2.Treat vein hemorrhage of the upper alimentary tract(lower esophagus and gastric bottom) 【Adverse effects】 Overdose of NA may cause arrhythmias,acute renal function failure (insufficiency).If the drug unexpectedly goes out of vese it may leads to the ischemic damage of the soft tissues Phenylephrine(fenilefrin](Neosynephrine) Non-catecholamine,-R,++B-R+B2-R-;promote the NA release from the terminals. 【Propertiesof pharmacology】 Phenylephrine is a strong aRagonist and acts much longer than NA.It is used for treating the patients with low BP symptoms and paroxysmal supraventricular tachycardia Because of its mydriasis with relatively shorter time than cholinergic blockers,and without obvious infuences of intraocular pressure and ciliary accommodation it is also used in ophthalmic practice.Overdose of phenylephrine may cause acute renal insufficiency. Isoprenaline[aisoupre(Isoproterenol,ISOP) Isoprenaline is a synthetic catecholamine with strong B-R and B-R activity and without a-R action.The B2-Rismore sensitivity to isoprenaline 【Actions of pharmacology】 l.Heart Br-R+,HRt个，contractility个，conduction个，cardiac output,O2 consumption↑， systolic pressureT. 2.Vessels The vessels of skeletal muscles B-R++relax and last long time,BPespecially diastolic pressure mean BP 3.Smooth muscle of bronchus B2-R+++,relax. 【Clinical uses】 1.Treat A-V conduction block,bradycardia,cardiac arrest 2.Treat asthma 【Adverse Effects】 Isoprenaline an induces arrhythmias and attack of angina pectoris Dobutamine[dObu:tmin] Dobutamine is a synthetic catecholamine.Dobutamine is also a selective B-R agonist() B2-R().a-R (+)It strengthens the contractility of the heart and increases cardiac output with few vascular effects and few changes of heart rates.It can be used for treatment of acute heart failure with decreasing the force of contraction,especially caused by heart surgery. Because ofheart by dobutamine.theatrial fibrillation mayoccur 之
21 2. Treat vein hemorrhage of the upper alimentary tract (lower esophagus and gastric bottom) 【Adverse effects】 Overdose of NA may cause arrhythmias, acute renal function failure (insufficiency). If the drug unexpectedly goes out of vessels it may leads to the ischemic damage of the soft tissues. Phenylephrine[fenilefrin] (Neosynephrine) Non-catecholamine, 1-R, +++; 1-R +, 2-R −; promote the NA release from the terminals. 【Properties of pharmacology】 Phenylephrine is a strong 1-R agonist and acts much longer than NA. It is used for treating the patients with low BP symptoms and paroxysmal supraventricular tachycardia. Because of its mydriasis with relatively shorter time than cholinergic blockers, and without obvious influences of intraocular pressure and ciliary accommodation it is also used in ophthalmic practice. Overdose of phenylephrine may cause acute renal insufficiency. Isoprenaline[aisouprenlin] (Isoproterenol, ISOP) Isoprenaline is a synthetic catecholamine with strong 1-R and 2-R activity and without 1-R action. The 2-R is more sensitivity to isoprenaline. 【Actions of pharmacology】 1. Heart 1-R +++, HR, contractility,conduction, cardiac output, O2 consumption, systolic pressure. 2. Vessels The vessels of skeletal muscles, 2-R +++, relax and last long time, BP, especially diastolic pressure; mean BP. 3. Smooth muscle of bronchus 2-R +++, relax. 【Clinical uses】 1. Treat A-V conduction block, bradycardia, cardiac arrest. 2. Treat asthma. 【Adverse Effects】 Isoprenaline can induces arrhythmias and attack of angina pectoris. Dobutamine[dbu:tmin] Dobutamine is a synthetic catecholamine. Dobutamine is also a selective 1-R agonist (+++), 2-R (± ), 1-R (+). It strengthens the contractility of the heart and increases cardiac output with few vascular effects and few changes of heart rates. It can be used for treatment of acute heart failure with decreasing the force of contraction, especially caused by heart surgery. Because of heart excitation caused by dobutamine, the atrial fibrillation may occur
