Adrenergic [ædrə‘nədʒik] agonists Chapter 10 Adrenergic [ædrə‘nədʒik] agonists 肾上腺素受体激动剂

Subtypes and effects of adrenergic receptors Presynaptic membrane α2 receptor inhibiting the release of NA β receptor promoting the release of NA α 1受体 Promoting the contracting of the vascular smooth muscle in skin, mucosa, and kidney β受体 β1 receptor excitation of the heart β2受体 Relaxing the smooth muscle of bronchus Relaxing the smooth muscle of coronary artery, and blood vessels in skeletal muscle Negative feedback Positive feedback Pupil 瞳孔 dilation  Postsynaptic membrane

α-receptor agonists Noradrenaline[nɔ:rə'drenəlin] (NA,去甲肾上腺素): Norepinephrine[nɔ:repi'nefrin] (NE） Effects: 1 Vascular constriction 2 BP elevation 3 Heart stimulation

Clinical uses: 1 Acute hypotension (induced by intoxication, septic shock et al); 2 Upper digestive track bleeding

Side effects: Contraindication: hypertension, tachycardia, local tissue necrosis [ne'krəʊsɪs]坏死, renal function failure. Contraindication: Hypertension, atherosclerosis [,æθərəʊsklɪə‘rəʊsɪs]动脉粥样硬化, oliguria [ɔli’gjuəriə] 少尿, anuria [ə‘njʊərɪə]无尿

Isoprenaline [aisəu'prenəlin] β-receptor agonists Isoprenaline [aisəu'prenəlin] (ISO,异丙肾上腺素)

Action： Effects: Stimulate 1、2 receptor 1 Stimulate heart Heart rate 心率↑ Contractility 心收缩力↑ Conduction velocity 传导↑ Cardiac output (CO) ↑

2 Blood pressure: Dilation of the blood vessels in skeletal muscle by stimulating β2 receptor Therapeutic dose: SBp↑/DBp↓ Large dose: SBp ↓/ DBp ↓↓ 3 Relax bronchial smooth muscle 4 Glycogenolysis [,ɡlaikəudʒi'nɔlisis]肝糖分解↑ , Lipolysis [li’pɔlisis]脂类分解↑, Oxygen consumption 耗氧量↑

Uses 1 Bronchial asthma 2 Cardiac arrest 心脏骤停 3 Atrioventricular /,eitriəuven'trikjulə/ block房室传导阻滞

Adverse effects Contraindication: Tachycardia, Arrhythmias ([ə'riðmiə]心律失常) Contraindication: Coronary heart disease冠心病, myocarditis /,maiəukɑ:'daitis/心肌炎, hyperthyroidism [,haipə'θairɔidizəm]甲亢

Adrenaline[ə‘drenəlin] (AD, 肾上腺素) α, β-receptor agonists Adrenaline[ə‘drenəlin] (AD, 肾上腺素) Action： Stimulates 1 , 1 , 2 receptor with sensitivity β>α Effects: 1 Stimulates heart 心脏 Heart rate 心率↑; Contractility 心收缩力↑ Conduction velocity 传导↑; Cardiac output ↑

2. Influence on blood vessel (1) Dilation of the blood vessels in skeletal muscle due to β2 receptor activation; (2) Vasoconstriction in many vascular beds especially in the precapillary resistance vessels of skin, mucosa, and kidney along with marked constriction of the veins due to 1 receptor activation.

3 Influence on blood pressure Small doses: Decrease BP Larger doses: biphasic response- rises rapidly to a peak then fall below normal before returning to control levels.

Stimulates 1 , 1 , 2 receptor with sensitivity β>α Mechanism of the decrease of BP induced by small dose of AD Dilation of the blood vessels in skeletal muscle due to β2 receptor activation; Mechanism of the increase of BP induced by higher dose of AD (1) increases the strength of ventricular contraction; (2) increases heart rate; (3) vasoconstriction in many vascular beds due to 1 receptor activation; Keep in mind Stimulates 1 , 1 , 2 receptor with sensitivity β>α

Epinephrine reversal Adrenaline only decreases blood pressure after pretreatment with α-antagonist, which is called “epinephrine reversal ”.

