Pharmacology: Adrenergic Drugs and Catecholamines

Catecholamines

• Catecholamines are compounds containing a catechol moiety and an amine side chain.
• They exert a powerful stimulant effect on the heart, increasing heart rate and force of contraction, resulting in a markedly increased cardiac output and cardiac oxygen consumption.

Adrenergic Receptors

• The heart is well supplied with β1 (predominant) and β2 receptors.
• β1 receptors stimulate the heart, increasing heart rate and force of contraction.
• β2 receptors cause relaxation of most kinds of smooth muscle.
• α1 receptors stimulate contraction of smooth muscle.
• α2 receptors are also present in vascular smooth muscle.

Effects on Different Organs

• Heart: Catecholamines increase cardiac output and cardiac oxygen consumption.
• Smooth Muscle:
  • α1 receptors cause contraction of smooth muscle.
  • β2 receptors cause relaxation of smooth muscle.
  • Bronchial smooth muscle is strongly dilated by β2 agonists.
• Vascular System:
  • α1 agonists contract vascular smooth muscle, increasing peripheral vascular resistance and venous pressure.
  • β2 agonists cause vasodilation, mainly endothelium-dependent and mediated by NO release.
• Gastrointestinal Tract:
  • Both α and β receptors are present, leading to relaxation of smooth muscle.
  • Selective β2 agonists are used to treat asthma.
• Genitourinary Tract:
  • α receptors mediate contraction of the bladder trigone and sphincter area.
  • β2 agonists cause relaxation of uterine smooth muscle.
• Respiratory System:
  • β2 agonists, especially selective ones (e.g., salbutamol), are used to treat acute asthmatic bronchoconstriction.

Clinical Applications

• Cardiovascular Applications:
  • β1 agonists (e.g., dobutamine) may be useful in acute heart failure and shock.
  • Epinephrine has been used in cardiac arrest.
• Genitourinary Tract:
  • β2 agonists (e.g., terbutaline) may be used to suppress premature labor.
• Miscellaneous Indications:
  • Epinephrine is used to treat anaphylactic shock.
  • Phenylephrine and oxymetazoline (α agonists) are used to reduce nasal congestion.
  • Tetrahydrozoline is used to relieve redness in the eyes caused by minor eye irritations.

Inactivation of Catecholamines

• Circulating catecholamines are usually inactivated by a combination of transporter uptake and/or metabolism by several enzymes.

Indirect-Acting Sympathomimetic

• Amphetamines:
  • Are central nervous system stimulants.
  • Have a spectrum of stimulant effects, from alerting to euphoria and insomnia.
  • Used to treat attention deficit hyperactivity disorder (ADHD).
  • Inhibit presynaptic monoamine transporters, increasing dopamine, serotonin, and NA.
  • Can lead to marked anxiety, aggressiveness, paranoia, and seizures at high doses.
  • Rapidly develop tolerance and dependence with repeated dosing.
• Cocaine:
  • Is a powerfully addictive stimulant drug.
  • Is made from the leaves of the coca plant native to South America.