Shivansh Pande Clinical Pharmacist Apollo Hospitals, Jubilee Hills, Hyderabad

Adrenergic Transmission
Sympathetic division of ANS
Controlled by three closely related endogenous

compounds known as catecholamines (Cas)

Noradrenaline (NA): NT at post ganglionic

sympathetic sites, certain brain sites. Adrenaline (Adr): NT at certain brain sites. Dopamine (DA): NT at basal ganglia, limbic system, CTZ, anterior pituitary, limited peripheral sites.

Synthesis of CAs

Storage of CAs
Granular membrane of neurons actively take up DA

from the cytoplasm. DA is converted to NA in granules (vesicles) containing dopamine -hydroxylase. Granules with NA are stored within the adrenergic nerve terminal. NA is stored as a complex with ATP

Release and uptake of CAs

Release of CAs: Nerve impulse causes exocytosis
Uptake of CAs: NA released from nerve terminals is

recaptured by the following mechanisms

Axonal uptake: Active amine pump present at neuronal

membrane transports NA back. Inhibited by cocaine, desimipramine, guanithidine, antihistamines. Granular uptake: Membrane of intracellular granules transports NA cytoplasm to within the granule. Extraneuronal uptake: Occurs in other tissue cells.

Metabolism of CAs

Adrenergic Receptors
Alpha () Receptors Rank order of potency of agonists: AdrNA>Iso

1
Location Postjunctional on effector organ

2
Postjunctional on nerve ending, brain, pancreatic cells, platelets, in certain blood vessels Inhibition of transmitter release Vasoconstriction Central sympathetic flow insulin release Platelet aggregation Clonidine Yohimbine, Phenoxybenzamine

Function

Smooth muscle: contraction Vasoconstriction Gland: Secretion Gut: relaxation Heart: arrhythmia Phenylephrine, Methoxamine Prazosin, phenoxybenzamine

Agonist Antagonist

Adrenergic Receptors
Beta () Receptors Rank order of potency of agonists: Iso>Adr>NA

1
Location Heart, JG cells of kidney

2
Bronchi, Blood vessels, uterus, GIT, urinary tract, eye

3
Adipose tissue

Function
Agonist Antagonist Dobutamine Metoprolol, Atenolol Salbutamol, terbutaline ICI118551, -methyl propranolol

Lipolysis
BRL37344 CGP20712A

Classification
Pressor Agents: Noradrenaline, Phenylephrine, ephedrine, methoxamine, dopamine Cardiac stimulants: Adrenaline, dobutamine, isoprenaline Bronchodilators: Adrenaline, terbutaline, isoprenaline, salmeterol, salbutamol, formoterol Nasal decongestants: Phenylephrine, naphazoline, Xylometazoline, pesudoephedrine, oxymetazoline CNS stimulants: Amphetamine, methamphetamine Anorectics: Fenfluramine, sibutramine Uterine relaxants and vasodilators: Ritodrine, salbutamol, isoxsuprine.

Pharmacological actions
Drugs with action similar to Adr or sympathetic

stimulation.
Direct sympathomimetics: Act directly on adrenergic

receptors: Adr, NA, Iso, phenylephrine, salbutamol.

Indirect sympathomimetics: Act on adrenergic

neurone to release NA: tyramine

Mixed Action sympathomimetics: Act directly as well

as indirectly: ephedrine, amphetamine.

Pharmacological actions
Actions are differentiated into those mediated by or

receptors depending on the receptor type present in a given tissue.

Adr: 1 + 2 + 3 + 1 + 2 + weak 3 NA: 1 + 2 + 3 + 1 + 3 : No 3 action Iso: 1 + 2 + 3 : No action

Pharmacological actions
Heart: (primary 1 action) HR, arrythmia, Force of contraction, cardiac output, oxygen consumption, conduction velocity, refractory period
Blood vessels: (vasoconstriction + vasodilation 2) Vasoconstriction at skin, mucous membrane, renal bed Vasodilation at skeletal muscles, liver, coronary arteries.

