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Adrenoceptor agonists

Adrenoceptor agonists. 1. ,  receptor agonists 2.  receptor agonists 3.  receptor agonists. Shock is a complex acute cardiovascular syndrome that results in a critical reduction in perfusion of vital tissues and a wide range of systemic effects.

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Adrenoceptor agonists

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  1. Adrenoceptor agonists • 1. ,  receptor agonists • 2.  receptor agonists • 3.  receptor agonists

  2. Shock is a complex acute cardiovascular syndrome that results in a critical reduction in perfusion of vital tissues and a wide range of systemic effects. Shock is usually associated with hypotension, an altered mental state, oliguria（尿过少）, and metabolic acidosis. If untreated, shock usually progresses to a refractory deteriorating state and death. The three major mechanisms responsible for shock are hypovolemia, cardiac insufficiency, and altered vascular resistance.While sympathomimetic drugs have been used in the treatment of virtually all forms of shock, their efficacy is unclear.

  3. Catechol dopamine 多巴胺 norepinephrine 去甲肾上腺素 epinephrine 肾上腺素

  4. sensitivity to the subunits of receptors

  5. Regulation of NE Synthesis and Turnover Presynaptic heteroreceptor Ach_reduce Presynaptic autoreceptor 2 receptor rate limiting 2 receptor Catecholamine Biosynthetic Pathway

  6. Metabolism of catecholamines CNS PNS

  7. Adrenergic Receptor (adrenoreceptors) These are receptors activated by NE, EPI, or drugs with similar actions Gs Gq Gi Gs b3 fat cells (not NE)

  8. Subtypes of adrenoceptors

  9. 去氧肾上腺素 甲氧明

  10. Effects of catecholamines（therapeutic doses）

  11. epinephrine  antagonist epinephrine BP Epinephrine reversal （adrenaline reversal）

  12.  receptors 1 receptors: (vasoconstriction: increased peripheral resistance, BP↑; contraction of radial muscle of iris: mydriasis) 2 receptors: (CNS, presynaptic membranes of adrenergic nerves: vasodilatation, inhibition of NE release; inhibition of insulin release) Summary:Adrenoceptors (adrenergic receptors)

  13.  receptors 1 receptors (contractility↑, automaticity↑, conduction↑, oxygen-consumption↑, cardiac output↑: heart stimulation; increased lipolysis) 2 receptors (relaxation of bronchial smooth muscles: bronchodilation; slight vasodilation; increased muscle and liver glycogenolysis; increased release of glucagon) 3 receptors (lipolysis, thermogenesis) Summary:Adrenoceptors (adrenergic receptors)

  14. Adrenoceptor agonists ,  receptor agonists epinephrine (adrenaline肾上腺素)，dopamine(多巴胺), ephedrine(麻黄碱) (2)  receptor agonists 12 receptor agonists:norepinephrine(去甲肾上腺素) 1 receptor agonists:phenylephrine(去氧肾上腺素) 2 receptor agonists:clonidine(可乐定) (3)  receptor agonists： 12 receptor agonists:isoproterenol(异丙肾上腺素) 1 receptor agonists:dobutamine (多巴酚丁胺) 2 receptor agonists:salbutamol(沙丁胺醇) Drug actions and classification

  15. 1. ,  receptor agonists Epinephrine 肾上腺素, Adrenaline

  16. 1. ,  receptor agonists • 1.1 Pharmacological effects* • (1) Cardiac effects • 1: HR , output , • oxygen consumption , inducing arrhythmia • (2) Vascular effects • 1：vasoconstriction, especially at larger doses • 2：vasodilatation of skeletal muscles and coronary vessels

  17. 1. ,  receptor agonists • (3) Blood pressure • SP , DP  (at therapeutic doses) ，脉压加大 • (4) Bronchodilatation • 2：dilatation of bronchial smooth muscles • 1：reducing congestion and edema of bronchial mucosa • (5) Metabolic effects • blood glucose ; free fatty acids  • (6)其它：抑制胃肠道平滑肌、大剂量产生中枢兴奋症状

