Hypertension outline Hypertension Definition, classification Prevalence Complications Contributing factors Update on VIIth report of the JNC Drugs that lower blood pressure

hypertensinsive agents

1. Antihypertensive AgentsAntihypertensive Agents
Emel Songu-Mize, PhDEmel Songu-Mize, PhD
568-2240568-2240
[email protected]@lsuhsc.edu

2. Lecture OutlineLecture Outline

HypertensionHypertension

Definition, classificationDefinition, classification

PrevalencePrevalence

ComplicationsComplications

Contributing factorsContributing factors

Update on VIIUpdate on VII
thth
report of the JNC report of the JNC

Drugs that lower blood pressureDrugs that lower blood pressure

3. Blood Pressure ClassificationBlood Pressure Classification
ClassificationClassification SBP (SBP (mmHgmmHg))DBPDBP ((mmHgmmHg))
____________________________________________________________________________________________________________
NormalNormal <120<120 andand <80<80
PrehypertensionPrehypertension 120–139120–139 or or 80–8980–89
HypertensionHypertension >140/90>140/90
Stage 1 HypertensionStage 1 Hypertension 140–159140–159 or or 90–9990–99
Stage 2 HypertensionStage 2 Hypertension >>160160 or or >>100100
__________________________________________________________________________________________

4. Essential HypertensionEssential Hypertension
In 90–95% of cases the cause isn'tIn 90–95% of cases the cause isn't
known = ESSENTIAL HYPERTENSIONknown = ESSENTIAL HYPERTENSION
Symptomatic treatment, i.e. reduceSymptomatic treatment, i.e. reduce
blood pressure. No real cure yet.blood pressure. No real cure yet.

5. Identifiable Causes of Identifiable Causes of
Secondary HypertensionSecondary Hypertension
Sleep apnea
Drug-induced or related causes
Chronic kidney disease
Primary aldosteronism
Renovascular disease
Chronic steroid therapy and Cushing’s
syndrome
Pheochromocytoma
Coarctation of the aorta
Thyroid or parathyroid disease

6. Prevalence Prevalence

High in this country: 50% of adults, High in this country: 50% of adults,
60% of whites, 71% of African 60% of whites, 71% of African
Americans, 61% Mexican Americans Americans, 61% Mexican Americans
over the age of 60over the age of 60

More prevalent in men than in More prevalent in men than in
womenwomen

Highest prevalence in elderly Highest prevalence in elderly
African-American femalesAfrican-American females

7. ComplicationsComplications

Cardiovascular systemCardiovascular system

CNSCNS

Renal systemRenal system

Retinal damageRetinal damage

8. Target Organ DamageTarget Organ Damage
Heart
 Left ventricular hypertrophy
 Coronary artery disease
 Myocardial infarcts
 Heart failure
Brain
 Stroke or transient ischemic
attacks
Chronic kidney disease, kidney failure
Retinopathy

9. Contributing FactorsContributing Factors

ObesityObesity

StressStress

Lack of exerciseLack of exercise

Diet (excess dietary salt)Diet (excess dietary salt)

Alcohol intakeAlcohol intake

Cigarette smokingCigarette smoking

10. National Heart Lung Blood Institute National Heart Lung Blood Institute
National High Blood Pressure National High Blood Pressure
Education ProgramEducation Program
The Seventh Report of the The Seventh Report of the JJoint oint
NNational ational CCommittee on Prevention, ommittee on Prevention,
Detection, Evaluation, and Treatment Detection, Evaluation, and Treatment
of High Blood Pressure (JNC 7, 2003)of High Blood Pressure (JNC 7, 2003)
http://www.nhlbi.nih.gov/guidelines/hypertension/http://www.nhlbi.nih.gov/guidelines/hypertension/
index.htmindex.htm

11. Why Guidelines for
Hypertension?
50 million people with hypertension
in USA 10 years ago – 1:4 overall
(Currently 31 %), half of people > age 60
Only 1 in 2 on drug treatment
to lower BP
Only 1 in 4 age 18-74 controlled to
<140/<90 in USA

13. New BP Goals
 <140/<90 and lower if tolerated
 <130/<80 in diabetics
 <130/<85 in cardiac failure
 <130/<85 in renal failure
 <125/<75 in renal failure with
proteinuria>1.0 g/24 hours

14. Highlights of Current
Guidelines
JNC, WHO/ISH, BHS,
Canada, and More
 New aggressive treatment
strategies based on a patient’s
medical profile
 Treat to goal and hit the target,
not to be satisfied with less

