1. Hypertension Treatment Dr.Negin Nezarat

2. 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.

3. 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.

4. Mechanisms Controlling CO and TPR Artery Vein 2. Hormonal Renal Ang II Adrenal Catecholamines Aldosterone 3. Local Factors 1. Neural SymNS PSNS

5. 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.

6. 1. Diuretics 2.Peripheral  Adrenergic Antagonists 4.  Adrenergic Antagonists 3. Central Sympatholytics (  agonists) 5. Anti-angiotensin II Drugs 6. Ca++ Channel Blockers 7. Vasodilators

7. 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

8. 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)

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

10. Contraindications hypersensitivity compromised kidney function cardiac glycosides (K+ effects) hypovolemia hyponatremia

11. 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)

12. Peripheral  Adrenergic Antagonists Prazosin Terazosin Vasodilation reduces peripheral resistance

13. 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

14. Central Sympatholytics (  -2 Agonists) Clonidine, Methyldopa,Guanfacine Sympathoinhibition Decreased norepinephrine release Decreased NE-->vasodilation--> Decreased TPR

15. 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

16.  drenergic Antagonists propranolol (Inderal) Pindolol Metoprolol Atenolol Carvedilol labetalol

17. Cardiac--  HR,  SV   CO Renal--  Renin   Angiotensin II   TPR Impotence; Bradycardia; Fatigue; Exercise Intolerance, Hypertriglyceridemia,

18.  Asthma  Bradycardia  Hypersensitivity  Hypoglycemia in DM

19. 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

20. Anti-Angiotensin II Drugs, cont Volume Aldosterone Vasopressin CO Angiotensin II Vasoconstriction TPR SymNS HR/SV Angiotensin II Norepinephrine CO SymNS        

21. 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

22. 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

24. Ca++ Channel Blockers Verapamil Nifedipine Diltiazem Amlodipine Vascular Relaxation Decreased TPR K+ Ca ++ Na+

25. 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

26. Vasodilators Hydralazine,Minoxidil,Nitroprusside,Diazoxide, Fenoldopam minoxidil diazoxide hydralazine fenoldopam NO nitroprusside Ca++ Na+ K+    DA

27. Adverse Effects reflex tachycardia Increase Sym activity (hydralazine, minoxidil,diazoxide) lupus (hydralazine) hypertrichosis (minoxidil) cyanide toxicity (nitroprusside)

28. 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!

29. When we have to start drug administraton for HTN?  Don’t response to goal with life style modification  > 160/100 at first

30. General Tx

32. Device Based Antihypertension Therapy