4 Effects on bronchus (1) Relaxation of bronchial smooth muscle; (2) inhibition of antigen-induced release of inflammatory mediators from mast cells: mediated by β2 receptors; (3) diminution of bronchial secretions and congestion [kən’dʒestʃ(ə)n] 充血within the mucosa; mediated by 1 receptors.

5 increase lipolysis [li‘pɔlisis]脂类分解 and glycogenolysis [glaikəudʒə’nɔlisis]肝糖分解→lead to hyperglycemia [,haɪpəɡlaɪ‘siːmɪə] 高血糖

1 Anaphylactic[ænəfə'læktik] shock (过敏性休克) Uses : 1 Anaphylactic[ænəfə'læktik] shock (过敏性休克) Anaphylactic shock Release of the allergy mediators Heart inhibition Dilation of the blood vessels, increase of the permeability of capillary vessel BP decreased Dyspnea caused by spasm of bronchial smooth muscle [dɪsp‘niə] 呼吸困难

1 Inhibits the release of allergy mediators; Mechanism of AD： 1 Inhibits the release of allergy mediators; 2 Relaxes bronchospasm, decreases mucous membrane congestion, angioedema; 3 Stimulates heart, increases BP 4 Constriction of the blood vessels, decrease of the permeability of capillary vessel.

2 Cardiac resuscitation [rɪ,sʌsɪ‘teɪʃən] 复苏 3 Bronchial asthma Mechanism: (1) Relaxation of bronchial smooth muscle; (2) Inhibition of antigen-induced release of inflammatory mediators from mast cells; (3) Diminution of bronchial secretions and congestion within the mucosa. 4 Used with local anesthetics [ænis'θitiks] 麻醉药

Contraindication Adverse effects Tachycardia hypertension Serve ventricular arrhythmia even lead to death Contraindication Hypertension, arrhythmia, coronary heart disease, hyperthyroidism, glaucoma.

Dopamine receptor agonist Dopamine ['dəʊpəmiːn] 多巴胺 Action: Activate DA receptor, β1, and α1 receptor dose dependently

Effects (1) Increase cardiac contractility, increase BP; (2) Increase peripheral vascular resistance; (3) Low dose: decrease renal vascular resistance, increase renal blood flow; High dose: increase renal vascular resistance, decrease renal blood flow.

Uses: (1) Shock (cardiogenic, septic, hemorrhagic ['hemərædʒɪk]出血的) (2) Acute renal insufficiency

Adverse effects Tachycardia Arrhythmia Headache Hypertension

大纲要求 Objective and requirements Understand the conception and classification of the adrenergic receptor agonists; Understand the mechanism and pharmacological effects of drugs acting on α, β1, and β2 receptors; Master the clinical applications, adverse reactions, and contraindications of adrenalin, noradrenalin, and isoprenalin; Understand the characteristics and clinical applications of dopamine and ephedrine.

Teaching contents (1) Chemical structure and SAP of adrenomimetics. (2) Noradrenalin: the major targets of noradrenalin are α and β1 receptors; the effects of noradrenalin on cardiovascular system and clinical applications, adverse reactions, and prevention and therapy. (3) Adrenalin: acting on α and β receptors; the pharmacological effects, clinical applications, side effects,and contraindications of adrenalin. (4) Isoprenalin: acting on β1 and β2 receptors; the pharmacological effects, clinical applications, side effects, and contraindications of isoprenalin. (5) Dopamine and ephedrine: the pharmacological characteristics and clinical applications of dopamine and ephedrine.

Essential vocabulary Adrenergic agonists Noradrenaline/norepinephrine/isoprenaline/adrenaline Hypertension /hypotension Tissue necrosis Renal function failure. Oliguria/anuria Heart rate/contractility/conduction velocity/cardiac output Bronchial asthma/bronchus Cardiac arrest Atrioventricular block

Arrhythmias Coronary heart disease Myocarditis Lipolysis Hyperglycemia Shock (anaphylactic, cardiogenic, septic, hemorrhagic) Dyspnea Epinephrine reversal