15. Treatment OverviewTreatment Overview
Goals of therapy
Lifestyle modification
Pharmacologic treatment
 Algorithm for treatment of
hypertension
Classification and management of
BP for adults
Follow-up and monitoring

16. Lifestyle ModificationsLifestyle Modifications

Reduce weight to normal BMI Reduce weight to normal BMI
(<25kg/m(<25kg/m
22
): 5-20 mmHg/10kg loss): 5-20 mmHg/10kg loss

DASH eating plan: 8-14 mmHgDASH eating plan: 8-14 mmHg

Dietary sodium reduction: 2-8 mmHgDietary sodium reduction: 2-8 mmHg

Increase physical activity: 4-9 mmHgIncrease physical activity: 4-9 mmHg

Reduce alcohol consumption: 2- 4 Reduce alcohol consumption: 2- 4
mmHgmmHg

17. DASH Diet
Dietary
Approaches
to
Stop
Hypertension
• Emphasizes: Fruits,
vegetables, low fat dairy
foods, and reduced
sodium intake
• Includes whole grains,
poultry, fish, nuts
• Reduced amounts of red
meat, sugar, total and
saturated fat, and
cholesterol
Sacks FM et al: NEJM 344;3-10, 2001

18. Algorithm for Treatment of HypertensionAlgorithm for Treatment of Hypertension
Not at Goal Blood Pressure (<140/90 mmHg)
(<130/80 mmHg for those with diabetes or chronic kidney disease)
Initial Drug Choices
Drug(s) for the compelling
indications
Other antihypertensive drugs
(diuretics, ACEI, ARB, BB, CCB)
as needed.
With Compelling
Indications
Lifestyle Modifications
Stage 2 Hypertension
(SBP >160 or DBP >100 mmHg)
2-drug combination for most
(usually thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
Stage 1 Hypertension
(SBP 140–159 or DBP 90–99
mmHg)
Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.
Without Compelling
Indications
Not at Goal
Blood Pressure
Optimize dosages or add additional drugs
until goal blood pressure is achieved.
Consider consultation with hypertension
specialist.

19. Renal
function
Blood
volume
Venous
tone
Venous
return
Heart
rate
Nervous
control
Muscular
responsiveness
Myocardial
contractility
Stroke
volume
Cardiac
output
CNS
factors
Renin
release
Angiontensin II
formation
Intrinsic vascular
responsiveness
Peripheral
resistance
Nervous
control
Renal
function
Mean arterial
pressure
Factors that Govern
the Mean Arterial
Pressure

20. Mean Arterial PressureMean Arterial Pressure
MAP = MAP = COCO
CO = HR X SVCO = HR X SV
SNSSNS Blood Blood
volumevolume
Heart Heart
contactilitycontactility
Venous toneVenous tone

X X PVRPVR
myogenic tonemyogenic tone
vascular vascular
responsivenesresponsivenes
nervous controlnervous control
vasoactive vasoactive
metabolitesmetabolites
endothelial factorsendothelial factors
circulating hormonescirculating hormones

21. Antihypertensive DrugsAntihypertensive Drugs
ClassificationClassification

DiureticsDiuretics

Agents affecting adrenergic Agents affecting adrenergic
functionfunction

VasodilatorsVasodilators

Agents affecting Agents affecting RRenin enin
AAngiotensin ngiotensin SSystem (RAS)ystem (RAS)

22. DiureticsDiuretics
Used as initial therapy alone or in combination with Used as initial therapy alone or in combination with
drugs from other groupsdrugs from other groups
Adverse effects: renin secretion due to volume and Na Adverse effects: renin secretion due to volume and Na
depletiondepletion


Thiazides:Thiazides: chlorothiazide, hydrochorothiazide chlorothiazide, hydrochorothiazide

Loop Diuretics:Loop Diuretics: furosemide, bumetanide, furosemide, bumetanide,
ethacrynic acidethacrynic acid

Potassium sparing diuretics:Potassium sparing diuretics: spironolactone, spironolactone,
triamterene, amiloridetriamterene, amiloride

23. About Diuretics
Antihypertensive and Lipid Lowering Treatment to
Prevent Heart Attack Trial (ALLHAT): Diuretics
have been virtually unsurpassed in preventing the
cardiovascular complications of hypertension.

Diuretics enhance the antihypertensive efficacy of
multidrug regimens, can be useful in achieving BP
control, and are more affordable than other anti-
hypertensive agents.
Despite these findings, diuretics remain under-
utilized.

