Nursing Pharmacology: Adrenergic Pharmacology

Nursing Pharmacology: Autonomic Pharmacology Adrenergic Drugs

At low concentration ß₂ selective adrenergic agonists have relatively minor ß₁ cardiac receptor-mediated effects.
Effective in managing asthma, ß₂ selective adrenergic agonists are orally active and metabolized more slowly compared to catecholamines
ß₂ selective adrenergic agonists examples include:
- Metaproterenol (Alupent)
- Terbutaline (Brethine)
- Albuterol (Ventolin,Proventil)
In asthma, pulmonary ß₂ receptors are targeted by drug administration by inhalation.
- This route of administration results in lower systemic drug concerntration, an effect which reduces the likelihood of cardioacceleration ( ß₁) or skeletal muscle tremor (ß₂ ).
Activation of pulmonary ß₂ adrenergic receptors results in smooth-muscle relation and bronchodilation.
ßadrenergic receptor agonists also decrease histamine and leukotriene release from lung mast cells.
- Recalling that asthma is first and foremost an inflammatory disease, reduction in histamine and leukotriene release would be beneficial.
ßadrenergic receptor agonists enhance mucociliary activity and diminish microvascular permeabilty.

Metaproterenol (Alupent)
- ß₂ adrenergic receptor-selective and is resistant to COMT (catechol-O-methyl transferase) metabolism in the body.
- Metaproterenol is less ß₂ selective, compared to terbutaline (Brethine) and albuterol (Ventolin,Proventil).
- Metaproterenol may be used for long-term and acute treatment of bronchospasm
Terbutaline [Brethine]
- This agent is ß₂ adrenergic receptor-selective and is also resistant to COMT (see above).
- Terbutaline is active after oral, subcutaneous, or administration by inhalation and typically shows a rapid onset of action.
- This agent may be used for management of chronic obstructive lung disease and for treatment of acute bronchospasm (smooth muscle bronchoconstriction), including status asthmaticus
Albuterol [Ventolin]
- Albuterol is another ß₂ adrenergic receptor-selective drug.
- This agent is effective following inhalation or oral administration and may be commonly used in chronic and acute asthma management.
Ritodrine (Yutopar)
- Ritrodrine, a ß₂ adrenergic receptor-selective drug was developed for use as a uterine relaxant.
- This agent may be administered by i.v. in certain patients for arresting premature labor; if successful, oral therapy may be started.
- ß₂ adrenergic receptor-selective agonists may not improve perinatal mortality and may increase maternal morbidity.
- In women being treated for premature labor, ritodrine (Yutopar) or terbutaline (Brethine) may cause pulmonary edema .

Adverse Effects associated with adrenergic agonists

Excessive cardiovascular stimulation
Skeletal muscle tremor (tolerance develops, unknown mechanism) due to ß₂ adrenergic receptor activation
Overusage may be a factor in morbidity and mortality in asthmatics.

Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.213-216.

α₁ Selective Adrenergic Agonists

α₁ selective adrenergic agonists activate α adrenergic receptors in vascular smooth muscle producing vasoconstriction.
- Peripheral vascular resistance is increased.
- Blood pressure may be increased, causing a reflex reduction heart rate
- α₁ adrenergic agonists are used clinically in management of hypotension and shock.
- Phenylephrine (Neo-Synephrine) and methoxamine (Vasoxyl) are direct-acting vasoconstrictors.
- Mephentermine (Wyamine) and metaraminol (Aramine) act both by direct receptor activation and by promoting epinephrine release (indirect activity).

Methoxamine (Vasoxyl)
- Methoxamine is a specific α₁ receptor agonist and as such both:
  - Increases peripheral resistance and
  - Causes an increase in blood pressure that precipitates sinus bradycardia (decreased heart rate) due to vagal reflex.
- Reflex bradycardia may be blocked by atropine (muscarinic antagonist)
- Clinical uses include management of hypotensive states and termination (by vagal reflex) of paroxysmal atrial tachycardia (adenosine or other agents may be preferable)

Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.216-219.

α₂ Selective Adrenergic Agonists and Miscellaneous Adrenergic Agonists

Introduction

α₂ selective adrenergic agonists are used to treat essential hypertension.
Their mechanism of action involves:
- (1) activation of central α₂ adrenergic receptors at cardiovascular control centers
- (2) this central activation decreases sympathetic outflow thereby reducing sympathetic vascular tone and blood pressure.
Clonidine (Catapres):
- Clonidine (Catapres) is primarily used in treating essential hypertension.
- A prolonged hypotensive response results from a decrease in CNS sympathetic outflow.
- This response is due to α₂ selective adrenergic receptor activation.
- Adverse Effects:
  - Dry mouth
  - Sedation
  - Sexual dysfuction
- Clonidine's α₂ selective adrenergic receptor activation of vascular smooth muscle may increase blood pressure in patients with severe autonomic dysfunction with profound orthostatic hypotension (in these patients the reduction of central sympathetic outflow in not clinically important.
Guanabenz Wytensin)
- Guanabenz (Wytensin)is primarily used in treating essential hypertension.
- A prolonged hypotensive response results from a decrease in CNS sympathetic outflow.
- This response is due to a₂ selective adrenergic receptor activation.
- Adverse Effects:
  - Dry mouth
  - Sedation
Guanfacine
- Guanfacine is used for treating essential hypertension.
- A prolonged hypotensive response results from a decrease in CNS sympathetic outflow.
- This response is due to a₂ selective adrenergic receptor activation. a₂ receptor selectivity is greater than that observed with clonidine despite similar efficacy in treating hypertension.
- Adverse Effects:
  - Dry mouth
  - Sedation
α-methyl DOPA-- (methyldopa (Aldomet))
- α-methyl DOPA (methyldopa (Aldomet)), metabolically converted to α-methyl norepinephrine, is used for treating essential hypertension.
- A prolonged hypotensive response results from a decrease in CNS sympathetic outflow.
- This response is due to a₂ selective adrenergic receptor activation.
- Adverse Effects:
  - Dry mouth
  - Sedation