part 3 antihypertensive drugs. hypertension: the most common disease causing various complications
Post on 13-Dec-2015
219 Views
Preview:
TRANSCRIPT
Hypertension:Hypertension:
The most common disease causing various complicationsThe most common disease causing various complications
OverviewOverview Classification ofClassification of antihypertensive drugsantihypertensive drugs Antihypertensive drugsAntihypertensive drugs Rational application ofRational application of antihypertensive drugsantihypertensive drugs
Antihypertensive DrugsAntihypertensive Drugs
A.A. Overview Overview
HypertensionHypertension essential hypertension essential hypertension ~ ~ 90%90%
secondary hypertension secondary hypertension ~ ~ 10%10%
CriterionCriterion of hypertension: of hypertension: diastolic blood pressure diastolic blood pressure 90 mmHg 90 mmHg
systolic blood pressure systolic blood pressure 140 mmHg 140 mmHg
Major factors influencing blood pressureMajor factors influencing blood pressure
Arterial bloodArterial blood pressurepressure
Cardiac Cardiac outputoutput
Peripheral Peripheral resistanceresistance
Venous Venous tonetone
Blood Blood volumevolume
Filling Filling pressurepressure
ContractilityContractilityHeart Heart raterate
arteriolararteriolartonetone
Baroreceptors and sympathetic nervous systemBaroreceptors and sympathetic nervous system Renin-angiotention-aldosterol system (RAAS)Renin-angiotention-aldosterol system (RAAS)
A.A. Overview Overview
Regulation of blood pressure Regulation of blood pressure (neural & endocrine pathways)(neural & endocrine pathways)
Regulation of Regulation of blood pressure: blood pressure:
Targets of Targets of antihypertensive antihypertensive drugsdrugs
SympatheticSympathetic
Endocrine/body fluidEndocrine/body fluid
Peripheral resistance and vascular tone and elasticity Peripheral resistance and vascular tone and elasticity
DiureticsDiuretics
Sympathetic nervous system inhibitorSympathetic nervous system inhibitors s mainly, adrenoceptor antagonistsmainly, adrenoceptor antagonists
Calcium channel blockersCalcium channel blockers
Regin-angiotensin system inhibitorsRegin-angiotensin system inhibitors
OthersOthers Central antihypertensive drugsCentral antihypertensive drugs VasodilatorsVasodilators
B.B. Classification of Antihypertensive Drugs Classification of Antihypertensive Drugs
Noradrenergic Noradrenergic nerve endingnerve ending blockersblockers
RAAS inhibitorsRAAS inhibitors
1. ACEIs1. ACEIs
2. AT2. AT11 blockers blockers
3. Renin inhibitors3. Renin inhibitors
Commonly used antihypertensive drugsCommonly used antihypertensive drugs(1) Diuretics:(1) Diuretics: HydrochlorothiazideHydrochlorothiazide
(2) Calcium antagonists:(2) Calcium antagonists: Nifedipine, amolodipine, verapamil, Nifedipine, amolodipine, verapamil, etcetc..(3) Angiotensin receptor antagonists:Ⅱ(3) Angiotensin receptor antagonists:Ⅱ Lasartan, Lasartan, etc.etc.
(4) Angiotensin-converting enzyme inhibitors:(4) Angiotensin-converting enzyme inhibitors: Captopril, enalapril, Captopril, enalapril, etcetc..
(5) (5) -Blockers:-Blockers: Propranolol, Propranolol, etcetc..
(6) (6) 11-Blockers:-Blockers: Prazosin, doxazosin, Prazosin, doxazosin, etcetc..
(7) Other sympatholytics:(7) Other sympatholytics: Clonidine, Clonidine, etcetc..
(8) Potassium channel agonists:(8) Potassium channel agonists: Minoxidil, diazoxide, Minoxidil, diazoxide, etcetc..
(9) Vasodilators:(9) Vasodilators: Sodium nitroprusside, Sodium nitroprusside, etc.etc.
DiureticsDiuretics
1. 1. Pharmacological effectsPharmacological effects
(1) Reducing plasma volume ((1) Reducing plasma volume (cardiac output cardiac output ))
(2) Reducing Na(2) Reducing Na++-Ca-Ca2+2+ exchange in vascular smooth exchange in vascular smooth
muscle cellsmuscle cells ((CaCa2+2+ii , peripheral resistance , peripheral resistance ) )
C. C. Antihypertensive Drugs Antihypertensive Drugs
NaNa++-Ca-Ca2+2+ exchange exchange , , CaCa2+2+
ii in vascular in vascular
smooth muscle cells smooth muscle cells
2. 2. Clinical usesClinical uses
(1) Hypertension(1) Hypertension
singlesingle or or combinedcombined with other drugs with other drugs
mild to moderate hypertensionmild to moderate hypertension
particularly useful in the treatment of elderly patients, particularly useful in the treatment of elderly patients, pure systolic hypertension, hypertension with heart pure systolic hypertension, hypertension with heart failurefailure
(2) Other uses:(2) Other uses: diuretic, diuretic, etc.etc.