24. Agents that affect Agents that affect
adrenergic functionadrenergic function
a)a)Agents that prevent adrenergic Agents that prevent adrenergic
transmission transmission (reserpine, guanethedine, (reserpine, guanethedine,
guanadrel)guanadrel)
b)b)Selective alpha-1 adrenergic receptor Selective alpha-1 adrenergic receptor
blockers blockers (prazosin, terazosin, doxazosin)(prazosin, terazosin, doxazosin)
c)c)Beta-adrenergic blocking agents Beta-adrenergic blocking agents
(propranolol and others)(propranolol and others)
d)d)Agents that act on the CNS Agents that act on the CNS (methyldopa, (methyldopa,
clonidine, guanabenz, guanfacine)clonidine, guanabenz, guanfacine)

25. a) a) Agents that prevent adrenergic Agents that prevent adrenergic
transmission:transmission: Reserpine (Serpasil)Reserpine (Serpasil)

Mechanism:Mechanism: depletes neurotransmitters (NE, depletes neurotransmitters (NE,
DA, 5HT) in the storage vesicle of the DA, 5HT) in the storage vesicle of the centralcentral
and and peripheralperipheral nerve endings nerve endings

Main effects:Main effects: depress SNS function centrally and depress SNS function centrally and
peripherally peripherally  decreased HR, contractility and decreased HR, contractility and
PVRPVR

Adverse effects:Adverse effects: depressiondepression, insomnia, , insomnia,
nightmares, ulcers, diarrhea, abdominal nightmares, ulcers, diarrhea, abdominal
cramping, nasal stuffinesscramping, nasal stuffiness, orthostatic orthostatic
hypotensionhypotension, dry mouth,, dry mouth, impotence impotence

Pharmacokinetics:Pharmacokinetics: onset is slow and full effect onset is slow and full effect
is seen in weeksis seen in weeks

Use:Use: infrequently infrequently

26. Mechanism:Mechanism: Depletes the nerve ending of NE Depletes the nerve ending of NE
in the in the peripheryperiphery
Main effects:Main effects: decrease in PVR and decrease decrease in PVR and decrease
in HR in HR  decrease in BP decrease in BP
Adverse effects:Adverse effects: Orthostatic hypotensionOrthostatic hypotension, Na, Na
++

and water retention. Other side-effects and water retention. Other side-effects
similar to reserpine except the CNS effectssimilar to reserpine except the CNS effects
Pharmacokinetics:Pharmacokinetics: Poorly absorbed from the Poorly absorbed from the
G.I. Onset slow (1-2 weeks). Metabolites G.I. Onset slow (1-2 weeks). Metabolites
excreted in urineexcreted in urine
Use:Use: Not used anymore because of severe Not used anymore because of severe
side effectsside effects
a) a) Agents that prevent adrenergic Agents that prevent adrenergic
transmission:transmission: Guanethedine (Ismelin)Guanethedine (Ismelin)

27. Mechanism and main effectsMechanism and main effects Similar to Similar to
guanethidineguanethidine
Adverse effects are less than gunethidine: Adverse effects are less than gunethidine:
lessless orthostatic hypotension, orthostatic hypotension, lessless diarrhea, diarrhea,
lessless effect on sexual function. effect on sexual function.
Pharmacokinetics:Pharmacokinetics: better absorption, rapid better absorption, rapid
onset, shorter duration of action than onset, shorter duration of action than
guanethidineguanethidine
a) a) Agents that prevent adrenergic Agents that prevent adrenergic
transmission: transmission: Guanadrel (Hylorel)Guanadrel (Hylorel)

28. b) Selective alpha-1 adrenergic b) Selective alpha-1 adrenergic
receptor blockers receptor blockers (prazosin-(prazosin-MinipresMinipres, ,
terazosin-terazosin-HytrinHytrin, doxazosin-, doxazosin-CarduraCardura))
They favorably influence plasma lipid profile, and do not They favorably influence plasma lipid profile, and do not
interfere with glucose metabolisminterfere with glucose metabolism..
Mechanism:Mechanism: block block 1 receptors in vasculature1 receptors in vasculature
Main effects:Main effects: decreased PVR decreased PVR  decrease BP decrease BP
Adverse effects:Adverse effects: 11
stst
dose phenomenon dose phenomenon, fluid , fluid
retention, dizziness, headacheretention, dizziness, headache
Pharmacokinetics:Pharmacokinetics: t t1/21/2= 4.5, 12, 20, respectively= 4.5, 12, 20, respectively
Use:Use: used in stage 1 and stage 2 HT in used in stage 1 and stage 2 HT in
combination with a diuretic and a combination with a diuretic and a -blocker-blocker

