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

2. Epinephrine reversal （肾上腺素作用的翻转）

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

4. 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 

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

6. 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

7. 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

8. 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

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

10. 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

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

12. 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.

13. 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

14. 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

15. 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

16. 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.

17. 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.

18. 2.  receptor antagonists
2.5 Drugs
Propranolol 普萘洛尔

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

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

21. 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

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

23. Chapter 21 Local Anesthetics

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

25. 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

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

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

28. 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

29. 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）

30. 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

31. 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

32. 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