C. C. Antihypertensive Drugs Antihypertensive Drugs
3. 3. Adverse effectsAdverse effects
plasma levels of renin plasma levels of renin
hypokalemiahypokalemia
hyperuricemia hyperuricemia
hyperglycemiahyperglycemia
hyperlipidemiahyperlipidemia
C. C. Antihypertensive Drugs Antihypertensive Drugs
Calcium channel blockersCalcium channel blockers
1. 1. Pharmacological effectsPharmacological effects Relaxing vascular smooth musclesRelaxing vascular smooth muscles
2. 2. Clinical usesClinical uses Mild to severe hypertension (usually combined Mild to severe hypertension (usually combined
with with receptor blockers ) receptor blockers )
C. C. Antihypertensive Drugs Antihypertensive Drugs
Nifedipine Nifedipine 硝苯地平硝苯地平
3.3. Adverse effects Adverse effects Peripheral edemaPeripheral edema Reflex sympathetic activationReflex sympathetic activation Renin activity Renin activity
Other calcium channel blockers:Other calcium channel blockers: amlamlodipine, odipine, etc.etc.
C. C. Antihypertensive Drugs Antihypertensive Drugs
Renin-angiotensin system inhibitorsRenin-angiotensin system inhibitors
ACEIs: ACEIs: captopril captopril 卡托普利卡托普利 , enalapril , enalapril 依那普利依那普利
ATAT11 receptor antagonists receptor antagonists :: losartan losartan 氯沙坦氯沙坦
Renin inhibitors: Renin inhibitors: enalkiren enalkiren 依那吉仑依那吉仑
C. C. Antihypertensive Drugs Antihypertensive Drugs
Angiotensin converting enzymeAngiotensin converting enzyme
AngiotensinogenAngiotensinogen
Angiotensin IAngiotensin I (decapeptide) (decapeptide)
Angiotensin IIAngiotensin II ( octapepetide) ( octapepetide)
Angiotension III (hepAngiotension III (heptapeptide)tapeptide)
Renin-Angiotensin-Aldosterone system (RAAS)Renin-Angiotensin-Aldosterone system (RAAS)
ReninRenin
Angiotensinase AAngiotensinase A
Adrenal cortex Adrenal cortex
AldosteroneAldosterone
• Constricting vessels, increase peripheral resistConstricting vessels, increase peripheral resistance and returned blood volume.ance and returned blood volume.
• Increasing sympathetic tension, promoting relIncreasing sympathetic tension, promoting release of sympathetic transmitter.ease of sympathetic transmitter.
• Stimulating release of aldosteroneStimulating release of aldosterone..
• Inducing expression of Inducing expression of c-fosc-fos 、、 c-mycc-myc、、 c-jun c-jun rapidly.rapidly.
Actions of angiotensin ⅡActions of angiotensin Ⅱ
C. C. Antihypertensive Drugs Antihypertensive Drugs
ACEIsACEIs
1. 1. Pharmacological effectsPharmacological effects Inhibiting the production of Ang IIInhibiting the production of Ang II
Inhibiting the degradation of bradykinin Inhibiting the degradation of bradykinin
Increasing ANP and scavenge free radicalsIncreasing ANP and scavenge free radicals
C. C. Antihypertensive Drugs Antihypertensive Drugs
Implications of inhibition of RAAS Implications of inhibition of RAAS
ATAT11 blockers blockers
(-)(-) (+)(+)
ACEIsACEIsACEIsACEIs
Smooth muscle hypertrophySmooth muscle hypertrophy
((vascular remodelingvascular remodeling))
2. 2. Clinical usesClinical uses
HypertensionHypertension
without reflex increase in the activity of without reflex increase in the activity of
sympathetic systemsympathetic system
effective in the management of patients with effective in the management of patients with CHF, diabetes and ischemic heart disease.CHF, diabetes and ischemic heart disease.