29. c) Beta-adrenergic blocking c) Beta-adrenergic blocking
agents agents (see table)(see table)
Classification Classification

Nonselective (Nonselective (11
stst
generation generation))

Cardioselective (Cardioselective (-1 selective, -1 selective, 22
ndnd
generation generation))

blockers with intrinsic sympathomimetic blockers with intrinsic sympathomimetic
activity (ISA)activity (ISA)

With additional CV actions (With additional CV actions (33
rdrd
generation generation))
Proposed mechanisms: Proposed mechanisms:
Block cardiac Block cardiac 1 receptors 1 receptors  lower CO lower CO
Block renal Block renal 1 receptors 1 receptors  lower renin, lower renin,
lower PVRlower PVR
Decrease SNS outputDecrease SNS output

30. Non-Selective

Propranolol
Timolol (hydrophylic)
*Pindolol
*Penbutolol
*Cartelol
*Labetalol ( & )
Carvedilol ( & )
*Carteolol
1-Selective
(in low dose)
Metoprolol
*Acebutolol
Atenolol (hydrophylic)
Betaxolol
Bisoprolol
(Diabetes and Asthma)
Intrinsic (ISA)
Pindolol
Acebutolol
Penbutolol
Cartelol
Labetalol ( & )
(Reynaud’s)
*has ISA as well
3
rd
generation

31. Propranolol (Inderal)Propranolol (Inderal)
Mechanism: Mechanism:
Block cardiac Block cardiac 1 receptors 1 receptors  lower CO lower CO
Block renal Block renal 1 receptors 1 receptors  lower renin, lower PVR lower renin, lower PVR
Main effects:Main effects: decrease HR and PVR decrease HR and PVR
Adverse effects:Adverse effects: bradycardiabradycardia, depression, , depression, 22
blockade in airwaysblockade in airways, glucose and lipid , glucose and lipid
metabolism, vasoconstriction in extremities metabolism, vasoconstriction in extremities
Pharmacokinetics:Pharmacokinetics: GI, GI, 30-50% metabolized in the30-50% metabolized in the
first-pass in liver. Tfirst-pass in liver. T
1/21/2: 3-5 hours, Slow- release : 3-5 hours, Slow- release
propranolol availablepropranolol available
Use:Use: used in stage 1 and 2 HT alone or in used in stage 1 and 2 HT alone or in
combinations with a diuretic and/or vasodilatorcombinations with a diuretic and/or vasodilator
Drug InteractionsDrug Interactions: verapamil, diltiazem, digitalis : verapamil, diltiazem, digitalis
(caution AV Block)(caution AV Block)

32. Labetalol (Trandate)Labetalol (Trandate)

A combined alpha-1, beta-1, and A combined alpha-1, beta-1, and
beta-2 blocker. Beta blocking beta-2 blocker. Beta blocking
action is more prominent. It also action is more prominent. It also
has some ISA property.has some ISA property.

Can be given Can be given i.v. i.v. for hypertensive for hypertensive
emergencies emergencies

33. d) Agents that act on the CNSd) Agents that act on the CNS
((methyldopamethyldopa--AldometAldomet,, clonidine-clonidine- CatapresCatapres, ,
guanabenzguanabenz--WytensinWytensin, , guanfacineguanfacine--TenexTenex))
Favorable effect: lower PRAFavorable effect: lower PRA
Mechanism:Mechanism: -me-dopa metabolized to -me-dopa metabolized to -me--me-
norepinephrine, an norepinephrine, an -2 agonist, that suppresses -2 agonist, that suppresses
SNS output from the CNS. Others are SNS output from the CNS. Others are -2 agonist -2 agonist
themselves.themselves.
Main effects:Main effects: decreases PVR and HR decreases PVR and HR
Adverse effects:Adverse effects: sedationsedation, drowsiness, dry mouth, , drowsiness, dry mouth,
impotence, bradycardia, withdrawal syndrome impotence, bradycardia, withdrawal syndrome
((rebound HTrebound HT), false (+) Coombs’ antiglobulin test), false (+) Coombs’ antiglobulin test
Pharmacokinetics:Pharmacokinetics: oral or parenteral, transdermal; oral or parenteral, transdermal;
TT1/2 1/2 = 2, 10, 6, 14-17 h, respectively= 2, 10, 6, 14-17 h, respectively
Use:Use: stage 1 and 2 HT stage 1 and 2 HT

