Part 5 Adrenoceptor Antagonists 1.  receptor antagonists 2.  receptor antagonists 3. ,  receptor antagonists

§ Epinephrine reversal （ 肾上腺素作用的翻转 ）

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

§1.1 Pharmacology §(1) Vasodilatation § Blocking  1 receptor; direct action §(2) Stimulating heart § Reflex ； blocking  2 receptor ～ NE release  §(3) Cholinergic and histamine-like effects § Contraction of GI smooth muscles, § Gastric acid secretion  1.  receptor antagonists

§1.2 Clinical uses §(1) Peripheral vascular diseases § Acrocyanosis, Raynaud’s disease §(2) Local vasoconstrictor extravasation 1.  receptor antagonists

§(3) Shock § cardiac output  ; § redistribution of blood flow; § shift of fluid from interstitial compartment to vascular compartment; § pulmonary pressure  ; § should be used after fully adequate replacement of intravascular fluid 1.  receptor antagonists

§(4) Acute myocardial infarction and congestive heart failure after-load  ； cardiac output  § after-load  ； cardiac output  1.  receptor antagonists

§(5) Pheochromocytoma § pre- and post-operation uses § diagnosis §(6) Others: impotency ( 阳痿 ) 1.  receptor antagonists

§1.3 Adverse effects §(1) Postural hypotension §(2) Reflex heart stimulation § tachycardia, arrhythmia, angina pectoris §(3) G.I. reactions §(4) Other § central depression 1.  receptor antagonists

§Tolazoline 妥拉唑啉 weak effects § weak effects § more severe adverse effects 1.  receptor antagonists

§Long-acting Longer action duration § Longer action duration peripheral vasculardiseases §used for peripheral vasculardiseases § anti-shock § pheochromocytoma § improving urinary flow in patients with benign prostatic hypertrophy Phenoxybenzamine 酚苄明 1.  receptor antagonists

§1-2  1 receptor antagonists § prazosin （ 哌唑嗪 ）, for hypertension treatment § tamsulosin （ 坦洛新 ）, for benign prostatic hypertrophy §1-3  2 receptor antagonists yohimbine （ 育亨宾 ） § yohimbine （ 育亨宾 ） 1.  receptor antagonists

§2.1 ADME §First-pass elimination, §lower bioavailability: propranolol §Hepatic metabolism and renal excretion, hepatic and renal functions alter the effects of the drugs and result in large individual variation §Thus, dose individualization is necessary. 2.  receptor antagonists

§2.2 Pharmacological effects §(1)  receptor blockade §A. Cardiovascular effects ： Depressing heart: reduction in HR, A-V conduction, automaticity, cardiac output, oxygen consumption § Depressing heart: reduction in HR, A-V conduction, automaticity, cardiac output, oxygen consumption § Hypotension: hypotensive effects only in hypertensive patients; peripheral blood flow , BP  in normal subjects. 2.  receptor antagonists

Blockade of  –adrenoceptor cardial responses by propranolol

§B. Bronchial smooth muscles §inducing bronchial smooth muscle contraction in asthmatic patients §C. Metabolism §lipolysis , glycogenolysis , potentiating insulin effects ~ hypoglycemia §D. Renin secretion §decreasing secretion of renin 2.  receptor antagonists

§(2) Intrinsic sympathomimetic effects §Some drugs: HR , output  §(3) Membrane-stabilizing effects §Larger doses of some drugs: quinidine-like effects due to Na + channel block §(4) Others §Lowering intraocular pressure; §Inhibiting platelet aggregation 2.  receptor antagonists

§2.3 Clinical uses §(1) Arrhythmia ： supraventricular, sympathetic activity  §(2) Hypertension §(3) Angina pectoris and myocardial infarction §(4) Chronic heart failure §(5) Others: hyperthyroidism, migraine headache, glaucoma （ timolol ）, etc. 2.  receptor antagonists

