ANS- ADRENERGIC DRGS

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By

2. Adrenergic systems
• Also called sympathetic system ,
• catecholamine's system
• Sympathomimetic drugs
• Adrenergic agonist
• Adrenoreceptor agonist
• Sympathetic transmission are catecholamine in
nature and it includes – adrenaline , nor-
adrenaline , and dopamine secretion.
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3. SYMPATHETIC RESPONSES
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4. SYNTHESIS , STORAGE ,RELEASE AND UPTAKE OF
ADRENALINE
All catecholamine are synthesized from amino acid
Phenylalanine in liver then hydrolyzed to tyrosine at end
of nerve.
• Methylation of Nor-adrenaline --adrenaline are
synthesized .
• Tyrosine hydroxylase is rate limiting enzyme and it
inhibited from METYROSINE.
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5. PHENYLALANINE
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TYROSINE
DOPA
DOPAMINE
NOR-ADRENALINE ADRENALINE
Hydroxylase
Tyrosine hydroxylase
Decarboxylase
Beta-hydroxylase
Methyltransferase
In liver
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6. Release mechanism
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7. Action Potential
Na+
Effect of chronic b-receptor blockade:
Receptor up-regulation
H+
Effector organ
Tyrosine
Tyrosine
Dopamine
DA
NE
Uptake
1NE
NENENE
NE

8. • STORAGE –
• Noradrenalin stored in synaptic vesicles or granules within
the sympathetic nerve ending. On methylation in cytoplasm
NE convert into adrenaline in adrenal medulla.
• Release – CAs release out by nerve impulse with
exocytosis and indirectly by amines pumps.
• Uptake of CA s – Recaptured of CA from S.Junction by
two steps through nerve ending –
• 1) Axonal uptake –
Amine pump works to recaptured the NA and Adr from
synaptic junction. NET (amine pump) present at neuronal
membrane transport NA coupled with Na ion. This called
uptake -1. This uptake inhibited by cocaine, desipiramine,
guanathidine and many H1-antihistaminic drugs.१२/०२/२० 8

9. 2) Granular uptake -Intracellular amino pump which transport
CA from cytoplasm to within granules. Vascular monoamino
transport (VMAT) exchange with H+ ion which recaptured the NA
from axoplasm to granules or vesicles. This pump inhibited by
Resarpine as irreversibly and act
depleted the CA.
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H+
Uptake
Na ion exchange
Uptake 1
Axoplasm
Note-Uptake 2- is extra
neuronal uptake which take
place in cells and inhibited by
corticosterone

10. Metabolism
• CAs metabolized by Mono-amino oxidase (MAO) at site of
axonal part and in periphery like liver, blood and tissues,
metabolized by COMT (catechol-o- methyl transferase)
enzymes.
Adrenaline - -3,4 dihydroxy NE
mandelilic acid
Vanillylmandelic acid(VMA)
Glucoronide or sulphate conjugation
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COMT
MAO

11. Receptors α, β
• Adrenergic receptors act on α and β through G-
Protein coupled receptor which function primarily
by increase decreasing the intracellular function.
• Alpha (α) (1 , 2 )
• Beta (β)(1, 2 , 3)
• α 1 –
• Blood vessels- contraction
• Eye –mydriatics
• Prostate / urethera- decrease
• α 2- Pre-synaptic as well as post syneptic nerve
ending.
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Main location
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12. • β -1: locate on – Heart
• - Justa-glomular cells
• β -2 : On Bronchus, BV
• GIT ,Bladder, uterus,
• Skeleton muscles, liver.
• β -3 : Adipose tissues.
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A----C
B----D

13. Molecular mechanism of adrenergic drugs
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14. Classification of Adrenergic drugs
• By mode of action
Direct acting- CA and Non CA
-Indirect acting- Tyramine, amphetamine, cocaine,
ephedrine, TCA
• By chemistry
– Catecholamines (CA)
– Non-catecholamines
• By selectivity (to types of receptor)
Direct acting
• classified by alpha, beta receptor subtypes
• a 1 -selective, a 2 -selective, nonselective
• b 1 -selective, b 2 -selective , nonselectiv
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15. Difference between CA and non CA
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Catecholamines
– Cannot be given orally
– Short half-life, short duration
– Not cross blood-brain barrier (BBB)
Reasons: due to having catachol group
– Rapid destruction by MAO and COMT
– MAO, COMT locate at gut wall, liver
– High polarity