C. C. Antihypertensive Drugs Antihypertensive Drugs
3. 3. Adverse effectsAdverse effects
hypotension hypotension ( first dose phenomenon )( first dose phenomenon )
renal injuryrenal injury dry coughdry cough hyperkalemiahyperkalemia angioneuroedemaangioneuroedema rashes and altered tastesrashes and altered tastesContraindications:Contraindications: renal artery stenosis, p renal artery stenosis, p
regnant and lactational womenregnant and lactational women
C. C. Antihypertensive Drugs Antihypertensive Drugs
ATAT11 receptor antagonists receptor antagonists
(angiotensin II receptor antagonist)(angiotensin II receptor antagonist)
C. C. Antihypertensive Drugs Antihypertensive Drugs
Losartan Losartan 氯沙坦氯沙坦
ATAT11 receptor antagonists receptor antagonists
Compared with ACEI:Compared with ACEI:
• Block actions of angiotensin II directlyBlock actions of angiotensin II directly
• Not influence bradykinin metabolismNot influence bradykinin metabolism
• Protect renal functionProtect renal function
• Used for mild to moderate hypertension Used for mild to moderate hypertension
• Less adverse effects Less adverse effects
C. C. Antihypertensive Drugs Antihypertensive Drugs
Renin inhibitorsRenin inhibitors• enalkirenenalkiren 依那吉仑依那吉仑
• Inhibiting whole RAASInhibiting whole RAAS
• Including Including renin antibody, peptide and nonpeprenin antibody, peptide and nonpeptide renin inhibitorstide renin inhibitors
C. C. Antihypertensive Drugs Antihypertensive Drugs
Sympathetic system inhibitorsSympathetic system inhibitors
CentrallyCentrally acting adrenergic drugs acting adrenergic drugs GanglionGanglion blockers blockers Noradrenergic nerve endingNoradrenergic nerve ending blockers blockers AdrenoreceptorAdrenoreceptor blockers blockers receptor blockersreceptor blockers
receptor blockersreceptor blockers
and and receptor blockers receptor blockers
C. C. Antihypertensive Drugs Antihypertensive Drugs
Sympathetic system: Sympathetic system: Targets of antihypertensive drugsTargets of antihypertensive drugs
Adrenoreceptor blockersAdrenoreceptor blockers
Receptor blockersReceptor blockers
1. 1. Pharmacological effectsPharmacological effects(1) Decreasing cardiac output(1) Decreasing cardiac output
(2) Decreasing sympathetic outflow from CNS and releasing of (2) Decreasing sympathetic outflow from CNS and releasing of noradrenalin from peripheral nerve endingsnoradrenalin from peripheral nerve endings
(3) Inhibiting the release of renin from kidney (formation of an(3) Inhibiting the release of renin from kidney (formation of angiotension and secretion of aldosterone)giotension and secretion of aldosterone)
(4) Increasing production of PGI(4) Increasing production of PGI22
(5) Increasing sensitivity of baroreceptor(5) Increasing sensitivity of baroreceptor
C. C. Antihypertensive Drugs Antihypertensive Drugs
Main actions of Main actions of ββ receptor blockers on blood pressure receptor blockers on blood pressure
3. 3. Clinical usesClinical uses
(1) Hypertension:(1) Hypertension: all kinds of hypertension all kinds of hypertension
more effective in young patients than elderlymore effective in young patients than elderly
useful in treating coexisting conditions such as supruseful in treating coexisting conditions such as supraventricular tachycardia, previous myocardial infaraventricular tachycardia, previous myocardial infarction, angina pectoris, glaucoma and migraine headction, angina pectoris, glaucoma and migraine headacheache
(2) Other uses:(2) Other uses: angina pectoris; arrhythmias angina pectoris; arrhythmias
C. C. Antihypertensive Drugs Antihypertensive Drugs
3.3. Adverse effects Adverse effects
alterations in serum lipid patternsalterations in serum lipid patterns drug withdrawal reactionsdrug withdrawal reactions worsening asthma & COPDworsening asthma & COPD cardiac depressioncardiac depression
C. C. Antihypertensive Drugs Antihypertensive Drugs
1 1 Receptor blockers Receptor blockers
C. C. Antihypertensive Drugs Antihypertensive Drugs
Prazosin Prazosin 哌唑嗪哌唑嗪 Terazosin Terazosin 特拉唑嗪特拉唑嗪
Doxazosin Doxazosin 多沙唑嗪多沙唑嗪 Trimazosin Trimazosin 曲马唑嗪曲马唑嗪
1 1 Receptor blockers Receptor blockers