Salbutamol [sIbju:m(Albuterol)and terbutaline[t:bu:tin] They are not catecholamine with a good B-Rselective stimulation and less B-Raction.They also have much higher bioavailabilities than other adrenergic agonists after given orally.In clinical practice,they are used for treating patients with asthma and premature delivery (labour). Adrenaline[drenlin](Epinephrine) Adrenaline is a natural catecholamine.ItsRand Ractivities are similar to NA,and BR B2-R actions are similar to Isor 【Actions of pharmacology】 1.Heart B-R similar to Isop.It causes HR contractility conduction cardiac output systolic pressure 2.Vessels Vessels of skin,mucosa,and viscera:aR.similar to NA,contraction.Vessels of skeletal muscles.B2-R.similar to Isop.relax and last long time. 3.Blood pressure Systolic pressure diastolic pressurewhich are relative with dose used.Mean BP,but following BP 4.Bronchi Smooth B2-R,its effect is similar to Isop.Mucosa vessels:a-R,it causes contraction and decreases conestion and penetration of vessels 5.Metabolism Enhance the lipolysis and glycogenolysis in the liver,make blood sugar increase 【Clinical uses】 1.Anaphylactic shock Adrenaline is the first choice drug for the treatment of patients with Type I allergic reactions.It can relieve the symptoms,such as bronchospasm,mucosa congestion, angioedema.penetration of vessels.and cardiovascular collapse. 2.Acute cardiac arrest Similar to Isop. 3.Complementary drug for local anesthesia It can be added little into local anesthetic drugs for prolonging the action duration of later,relieving bleeding.and decreasing the absorption of the anesthetics from local tissues. 4.Acute bronchial asthma It can quickly improve the symptoms,but effects last very short time. 【Adverse effects】 Adrenaline can produce adverse effects similar to Isop and NA,such as arrhythmias,attack of angina pectoris,high BP,and even cerebral hemorrhage. Ephedrine(efedrin Ephedrine is a non-catecholamine originally isolated from Chinese herb Ma Huang.Now it is synthesized.Because of losing hydroxyl on the phenyl ring of the chemical structure it has a good bioavailability after given orally and can much easily enters CNS. 2
22 Salbutamol [slbju: tml](Albuterol) and terbutaline[t:bu:tli:n] They are not catecholamine with a good 2-R selective stimulation and less 1-R action. They also have much higher bioavailabilities than other adrenergic agonists after given orally. In clinical practice, they are used for treating patients with asthma and premature delivery (labour). Adrenaline[drenli:n] (Epinephrine) Adrenaline is a natural catecholamine. Its 1-R and 2-R activities are similar to NA, and 1-R, 2-R actions are similar to Isop 【Actions of pharmacology】 1. Heart 1-R, similar to Isop. It causes HR, contractility, conduction, cardiac output, O2 consumption, and systolic pressure. 2. Vessels Vessels of skin, mucosa, and viscera: 1-R, similar to NA, contraction. Vessels of skeletal muscles, 2-R, similar to Isop, relax and last long time. 3. Blood pressure Systolic pressure, diastolic pressure, →, which are relative with dose used. Mean BP, but following BP. 4. Bronchi Smooth: 2-R, its effect is similar to Isop. Mucosa vessels: 1-R, it causes contraction and decreases congestion and penetration of vessels. 5. Metabolism Enhance the lipolysis and glycogenolysis in the liver, make blood sugar increase. 【Clinical uses】 1. Anaphylactic shock Adrenaline is the first choice drug for the treatment of patients with Type I allergic reactions. It can relieve the symptoms, such as bronchospasm, mucosa congestion, angioedema, penetration of vessels, and cardiovascular collapse. 2. Acute cardiac arrest Similar to Isop. 3. Complementary drug for local anesthesia It can be added little into local anesthetic drugs for prolonging the action duration of later, relieving bleeding, and decreasing the absorption of the anesthetics from local tissues. 