DOPAMINE DOPAMINE: Used in renal failure with shock. Acts on dopamine, alpha 1 and beta 1 receptors. Low dose activates dopamine-1 receptors in the renal blood vessels – increase cAMP – vaso dilation. Moderate dose act on beta-1 in the heart - positive inotropic and chronotropic action. Large dose acts on alpha-1 vasoconstriction. Dopamine agonist: FENOLDOPAM is used in hypertensive crises

DOBUTAMINE DOBUTAMINE : It does not act on dopamine receptors. Considered as predominantly beta-1 agonist. It increases the contraction of the heart but not significantly increase the heart rate. Used in acute heart failure and cardiogenic shock.

MIXED ADRENERGIC AGONIST EPHEDRINE : Acts directly on alpha and beta receptors and indirectly by releasing norepinephrine also. Effective orally - resistant to MAO Crosses the BBB – CNS stimulation. Can be used in the treatment of bronchial asthma, hypotension after spinal anesthesia.

INDIRECTLY ACTING ADRENERGIC AGONIST AMPHETAMINE : Orally active CNS action more prominent. Alertness, increased concentration, increased work capacity. RAS is activated – wakefulness. Used in ADHD and narcolepsy.

INDIRECTLY ACTING ADRENERGIC AGONIST

ALPHA-1 ADRENERGIC AGONIST Phenylephrine PHENYLEPHRINE

BETA ADRENERGIC DRUGS Isoproterenol ISOPROTERENOL

NOREPINEPHRINE Norepinephrine has little or no effect on beta 2 receptors.

ALPHA-2 AGONIST CLONIDINE: Activation of alpha 2 receptors in the brain causes inhibition of sympathetic system Suppression of release of NE by presynaptic alpha 2 receptors. Excellent oral bioavailability and transdermal preparation also available. Used in the treatment of hypertension and ADHD. Adverse effects includes sedation, bradycardia, rebound hypertension.

ALPHA-2 AGONIST ALPHA METHYL DOPA: It is converted to α -methylnorepinephrine, an agonist of presynaptic α 2 adrenergic receptors. Activation of α 2 receptors in the brainstem inhibit sympathetic nervous system output and lower blood pressure. It is the drug of choice in hypertension with pregnancy.

BETA ADRENERGIC AGONIST BETA 2 AGONIST : Albuterol – short acting Formoterol long acting Salmeterol long acting Terbutaline Ritodrine

SYMPATHETIC NERVOUS SYSTEM USES OF SYMPATHOMIMETICS : Treatment of hypotension due to spinal anesthesia – Ephedrine, Midodrine Nasal decongestants and Mydriatic – Phenyephrine Bronchial asthma – Albuterol Anaphylaxis – Epinephrine (EPIPEN-Autoinjectors) Uterine relaxants – Ritodrine ADHD – Amphetamine, Clonidine, Guanfacine Narcolepsy – Amphetamine Glaucoma – Apraclonidine

Adrenergic drugs

Drug intervention -- Adrenergic transmission Tyrosine Dopa  DA Metyrosine Vesicle (DA  NE) Reserpine Release Bretylium, guanethidine Recapture by Uptake-1 Receptor + action NE Adrenergic agonists (direct acting) Phenylephrine Isoproterenol Albuterol (Rate-limiting) Cocaine Tricyclic antidepressants (e.g. imipramine) Adrenergic antagonists Phentolamine (  -blocker) Propranolol (  -blocker) TH Amphetamine, tyramine, ephedrine  : Stimulatory  : Inhibitory Solid: Agonist Dotted: Antagonist

EFFECTS OF INTRAVENOUS INFUSION OF NOREPINEPHRINE, EPINEPHRINE OR ISOPROTERENOL IN HUMANS. Norepinephrine (predominantly  -agonist) causes vasoconstriction and increased systolic and diastolic BP, with a reflex bradycardia. Isoproterenol (  -agonist) is a vasodilator, but strongly increases cardiac force and rate (  -agonist). Mean arterial pressure falls. Epinephrine combines both actions.