1. 1. Pharmacological effectsPharmacological effects RelaxingRelaxing arterial and venous smooth muscles arterial and venous smooth muscles DecreasingDecreasing peripheral resistance peripheral resistance
2.2. Clinical uses Clinical uses Hypertension:Hypertension: mild to moderate (single) and seve mild to moderate (single) and seve
re hypertension (combined with diuretics and re hypertension (combined with diuretics and blockers)blockers)
minimal changes in cardiac output, renal blood flow reminimal changes in cardiac output, renal blood flow renin release and glomerular filtration regulation of bloonin release and glomerular filtration regulation of blood lipidd lipid
C. C. Antihypertensive Drugs Antihypertensive Drugs
3.3. Adverse effects Adverse effects
first dose phenomenonfirst dose phenomenon (postural hypotension)(postural hypotension)
water and sodium retentionwater and sodium retention
C. C. Antihypertensive Drugs Antihypertensive Drugs
and and 1 1 Receptor blockersReceptor blockers
C. C. Antihypertensive Drugs Antihypertensive Drugs
Labetalol Labetalol 拉贝洛尔拉贝洛尔
Carvedilol Carvedilol 卡维地洛卡维地洛
Amosulalol Amosulalol 氨磺洛尔氨磺洛尔
and and 1 1 Receptor blockersReceptor blockers
Mild decrease of blood pressureMild decrease of blood pressure Minimal changes in cardiac output and heart rateMinimal changes in cardiac output and heart rate Used for all kinds of hypertension, including Used for all kinds of hypertension, including
hypertensive emergencyhypertensive emergency Less adverse effectsLess adverse effects
C. C. Antihypertensive Drugs Antihypertensive Drugs
Centrally acting drugsCentrally acting drugs
C. C. Antihypertensive Drugs Antihypertensive Drugs
Clonidine Clonidine 可乐定可乐定
Methyldopa Methyldopa 甲基多巴甲基多巴
Clonidine MethyldopaClonidine Methyldopa
1. 1. Pharmacological effectsPharmacological effects Diminishing central adrenergic outflowDiminishing central adrenergic outflow
Activating Activating 2 2 and Iand I11 receptor in medulla receptor in medulla
2.2. Clinical uses Clinical uses Hypertension:Hypertension: mild to moderate hypertension that mild to moderate hypertension that
has not has not respondedresponded adequately to treatment with di adequately to treatment with diuretics alone.uretics alone.
minimal changes in renal blood flow and glomerular filtraminimal changes in renal blood flow and glomerular filtra
tion inhibit gastrointestinal secretion and mobilitytion inhibit gastrointestinal secretion and mobility
C. C. Antihypertensive Drugs Antihypertensive Drugs
3. 3. Adverse effectsAdverse effects
central and atropine-like side effectscentral and atropine-like side effects
long-term uses: long-term uses:
water and sodium retention water and sodium retention
rebound phenomenonrebound phenomenon
C. C. Antihypertensive Drugs Antihypertensive Drugs
II11 receptor agonists receptor agonists
rilmenidine rilmenidine (利美尼定)(利美尼定)
moxonidine moxonidine (莫索尼定)(莫索尼定)
C. C. Antihypertensive Drugs Antihypertensive Drugs
Ganglionic blockersGanglionic blockers
Trimetaphan Trimetaphan (( 米噻芬米噻芬 ))
MecamylamineMecamylamine (美卡拉明)(美卡拉明)
Shor-actingShor-acting
ToleranceTolerance
For controlling hypotensionFor controlling hypotension
C. C. Antihypertensive Drugs Antihypertensive Drugs
Noradrenergic nerve ending blockersNoradrenergic nerve ending blockers
ReserpineReserpine (利舍平,利血平(利舍平,利血平 ))
Guanethidine Guanethidine (胍乙啶)(胍乙啶)
Decreasing NE storage in noradrenergic nerve endingsDecreasing NE storage in noradrenergic nerve endings
Slow and lasting effectsSlow and lasting effects
Central depressionCentral depression
C. C. Antihypertensive Drugs Antihypertensive Drugs
C. C. Antihypertensive Drugs Antihypertensive Drugs
Hydralazine Hydralazine
肼曲嗪肼曲嗪
Dihydralazine Dihydralazine
双肼曲嗪双肼曲嗪
Sodium NitroprussideSodium Nitroprusside
硝普钠硝普钠
VasodilatorsVasodilators
VasodilatorsVasodilators
HydralazineHydralazine (肼屈嗪)(肼屈嗪)
Dilating arteries and arteriolesDilating arteries and arterioles Decreasing peripheral resistanceDecreasing peripheral resistance Reflexly elevating heart rate, cardiac output and Reflexly elevating heart rate, cardiac output and
renin release.renin release. Combined with Combined with blockers and diuretics. blockers and diuretics. Adverse effects due to vasodilation and lupus-like Adverse effects due to vasodilation and lupus-like
syndrome can occur.syndrome can occur.
