Sympathomimetics advance

SYMPATHOMIMETICS
(ADRENERGIC DRUGS)
PRESENTED BY:
NAVEEN K L
1ST M Pharma
Dept. of Pharmacology
Srinivas College Of Pharmacy
Valachil, Mangalore.
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CONTENTS:
 Introduction
 Definition
 Classification of Sympathomimetic agents
 Pharmacological Actions
 Reference
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Definition :
 These are drugs with actions similar to that of adrenaline or
that of sympathetic stimulation . They can be classified as
Direct sympathomimetic--- Adr, NA, Isoprenaline,
Phenylephrine, Salbutamol, etc
Indirect sympathomimetic--- Tyramine, Amphetamine,
Mixed sympathomimetic---- Ephedrine, Mephentermine
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Therapeutic classification
 Vasopressor agents:
α1 receptor agonist : Noradrenaline, Phenylephrine, Methoxamine,
Mephantermine.
 Cardiac stimulants:
Non selective : Adrenaline, Isoprenaline.
β1 receptor agonist : Prenalterol, Dopamine, Dobutamine.
 Bronchodilators:
Non selective: Adrenaline, Isoprenaline.
Selective β2 agonist: Salbutamol, Terbutaline, Salmetrol, Formoterol.
 CNS Stimulant:
Amphetamine, Methamphetamine, Dexamphetamine, Ephedrine
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 Nasal decongestant:
α1-receptor agonist: Phenylephrine, Pseudoephedrine,
Phenylpropanolamine.
α2-receptor agonist: Oxymetazoline, Xylometazoline, Naphazoline.
 Uterine relaxant:
Selective β2 agonist: Isoxsuprine, Ritodrine, Salbutamol, Terbutaline,
Orciprenaline.
 Anorectic agents:
Amphetamine, Methamphetamine, Dexamphetamine,
Phenylpropalamine.
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Adrenaline as prototype
 Potent stimulant of alpha and beta receptors
 Complex actions on target organs
Adr→ α1+α2+β1+β2 and weak β3 action
NA→ α1+α2+β1+β3 and no β2 action
Iso→ β1+β2+β3 action but no α action
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Pharmacological effects:
 On Cardiovascular System:
 The effects are prominent bcz of wide spread distribution of alpha & beta
receptors in heart, BV, neural & hormonal system involved in control of
blood pressure.
Effects on Cardiovascular System: Heart
Blood vessel
Blood pressure
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Heart:
Mainly acts on β1 → ↑ Ca+ influx in cardiac cells.
o HR---- ↑ +ve chronotropic effect. Pace maker activity of both SA node &
purkinje fibers is ↑
o Contractility --- ↑↑ +ve inotropic effects, relaxation is accelerated.
o Excitability and automaticity is ---- ↑
o Conduction velocity ---- ↑ in AV node & refractory period is ↓
o Stroke volume---- ↑ & cardiac output also ↑
o Work load ---- ↑ and also ↑ oxygen demand.
o Mechanical efficiency of heart is decreased.
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 Blood Vessels:
 Both vasoconstriction (Alpha) and vasodilatation (Beta) can
occurs depends on drug, its dose and vascular bed.
 Contraction --- Cutaneous, Mucous membrane & Renal
beds (Alpha -1)
 Vasoconstriction occurs through both alpha 1 & 2 receptors
, however, location of alpha 2 ------ activated by circulating
CAs, whereas
alpha 1 ---- responded to neuronally released NA.
 Dilatation ---- Predominate in skeletal muscles, liver and
coronaries.
 Larger arteries and veins are affected at higher doses.
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Blood Pressure:
Effects depends on amine, its dose, rate of administration.
 Adr:
Slow i.v. infusion or s.c. injection ------ Rise in systolic, fall in diastolic BP
PR ↓ bcz of vascular Beta 2 receptors
are more sensitive than Alpha receptor and mean BP, Pulse pressure is increased.
Rapid i.v. injection ------- marked increased in both systolic and diastolic BP
At high concentration alpha response predominates
BP returns to normal within few min and secondary fall
in mean BP --- rapid uptake and dissipation of Adr → concentration around the
receptor is reduced → low concentration are not able to act on Alpha receptor but
continue to act on Beta 2 receptor.
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When alpha blocker is given only fall in BP seen --- vasomotor reversal of dale
 Noradrenaline : Rise in systolic BP ↑↑
Rise in diastolic BP ↑↑
Rice in mean BP ↑↑
No Beta 2 action -- no vasodilatation
 Isoprenaline: Rise in systolic BP ↑
Fall in diastolic ↓↓
Fall in mean BP ↓
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 Respiration:
 Adr and isoprenaline having powerful bronchodilator effects but not NA.
 Rapid i.v. injection causes transient apnoea due to reflex inhibition of RC.
 Adr cause pulmonary oedema by shifting blood from systemic to pulmonary
circuit----- Toxic doses.
 Eye:
Mydriasis ----- due to pupil dilation; contraction of radial muscles of iris (α-1)
↓ IOP Especially in wide angle Glaucoma
 GIT :
Relaxation effects seen by both activation of alpha and beta receptors.
reduction in peristalsis and contraction of sphincters.
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15
 Bladder:
relaxation of detrusor muscles (β2 & β3) constriction of trigone sphincter (α)
 Uterus :
action is depends on species, hormonal and gestational status, so Adr can both
contraction and relaxation of uterine muscles (α & β).
Contraction ----- non pregnant ----- alpha
Relaxation ----- pregnant.
Skeletal muscle :
alpha receptor activation----motor nerve endings ----- Ach release.
Enhanced firing of muscle spindles is responsible for tremor produced by β2.

