1. Chapter 34 Antihypertensive Drugs

2. Antihypertensive Drugs
Overview
Classification of antihypertensive drugs
Antihypertensive drugs
Rational application of antihypertensive drugs

3. A. Overview Hypertension Criterion of hypertension:
essential hypertension
secondary hypertension
Criterion of hypertension:
diastolic blood pressure  90 mmHg
systolic blood pressure  140 mmHg

4. A. Overview   Major factors influencing blood pressure
Arterial blood
pressure 
Cardiac
output 
Peripheral
resistance
arteriolar
tone
Blood
volume
Heart
rate
Contractility
Filling
pressure
Venous
tone
Baroreceptors and sympathetic nervous system
Renin-angiotention-aldosterol system (RAAS)

5. Peripheral resistance and vascular tone and elasticity

6. Arterial wall hypertrophy and sclerosis

7. B. Classification of Antihypertensive Drugs
Diuretics
Calcium channel blockers
Regin-angiotensin system inhibitors
Sympathetic inhibitors
Vasodilators

8. Noradrenergic nerve ending blockers

9. C. Antihypertensive Drugs
Diuretics
1. Pharmacological effects
(1) Reducing plasma volume (cardiac output )
(2) Reducing Na+-Ca2+ exchange in vascular smooth muscle cells (Ca2+i , peripheral resistance  )

10. Na+-Ca2+ exchange , Ca2+i 
in vascular smooth muscle cells

11. C. Antihypertensive Drugs
2. Clinical uses
(1) Hypertension
single or combined with other drugs
mild to moderate hypertension
particularly useful in the treatment of elderly patients, pure systolic hypertension, hypertension with heart failure
(2) Other uses: diuretic, etc.

12. C. Antihypertensive Drugs
3. Adverse effects
plasma levels of renin 
hypokalemia
hyperuricemia
hyperglycemia
hyperlipidemia

13. C. Antihypertensive Drugs

14. C. Antihypertensive Drugs Calcium channel blockers
1. Pharmacological effects
Relaxing vascular smooth muscles
2. Clinical uses
Mild to severe hypertension (usually combined with  receptor blockers )
Nifedipine 硝苯地平

15. C. Antihypertensive Drugs
3. Adverse effects
Peripheral edema
Reflex sympathetic activation
Renin activity 
Other calcium channel blockers: amlodipine, etc.

17. C. Antihypertensive Drugs

18. C. Antihypertensive Drugs Renin-angiotensin system inhibitors
ACEIs: captopril 卡托普利, enalapril 依那普利
AT1 receptor antagonists：losartan 氯沙坦
Renin inhibitors: enalkiren 依那吉仑

22. Renin-Angiotensin-Aldosterone system (RAAS)
Angiotensinogen
Renin
Angiotensin I (decapeptide)
Angiotensin converting enzyme
Angiotensin II ( octapepetide)
Angiotensinase A
Adrenal cortex
Angiotension III (heptapeptide)
Aldosterone
Renin-Angiotensin-Aldosterone system (RAAS)

23. C. Antihypertensive Drugs
Actions of angiotensin Ⅱ
Constricting vessels, increase peripheral resistance and returned blood volume.
Increasing sympathetic tension, promote release of sympathetic transmitter.
Stimulating release of aldosterone.
Inducing expression of c-fos、c-myc、c-jun rapidly.

24. C. Antihypertensive Drugs
ACEIs

25. C. Antihypertensive Drugs
ACEIs
1. Pharmacological effects
Inhibiting the production of Ang II
Inhibiting the degradation of bradykinin
Increasing ANP and scavenge free radicals

26. C. Antihypertensive Drugs
Angiotensin II
Inactive peptide
brandykinin
Angiotensin I
ACEI
(—)
ACEI
B2 receptor
(—)
ACE
Circulation and local tissues
PGI2 NO
ACE
Circulation and local tissues
Vasodilatation,
anti-proliferation, anti-hypertrophy

27. C. Antihypertensive Drugs
2. Clinical uses
Hypertension
without reflexly increasing the activity of sympathetic system
effective in the management of patients with CHF, diabetes and ischemic heart disease.

28. C. Antihypertensive Drugs
3. Adverse effects
hypotension ( first dose phenomenon )
renal injury
dry cough
hyperkalemia
angioneuroedema
rashes and altered tastes
Contraindications: renal artery stenosis, pregnant and lactational women

29. C. Antihypertensive Drugs
AT1 antagonists
Losartan 氯沙坦

30. C. Antihypertensive Drugs
AT1 antagonists
Compared with ACEI:
Block actions of angiotensin II directly
Not influence bradykinin metabolism
Protect renal funtion
Used for mild to moderate hypertension
Less adverse effects

31. C. Antihypertensive Drugs
Renin inhibitors
Inhibiting whole RAAS
Including renin antibody, peptide and nonpeptide renin inhibitors

32. C. Antihypertensive Drugs

33. C. Antihypertensive Drugs Sympathetic system inhibitors
Centrally acting adrenergic drugs
Ganglion blockers
Noradrenergic nerve ending blockers
Adrenoreceptor blockers
 receptor blockers
 receptor blockers
 and  receptor blockers

34. C. Antihypertensive Drugs Adrenoreceptor blockers
1. Pharmacological effects
(1) Decreasing cardiac output
(2) Decreasing sympathetic outflow from CNS and releasing of noradrenalin from peripheral nerve endings
(3) Inhibiting the release of renin from kidney (formation of angiotension and secretion of aldosterone)
(4) Increasing production of PGs
(5) Increasing sensitivity of baroreceptor

