    • Salmeterol

All of these drugs have onset of action of 1 – 5 minutes, except salmeterol, which needs at least 30 minutes to work.


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17. Agents acting on the biosynthesis, storage, release and elimination of catecholamines

Next page:
19. Adrenergic receptor antagonists

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