Hypertension TreatmentDr.Negin Nezarat

1. mechanisms and cardiovascular pathophysiology (Review).

2. major forms of clinical hypertension. 3. major classes of anti-hypertensive agents and

mechanisms of action 4. General treatment strategy for hypertension.

Determinants of Arterial Pressure

Mean Arterial Pressure = X

ArteriolarDiameter

BloodVolume

StrokeVolume

HeartRate

Filling PressureContractility

Blood Volume Venous Tone

CRITICAL POINT!Change any physical factors

controlling CO and/or TPR and MAP can be altered.

Mechanisms Controlling CO and TPR

Artery Vein

2. Hormonal Renal Ang II Adrenal Catecholamines Aldosterone

3. Local Factors

1. Neural SymNS PSNS

Secondary hypertension

1. renal artery stenosis2. pheochromocytoma3. aortic coarctation4. adrenal tumor

Types and Etiology of Hypertension

White coat hypertension

Essential Hypertension No known cause. CRITICAL POINT!

Pharmacological Therapy used primarily for essential hypertension.

1. Diuretics2.Peripheral -1 a Adrenergic Antagonists

4. -b Adrenergic Antagonists

3. Central Sympatholytics ( -2 a agonists)

5. Anti-angiotensin II Drugs

6. Ca++ Channel Blockers

7. Vasodilators

Diuretics Urinary Na+ excretion

Urinary water excretion

Extracellular Fluid and/or Plasma Volume

Acute decrease in COChronic decrease in TPR, normal COMechanism(s) unknown

1. Thiazideshydrochlorothiazide

chlorthalidone metolazon

2. Loop diuretics furosemide (Lasix)

bumetadine ethacrynic acid 3. K+ Sparing

amiloride , spironolactone (Aldactone);triamterene 4. Osmotic

mannitol ,urea5. Other

Combination - HCTH + triamterene acetazolamide (Diamox)

dizziness, electrolyte imbalance/depletion,hypokalemia, hyperlipidemia,hyperglycemia (Thiazides)gout

Contraindicationshypersensitivity compromised kidney functioncardiac glycosides (K+ effects)hypovolemiahyponatremia

A 55 y/o Hypertensive man under HCT TX

BP:160/95 Peripheral Edema Cr:1.3 Na:129 K:3.2

lower dietary Na+ intake,

K+ supplement or high K+ food

K+ Sparing Loop diuretics (severe

HTN,CRF or with CHF)

Peripheral -1a Adrenergic Antagonists

Prazosin Terazosin

Vasodilation reduces peripheral

resistance

Peripheral -1a Adrenergic Antagonistsnausea; drowsiness; postural hypotenstion;

1st dose syncope

does not impair exercise toleranceuseful with diabetes, asthma, and/or

hypercholesterolemiaoften used with diuretic, antagonist

Orthostasis Volume overload

CHF

Central Sympatholytics (a-2 Agonists)Clonidine , Methyldopa ,Guanfacine

Sympathoinhibition

Decreased norepinephrine release

Decreased NE-->vasodilation--> Decreased TPR

Dry mouth Sedation Impotence

Generally Not 1st Line Drugs;Methyldopa Drug Of Choice For Pregnancy

prolonged use--salt/water retention, add diureticRebound increase in blood pressure

b Adrenergic Antagonistspropranolol (Inderal)

Pindolol

Metoprolol

Atenolol

Carvedilol

labetalol

Cardiac-- HR, SV CO

Renal-- Renin Angiotensin II TPR

Impotence; Bradycardia; Fatigue; Exercise Intolerance, Hypertriglyceridemia,

Asthma Bradycardia Hypersensitivity Hypoglycemia in DM

Anti-Angiotensin II DrugsAngiotensin II Formation

2. Ang II Receptor Antagonists losartan candesartan

valsartan (Diovan)

1. Angiotensin Converting Enzyme- Inhibitors enalopril quinapril fosinopril moexipril lisinopril benazepril captopril

Ang I

Ang II

ACE

ACE

Ang II

Renin

Angiotensinogen

Ang IAT1

AT2

LungVSMBrainKidneyAdr Gland

Anti-Angiotensin II Drugs, cont

Volume Aldosterone Vasopressin

CO

Angiotensin II

Vasoconstriction

TPR

SymNS

HR/SV Angiotensin II Norepinephrine

CO

SymNS

Adverse Effectshyperkalemiaangiogenic edema (ACE inhib); cough (ACE inhib); rash; itching;

Pregnancy,hypersensitivity, bilateral renal stenosis

Use With Diabetes Or Renal Insufficiency; Adjunctive Therapy In Heart Failure; Often Used With Diuretic;Enalapril, Iv For Hypertensive Emergency

A 25 y/o hypertensive woman under low dose diuretic and 12.5 mg captopril

Positive pregnancy test

BP:125 / 75

Contraindications in pregnancy for ACEI & ARB

Continuse diuretics

Add methyldopa if necessary

Ca++ Channel BlockersVerapamil

Nifedipine

Diltiazem

Amlodipine

Vascular RelaxationDecreased TPR

K+Ca++Na+

ContraindicationsCongestive heart failure; pregnancy and lactation;Post-myocardial infarction

Therapeutic ConsiderationsVerapamil- Mainly Cardiac; Interactions W/ Cardiac

GlycosidesNifedipine- Mainly Arterioles,reflex TachycardiaDiltiazem-both Cardiac And Arterioles,AV Node Block

Adverse Effectsnifedipine --Increase SymNS activity;

headache; dizziness; peripheral edema

Vasodilators Hydralazine ,Minoxidil ,Nitroprusside ,Diazoxide ,

Fenoldopam

minoxidildiazoxide

hydralazine

fenoldopamNO

nitroprusside

Ca++

Ca++Na+ K+

DA

Adverse Effects reflex tachycardia Increase Sym activity (hydralazine, minoxidil,diazoxide)

lupus (hydralazine)

hypertrichosis (minoxidil)

cyanide toxicity (nitroprusside)

SummarySites and Mechanisms of Action

Can alter CO/TPR at number of sites and/or mechanisms.

3. -2 agonists4. b-blockers Receptor antag.

2. -a antag. 5. ang II antag.7. Vasodilators6. Ca++ antag.

1. Diuretics4. b-blockers

Other- 5. ACE inhibitors Lung, VSM, Kidney, CNS

CRITICAL POINTS!

When we have to start drug administraton for HTN?

Don’t response to goal with life style modification

> 160/100 at first

General Tx

Device Based Antihypertension Therapy