Hypertension Treatment Dr.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 Arteriolar Diameter Blood Volume Stroke Volume Heart Rate Filling PressureContractility Blood VolumeVenous 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 stenosis 2. pheochromocytoma 3. aortic coarctation 4. 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. Diuretics 2.Peripheral Adrenergic Antagonists 4. Adrenergic Antagonists 3. Central Sympatholytics ( 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 CO Chronic decrease in TPR, normal CO Mechanism(s) unknown
1. Thiazides hydrochlorothiazide chlorthalidone metolazon 2. Loop diuretics furosemide (Lasix) bumetadine ethacrynic acid 3. K+ Sparing amiloride, spironolactone (Aldactone); triamterene 4. Osmotic mannitol,urea 5. Other Combination - HCTH + triamterene acetazolamide (Diamox)
dizziness, electrolyte imbalance/depletion, hypokalemia, hyperlipidemia, hyperglycemia (Thiazides) gout
Contraindications hypersensitivity compromised kidney function cardiac glycosides (K+ effects) hypovolemia hyponatremia
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 Adrenergic Antagonists Prazosin Terazosin Vasodilation reduces peripheral resistance
Peripheral Adrenergic Antagonists nausea; drowsiness; postural hypotenstion; 1st dose syncope does not impair exercise tolerance useful with diabetes, asthma, and/or hypercholesterolemia often used with diuretic, antagonist Orthostasis Volume overload CHF
Central Sympatholytics ( -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 diuretic Rebound increase in blood pressure
drenergic Antagonists propranolol (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 Drugs Angiotensin 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 Ang II Renin Angiotensinogen Ang I AT1 AT2 Lung VSM Brain Kidney Adr Gland
Anti-Angiotensin II Drugs, cont Volume Aldosterone Vasopressin CO Angiotensin II Vasoconstriction TPR SymNS HR/SV Angiotensin II Norepinephrine CO SymNS
Adverse Effects hyperkalemia angiogenic 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 Blockers Verapamil Nifedipine Diltiazem Amlodipine Vascular Relaxation Decreased TPR K+ Ca ++ Na+
Contraindications Congestive heart failure; pregnancy and lactation; Post-myocardial infarction Therapeutic Considerations Verapamil- Mainly Cardiac; Interactions W/ Cardiac Glycosides Nifedipine- Mainly Arterioles,reflex Tachycardia Diltiazem-both Cardiac And Arterioles,AV Node Block Adverse Effects nifedipine --Increase SymNS activity; headache; dizziness; peripheral edema
Vasodilators Hydralazine,Minoxidil,Nitroprusside,Diazoxide, Fenoldopam minoxidil diazoxide hydralazine fenoldopam NO nitroprusside Ca++ Na+ K+ DA
Adverse Effects reflex tachycardia Increase Sym activity (hydralazine, minoxidil,diazoxide) lupus (hydralazine) hypertrichosis (minoxidil) cyanide toxicity (nitroprusside)
Summary Sites and Mechanisms of Action Can alter CO/TPR at number of sites and/or mechanisms. 3. -2 agonists -blockers Receptor antag. 2. antag. 5. ang II antag. 7. Vasodilators 6. Ca++ antag. 1. Diuretics -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