Treatment of Hypertension by Dr Sarma - PowerPoint

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					1 www.drsarma.in   Dr.Sarma@works
                  Welcome, Dear Friends




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Dr.Sarma@works
                                 The Almighty


                  Pardons and Grants me heaven
                     Even if I don't know a single letter about
                     Crutz Feld Jacob’s Disease
                     Tsutsugamushi Fever
                     Criggler Nazzar Syndrome
                     South American equine encephalitis and
                     Many and much more rarer topics
                                             BUT …….

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Dr.Sarma@works
                                The Almighty


           Will drag me to hell and will not pardon
                  My ignorance of even the minute details of HT
                  My indifference to apply the current knowledge
                  My negligence in screening for HT, TOD
                  My despondency about preventing TOD
                  My inadequacy in maintaining my patients
                      as normo-tensive as possible –
                  (This is applicable to all common diseases)

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Dr.Sarma@works
                 Treatment of Hypertension




                  A CLINICAL APPROACH
                 Dr.Sarma RVSN, M.D., M.Sc (Canada)
                 Consultant Physician and Chest Specialist,

                    # 5, Jayanagar, Tiruvallur – 602 001

                       93805 21221, (044) 27660593




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                   Treatment of Hypertension




                     A CLINICAL APPROACH
                     Management of Hypertension
                 Based on the latest recommendations of
                        JNC VII, ISH, ESH, WHO




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                   Globally Renowned HT Societies


                 1. JNC VII – Joint National Committee on HT, USA
                 2. ISH – WHO International Society on HT
                 3. AHA – American Heart Association, USA
                 4. ACC – American College of Cardiologist
                 5. BHS – British Hypertension Society
                 6. NIHLB – National Inst. Heart Lung & Blood vessels
                 7. EHS – European Hypertension Society
                 8. CHS – Canadian Hypertension Society
                 9. NKF – National Kidney Foundation, USA
                 10.AKA – American Kidney Association, USA

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     WHAT IS NEW IN HYPERTENSION?




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                           HYPERTENSION


        What we record as B.P.
                 It is only a marker of the bigger problem

        The Truth is
                 Hypertension is a multi-organ systemic disease

        The Problem is
                 Hypertension is asymptomatic in 85% of cases
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                   How to be wise in HT?

    It is wrong
    To consider Hypertension as an isolated disease
    The Truth is
    Hypertension, DM, Dyslipidemia, Obesity often coexist
    They are the 4 pallbearers to the grave of CHD, CVD
    For all of them
    Primary and secondary prevention by TLC is the answer
    Afflicted with one, must be screened for all other thieves
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                        Treatment Goal


        Goal BP
             Keep B.P. < 140/90 mm Hg in each patient
             This may be revised to 120/80 may be ? 110/70
             MRFIT’s cut off values are 115/75 mm Hg
        The Truth is
          It is essential to keep the B.P at or below the goal
          But, It also matters how the goal B.P. is achieved !
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                             Definitions


                 As per JNC VII and ISH (WHO) 2004
                 1. What is normal B.P ?
                 2. What is pre hypertension ?
                 As per JNC VII and ISH (WHO) 2004
                   Normal SBP < 120 and DBP < 80
                   Pre HT SBP 120 to 139 mm Hg
                            DBP 80 to 99 mm Hg
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                              Definitions



                 1. What is stage 1 HT ?
                 2. What is stage 2 HT ?

                 Stage 1     SBP 140 to 159
                             DBP 90 to 99
                 Stage 2     SBP 160 and more
                             DBP 100 and more

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           JNC VII Classification

Category             SBP (mm Hg)     DBP (mm Hg)

Normal                   < 120           < 80

Pre – hypertension      120-139          80-90

Hypertension

Stage 1                140 – 159        90 – 99

Stage 2              160 and above   100 and above



                                                     15
                              Definitions


                 Are the values same for Diabetics , CKD?