Effect of a  receptor antagonist on the mortality of chronic heart failure

§2.4 Adverse effects §(1) Worsening of asthma: contraindicated in bronchial asthmatic patients §(2) Heart depression: contraindicated in heart failure, severe A-V block, sinus bradycardia §(3) Worsening of peripheral vascular constriction §(4) Withdrawal syndrome ： up-regulation of  receptors §(5) Others ： central depression, hypoglycemia, etc. 2.  receptor antagonists

§2.5 Representative drugs Propranolol 普萘洛尔 Propranolol 普萘洛尔

 1,  2 receptor blocking §  1,  2 receptor blocking § no intrinsic activity § first-elimination after oral administration, individual variation of bioavailability Propranolol 普萘洛尔 2.  receptor antagonists

§For treatment of glaucoma (wide-angle) Timolol 噻马洛尔 2.  receptor antagonists

§  1 receptor antagonists, no intrinsic activity §atenolol : longer t 1/2, once daily §usually used for treatment of hypertension Atenolol 阿替洛尔 Atenolol 阿替洛尔 Metoprolol 美托洛尔 2.  receptor antagonists

3. α,  receptor antagonists blockingα, β receptors, β> α § blocking α, β receptors, β> α § usually used for treatment of hypertension Labetolol 拉贝洛尔

3. α,  receptor antagonists α, β receptor blocking, β> α § α, β receptor blocking, β> α §S(-) isomer: βand α receptor blocking §R(+) isomer: α receptor blocking §usually used for treatment of hypertension and chronic heart failure Carvedilol 卡维地洛

Part 6 Local Anesthetics

procaine普鲁卡因 lidocaine利多卡因 tetracaine 丁 卡 因

Local anesthetics §1. Pharmacological effects §(1) Local anesthetic effects inhibiting Na + inward flow and the conduction of nerve fibers § inhibiting Na + inward flow and the conduction of nerve fibers § sensory (fine – thick)  CNS(inhibiting - excitatory)  ANS  motor nerves  muscles § sensory (fine – thick)  CNS (inhibiting - excitatory)  ANS  motor nerves  muscles

The mechanism of local anesthetics Blocking Na + channels on the nerve fibers

The mechanism of local anesthetics Intracellular blockade of Na + channel

Local anesthetics §(2) Systemic effects （ Adverse effects ） Depressing CNS ： excitation - depression § Depressing CNS ： excitation - depression § Cardiovascular effects ： heart depression; vasodilatation; lowering BP § combined with epinephrine: reducing absorption and systemic effects § ( but contraindicated in: terminal tissues; epinephrine contraindications )

§2. Clinical uses §(1) Surface anesthesia ( 表面麻醉 ） penetration § penetration §(2) Infiltration anesthesia （ 浸润麻醉 ） §(3) Conduction anesthesia （ 传导麻醉 ） Local anesthetics

§(4) Epidural anesthesia ( 硬脊膜外麻醉 ) Avoiding misdirection into cerebrospinal fluid § Avoiding misdirection into cerebrospinal fluid §(5) Subarachnoid anesthesia ( 蛛网膜下腔麻 § 醉, 腰麻 ） § head-up position; § hyperbaric solution; § hypotension: prevention with ephedrine Local anesthetics

§3. Adverse effects §(1) Systemic effects § depression of CNS: excitation – depression – respiratory depression § cardiovascular effects: hypotension; arrhythmia §(2) Allergic reactions § urticaria, bronchoconstriction; anaphylactic shock Local anesthetics

§4. Special agents Efffect Toxicity Pene- Uses Efffect Toxicity Pene- Uses tration tration procaine weak weak weak can not be used 普鲁卡因 (allergic) for surface skin allergic test skin allergic test lidocaine stronger lower stronger for various uses ； 利多卡因 anti-arrhythmia tetracaine stronger stronger stronger mainly for surface 丁卡因 Local anesthetics