34. Vasodilator DrugsVasodilator Drugs
Common adverse effects: fall in BP Common adverse effects: fall in BP  reflex reflex
tachycardia, also fall in BP tachycardia, also fall in BP  renin renin  Na/H Na/H22O O
retentionretention
a)a)Calcium entry blockers Calcium entry blockers (nifedipine (nifedipine
and others)and others)
b)b) Potassium channel openers Potassium channel openers
(minoxidil, diazoxide (minoxidil, diazoxide i.vi.v., pinacidil)., pinacidil)
c)c) Direct acting vasodilators Direct acting vasodilators
(hydralazine, Na-nitroprusside (hydralazine, Na-nitroprusside i.vi.v.).)

35. a) Calcium entry blockersa) Calcium entry blockers
((mechanismmechanism: inhibit Ca entry through L-: inhibit Ca entry through L-
type voltage gated channels)type voltage gated channels)
Phenylalkylamines:Phenylalkylamines: verapamil verapamil
Benzothiazepines:Benzothiazepines: diltiazem diltiazem
Dihydropyridines:Dihydropyridines: nifedipine, nifedipine,
nicardapine, isradapine, nicardapine, isradapine,
felodopine, amlodipinefelodopine, amlodipine

36. Nifedipine Nifedipine (Procardia)(Procardia)
Mech: Mech: selective blockade of selective blockade of vascularvascular Ca Ca
channelschannels
Main effectMain effect:: vasodilatation vasodilatation  lower PVR lower PVR 
lower BPlower BP
Adverse effects:Adverse effects: headache, flushing, headache, flushing,
nausea, nausea, ankle edemaankle edema, dizziness, , dizziness, reflex reflex
tachycardiatachycardia with short acting version with short acting version
(now have Procardia SR)(now have Procardia SR)
((nono reflex tachycardia with reflex tachycardia with verapamilverapamil and and
diltiazemdiltiazem))
Use:Use: Hypertension (more effective in Hypertension (more effective in
African-Americans), angina. Not useful as African-Americans), angina. Not useful as
an antiarrhythmic drug an antiarrhythmic drug

37. Verapamil and DiltiazemVerapamil and Diltiazem
Mechanism:Mechanism: Blockade of Ca channels in the Blockade of Ca channels in the
vasculature, heart muscle and the AV nodevasculature, heart muscle and the AV node
Main effects:Main effects: same as nifedipine group same as nifedipine group
Adverse effectsAdverse effects: Similar to nifedipine except that : Similar to nifedipine except that
they they do notdo not cause reflex tahycardia cause reflex tahycardia
Drug interactionsDrug interactions: Caution for AV block with beta : Caution for AV block with beta
blockers, and digitalisblockers, and digitalis
Use:Use: Hypertension, angina, arrhythmias Hypertension, angina, arrhythmias

38. b) Potassium channel openers b) Potassium channel openers
(minoxidil-(minoxidil-LonitenLoniten, diazoxide , diazoxide i.vi.v.-.-HyperstatHyperstat, ,
pinacidil)pinacidil)
Mechanism:Mechanism: open K-channels of vascular smooth open K-channels of vascular smooth
muscle cells muscle cells  K-efflux K-efflux  hyperpolarization hyperpolarization 
vasodilatationvasodilatation
Main effectMain effect:: vasodilation vasodilation  lower PVR lower PVR  lower lower
BP BP
Adverse effectsAdverse effects: : reflex tachycardiareflex tachycardia, , Na and Na and
fluid retentionfluid retention, (minoxidil: hirsutism-Rogaine. , (minoxidil: hirsutism-Rogaine.
Diazoxide: hyperuricemia, hyperglycemia –Diazoxide: hyperuricemia, hyperglycemia –
used in hypoglycemia)used in hypoglycemia)
Use:Use: Diazoxide Diazoxide i.v.i.v. in hypertensive emergencies in hypertensive emergencies

