Adrenergic system

Adrenergic agonists

Classification
Direct acting agents Indirect acting agents Direct acting and indirect
acting agents
Albuterol Amphetamine Ephedrine
Dobutamine Cocaine Psudoephedrine
Dopamine
Epinephrine, nor-epinephrine
Isoproterenol
Phenylephrine
Terbutaline
 Adrenergic receptors (Adrenoceptors)
• Alpha (α)
Two types: α1, α2

• Beta (β)
Two types: β1, β2
 α1
Location: Vasculature, smooth muscles of eyes
Actions: Vasoconstriction, Increased peripheral
resistance, Hypertension, Mydriasis.
β1
Location: Heart, adipose tissues and kidneys
Actions: Tachycardia, Increased lipolysis,
Increased release of renin.
α2
Location: Presynaptic neurons, Pancreas
Actions: Inhibition of epinephrine release,
Inhibition of ACH release, Inhibition of insulin
release.
β2
Location: Vasculatures, Lungs, Liver, pancreas
and smooth muscles.
Actions: Vasodilation, decreased peripheral
resistance, bronchodilation, increased liver
glycogenolysis, increased released of glucagon.
 Neurotransmission at adrenergic neurons
It involves five steps
• Synthesis of nor-epinephrine:
Tyrosine
Tyrosine hydroxylase
DOPA
DOPA decarboxylase
Dopamine
Dopamine hydroxylase
Norepinephrine
• Storage of norepinephrine in vesicles
• Release of norepinephrine
• Binding to receptors
• Removal of norepinephrine
• Diffuse out to general circulation
• Metabolized to derivatives by COMT
• Recaptured back into neuron
 Sites of action of direct, indirect and mixed acting
adrenergic agonists
• Direct acting agents:
Drug directly activates receptors.
• Indirect acting agents:
Drug enhances release of nor-epinephrine from vesicles.
• Mixed acting agents:
Drug acts both directly and indirectly.
 Epinehrine
Epinephrine is one of the four catecholamines (epinephrine,
norepinephrine, dopamine and dobutamine). Epinephrine interacts
with both α and β receptors. At low doses β-effects on vasculature
predominate whereas at high doses, α-effects are the strongest.
 Actions of Epinehrine
• Cardiovascular effects:
The major actions of epinephrine are on the cardiovascular system.
Epinephrine strengths the contractility of myocardium (positive
inotropic: β1 action) and increases its rate of contraction (positive
chronotropic: β1 action). Therefore, cardiac output increases.
• Respiratory effects:
Epinephrine causes powerful bronchodilation by acting directly on
bronchial smooth muscle (β2 action). This action relieves all known
allergic or histamine induced bronchoconstriction. In the case of
anaphylactic shock this can be life saving.
• Hyperglycemia:
Epinephrine has a significant hyperglycemic effect because of increased
glycogenolysis in the liver (β2 action), increased release of glucagon (β2
action) and a decreased release of insulin (α2 action).
• Lipolysis:
Epinephrine initiates lipolysis through its agonist activity on β receptors
of adipose tissue.
 Therapeutic uses of Epinephrine
• Bronchospasm
• Anaphylactic shock
• Cardiac arrest
• Local anesthetics
 Adverse effects of Epinephrine
• CNS disturbances (anxiety, fear, tension, headache and tremors).
• Hemorrhage due to elevation of blood pressure.
• Cardiac arrythmias.
• Pulmonary edema.
 Norepinephrine
Because it is the neuromediator of adrenergic nerves, theoretically it
should stimulate all types of adrenoceptors. In practice when the drug
is given in therapeutic doses to humans, the α-adrenergic receptors is
the most affected.
 Actions of Norepinephrine
• Vasoconstriction.
• Baroreceptor reflex.
• Reflex bradycardia.
 Adrenergic Antagonists
Classification
α - Blockers β - Blockers Drugs affecting neurotransmitter
uptake or release
Alphazosin Atenolol Guanithidin
Doxazosin Bisoprolol Reserpine
Phentolamine Carvedilol
Prazosin Labetolol
Tamsulosin Metoprolol
Terazosin Nebivolol
Propranolol
 Actions of β - Blockers
• Cardiovascular: negative inotropic and chronotropic effects,
decreases cardiac output.
• Peripheral vasoconstriction
• Bronchoconstriction
• Increased sodium ion retention: reduced blood flow causes a
decrease in renal perfusion, resulting in an increase in sodium ion
retention and blood plasma volume.
• Disturbances in glucose metabolism
 Therapeutic effects of β - Blockers
• Hypertension
• Migraine
• Hyperthyroidism
• Angina pectoris
• Myocardial infarction
 Adverse effects of β - Blockers
• Bronchoconstriction
• Arrhythmias
• Sexual impairment
• Metabolic disturbances
• Fatigue