4. Acute bronchial asthma It can quickly improve the symptoms, but effects last very short time. 【Adverse effects】 Adrenaline can produce adverse effects similar to Isop and NA, such as arrhythmias, attack of angina pectoris, high BP, and even cerebral hemorrhage. Ephedrine[efedrin] Ephedrine is a non-catecholamine originally isolated from Chinese herb Ma Huang. Now it is synthesized. Because of losing hydroxyl on the phenyl ring of the chemical structure it has a good bioavailability after given orally and can much easily enters CNS
【Mechanism】 Ephedrine either directly stimulates adrenoceptorsindirectly acts by promoting release of NA from noradrenergic terminals. 【Actions and clinical uses】 Ephedrine has similar effects to adrenaline,but much weaker for potency and longer for lasting time than later. 1.Cardiovascular system It makes heart excitation(HRT,contractility T,conductionT,and O consumption),contracts vessels and raises BP.In clincal practice it is used for treating low BP. angioedema,and urticaria It is also topically used to relieve nasal mucosa congestion and local bleeding. 2.Bronchial tracts Ephedrine relaxes the bronchial smooth and can be used to treat patients with asthma 3.CNS stimulation It produces mild CNS stimulation,increases alertness,decreases fatigue and disturbs sleep.It may be used with antihistamine drugs to prevent motion sickness. 【Adverse effects】 Except CNS stimulation and fast tolerance.Ephedrine has similar adverse effects to adrenaline Dopamine(pmi:n] Dopamine is a natural catecholamine and precursor of NA.It is a dopamine receptor agonist with mild B-RandRstimulations.The pharmacological actions depend on the dose used:With usual dose it stimulates dopamine receptor of the visceral vessels(,as a result,dilates the renal vessels and enhances the glomerular filtration rate with natrium diuresis.It also stimulates B-R of heart (++and strengthens the contractility of heart and increases cardiac output with less influence on the heart rates and BP 【Clinical uses】 Dopamine is used to treat shock with the renal and cardiac function insufficiency 【Adverse effects】 Dopamine can cause skin rash.If high concentration is used it may cause nausea,vomiting. hypertension,and arrhythmias. (Z Dong.Q-X Zhou) 23
23 【Mechanism】 Ephedrine either directly stimulates adrenoceptors or indirectly acts by promoting release of NA from noradrenergic terminals. 【Actions and clinical uses】 Ephedrine has similar effects to adrenaline, but much weaker for potency and longer for lasting time than later. 1. Cardiovascular system It makes heart excitation (HR, contractility , conduction, and O2 consumption), contracts vessels and raises BP. In clinical practice it is used for treating low BP, angioedema, and urticaria. It is also topically used to relieve nasal mucosa congestion and local bleeding. 2. Bronchial tracts Ephedrine relaxes the bronchial smooth and can be used to treat patients with asthma. 3. CNS stimulation It produces mild CNS stimulation, increases alertness, decreases fatigue, and disturbs sleep. It may be used with antihistamine drugs to prevent motion sickness. 【Adverse effects】 Except CNS stimulation and fast tolerance, Ephedrine has similar adverse effects to adrenaline. Dopamine[d:pmi:n] Dopamine is a natural catecholamine and precursor of NA. It is a dopamine receptor agonist with mild 1-R and 1-R stimulations. The pharmacological actions depend on the dose used: With usual dose it stimulates dopamine receptor of the visceral vessels (+++), as a result, dilates the vessels, especially renal vessels, and enhances the glomerular filtration rate with natrium diuresis. It also stimulates 1-R of heart (++) and strengthens the contractility of heart and increases cardiac output with less influence on the heart rates and BP. 【Clinical uses】 Dopamine is used to treat shock with the renal and cardiac function insufficiency. 【Adverse effects】 Dopamine can cause skin rash. If high concentration is used it may cause nausea, vomiting, hypertension, and arrhythmias. (Z Dong, Q-X Zhou)
