Download αβreceptor agonist

Adrenomimetic drugs
adrenoceptor agonists
Department of pharmacology
Zhu ling (朱玲)
2010.3
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Adrenomimetic drugs
adrenoceptor agonists

A kind of drugs that mimic the actions
and the chemistry structure （amine） of
epinephrine or norepinephrine.
 Because the action similar to
sympathetic effects that stimulation are
mediated by release of norepinephrine
sympathomimetic drugs
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Adrenomimetic drugs
adrenoceptor agonists
Groups
αR agonist
α1 α2 R agonist
α1 R agonist
α2R agonist
β R agonist
β1 β2 R agonist
β1 R agonist
β2 R agonist
αβR agonist
αβDAR agonist
Drugs
noradrenalin metaraminol
methoxamine
clonidine
isoprenaline
dobutamine
salbutamol
adrenaline ephedrine
Dopamine
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αreceptor： blood vessels of skin, gut
contracts
β1receptor：heart function enhancement
β2receptor：
bronchial smooth muscles: relaxation
skeletal muscle vessels: relaxation
coronary artery: relaxation
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Adrenomimetic drugs
adrenoceptor agonists
Commonness
1 Basic structure :β--phenylethylamine
2 main effects in the cadiovascular
systerm
3 elimination from uptake, MAO, COMT
4 main application: shock
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Noradrenaline synthesize and elimination
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Adrenomimetic drugs
adrenoceptor agonists

individuality
1 structure: different substituted groups
2 different of receptor selectivity
3 different effects mostly on the systolic
and diastolic blood pressure (pulse
pressure)
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αβreceptor agonist
Adrenaline Ad
肾上腺素
Epinephrine E
 Rooted in adrenal gland medulla，instability
 Pharmacokinetics：
absorption : is poor with oral administration ，
sc or i.m injection .
distrbution: the area of noradrenergic nerve
domination；
elimilation: uptake，or inactivation by MAO,
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COMT
αβreceptor agonist --adrenaline
Effects
a very potentαβreceptor agitated action
1 heart : β1receptor
excitement
2 blood vessels: α1 and β2 receptor
skin vessels, mucous membrane vessels,
viscus vessels
contraction；
brain, pulmonary blood vessels
feeble vasoconstriction;
skeletal muscle vessels ,coronary artery
dilation
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αβreceptor agonist -adrenaline
β2 receptor agitate
blood pressure
coronary artery
perfusion pressure
flux
adenosine increase
 3 blood pressure
systolic blood pressure increase,
diastolic pressure steadiness or slightly
fall
pulse pressure
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αβreceptor agonist --adrenaline
4 bronchia smooth muscle relaxation
5 metabolism: activates fat lipolysis, blood
glucose↑
6 CNS
application
1 anaphylactic shock first choose drug
2 bronchial asthma( urgent outbreak)
3 sudden cardiac arrest
4 local application local anesthetics and
rhinorrhagia
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αβreceptor agonist -adrenaline
Adverse reaction
heart-throb, headache, arrhythmia
(extensions of their receptor effects in
the cardiovascular )
Contraindication
hypertension , hyperthyroid etc
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αβreceptor agonist --ephedrine
pharmacokinetics：
substitution on benzene ring (Absence of ring-OH groups)
and substitution on alpha carbon
preferably lipid-soluble, stabilization,
orally active, increase the distribution, prolong the
action(resistant to COMT,MAO)
effects：
Agitate, accelerate NA release
1 peripheral effects like Ad but the function is
slow, feeble, long duration
2 CNS effects elevation of mood
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Methyl-benzedrine甲基苯丙胺(冰毒)
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αβreceptor agonist --ephedrine
application ：

bronchial asthma
 congestive snuffle
(as a nasal decongestant )
 Prevent some hypotension (as a pressor agent)
arachnoid below cavity and outside putamen anesthesia,
local anesthetics poisoning

