hypertension treatment dr.negin nezarat. 1.mechanisms and cardiovascular pathophysiology (review)....
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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