Pharmacological actions
Blood Pressure
NA: Systolic and diastolic pressure (no 2 action) Iso: Systolic but diastolic pressure (1 cardiac stimulation, 2

vasodilation) Adr: slow i.v Systolic but diastolic pressure (2 vasodilation more potent than action) Rapid i.v. Systolic and diastolic pressure( action) but returns to normal within few minutes. When blocker is given only fall in BP is seen: Vasomotor reversal of Dale

Pharmacological actions
Respiration: (primary 2 action) Adr and Iso: Bronchodilation
Eye: (1 action) Mydriasis due to contraction of radial muscle. IOT especially in open angle glaucoma. Poor action as Adr penetrates cornea poorly

GIT: (both and action) Gut relaxation, peristalsis, sphincters constrict. Effect brief, no clinical importance.

Pharmacological actions
Bladder: Detrusor relaxed () and trigone constricted (). Micturition.
Uterus:( receptors contraction, receptors relaxation) Effect of Adr varies according to species
Species Rat Rabbit Cat Human Nonpregnant Relaxation Contraction Relaxation Contraction Pregnant Relaxation Contraction Contraction Relaxation

Pharmacological actions
Splenic Capsule: Contraction () more RBC in circulation.
Skeletal muscle: NMJ, receptor activation on motor nerve ending. Tremors: Enhanced firing of muscle spindles.(2) CNS Normal Dose: No effect due to poor penetration High dose: Restlessness, apprehension, tremor, excitation followed by depression. BP, bradycardia (central 2)

Pharmacological actions
Metabolism 2: glycogenolysis, hyperglycemia, hyperlactacidemia, glucagon secretion. 2+3: Lipolysis, caloriegenesis, hyperkalemia followed by hypokalemia. 2: insulin

Adverse Effects (Adr)

Transient restlessness, palpitation, anxiety, pallor
BP leading to cerebral haemorrhage, ventricular

tachycardia/fibrillation

Therapeutic uses
Vascular use Hypotensive States (shock, spinal anaesthesia, hpotensive drugs) dopamine, dobutamine used with volume prelacement measures. Maintain cerebral circulation. Anaphylactic Shock: Adr is used; BP, bronchospasm, laryngeal edema. Rapid action, life saving drug. Postural hypotension due to autonomic neuropathy: ephedrine used. Local anaesthesia: Adr used with local anaesthetics, duration of action, systemic toxicity. Local bleeding: Adr, phenylephrine, ephedrine used.

Therapeutic uses
Nasal Decongestants: Pseudoephedrine, phenylephrine;

Shrinkage of mucosa. Peripheral vsacular diseases: Isoxsuprine used as vasodilator in Buergers disease, Raynauds phenomenon, diabetic vascular insufficiency, gangrene, frost bite, ischaemic ulcers, night leg cramps, cerebral vascular inadequacy.

Cardiac Uses: Cardiac arrest: Adr is drug of choice. Strokes-Adams syndrome: Adr, Iso used secondary to mechanical and electrical measures. Partial or complete A-V Block: Iso used to maintain ventricular rate

Therapeutic uses
Bronchial Asthma: 2 Stimulants
Allergic Disorders: Adr etc; used for urticaria,

angioedema, anaphylactic shock.

Mydriatic: Phenylephrine; used for fundus

examination, IOT in wide angle galucoma.

Central Uses: Narcolepsy: Amphetamines; used in Sleep fits

Therapeutic uses
Epilepsy: Amphetamines: occasionally used to counteract

sedation caused by antiepileptics. Parkinsonism: Amphetamines; adjuvants in treatment of rigidity and mood. No benefit in tremors. Hyperkinetic children: (minimal brain dysfunction, ADHD) Amphetamines used to calm dowm hyperkinetic children, increase attention span. Obesity: Help in tolerating reduced diet. Short term use only. Not used for cosmetic reasons.

Nocturnal enuresis in children and urinary incontinence:

Amphetamine used.

Therapeutic uses
Utrine Relaxant: Isoxsuprine used in threatened

abortion, dysmenorrhoea, postpone labour. Use limited due to serious side effects.
Insulin hypoglycemia: Adr used as adjuvant to glucose.