35. Main actions of β receptor antagonists on blood pressure

36. C. Antihypertensive Drugs
3. Clinical uses
(1) Hypertension: all kinds of hypertension
more effective in young patients than elderly
useful in treating coexisting conditions such as supraventricular tachycardia, previous myocardial infarction, angina pectoris, glaucoma and migraine headache
(2) Other uses: angina pectoris; arrhythmias

37. C. Antihypertensive Drugs
3. Adverse effects
alterations in serum lipid patterns
drug withdrawal
Cardiac depression

38. C. Antihypertensive Drugs

39. C. Antihypertensive Drugs
1 Receptor blockers
Prazosin 哌唑嗪
Terazosin 特拉唑嗪
Doxazosin 多沙唑嗪
Trimazosin 曲马唑嗪

40. C. Antihypertensive Drugs
1 Receptor blockers
1. Pharmacological effects
Relaxing arterial and venous smooth muscles
Decreasing peripheral resistance
2. Clinical uses
Hypertension: mild to moderate (single) and severe hypertension (combined with diuretics and  blockers)
minimal changes in cardiac output, renal blood flow renin release and glomerular filtration regulation of blood lipid

41. C. Antihypertensive Drugs
3. Adverse effects
first dose phenomenon (postural hypotension)
water and sodium retention

42. C. Antihypertensive Drugs

43. C. Antihypertensive Drugs  and 1 Receptor blockers
Labetalol 拉贝洛尔
Carvedilol 卡维地洛
Amosulalol 氨磺洛尔

44. C. Antihypertensive Drugs  and 1 Receptor blockers
Mild decrease of blood pressure
Minimal changes in cardiac output and heart rate
Used for all kinds of hypertension, including hypertensive emergency
Less adverse effects

45. C. Antihypertensive Drugs Centrally-acting drugs
Clonidine 可乐定

46. C. Antihypertensive Drugs
1. Pharmacological effects
Diminishing central adrenergic outflow
Activating 2 and I1 receptor in medulla
2. Clinical uses
Hypertension: mild to moderate hypertension that has not responded adequately to treatment with diuretics alone.
minimal changes in renal blood flow and glomerular filtration inhibit gastrointestinal secretion and mobility

47. C. Antihypertensive Drugs
3. Adverse effects
central and atropine-like side effects
long-term uses:
water and sodium retention
rebound phenomenon

48. C. Antihypertensive Drugs
I1 receptor agonists
rilmenidine
moxonidine

49. C. Antihypertensive Drugs

50. C. Antihypertensive Drugs
Ganglionic blockers
Trimetaphan(米噻芬)
Mecamylamine（美卡拉明）
Shor-acting
Tolerance
For controlling hypotension

51. C. Antihypertensive Drugs

52. C. Antihypertensive Drugs Noradrenergic nerve ending blockers
Reserpine（利舍平，利血平)
Guanethidine （胍乙啶）
Decresing NE storage in noradrenergic nerve endings
Slow and lasting effects
Central depression

53. C. Antihypertensive Drugs
Vasodilators
Hydralazine
肼曲嗪
Dihydralazine
双肼曲嗪
Sodium Nitroprusside
硝普钠

54. C. Antihypertensive Drugs
Vasodilators
Hydralazine（肼屈嗪）
Dilating arteries and arterioles
Decreasing peripheral resistance
Reflexly elevating heart rate, cardiac output and renin release.
Combined with  blockers and diuretics.
Adverse effects due to vasodilation and lupus-like syndrome can occur.

55. C. Antihypertensive Drugs Nitroprusside sodium（硝普钠）
Dilating small arteries and veins
Used for treatment of emergency hypertension, hypertension with CHF, controlled hypotension and obstinate CHF
Adverse effects due to hypotension in excess and sulfocyanate poisoning.

56. C. Antihypertensive Drugs Potassium channel openers
Including minoxidil, nicorandil, diazoxide, etc.
Dilating arteries (Ca2+ influx )
Reflexly elevating heart rate, cardiac output and renin release
Used for treatment of obstinate and severe hypertension
Adverse effects include sodium retention, palpitation, etc.

57. C. Antihypertensive Drugs

58. D. Rational application of Antihypertensive Drugs
Diuretics
Calcium channel blockers
Regin-angiotensin system inhibitors
Sympathetic inhibitors
Vasodilators

59. D. Rational application of Antihypertensive Drugs
1. Prescribe according to the severity degree of hypertension
(1) Mild: diuretics,  blockers, ACEI, calcium channel blockers, 1 blockers, AT1 blockers, single drug.
(2) Moderate: combined with two above drugs
(3) Severe: adding centrally acting drugs or vasodilators to the two combined drugs

60. D. Rational application of Antihypertensive Drugs
2. Prescribe according to complications
indicated
contraindicated
CHF and/or
COPD
Diuretics, ACEI, prazosin
 Blockers
Renal failure
ACEI, CCB methyldopa
Tachycardia
GI ulcer
Clonidine
Reserpine
Diabetes and gout
ACEI, prazosin
Thiazides

62. D. Rational application of Antihypertensive Drugs
hypertensive emergency: vasodilators (nitroprusside sodium, diazoxide), labetalol, loop diuretics
elderly patients:
avoiding drugs that could induce postural hypotension (1 blocker) and influence the cognizant ability (clonidine, methyldopa)
Cardiac ischemia:
avoiding vasodilators

63. D. Rational application of Antihypertensive Drugs
3. Combination of drugs
4. Avoid blood pressure to decrease too rapidly and excessively
5. Individual therapy