16. • Indirect acting sympathomimetic drugs
• tyramine
• amphetamine
• Mixed action sympathomimetics-
• Ephedrine
• Dopamine
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Classification based on
therapeutic action
see in BOOK –page no. 88
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17. PRESSOR
AGENTS
CARDIAC
STIMULANT
BRONCHODILATORS NASAL
DECONGESTANT
•Noradrenaline
•Phenylephrine
•Ephedrine
•Dopamine
•Methoxamine
•Mephentermine
•Adrenaline
•Dobutamine
•Isoprenaline
•Isoprenaline
•Salbutamol
(Albuterol)
•Terbutaline
•Salmeterol
•Formoterol
•Bambuterol
•Phenylephrine
•Naphazoline
•Xylometazoline
•Oxymetazoline
•Pseudoephedrine
•Phenyl
propanolamine
CNS STIMULANT ANORECTICS UTERINE
RELAXANT
•Amphetamine
•Methamphetamin
e
•Dexamphetamine
•Fenfluramine
•Dexfenfluramin
e
•Sibutramine
(Banned)
•Ritodrine
•Isoxsuprine
•Salbutamol
•Terbutaline
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18. PHARMACOLOGICAL ACTION
• In periphery adrenaline acts on alpha and beta
receptors of different tissues and organs . Some
important actions are –
• On Heart ;- Adrenaline increase the heart rate , by
acting on Beta-1 receptor and its result
Systole is shortened then diastole
Cardiac output and oxygen
consumption markedly increased.
Increase in atomicity, excitability which cause
cardiac arrhythmia.
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+ve chronotropic
+ve ionotropic
+dromotropic
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19. Action on heart
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• Biphasic
• Small dose – Fall in BP – due to beta receptor stimulation
• High dose – Rise in BP – due to alpha receptor
stimulation
alpha Beta

20. • Blood vessels – Vasoconstrictor(alpha-1) as well as
vasodilator (bata-2), depends on the action of
drugs. Action is most marked on arterioles due to
alpha-1, and larger arteries and veins due to beta-
2.
• BP- Noradrenaline causes vasoconstriction (alpha-1),
beta-1 receptor is responsible for increased in BP.
Result- increased BP, but it cause bradycardia- but adr
caused- tachycardia
• Respiratory systems – Adr and isoprenaline and NA acts
on beta-2 of bronchus results dilation of bronchial smooth
muscles . NA Potent bronchodilator (indirectly)but short
duration of action. Reduce secretions release mucosal
congestion by vasoconstriction.
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21. • Eye- Mydriatics occurs due to relaxation of radial
muscles of iris (alpha-1) .
• GIT – Gut relaxation occurs through activation of both
Alpha and Beta – receptors. Peristalsis and sphincter are
reduced but is not such effective, so no any clinical
importance .
• Bladder –Detrusor is relaxed (beta-2) and trigone is constrict
(alpha-1) – resulting hinder micturition.
• Uterus –Contraction through alpha while relaxation
through beta receptors .
• Skeleton muscles –Contraction of muscles, tension developed
in muscles fibers which may cause tremor mediated by Beta –
receptors.
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22. • CNS – Clinical dose of adrenaline produced NO any
marked effects on CNS, because of poor penetration of
BBB. When injected in brain it produced excitation
followed by depression .
Activation of alpha -2 receptors of brainstem results in decrease in
sympathetic outflow and cause bradycardia.
• Metabolic – Increase blood glucose level by increasing
the cAMP in liver cell and stimulating glycogenolysis
through Beta -2 receptors . Reduction of insulin and
Glycogenolysis may cause increase glucose level in blood.
• Glands – Decrease the secretion of glands.
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23. Pharmacokinetics
Adrenaline / CA are not suitable for oral route
due to different enzymes metabolism present in
GIT and liver like COMT and MAO.
Absorption is more rapid after intramuscular
injection but sometimes given as IV.
In anaphylactic it given as IV, due to poor
absorption.
catecholamine does not cross BBB.
No neuronal uptake like CA
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24. ADVERSE EFFECTS
Restlessness
Palpitation
Pallor
Tremor
Anxiety
Tachycardia
Marked rise in BP
Cerebral hemorrhage
Cardiac arrest , cardiac arrhythmias.
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25. Contradicted
• In hypertension condition
• Hyperthyroid
• Angina pectoris
• With anesthesia like halothene
• Adrenaline contradicted in GTN , angina ,
CCF , arrhythmias
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26. Adrenergic USES
• Nocturnal enuresis in
children and urinary
incontinence
• Uterine relaxant
• Insulin hypoglycaemia
• Hyperkinetic children
• Narcolepsy
• Obesity
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VASCULAR USES
• Hypotensive state
• Along with local anaesthetics
• Control of local bleeding
• Nasal decongestant
CARDIAC USES
• Cardiac arrest
• Partial or complete A-V block
• Congestive heart failure (CHF)
• Bronchial asthma
• Allergic disorders
• Mydriatic 26