39. c) Direct acting vasodilatorsc) Direct acting vasodilators ((Na-Na-
nitroprusside nitroprusside i.vi.v. . NiprideNipride))
Mechanism:Mechanism: metabolite is nitric oxide metabolite is nitric oxide 
cGMP. NO is a rapid acting venous and cGMP. NO is a rapid acting venous and
arteriolar vasodilatorarteriolar vasodilator
Main effectMain effect:: vasodilation vasodilation  lower PVR lower PVR 
lower BPlower BP
Adverse EffectsAdverse Effects: : Reflex tachycardiaReflex tachycardia, severe , severe
hypotension, possible cyanide poisoning hypotension, possible cyanide poisoning
PharmacokineticsPharmacokinetics:: rapid acting, rapid acting, i.v.i.v. drip, drip,
short plasma half-lifeshort plasma half-life
Use:Use: Hypertensive Hypertensive emergenciesemergencies

40. c) Direct acting vasodilatorsc) Direct acting vasodilators
((hydralazine-hydralazine-ApresolineApresoline))
Mechanism:Mechanism: Direct vasodilator of arterioles Direct vasodilator of arterioles
Main effectMain effect:: vasodilation vasodilation  lower PVR lower PVR 
lower BPlower BP
Adverse effects:Adverse effects: reflex tachycardiareflex tachycardia, , Na Na
retentionretention, hirsutism, lupus–like syndrome, hirsutism, lupus–like syndrome
Pharmacokinetics:Pharmacokinetics: oral, slow onset oral, slow onset
Use:Use: with a beta blocker and a diuretic with a beta blocker and a diuretic

41. AAngitensin ngitensin CConverting onverting EEnzymenzyme
ACEACE

Angiotensin I Angiotensin I  Angiotensin II Angiotensin II
ACEACE

Bradykinin (vasodilator) Bradykinin (vasodilator)  Inactive Inactive
peptidepeptide
ANGIOTENSIN I ANGIOTENSIN II
ACE
ANGIOTENSIN I ANGIOTENSIN II
ACE
BRADYKININ (vasodialtor) INACTIVE PEPTIDE
ACE
BRADYKININ (vasodialtor) INACTIVE PEPTIDE
ACE


42. Agents that affect RASAgents that affect RAS
a) ACE inhibitorsa) ACE inhibitors
captopril, enalapril, lisinoprilcaptopril, enalapril, lisinopril
b) Angiotensin II receptor b) Angiotensin II receptor
blockers (ARB)blockers (ARB)
losartan, valsartan, irbesartanlosartan, valsartan, irbesartan

43. a) ACE inhibitors (a) ACE inhibitors (captopril-captopril-CapotenCapoten, ,
enalapril-enalapril-VasotecVasotec, lisinopril-, lisinopril-PriviniPrivinil, rampiril-l, rampiril-
Altace)Altace)
No adverse effects on plasma lipids, glucose, sexual No adverse effects on plasma lipids, glucose, sexual
function. Drug of choice in diabetes-related early stage function. Drug of choice in diabetes-related early stage
proteinuria. Contraindicated in pregnancy. Not as effective proteinuria. Contraindicated in pregnancy. Not as effective
in African-Americansin African-Americans
Mechanism: Mechanism: inhibit ACE inhibit ACE  low circulating Ang II low circulating Ang II 
decreased PVRdecreased PVR
Main effectsMain effects:: decreased PVR decreased PVR  decreased BP decreased BP
Adverse effectsAdverse effects:: skin rash, taste, skin rash, taste, coughcough, , hyperkalemiahyperkalemia
PharmacokineticsPharmacokinetics:: TT
1/21/2 = 3, 11, 12, respectively = 3, 11, 12, respectively
Use:Use: used in stage 1 and 2 HT; also for congestive heart used in stage 1 and 2 HT; also for congestive heart
failurefailure

44. b) Angiotensin II receptor blockers b) Angiotensin II receptor blockers
(ARB) (ARB) (losartan-(losartan-CoozarCoozar, valsartan-, valsartan-DiovanDiovan, ,
irbesartan-irbesartan-AvaproAvapro))
Mechanism: Mechanism: selectivelyselectively block Ang II AT-1 block Ang II AT-1
receptor receptor  decrease PVR decrease PVR  decrease BP decrease BP
Adverse effectsAdverse effects:: NoNo Cough, very few adverse Cough, very few adverse
similar to ACE inhibitorssimilar to ACE inhibitors

45. BP 
BV 
Na
+
depletion
NE release
from nerve
ending
RENIN RELEASE
BP 
BV 
Na
+
retention
+ -
Vasoconstriction
Aldosterone
secretion
Angiotensin release
+
+
+
++
+
Stimulants for ADH
1)  ECF volume
2) osmolality of plasma
+

46. Renin-Angiotensin-Aldosterone SystemRenin-Angiotensin-Aldosterone System