 CNS:
Adr, at clinical doses ---- doesn’t produce any marked CNS effects-----
bcz of poor penetration in brain -----restlessness, apprehension, tremor may
occurs .
α2 receptor activation in brainstem (selective alpha 2 agonist like clonidine) -----
sympathetic outflow → fall in BP and bradycardia occurs.
 Metabolic :
Adr causes Glycogenolysis → hyperglycaemia, hyperlactacidaemia (β2).
lipolysis ---- rise in plasma free fatty acid and calorigenesis (β2 + β3)
on alpha 2 ----- reduction in insulin Secretion
on beta 2 ----- augmentation of glucagon
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Pharmacokinetic:
 Destroyed in the gut wall by MAO And COMT So not given orally.
 Given by s.c, i.m, by inhalation, topically on mucous membrane, eye.
 i.v injection is avoided ----- risk of fatal ventricular fibrillation.
 Onset 1-2 min.
 Crosses placenta but not BBB.
 Excreted mainly in urine (84-95%)
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Adverse effect and contraindication
 Transient restlessness, headache, palpitation, anxiety, tremor.
 Marked rise in BP leads to cerebral haemorrhage, ventricular
tachycardia or fibrillation, angina.
 Adr contraindicated in hypertensive, hyperthyroidism and
angina patient.
 Adr shouldn't be given during anaesthesia with halothane (risk
of arrhythmias )
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Therapeutic uses:
 Vascular uses : Hypotensive state
Along with LA
Nasal decongestant
 Cardiac uses : Cardiac arrest
CHF
 Central uses : ADHD
Epilepsy
Parkinson's
Obesity
 Uterine relaxant .
 Allergic disorders.
 Mydriatic .
 Bronchial asthma & COPD
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DOPAMINE :
 Immediate metabolic precursor of NA.
 High concentration in basal ganglia, limbic system and hypothalamus.
 Central neurotransmitter.
 Metabolized by MAO and COMT.
 In effective orally and used in IV only.
 Short t 1/2 ---- 3-5min
 Agonist at dopaminergic D1. D2 Receptors.
 Agonist at Adrenergic alpha 1 & beta 2.
 Used in hypovolemic shock and cardiac failure
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 Small doses (2-5 µg/kg/min) :
 Stimulate D1 receptors in renal, mesenteric, and coronary vessels -----
vasodilation.
 Increases renal blood flow, GFR.
 Moderate doses (5-10µg/kg/min):
 Stimulate β1 receptor --- heart--- +ve inotropic & little chronotropic actions.
 Releases NA from nerves by β1 stimulation.
 No changes in PR & HR.
 High doses (10-20µg/kg/min):
 Stimulation alpha 1 receptors----- vasoconstriction and renal blood flow
decreased.
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Dobutamine:
 Derivative of dopamine.
 Doesn’t act on D1 & D2 receptors.
 Its act on both alpha and beta adrenergic receptors, mainly on beta 1
receptor ----- prominent action of clinically employed doses 2-8 µg/kg/min-
--- i.v infusion.
 ↑ force of contraction of cardiac cells & output, no changes in HR, PR, BP.
 Used as inotropic agent.
 Half life 2 min.
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Phenylephrine: 23
 Selective alpha 1 agonist. No beta action.
 Topically used as nasal decongestant and mydriasis agent.
 It raise BP by causing vasoconstriction.
 Reduces the IOT by constricting ciliary body blood vessels.

Reference:
 KD Tripathi. Essential of MEDICAL PHARMACOLOGY, 8th edition. New
dehli;Jaypee brothers medical publisher;2019 p 136 -152.
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