27. • In cardiac arrest and heart block ,the drug of choice is
adrenaline (0.3-0.5 ml of 1;1000 solution) .
• Used in anaphylactic shock
• In acute bronchial asthma (beta-2 agonist)
• Inhibition of premature labour (salbutamol).
• In bronchial asthma ,
• Allergic
• for mydriatic ,
• Narcolepsy
• Obesity ,
• uterine relaxant , in hypoglycemia .
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28. Dopamine
• It is central neurotransmitter and it acts on dopaminergic and adrenergic
receptors .
• It is catecholamine, present in CNS as well as periphery, transported in vesicles
and blocked by reserpine .
• MOA- it acts on centrally present dopaminergic receptors D1, D2 as well as
beta-1, alpha-1 receptors (with increasing dose).
• PHARMACOKINETICS-
• Show High 1st pass effect. It metabolised by both MAO and COMT.
• Thus it is ineffective when administered orally. Most sensitive to IV at low
dose.
• Prodrug of dopamine is ineffective to metabolized enzyme and cross BBB.
•
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29. • Pharmacological effects
• Heart –dopamine has direct action on beta -1 receptor
and act like positive chronotropic and inotropic and
increase HR
• Blood vessels – act as vasoconstrictor (alpha-1) –increase BP on
high dose .
• Renal – INCREASING g.f.r. and Na excretion. Activation of
D1 receptors in several vascular beds, of kidney which
leads to vasodilation. Diminished Na+ reabsorption by
the proximal tubular cells cause natriuretic (beta-1)
• CNS-There is no effect on CNS , due to DA not cross BBB .
• Therapeutic use – In treatment of septic shock specially with oliguria
patient's (dose is >2-10 mcg/body wt.) .In renal dysfunction and cardiac arrest
, CHF
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30. Amphetamine
• Non-catacholamine synthetic and sympathomimetic
drugs . It having both central and peripheral effect.
• MOA- It having indirectly stimulate adrenergic receptor
by increasing release of catecholamine including 5-HT .
P’COLOGICAL ACTION-
• CNS – Crosses BBB and act potent CNS stimulant ,
physical activity, alertness ,euphoria , reduces sleep
,reduces hunger and appetite. It also increase initiative
and self-confidence and increase capacity to work.
• Respiration – stimulate respiratory Centre
• Heart – low dose not effect but high dose cause positive
chronotropic. १२/०२/२०

31. • p’kinetic – orally effective for long duration .
Crosses BBB. metabolized by liver enzymes.
Excreted through acidic urine easily.
• Therapeutic Use – In CNS stimulant
• In ADHD (attention disorder hyperkinetic
deficiency) in children.- drug-Methylphenidate
• In obesity.
• Increase Attention spasm
• Reduce sleep (Drug of choice- medafinil)
• Epileptics and parkinsonism .
• Week anticonvulsants, analgesic antiemetic, and acta
as synergetic to above drugs.१२/०२/२० 31

32. It is one of the drug which used in Dope Test
• ADR-
• Amphetamine come under shedule-2
• These are drug of abuse and are producing
psychological dependency . (DOPING)
• Higher dose causes confusion delirium, acute
psychosis , coma and death also.
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Thank u
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