1. Antihypertensive drugs

2. BACKGROUND NBP 120-90/90-60mmHg, Affecting factors: Volume of blood, Cardiac Output, resistance of Arterioles HBP SBP>140/ DBP>90 mmHg Morbidity 30% CLASSES OF HYPERTENISON Essential hypertension Secondary hypertension

3. CLASSES OF DRUGS DRUGSTargets DRUGS Targets Diuretics Agents act on ANS. Direct Vasodilators CCB RAS blockers (ACEI, AT 1 B) Blood Volume Cardiac Output Resistance of Vessel Arterioles RAS Neuroregulation

4. Diuretics Agents Furosemide (Lasix) thiazides Mechanism Mechanism  Blood Volume  Na Na Ca Ca  Na PGE2, Kinin  reactivity to vaso-excitor material(NA)

5. Diuretics Clinic uses Clinic uses  Alone: Mild hypertension  United: Mediate & serious ADR ADR  K Na  CE TG LDL  Renin activity

6. RAS blockers ACEI ( … pril) Captopril Mechanism Mechanism  Angiotensin Renin AI ACE AII  Bradykinin NO,EDHF Vasoconstriction Aldosterone Proliferation

7. Renin angiotensin aldosterone system, RAAS Ag Ⅰ Ag Ⅱ ACE BP↑ aldosterone ↑ 心室重构 血管重构 血管紧 张素原 renin 降解产物 BP↓

8. RAS blockers Clinic uses: Clinic uses: hypertension & CHF ADR ADR  Hypotension  Dry Cough  Hyperkalaemia  Antagonists of AT1 Losartan AII: AT1-R, AT2-R

9. ANS Blockers Antagonists of β-R Propranolol,Metoprolol, atenolol Mechanism Mechanism Heart Rate Cardiac Output Rinin, positive feedback-NA Clinic uses Clinic uses Mild-mediate hypertension ADR ADR constriction

10. ANS Blockers sympathetic nerve inhibitor 1.Central hypotensive drugs:clonidine 2.Ganglion blockers:mecamylamine 3.Drugs affecting NA stores or release Reserpine; Quanethidine 4. Adrenoceptor blokers Antagonists of α-R: Prazosin, Urapidil Antagonists of α, β – R:Labetalol

11. Calcium antagonists Target at vascular smooth muscle nifedipine amlodipine tetrandrine

12. Direct Vasodilators Sodium nitroprusside Mechanism Mechanism NO Pharmacokinetics(P.K.) Pharmacokinetics(P.K.) P.E. P.E. Directly on a. & v. Clinic uses Clinic uses Serious hypertension ADR : ADR : hypotension, thiocyanate toxicity ivgtt only Rapid onset(<2 min ) Cease in 5 min

13. Direct Vasodilators Potassium Channel Openers Pinacidil Mechanism Mechanism K hyperpolarization Ca Clinic use Clinic use mild-midiate hypertention ADR ADR edema

14. Review & questions Classes of antihypertensive Agents & main mechanisms of each. Serious hypertension use ____ first. Common ADR of them is ____. Mild hypertension use ___ first, if no use, add ___ / -------.