Antihypertensive drugs

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

CLASSES OF DRUGS DRUGSDRUGS TargetsTargets Diuretics Agents act on ANS. Direct Vasodilators CCB RAS blockers (ACEI, AT1B)

Blood Volume Cardiac Output Resistance of Vessel Arterioles RASNeuroregulation

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

Diuretics Clinic usesClinic uses Alone: Mild hypertension United: Mediate & serious ADRADR K Na CE TG LDL Renin activity

RAS blockers ACEI (…pril) Captopril MechanismMechanism Angiotensin Renin AI ACE AII Bradykinin NO,EDHF

Vasoconstriction

Aldosterone

Proliferation

Renin angiotensin aldosterone system, RAAS

AgⅠ AgⅡACEBP↑

aldosterone ↑

心室重构血管重构血管紧

张素原

renin

缓激

肽降解产物

BP↓

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

ANS Blockers Antagonists of β-R Propranolol,Metoprolol, atenolol MechanismMechanism Heart Rate Cardiac Output Rinin, positive feedback-NA Clinic usesClinic uses Mild-mediate hypertension ADRADR

constriction

ANS Blockers sympathetic nerve inhibitor 1.Central hypotensive drugs:clonidine2.Ganglion blockers:mecamylamine3.Drugs affecting NA stores or release • Reserpine; Quanethidine4. Adrenoceptor blokers • Antagonists of α-R: Prazosin, Urapidil • Antagonists of α, β –R:Labetalol

Calcium antagonists Target at vascular smooth muscl

e • nifedipine • amlodipine • tetrandrine

Direct Vasodilators Sodium nitroprusside MechanismMechanism 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 onlyRapid onset(<2min)Cease in 5 min

Direct Vasodilators Potassium Channel Openers Pinacidil MechanismMechanism K hyperpolarization Ca Clinic useClinic use mild-midiate hypertention ADR ADR edema

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 ___ /-------.