Adrenoceptor Agonists definition n n Drugs that mimic

Adrenoceptor Agonists

definition n n Drugs that mimic the actions of epinephrine or norepinephrine Sympathomimetic drugs

Classification Depend on the affinity for different groups of receptor n α-adrenoceptor agonists n β-adrenoceptor agonists n α, β-adrenoceptor agonists n

Chemistry n n n Parent compound: phenylethylamine Change the affinity for α or β receptors Change pharmacokinetics properties

Chemistry and pharmacokinetics n Substitutions On the terminal amino group: increase β receptors activity n On the benzene ring: increase bioavailability and prolongs the duration of action; increase the distribution of molecule to CNS n On the alpha or beta carbons: block oxidation by MAO n

α-adrenoceptor agonists Norepinephrine n Metaraminol n α 1 -adrenoceptor agonists: phenylephrine and methoxamine n

Norepinephrine Potent effect of α receptor n Relative little effect on β 1 receptor n Little effect on β 2 receptor n

Pharmacological Effects n n 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 n Blood pressure: systolic pressure increase at low concentration; at high concentration both systolic and diastolic pressure increase

pharmacokinetics n i. v. drip. n Be uptake and metabolized quickly

Therapeutic Uses neurogenic shock, cardiogenic shock n Hypotension n hemorrhage of upper digestive tract n

Adverse reaction Avascular necrosis n Acute renal failure n Contraindication: hypertension, atherosclerosis, cardiopathy n

Metaraminol n n 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 n n n 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 n n n α 1 -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 n hypotension state; n supraventricular paraxosmal n pupil mydriasis

α、β-R agonist n Adrenaline n Dopamine n ephedrine

Adrenaline n n At low concentration , β effects predominate; at high concentration , α effects predominate. β 2 -R are more sensitive to Adr than the α-R.

pharmacokinetics n n Adr- absorption is poor with oral administration can be given iv or im

Pharmacological Effects n Heart n a direct effect on β 1 -R ; increase in heart rate , and increase cardiac output; n a propensity toward arrhythmias n coronary artery dilate

Pharmacological Effects n Blood vessel Constrict (skin vessels, renal vessels) n Dilate: vessels in skeletal muscle , hepatic vessels n coronary blood flow n

Pharmacological Effects n blood pressure At low concentration: systolic pressure increase n At high concentration: both systolic and diastolic pressure increase n

Pharmacological Effects n Smooth muscle: Bronchiolar smooth muscle relaxes n blood vessel constrict n Block the release of histamine n

Pharmacological Effects n Metabolic effects increase in glucoses and lactate production via glycogenolysis n inhibition of insulin secretion (αR) n increase in free fatty acid and oxygen consumption. n

Therapeutic Uses cardiac arrest n acute or severe hypersensitivity reaction , it is primary treatment for anaphylactic shock , asthma n prolong the duration of local anesthesia n

Adverse Effects n n Palpitation, BP Hypertension, diabetes mellitus, hyperthyroidism

Dopamine n n n activate α、β 1 and dopa-receptor Be metabolized by MAO and COMT quickly No effect on CNS

Dopamine n n heart: positive inotropic effect on the myocardium, increase cardiac output blood vessels n n At low or intermediate concentration: act on D 1 receptor, dilate At high concentration : act on αreceptor, constrict

Pharmacological Effects n Kidney At low or intermediate concentration: reduce arterial resistance in the mesentery and kidney n At high concentration: cause vasoconstriction with consequent reduction in renal function n

Clinical uses Shock n Acute renal failure n Adverse reaction: arrhythmia, reduction in renal function n

Ephedrine n n 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 n Relax smooth muscle n CNS: excitement n

Clinical Uses bronchial asthma n nasal decongestant n hypotension without crisis n Adverse reactions: CNS n

β-R agonist n n β 1 and β 2 -R agonist Isoprenaline: lower selectivity to both β 1 and β 2 -R, little effect on α-R

pharmacological Effects n n 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 n Relax both bronchial and gastrointestinal smooth muscle n Metabolic effects n

pharmacokinetics Resistance to MAO n less be uptaken n aerosol n

Clinical uses bronchial asthma n Atrioventricular block n cardiac arrest n Infectious shock n

Adverse Effects palpitation; dizziness n overdosage by inhalation can produce fatal ventricular arrhythmia n Contraindication: myocarditis , coronary heart disease; hyperthyroidism n

β 1 -R agonist n n β 1 reaction is more potent thanβ 2 reaction Dobutamine

Dobutamine n n direct β 1 -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 n n BP , palpitation Contraindication: IHSS, atrial fibrillation

β 2 -R agonist n bronchial asthma