Chaper 20 Adrenoceptor Antagonists 1. αreceptor antagonists 2.  receptor antagonists 3. α,  receptor antagonists

Epinephrine reversal （肾上腺素作用的翻转）

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

1.  receptor antagonists 1.1 Pharmacology (1) Vasodilatation Blocking 1 receptor (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 ; fully adequate replacement of intravascular fluid

1.  receptor antagonists (4) Acute myocardial infarction and congestive heart failure after-load  cardiac output  (5) Pheochromocytoma pre- and post-operation diagnosis (6) Others: impotency

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

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

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

1.  receptor antagonists prazosin, for hypertension treatment 1-3 2 receptor antagonists yohimbine

2.  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 So, 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 Hypotension: peripheral blood flow , hypotensive effects in hypertensive patients

2.  receptor antagonists B. Bronchial smooth muscles induces 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, Na+ channel block (4) Others Lowering intraocular pressure; Inhibiting platelet aggregation

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

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

2.  receptor antagonists 2.5 Drugs Propranolol 普萘洛尔

2.  receptor antagonists 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 For treatment of glaucoma (wide-angle)

2.  receptor antagonists Atenolol 阿替洛尔 Metoprolol 美托洛尔 1receptor antagonists, no intrinsic activity atenolol : longer t1/2, once daily usually used for treatment of hypertension

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

Chapter 21 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 sensory (fine – thick) －CNS (inhibiting - excitory)－ANS－motor nerves－muscles

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

Intracellular blockade of Na+ channel The mechanism of local anesthetics Intracellular blockade of Na+ channel

Local anesthetics (2) Systemic effects（Adverse effects） Depressing CNS：excitation -depression Cardiovascular effects：heart; vasodilatation; lowering BP combined with epinephrine: reducing absorption and systemic effects

Local anesthetics 2. Clinical uses (1) Surface anesthesia (表面麻醉） 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 (5) Subarachnoidanesthesia (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 tration procaine weak weak weak can not be used 普鲁卡因 (allergic) for surface 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