Chapter 10 . Adrenoceptor Agonists :

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Adrenoceptor Agonists
definition


Drugs that mimic the actions of
epinephrine or norepinephrine
Sympathomimetic drugs
Classification




Depend on the affinity for
different groups of receptor
α-adrenoceptor agonists
β-adrenoceptor agonists
α, β-adrenoceptor agonists
Chemistry



Parent compound: phenylethylamine
Change the affinity for α or β
receptors
Change pharmacokinetics properties
Chemistry and pharmacokinetics

Substitutions
On the terminal amino group:
increase β receptors activity
 On the benzene ring: increase
bioavailability and prolongs the
duration of action; increase the
distribution of molecule to CNS
 On the alpha or beta carbons:
block oxidation by MAO

α-adrenoceptor agonists



Norepinephrine
Metaraminol
α 1 -adrenoceptor agonists:
phenylephrine and methoxamine
Norepinephrine
Potent effect of α receptor
 Relative little effect on β1
receptor
 Little effect on β2 receptor

Pharmacological Effects


Blood vessels: constrict (skin
vessels, renal vessels); coronary
artery dilate
Heart: pacemaker activity,
conduction velocity, and intrinsic
contractility increase. HR
decrease by a reflex response.
Pharmacological Effects

Blood pressure: systolic
pressure increase at low
concentration; at high
concentration both systolic and
diastolic pressure increase
pharmacokinetics

i.v. drip.

Be uptake and metabolized quickly
Therapeutic Uses



neurogenic shock, cardiogenic
shock
Hypotension
hemorrhage of upper digestive
tract
Adverse reaction



Avascular necrosis
Acute renal failure
Contraindication: hypertension,
atherosclerosis, cardiopathy
Metaraminol




excite α-R
replace the NA in vesicles,increase
NA release from vesicles directly
More stable to MAO, prolong the
action
Acute tolerance
Pharmacological Effects



similar to NA in its action, but less
potent
increase systolic and diastolic blood
pressure
its major therapeutic use is in the
treatment of hypotensive state
Phenylephrine, Methoxamine



α1-R agonists
similar to those of NA, but less
potent and has a longer duration of
action
vasoconstriction, increase arterial
pressure, and reflex bradycardia
Clinical Uses

hypotension state;

supraventricular paraxosmal

pupil mydriasis
α、β-R agonist

Adrenaline

Dopamine

ephedrine
Adrenaline


At low concentration ,β effects
predominate; at high concentration ,
α effects predominate.
β2-R are more sensitive to Adr
than the α-R.
pharmacokinetics


Adr- absorption is poor with
oral administration
can be given iv or im
Pharmacological Effects

Heart
 a direct effect on β1-R ;
increase in heart rate , and
increase cardiac output;
 a propensity toward arrhythmias

coronary artery dilate
Pharmacological Effects

Blood vessel
Constrict (skin vessels, renal
vessels)
 Dilate: vessels in skeletal muscle ,
hepatic vessels
 coronary blood flow

Pharmacological Effects

blood pressure
At low concentration: systolic
pressure increase
 At high concentration: both
systolic and diastolic pressure
increase

Pharmacological Effects

Smooth muscle:
Bronchiolar smooth muscle relaxes
 blood vessel constrict
 Block the release of histamine

Pharmacological Effects

Metabolic effects
increase in glucoses and lactate
production via glycogenolysis
 inhibition of insulin secretion
(αR)
 increase in free fatty acid and
oxygen consumption .

Therapeutic Uses



cardiac arrest
acute or severe hypersensitivity
reaction , it is primary
treatment for anaphylactic
shock , asthma
prolong the duration of local
anesthesia
Adverse Effects


Palpitation, BP
Hypertension, diabetes mellitus,
hyperthyroidism
Dopamine



activate α、β1 and dopa-receptor
Be metabolized by MAO and COMT
quickly
No effect on CNS
Dopamine


heart: positive inotropic effect on
the myocardium, increase cardiac
output
blood vessels


At low or intermediate concentration:
act on D1 receptor, dilate
At high concentration : act on αreceptor, constrict
Pharmacological Effects

Kidney
At low or intermediate
concentration: reduce arterial
resistance in the mesentery and
kidney
 At high concentration: cause
vasoconstriction with consequent
reduction in renal function

Clinical uses
Shock
 Acute renal failure
 Adverse reaction: arrhythmia,
reduction in renal function

Ephedrine




absorbed when taken orally
resistant to COMT and MAO, so
that its action is prolonged
CNS effects may occur: such as
insomnia, nervousness, nausea and
agitation
Acute tolerance
pharmacological Effects
increase cardiac output,
increase blood pressure
 Relax smooth muscle
 CNS: excitement

Clinical Uses
bronchial asthma
 nasal decongestant
 hypotension without crisis
 Adverse reactions: CNS

β-R agonist


β1 and β2-R agonist
Isoprenaline: lower selectivity
to both β1 and β2-R, little
effect on α-R
pharmacological Effects


heart: positive inotropic
effect ,increase the heart rate and
conduction, cardiac output increase
blood vessels : reduction of
peripheral vascular resistance in
skeletal muscle, renal and
mesenteric vascular beds;
pharmacological Effects



blood pressure: diastolic blood
pressure falls , systolic blood
pressure may increase
Relax both bronchial and
gastrointestinal smooth muscle
Metabolic effects
pharmacokinetics
Resistance to MAO
 less be uptaken
 aerosol

Clinical uses
bronchial asthma
 Atrioventricular block
 cardiac arrest
 Infectious shock

Adverse Effects



palpitation; dizziness
overdosage by inhalation can
produce fatal ventricular
arrhythmia
Contraindication:
myocarditis ,coronary heart
disease; hyperthyroidism
β1-R agonist


β1 reaction is more potent
thanβ2 reaction
Dobutamine
Dobutamine




direct β1-R agonist
greater inotropic effect than
chronotropic effect
little effects on peripheral vascular
resistance.
Clinical uses: improve myocardial
function in congestive heart failure .
Adverse reactions


BP , palpitation
Contraindication: IHSS, atrial
fibrillation
β2-R agonist

bronchial asthma
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