Some disease induced by allergic reaction
Adverse reaction：
like Ad, further insomnia (CNS effects)
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αreceptor agonist -noradrenaline
Pharmacokinetics
chemical quality like Ad，
orally taking easily be destroyed，
maybe ischemia or putrescence with sc
or im ，
only can be applied by iv
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αreceptor agonist -noradrenaline
Effect
mostly agitateαβ1 receptor
1 heart positive klinotropic effect,
positive chronotropic effect
positive inotropic effects
2 blood vessel vasoconstriction
except coronary artery
peripheral resistance
3 blood pressure
both diastolic and systolic blood pressure
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αreceptor agonist -noradrenaline
Clinical uses：
① shock and hypotension
② hemorrhage of the upper alimentary tract
oral administration (local application)
Adverse reaction：
marked vasoconstriction , arrhythmia
① local tissues necrosis
② acute kidney failure
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αreceptor agonist
 metaraminal
direct and indirect action
weak, long-duration
substitute of NA
 Phenylephrine and methoxamine
kidney blood vessels contract ＞NA
treatmemt of paroxysmal atrial
tachycardia and effictive mydriatic agent
(Phenylephrine)
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β receptor agonist Isoproterenol
(Isoprenaline 异丙肾上腺素)
Isoproterenol （Isoprenaline）
1 pharmacokinetics：
absorption: low bioavailability of oral
administration，usually iv, sublingua
administration, aerosol inhalation （through
capillary vessel , rapid absorption )
biotransformation: main metabolized by
COMT，some by MAO，some by uptake

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β receptor agonist Isoproterenol
(Isoprenaline 异丙肾上腺素)
effects：more active βreceptor agonist
① heart
exciting
② blood vessels
potent vasodilator
③ blood pressure systolic pressure slightly
increased, diastolic pressure decreased
④ bronchia
smooth muscle: relaxation
⑤ metabolism glycogenolysis and lipolysis ↑
increased oxygen consumption
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β receptor agonist Isoproterenol
(Isoprenaline 异丙肾上腺素)
Therapeutic application：
① Sudden cardiac arrest： (cause:
ventricular automaticity slowness,
severity atrioventricular block and SA
nodes function failure)
② atrioventricular block
③ bronchial asthma acute outbreak
④ Infected shock
Adverse reaction：
heart-throb, arrhythmia etc
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β1 receptor agonist
Dobutamine 多巴酚丁胺
 effects ： relatively β1 selective synthetic
catecholamine ， positive inotropic effects
characteristic:
in low to moderate doses, it can increase,
constriction and cardiac output , but slightly
influence on the heart rate, cause relatively
little peripheral vasoconstriction and little
increase oxygen consumption
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β1 receptor agonist
Therapeutic application：
1 shock
well curative effect when
companying with weak contract or renal
failure
2 congestive heart failure
3 acute renal failure always with
diuretic
Adverse reaction：
tachycardia, hypertension, angina，
inducing tolerance
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αβDA receptor agonist –
Dopamine 多巴胺
Dopamine（ DA 多巴胺）
 the immediate metabolic precursor of
norepinephrine

Exist in peripheral nerve, ganglion and central
nerve
pharmacokinetics：
absorption: low bioavailability of oral
administration，usually iv
distribution: difficult pass through blood-brain
barrier
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αβDA receptor agonist –
Dopamine 多巴胺
effect：agitate αβDA receptor
1 heart β1 R
2 blood vessel and blood pressure
 low doses
activate D1 receptor in several vascular
beds
vasodilation, reduce peripheral resistance
 moderate doses β1R
systolic pressure↑ diastolic
pressure -unchanged
 higher doses α β1R systolic pressure ↑ diastolic
pressure ↑
3 kidney renal vascular dilation blood flow↑ (raise
glomerulus filtration rate) (clinical value)
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αβDA receptor agonist –
Dopamine 多巴胺
Therapeutic application ：
1 shock especially oliguria
2 congestive heart failure
3 acute renal failure (with diuretic)
Ibopamine （异波帕胺）
heart failure (difficult controlling)
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Sympathomimetic drugs
NA
classi α
fied
α
+++
metaraminol α
β1
β2
direct indirect
++
±
+
++
+
+
+
+
AD
αβ
++++
+++
+++
+
DA
αβ
+
++
±
+
+
Ephedrine
αβ
++
++
++
+
+
—
+++
+++
+
isoproterenol β
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