Adrenergic System And Drugs  Adrenergic transmission  Adrenergic receptor  Adrenergic drugs  Therapeutic classification of adrenergic drugs  Pharmacological actions  Administration  Adverse effects and contraindication  Therapeutic uses

Adrenergic transmission  Restricted to the sympathetic division of ANS  There are three closely related endogenous catecholamines(CAs) 1. Noradrenaline(NA) -it acts as transmitter at post ganglionic sympathetic sites and in certain areas of brain. 2. Adrenaline(Adr) -it is secreted by adrenal medulla and may have a Transmitter role in the brain. 3. Dopamine- it is a major transmitter in basal ganglia,limbic system, Anterior pituitary,etc. and in a limited manner in the periphery.

 They are compounds containing catechol nucleus that is a benzene ring with two adjacent OH groups and amine containing side chain.  There are two endogenous catecholamines; noradrenaline, adrenaline, and dopamine.  Adrenergic transmission is restricted to sympathetic division of ANS. Catecholamines

1.Synthesis of CAs 2.Storage of CAs 3.Release of CAs 4.Reuptake of CAs 5.Metabolism of CAs

Location Prejunctional on effector organsPrejunctional on nerve ending(α2A) also postjunctional in brain,pancreatic (β)cells and extrajunctional in certain blood vessels, platelates Function subserved GU smooth muscle- contraction Vasoconstriction Gland- secretion Gut- relaxation Liver- glycogenolysis Heart-arrhythmia Inhibition of transmitter release Vasocontriction Deceased central sympathetic flow Decreased insulin release Platelet aggregation Selective agonist Phenylephrine, methoxamineclonidine Selective antagonist prazosinYohimbine, rauwolscine Effector pathway IP3/DAG phospholipaseA2 -PG release Adrenergic receptors

Location heart, JG cells in kidney Bronchi, blood vessels, Uterus, liver, g.i.t, urinary tract, eye Adipose tissue Selective agonist DobutamineSalbutamol, terbutalin BRL, Selective antagonist metoprolol, atenolol ICI α -methyl propranolol Potency of NA as agonist moderateweakstrong

Adrenergic drugs (sympathomimetics ) Direct sympthomimetics Indirect sympthomimetics Mixed Action sympthomimetics  Agonists on α and/ or β adrenoceptors  Eg.Adr,NA,isoprenaline(iso), methoxamine,salbutamol and many other drugs  Adrenergic neuron to release NA  Acts on the adrenoceptors  Eg.tyramine,amphetamine  Direct as well as indirect  Eg.ephedrine,dopamine, mephentermine

Therapeutic classification of adrenergic drugs I. Pressor agents II. Cardiac stimulants III. Bronchodilators IV. Nasal decongestants Noradrenaline Adrenaline Isoprenaline Phenylephrine Ephedrine Dobutamine Salbutamol Naphazoline Dopamine Isoprenaline Formoterol Xylometazoline Phenylephrine Bambuterol Pseudoephedrine Methoxamine Terbutaline Oxymetazoline Mephentermine V. CNS stimulants VI. Anorectics VII. Uterine relaxant and vasodilations Amphetamine Fenfluramine Rotodrine Methamphetamine Sibutramine Salbutamol Dexamphetamine Dexfenfluramine Isoxsuprine

Dopamine(DA)- Dopamine is used in patients of cardiogenic or septic shock and severe CHF wherein it increases BP urine flow. It is administered i.v. infusion(0.2-1mg/min) which is regulated by monitoring BP and rate of urine formation. Dobutamine- A derivative of DA, but not a D1 or D2 receptor agonist. Though it act on both α and β adrenergic receptor, the only prominent action of clinically employed dese (2-8µg/kg/min. i.v. infusion) It increases force of cardiac contraction and output without significant change in heart rate. Ephedrine- It is an alkaloid obtained from Ephedrine vulgaris. Mainly acts indirectly but has some direct action on α and β receptors also. Ephedrine crosses to brain and causes stimulations, but central activity ratio is lower than of amphetamine.

Amphetamine- These are synthetic compounds having pharmacological profile similar to ephedrine. The CNS actions are more prominent maximal selectivity is exhibited by dextroamphetamine and methamphetamine, which in the usual dose produce few peripheral effects like increased contraction, increased work capacity. Phenylephrine- It is selective α1 agonist, has negligible β action. It raise BP by causing vasoconstriction. Topically it is used as a nasal decongestant and for hen cycloplegia is not required. Central effects are not seen with usual clinical doses. Methoxamine- Another selective α1 agonist with no β action (has weak β blocking action). Resembles phenylephrine very closely. Occasionally used as pressor agent.

Pharmacological Action 1.Heart- All cardiac properties( contractility, heart rate, AV conduction, excitability, automaticity) 2.Blood vessels- Vasoconstriction α (skin, mucous membrane, renal) Vasodilation β2 (skeletal muscle, coronary blood vessels) 3.Blood pressure- Systolic blood pressure, diastolic blood pressure 4.Respiratory system- Bronchodilatation (β2) Decongestion of bronchial mucosa (α1) 5.Eye- Vasoconstriction of conjunctival blood vessels(decongestion) intraocular pressure Mydriasis(due to contraction of radial muscle of iris [α1] )

6.GIT- Man peristalsis is reduced Sphincters are constricted 7.Bladder- Detrusor is relaxed (β) Trigone is constricted (α) 8.Uterus- Contract and relax uterine muscle(through α and β receptor) 9.Skeletal muscle- Facilitate neuromuscular transmission Vasodilation (β2) 11.CNS- No CNS effects because of poor penetration in brain But restlessness and tremor may occur 12.metabolic- Increase blood glucose lipolysis

Administration  CAs are absorbed from intestine but are rapidly degraded by MAO and COMT present in intestinal wall and liver.  They are orally inactive. 1.Adrenaline(ephinephrine)- for systemic action  mg s.c,i.m  Action lasts for ½ to 2hrs  ADRENALINE 1 mg/ml inj. 2.Noradrenaline(Norephinephrine,levarterenol)- pressor agent  2-4µg/min i.v.infusion  Action starts declining within 5 min of discontinuing infusion  ADRENOR,NORAD,VASCUE,NORDRIN 2mg/2ml amp 3.Isoprenaline(isoproterenol)- for bronchial asthma  20mg sublingual, 1-2 mg i.m, 5-10µg/min i.v  Action lasts for 1-3 hrs  Non selective β agonist (stimulateβ1 and β2)  ISOPRIN 4 mg/2 ml inj.

Adverse Effect and Contraindications  Adverse effects  Transient restlessness  Palpitation  Anxiety  Tremor (may occur after s.c./i.m injection of Adr)  Rise in BP leads to cerebral haemorrhage  Contraindications  Hypertension  Hyperthyroid  Angina patients  Arrhythmias

Therapeutic Uses 1.Vascular uses 2.Cardiac uses 3.Bronchial asthma 4.Allergic disorders 5.Mydriatic 6.Central uses 7.Nocturnal enuresis in children and urinary incontinence 8.Uterine relaxant 9.Insuline hypoglycaemia