Chapter 9 Adrenoceptor antagonists(blockers) Adrenoceptor antagonists are also called as adrenergic antagonists or blockers.They are divided and B-Rantagonists I.a-Rantagonists They include:1)a-Rantagonists (eg prazosin))a-Rantagonists(eg yohimbine).3)aR -Rantagonists(eg phentolamine). Phentolamine[fentmi:n](Regitin) 【Properties of Pharmacology】 1.Competitive -R and aR antagonists phentolamine blocks a-R makes the peripheral vessels dilatation and BP decrease,and turns over the BP increase caused by adrenaline.It also the presynaptic membrane,as NA release and HR 2.Stimulation of histamine receptor At ordinary dose phentolamine makes the peripheral vessels dilate.BP decrease,and gastric gland secretion increase through H2-R Because of BP decrease,sympathetic nerve excitation is induced by reflex activity.As a result, NA release alsoT and heart excitation. 3.Stimulation of muscarine receptor Phentolamine makes gastrointestinal smooth constrict causes diarrhea and stomachache. 【Clinical uses】 The inical uses of phentolamineare very limited.It could be used totreat pheochromocytoma relieve excessive limb vasospasm from Raynaud's disease,and deal with some refractory heart failure,some acute hypertensive episodes,and microcirculatory disorders 【Adverse reactions】 The adverse reactions of phentolamine are mainly related to a-R blocking.as well as M-R and H-Rstimulations.They are headache,postural,nasal stuffness,ahythmias,and upper- abdominal pain.inducing or exacerbating elementary ulcers. Prazosin[preiz'sin] 【Properties】 Prazosin is a competitive Rantagonist.It makes vessels dilated,decreases BP and post-load of patients with heart failure.In clinical practice it is used for treatment of hypertension and refractory heart failure. The main adverse reaction is first dose phenomenon,which is caused by strong dilatation of vessels. II.B-receptorantagonists 【Pharmacological actions】 24
24 Chapter 9 Adrenoceptor antagonists (blockers) Adrenoceptor antagonists are also called as adrenergic antagonists or blockers. They are divided into -R antagonists and -R antagonists. I. -R antagonists They include: 1) 1-R antagonists (eg prazosin ); 2) 2-R antagonists (eg yohimbine); 3) 1-R, 2-R antagonists (eg phentolamine). Phentolamine[fentlmi:n] (Regitin) 【Properties of Pharmacology】 1. Competitive 1-R and 2-R antagonists phentolamine blocks 1-R, makes the peripheral vessels dilatation and BP decrease, and turns over the BP increase caused by adrenaline. It also blocks 2-R on the presynaptic membrane, as a result, causes NA release and HR. 2. Stimulation of histamine receptor At ordinary dose phentolamine makes the peripheral vessels dilate, BP decrease, and gastric gland secretion increase through H2-R. Because of BP decrease, sympathetic nerve excitation is induced by reflex activity. As a result, NA release also and heart excitation. 3. Stimulation of muscarine receptor Phentolamine makes gastrointestinal smooth constrict, causes diarrhea and stomachache. 【Clinical uses】 The clinical uses of phentolamine are very limited. It could be used to treat pheochromocytoma, relieve excessive limb vasospasm from Raynaud’s disease, and deal with some refractory heart failure, some acute hypertensive episodes, and microcirculatory disorders. 【Adverse reactions】 The adverse reactions of phentolamine are mainly related to -R blocking, as well as M-R and H-R stimulations. They are headache, postural hypotension, nasal stuffiness, arrhythmias, and upperabdominal pain, inducing or exacerbating elementary ulcers. Prazosin[preiz’sin] 【Properties】 Prazosin is a competitive 1-R antagonist. It makes vessels dilated, decreases BP and post-load of patients with heart failure. In clinical practice it is used for treatment of hypertension and refractory heart failure. The main adverse reaction is first dose phenomenon, which is caused by strong dilatation of vessels. II. -receptor antagonists 【Pharmacological actions】