  18. 1. ,  receptor agonists • 1.2 Clinical uses* • (1) Cardiac arrest：辅助心脏按摩、人工呼吸和纠正酸中毒 • (2) Anaphylactic shock:糖皮质激素、抗组胺药物 • (3) Acute bronchial asthma:控制痉挛、抑制组胺释放 • (4) Local uses • adjuvant for local anesthetics; control of bleeding • (5) 治疗青光眼，降低眼内压

  19. Systmatic uses: Cardiac arrest Anaphylactic shock Acute bronchial asthma Topical uses: Adjuvant of local anesthesia Bleeding Clinical uses of epinephrine

  20. 1. ,  receptor agonists • 1.3 Adverse effects* • (1) Cardiac arrhythmia: BP , arrhythmia • (2) Acute and Excessive rise of BP: cerebral or subarachnoid hemorrhage • (3) Central excitation：anxiety • (4) Contraindications: heart diseases, hypertension, coronary arterial disease, arteriosclerosis, hyperthyroidism（甲亢）

  21. 1. ,  receptor agonists Ephedrine 麻黄碱 Ephedrine 麻黄碱 Epinephrine 肾上腺素

  22. 1. ,  receptor agonists • 1.1 Pharmacological effects • Promoting release of NE, weak agonist effectson 1、2、1、2 receptors • Properties： • chemically stable, orally effective； • less potent and longer action duration; • central stimulating（强于肾上腺素、弱于苯丙胺）； • tachyphylaxis快速耐药性

  23. 1. ,  receptor agonists • 1.2 Clinical uses • (1) Prevention of hypotension: anesthetics－induced • (2) Nasal decongestion: nasal drop • (3) Bronchial asthma: mild, chronic cases • (4) Relieving allergic disorders: urticaria风疹, angio-neurotic edema

  24. 1. ,  receptor agonists • 1.3 Adverse effects • (1) Central stimulation • (2) CVS effects • (3) Dependence

  25. 1. ,  receptor agonists Dopamine 多巴胺 These receptors are distinct from and receptors and are particularly important in the brain and in the splanchnic and renal vasculature. There is now considerable evidence for the existence of at least five subtypes of dopamine receptors.

  26. The D1 receptor is typically associated with the stimulation of adenylyl cyclase ; for example, D1-receptor-induced smooth muscle relaxation is presumably due to cAMP accumulation in the smooth muscle of those vascular beds where dopamine is a vasodilator. D2 receptors have been found to inhibit adenylyl cyclase activity, open potassium channels, and decrease calcium influx.

  27. Dopamine (多巴胺):DIRECT Pharmacological effects : ,  receptor, dopaminergic receptor agonists (1) Cardiac effects：1 receptor, weak (2) Vascular effects： DA receptor：vasodilatation of renal and mesenteric arteries , blood flow (small doses); 1 receptor：vasoconstriction of skin, mesenteric vessels (larger doses) (3) Renal effects：renal vasodilatation; natriuretic effects(尿钠排泄作用)

  28. 1.2 Clinical uses • (1) Shock • cardiac and septic shock: low output, urinary volume , fully adequate replacement of intravascular fluid • (2) Acute renal failure • combined with furosemide • 1.3 Adverse effects • tachycardia, arrhythmia, renal vasoconstriction

  29. 2.  receptor agonists • 2-1 1, 2 receptor agonists Norepinephrine 去甲肾上腺素, noradrenaline

  30. 2.  receptor agonists • 2.1 Pharmacological effects • (1) Vascular effects： • 1：vasoconstriction (skin, renal, brain, hepatic, mesenteric, etc.) • vasodilatation of coronary arteries • 2：inhibiting NE release (auto-regulation)

  31. 2.  receptor agonists • (2) Cardiac effects： • weak direct stimulation (1); • inhibition via reflex • (3) Blood pressure： • SP , DP (especially at larger doses), • larger doses:pulse pressure , blood flow 

  32. 2.  receptor agonists • 2.2 Clinical uses* • (1) Shock • BP , blood flow , tissue damage • used in early phase of some types of shock or BP rise too slow after treatment: 早期神经源性休克及嗜铬细胞瘤切除后或药物中毒导致的低血压 • small doses and shorter duration • (dopamine is better; replaced by Metaraminol间羟胺)