C. C. Antihypertensive Drugs Antihypertensive Drugs
Nitroprusside sodiumNitroprusside sodium (硝普钠)(硝普钠)
Dilating small arteries and veins Dilating small arteries and veins Used for treatment of emergency hypertension, Used for treatment of emergency hypertension,
hypertension with CHF, controlled hypotension hypertension with CHF, controlled hypotension and obstinate CHF and obstinate CHF
Adverse effects due to hypotension in excess anAdverse effects due to hypotension in excess an
d sulfocyanate d sulfocyanate (( 硫氰酸盐 )) poisoning. poisoning.
C. C. Antihypertensive Drugs Antihypertensive Drugs
Potassium channel openersPotassium channel openers
IncludingIncluding minoxidil minoxidil (( 米诺地尔米诺地尔 )), nicorandil, diazoxi, nicorandil, diazoxide de (( 二氮嗪二氮嗪 )), , etcetc..
Dilating arteries (CaDilating arteries (Ca2+2+ influx influx )) Reflexly elevating heart rate, cardiac output and Reflexly elevating heart rate, cardiac output and
renin releaserenin release Used for treatment of obstinate and severe hyperUsed for treatment of obstinate and severe hyper
tensiontension Adverse effects include sodium retention, palpitaAdverse effects include sodium retention, palpita
tion, tion, etcetc..
C. C. Antihypertensive Drugs Antihypertensive Drugs
D. D. Rational application of Rational application of Antihypertensive DrugsAntihypertensive Drugs
DiureticsDiuretics
Calcium channel blockersCalcium channel blockers
Regin-angiotensin system inhibitorsRegin-angiotensin system inhibitors
Sympathetic inhibitorsSympathetic inhibitors
VasodilatorsVasodilators
1. 1. Prescribe according to the severity degree of Prescribe according to the severity degree of hypertensionhypertension
(1) Mild:(1) Mild: diuretics, diuretics, blockers, blockers, ACEI, calcium channel ACEI, calcium channel blockers (CCB), blockers (CCB), 11 blockers, AT blockers, AT11 blockers, blockers, single single
drug.drug.
(2) Moderate:(2) Moderate: combined with combined with two above drugstwo above drugs
(3) Severe:(3) Severe: adding centrally acting drugs or adding centrally acting drugs or vasodilators to the vasodilators to the two combined drugstwo combined drugs
D. D. Rational application of Rational application of Antihypertensive DrugsAntihypertensive Drugs
2.2. Prescribe according to complications Prescribe according to complications
CHF and/or CHF and/or
COPDCOPDDiuretics, ACEI, CCDiuretics, ACEI, CCB, prazosinB, prazosin
BlockersBlockers
Renal failureRenal failureACEI, CCB ACEI, CCB methyldopamethyldopa
TachycardiaTachycardia BlockersBlockers
GI ulcerGI ulcer ClonidineClonidine ReserpineReserpine
Diabetes and Diabetes and goutgout
ACEI, prazosin, CCACEI, prazosin, CCBB
Thiazides Thiazides
D. D. Rational application of Rational application of Antihypertensive DrugsAntihypertensive Drugs
indicatedindicated contraindicatedcontraindicated
hypertensive emergency:hypertensive emergency: vasodilators (nitroprussvasodilators (nitroprusside sodium, diazoxide), loop diuretics (furoseide sodium, diazoxide), loop diuretics (furosemide)mide)
elderly patients:elderly patients: avoiding drugs that could induce postural hyavoiding drugs that could induce postural hy
potension (potension (11 blocker, larger dose of diuretic blocker, larger dose of diureticss) and influence the cognizant ability () and influence the cognizant ability (clonidiclonidinene))
Cardiac ischemia:Cardiac ischemia: avoiding vasodilatorsavoiding vasodilators
D. D. Rational application of Rational application of Antihypertensive DrugsAntihypertensive Drugs
3.3. Combination of drugs Combination of drugs
4.4. Avoid blood pressure to decrease too Avoid blood pressure to decrease too rapidly and excessivelyrapidly and excessively
5.5. Individual therapy Individual therapy
D. D. Rational application of Rational application of Antihypertensive DrugsAntihypertensive Drugs
top related