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Antihypertensive Drugs

Antihypertensive Drugs. Overview Classification of antihypertensive drugs Antihypertensive drugs Rational application of antihypertensive drugs. A. Overview. Hypertension essential hypertension secondary hypertension Criterion of hypertension:

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Antihypertensive Drugs

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  1. Antihypertensive Drugs

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

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

  4. Major factors influencing blood pressure Arterial blood pressure  Cardiac output Peripheral resistance arteriolar tone  Blood volume Heart rate Filling pressure Contractility 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. 血管运动中枢 交感神经末梢 Sites of action of the major classes of antihypertensive drugs. 交感神经节 肾小球旁细胞

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

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

  16. C. Antihypertensive Drugs

  17. 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

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

  19. C. Antihypertensive Drugs ACEIs

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

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

  22. 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.

  23. 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

  24. C. Antihypertensive Drugs AT1 antagonists Losartan氯沙坦

  25. 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

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

  27. C. Antihypertensive Drugs

  28. 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

  29. C. Antihypertensive Drugs Adrenoreceptor blockers  Receptor 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(压力感受器)

  30. Main actions of β receptor antagonists on blood pressure

  31. 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

  32. C. Antihypertensive Drugs 3. Adverse effects Alterations in serum lipid patterns Drug withdrawal Cardiac depression

  33. C. Antihypertensive Drugs

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

  35. 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

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

  37. C. Antihypertensive Drugs

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

  39. 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

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

  41. C. Antihypertensive Drugs 1. Pharmacological effects • Diminishing central adrenergic outflow Activating I1 receptor in medulla –降压 Activating 2 receptor in medulla—嗜睡 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

  42. C. Antihypertensive Drugs 3. Adverse effects central and atropine-like side effects long-term uses: water and sodium retention rebound phenomenon（反弹现象）

  43. C. Antihypertensive Drugs I1 receptor agonists rilmenidine（利美尼定） moxonidine（莫索尼定）

  44. C. Antihypertensive Drugs

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

  46. C. Antihypertensive Drugs

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