  33. 2.  receptor agonists • (2) Hypotension due to drug poisoning • especially for chlorpromazine(氯丙嗪) • (3) Hemorrhage in upper alimentary tract（上消化道） • orally given after dilution

  34. 2.  receptor agonists • 2.3 Adverse effects* • (1) Ischemia and necrosis at the site of iv administrationrelieved by filtration with procaine or phentolamine • (2) Acute renal failure avoiding larger doses and longer duration; monitoring urinary volume • (3) Contraindication hypertension, arteriosclerosis, heart diseases, severe urinary volume , microcirculation disorders

  35. 2.  receptor agonists Metaraminol 间羟胺, Aramine • Acting on  receptors directly, promoting NE release indirectly； • Weaker effects and longer duration than NE, • weak for renal vessels; • Used in early phase of shock, hypotension

  36. 2.  receptor agonists • 2-2 1 receptor agonists • Acting Weakly and longer than that of NE • used in hypotension, paroxysmal supraventricular tachycardia (to decrease BP by reflex)； • Mydriasis (扩瞳，phenylephrine): pupillary dilator muscles, no or less effect on intraocular pressure, short-acting (for several hours) Phenylephrine 去氧肾上腺素 Methoxamien 甲氧明

  37. Alpha2-selective agonists（自学） Alpha2-selective agonists have an important ability to decrease blood pressure through actions in the central nervous systemeven though direct application to a blood vessel may cause vasoconstriction. Such drugs (eg, clonidine, methyldopa, guanfacine, guanabenz) are useful in the treatment of hypertension (and some other conditions) and Antihypertensive Agents. Dexmedetomidine is a centrally acting 2-selective agonist that is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting.

  38. 3.  receptor agonists Isoproterenol, Isoprenaline 异丙肾上腺素: Pharmacological effects : 1 , 2 receptor agonists 扩张支气管 扩张冠脉和骨骼肌血管 促进代谢 正性肌力和频率

  39. 3.  receptor agonists • 3.2 Clinical uses • (1) Cardiac arrest • (2) A-V block • (3) Septic shock（感染性休克）：fitable for low-output patient（less to be used now） • (4) Bronchial asthma： • usually using 2 receptor agonists

  40. 3.  receptor agonists • 3.3 Adverse effects • (1) Heart stimulation, arrtythmia • (2) Contraindications: • coronary heart disease, myocarditis, hyperthyroidism

  41. 3.  receptor agonists • 3-2 1 receptor agonists • Heart failure (after cardiac surgery or congestive HF or acute myocardial infarction; short-term treatment) • Cardiac stimulation Dobutamine 多巴酚丁胺

  42. 2 receptor agonists Terbutaline:特布他林（博利康尼） • Uses: Bronchial asthma Dilation of bronchial smooth muscle; 2 > 1 agonist (partially selective): preferential activation of pulmonary 2 receptors by inhalation. Premature Labor (早产，combine with ritodrine，羟苄羟麻黄碱). • Adverse effects: headache, cardiac stimulation and skeletal muscle fine tremor (2 receptors on presynaptic motor terminals; their activation enhances ACh release).

  43. 肾上腺素 异丙肾上腺素 沙丁胺醇(舒喘灵) 沙美特罗 特布他林（博利康尼）

  44. Adrenoceptor Antagonists 1. αreceptor antagonists 2.  receptor antagonists 3. α,  receptor antagonists

  45. Drug actions and classification Adrenoceptor antagonists （1） receptor antagonists • 12 receptor antagonists: short-acting: phentolamine（酚妥拉明） long-acting: phenoxybenzamine（酚苄明） • 1 receptor antagonists:prazosin（哌唑嗪） • 2 receptor antagonists:yohimbine（育亨宾）

  46. Drug actions and classification Adrenoceptor antagonists （2） receptor antagonists • 12 receptor antagonists:propranolol （普萘洛尔） • 1 receptor antagonists:atenolol（阿替洛尔） • 2 receptor antagonists:butoxamine（布他沙明） （3）,  receptor antagonists • labetalol（拉贝洛尔）

  47. 1.  receptor antagonists • 1-1 1, 2 receptor antagonists • Short-acting Phentolamine 酚妥拉明

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