DOES ADRENERGIC LOVING AGENTS MIMICS THE SYMPATHETIC SYSTEM ?

Sympathomimetics/Adrenergic agonists

These drug act on adrenergic receptors by activating it ..   

Classification:

Direct-Acting Agents 

Epinephrine, Nor-Epinephrine,

phenylephrine, Dopamine,Dobutamine,

Albuterol, Clonidine, Fenoldopam,

Formeterol, Isoproterenol,

Metaproterenol,

Salmeterol, Terbutaline,

Indirect-Acting Agents

 Amphetamine, Cocaine

Direct & Indirect Acting Ephedrine, Pseudoephedrine

Neurotransmission at Adrenergic Neurons

Sysnthesis of Nor-epinephrine: 

Tyrosine transported by Na+ dependent energy

carrier..into axoplasm of adrenergic neuron..it is hydroxylated to DOPA

(DiHydroxyPhenylAlanine)...it is Rate limiting step..DOPA decarboxylated by DOPA-

decarboxylase to form DOPAMINE…

Storage:

 DOPAMINE enters into the vesicle & converted into Reserpine ϴ this transport 

Release of Neurotransmitter= Ca++ influx cause fusion of vesicle.. 

Guanethidine & Bretylium ϴ this release

Metabolism:

Nor-Epinephrine methylated by COMT (catechol-o-methyl transpherase) & 

oxidized by MOA (Monoamine oxidase).. 

Cocaine & Imipramine ϴ reuptake of Nor-epinephrine 

ADRENORECEPTORS 

α 1 liver, GIT, , Vasoconstriction,increased 

B.P, Mydriasis, 

α 2 ϴ of Norepinephrine release, ϴ of Ach 

release, ϴ of insulin release 

β 1 heart,kidney

 Tachycardia, increased Lipolysis, 

Increased release of Renin, Increased

Myocardial contractility

β 2 lungs,Blood vessels,GIT 

Vasodilation, Bronchodilation, 

decreased peripheral resistance,

increased release of Glucagon, 

relaxed uterine smooth muscle,

increased glycogenolysis 

B3= Adipose tissue 

Epinephrine= naturally occur in adrenal medulla, 

Actions=At low dose β effects (vasodilation)…

At high dose α effects (vasoconstriction)

+Ve iontropic β1 action (increased myocardium contractility)…

+Ve chronotropic β1 action ( increased rate of contraction).. 

activate β1 on kidney..increased Renin release..

activate Angiotensin ll…vasoconstriction.

Dilates vessels of liver and skeletal muscle β2 action..

constricts arterioles in skin α 

action…

bronchodilation β2 action…Hyperglycemia due to glygenolysis in liver β2 

action & decreased insulin release α2 effect…

Lipolysis β effect 

T.E

 used in Bronchospasm, Anaphylactic shock(DOC in type 1 hypersensitivity),

cardiac arrest, Adjunct with local anaesthetic by increasing duration of anaesthesia 

through vasoconstriction 

S.E:

anxiety, tremor, headache, Hemorrhage, cardiac arrhythmia, pulmonary edema

Interactions :

epinephrine with cocaine exaggerated the actions…. 

dangerous in Diabetes ..enhanced CVS action in Hyperthyroidism… 

with inhalation anaesthetics cause tachycardia 

Nor-Epinephrine:

 α-adrenergic receptor mostly effected…Nor-Epinephrine..

Actions=Vasoconstriction…Reflex tachycardia by stimulating Baroreceptor…

T.E:

used in shock b/c increased vascular resistance & BP….

S.E:

caused extravasation (discharge of blood from vessels into tissue)…blanching &

sloughing of skin (due to extreme vasoconstriction)

Nor-epinephrine called Levarterenol

Isoproterenol:

 Direct acting synthetic catecholamine…β1 , β2 receptor

Actions=increase heart rate & force of contraction...hyperglycemia & lipolysis

T.E:

used to stimulate the heart in emergency situation

S.E:

similar to epinephrine

Dopamine:

 α , β, D1, D2 receptors

Actions= ionotropic & chrontropic effects…vasoconstriction…vasodilation..increase

GFR

T.E:

 DOC in Cardiogenic & septic shock…treat hypotension & C.H.F

S.E:

 metabolized into Homovanillic acid cause ( hypertension, nausea, arrhythmia) ..

Fenoldopam= racemic mixture..R-isomer is active...agonsit of D1 receptor

Dobutamine= β1 agonsit, racemic mixture

T.E:

 Acute C.H.F(Congestive Heart Failure), ionotropic support after cardiac surgery

S.E:

used in caution with atrial fibrillation….tolerance may develop on prolonged use

Oxymetazoline:

 α1 & α2 agonsit

T.E:

nasal decongestant & ophthalamic drops

S.E:

Sneezing, burning of nasal mucosa, Rebound congestion,,,dependence

Phenylephrine :

α1 receptor..synthetic drug..not catechol derivative..not substrate of COMT

T.E:

nasal decongestant...ophthalamic soln. for mydriasis..

S.E:

increase B.P, Reflex Bradycardia,

Clonidine 

 α2 agonist.

T.E:

 used in Essential Hypertension...decrease withdrawl effects of Opiates, BZD, and

tobacco smoking

S.E:

constipation...xerostomia...Rebound hypertension

Metaproterenol :

 not catecholamine...resistant to COMT...β2 agonist

Albuterol & Terbutaline:

β2 agonist….short-acting....Bronchodilators..3hr dilation 

Albuterol 

T.E:

 terbutaline off-label use Uterine relaxant to delay Labour..

S.E:

Tremor. 

Salmeterol & Formoterol:

β2 agonist…long acting ...bronchodilators...12hrs dilation 

DOC in Nocturnal Asthma 

Indirect-Acting Adrenergic Agonists 

They cause release of Nor-Epinephrine from presynaptic terminals OR inhibit the 

reuptake of Norepinephrine. 

Amphetamine:

α1 agonsit as well as β-stimulatory effects 

T.E:

for treating Hyperactivity in children,…Appetite control…in Narcolepsy

S.E:

risk of Abuse...Suicidal tendency...hypertension...Arrythmia.. 

Tyramine:

found in Fermented foods cheese & chipanti wineetc….byproduct of Tyrocine 

…oxidized by MOA in GIT...with MOAI increased catecholamine 

Cocaine :

 local anaesthetic…block Na+/K+ activated ATPase…norepinephrine 

accumulate in synaptic cleft...increased sympathetic activity.. 

Mixed-Action Adrenergic Agents 

Induce the release of Norepinephrine from presynaptic terminals & activate adrenergic 

receptor on postsynaptic receptor 

Ephedrine & PseudoEphedrine:

 plant alkaloid...not catechol...long duration of 

action...vasoconstriction…bronchodilation

T.E:

 Ashma...improve athletic performance by increasing alert,decreases 

fatigue,stimulate cns….nasal decongestant..

S.E:

 ephedrine with herbal supplement banned in USA due to CVS 

risk….Pseudoephedrine illegdly convert into Methamphetamine to abuse