L.Heart Br-R block,HR↓，contraction↓，A-V conduction,cardiac output,systolic pressure↓， consumption of oxygen 2.Juxtaglomerular cells B-R block renin release the activities of renin-angiotensin-aldosterone system. 3.Presynaptic membrane B-R block,NA release. 4.CNS They make the efferent impulses from the vessel center weak.As a result,the peripheral sympathetic tension decreases. 【The properties of main drugs】 From table9-.it can be seen that nearly all the B-R antagoniss will undergo the first pass effect after given orally except pindolol.Some drugs have similar effects to B-Rpartial agonists. Table9-1 The properties of several B-receptor antagonists Receptor Intrinsic Local Lipid Oral Elimination selectivity activity anesthetic solubility bioavailabilit halflife(h) activity y Acebutolol B B2 Yes Ves Low 50 3-4 Atenolol No No Low 40 6-9 Carvedilol a*,B1,B2 No No No data 30 68 Labetalol a*,B1,B2 Yes Yes Moderate 30 5 Metoprolo No Yes Moderate 3-4 Pindolol Yes Yes Moderate 90 3-4 B1,B2 Propranolol B1,B2 No Yes High 30 3.5-6 Timolol No No Moderate 50 4-5 B1,B2 a-Rblock 【Clinical uses】 1.They are mainly used for treatment of cardiovascular diseases,such as hypertension,angina pectoris,and arrhythmias. 2.Other uses hyperthyroidism,glaucoma,migraine,myocardial infarction,and some heart failure. 【Adverse reactions】 They may induce attack of bronchial asthma heart conduction block,and heart failure.Long- of these drugs may cause up-regulation of B-R number,this may be worse for the patients with angina pectoris and hypertension. 【Contraindication】 B-R antagonists must never be used for treatment of the patients with obstructive pumonary disease,A-V conduction block,bradycardia,and serious heart failure. (Z Dong.Q-X Zhou) 3
25 1. Heart 1-R block, HR,contraction ,A-V conduction, cardiac output, systolic pressure, consumption of oxygen. 2. Juxtaglomerular cells -R block, renin release, the activities of renin-angiotensin-aldosterone system. 3. Presynaptic membrane -R block, NA release. 4. CNS They make the efferent impulses from the vessel center weak. As a result, the peripheral sympathetic tension decreases. 【The properties of main drugs】 From table 9-1, it can be seen that nearly all the -R antagonists will undergo the first pass effect after given orally except pindolol. Some drugs have similar effects to -R partial agonists. Table 9-1 The properties of several -receptor antagonists Receptor selectivity Intrinsic activity Local anesthetic activity Lipid solubility Oral bioavailabilit y Elimination half life (h) Acebutolol Atenolol Carvedilol Labetalol Metoprolol Pindolol Propranolol Timolol 1 2 1 *, 1, 2 *, 1, 2 1 1, 2 1, 2 1, 2 Yes No No Yes No Yes No No Yes No No Yes Yes Yes Yes No Low Low No data Moderate Moderate Moderate High Moderate 50 40 30 30 50 90 30 50 3-4 6-9 6-8 5 3-4 3-4 3.5-6 4-5 * 1-R block 【Clinical uses】 1. They are mainly used for treatment of cardiovascular diseases, such as hypertension, angina pectoris, and arrhythmias. 2. Other uses hyperthyroidism, glaucoma, migraine, myocardial infarction, and some heart failure. 【Adverse reactions】 They may induce attack of bronchial asthma, heart conduction block, and heart failure. Longterm use of these drugs may cause up-regulation of -R number; this may be worse for the patients with angina pectoris and hypertension. 【Contraindication】 -R antagonists must never be used for treatment of the patients with obstructive pulmonary disease, A-V conduction block, bradycardia, and serious heart failure. (Z Dong, Q-X Zhou)