                 No, for DM, IHD and CKD the criteria
                 are more stringent
                 The cut off values are 10 mm lower
                 Stage 1     SBP 130 to 149
                             DBP 80 to 89
                 Stage 2     SBP 150 and more
                             DBP 90 and more
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    Hypertension Optimal Treatment (HOT) Study


                                25                        Reduction in CV events
                                                                 p=0.005 (DM)

                                20
                                                                        DM
                                                                        non-DM
         Events/1000 pt-years




                                15



                                10



                                5



                                0
                                     <90           <85                 <80
                                           Target diastolic BP
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                                                                  Lancet 1998; 351: 1755–62
                          Rule of Halves

            What is this rule of halves in HT ?
        •    For every 800 adults in the community
        •    400 are HT (either ↑ SBP or ↑ DBP or both)
        •    Of them only 200 are diagnosed HT
        •    Of them only 100 are started on treatment
        •    Of them only 50 are on correct drug
        •    Of them in only 25 the goal B.P. is attained
        •    Means 25 ÷ 400 = 6% only have goal BP
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                   How many are really Dx. and Rx.ed ??




                                                                  Under control (40%)
                                                                    (7.5% of the total
                             Diagnosed
                                                    Under            hypertensives)
                                 HT
                                           Un Rx.
                                 37%              treatment
                                            HT
                                                    (50%)

                 Hypertensives
                                                                     Uncontrolled
                 (22%)           63%                              hypertension (60%)
   Normotensives (78%)       Undiagnosed
                                  HT




                                              A study from Europe on 23,339 patients

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               Global Hypertension Control
           Percentages of Patients whose
             Hypertension is Controlled
          < 140/90 mmHg                                    < 160/95 mmHg
          USA      Canada                            Finland     Spain  Australia
                                   13                       20.5                20              19
                   27



         England            France                 Germany Scotland                          India
               6                    24                                         17.5            9
                                                            22.5

                                                      > 65 years


  USA: JNC VI. Arch Intern Med 1997            Marques-
                                               Marques-Vidal P et al. J Hum Hypertens 1997
  Canada: Joffres et al. Am J Hypertens 2001

  England: Colhoun et al. J Hypertens 1998                              Adapted from G. Mancia / L.
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  France: Chamontin et al. Am J Hypertens
   1998
                                                                                          Ruilope 20
  1998
                 Isolated Systolic Hypertension



         1. What is ISH ? –
         2. What percentage of 65+ aged have ISH ?
         3. Which is more harmful – ↑ SBP or DBP ?
         4. Why is ISH important ?




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             Relative prevalence of SBP and DBP


                               40 + yrs

                      ISH
                                          S&DHT




                                    DHT

                      Normal




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                 R R for CVD - SBP and DBP




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                     ISH is universal after 65+




                  Persons who are normo-tensive at age 55
                 have a 90% lifetime risk for developing HTN.
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                                         HT- RR of stroke and MI



                           20

                                         Normotensives                           Hypertensives
         5 Year Risk (%)




                           15



                           10
                                              Stroke

                                              Myocardial
                            5
                                              Infarction


                            0
                                0   20   40   60    80   100   120   140   160   180   200   220   240   260   280   300

                                                   Systolic Blood Pressure (mmHg)
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                                                           Brown, M.J. Lancet 2000; 355: 659 - 660
                 Is SBP more dangerous or DBP ?




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                   Isolated Systolic Hypertension


         1. What is ISH ? –
                 SBP 140+ , DBP < 90
         2. What percentage of 65+ aged have ISH ?
                 More than 90%
         3. Which is more harmful – ↑ SBP or DBP ?
                 Of course ↑ SBP
         4. Why is ISH important ?
                 Because of ↑↑ CVA and CHD mortality

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                    For adequate control of B.P.


          Do you think we can control most of the
          patients of hypertension with –
                 One drug
                 Two drugs
                 Three drugs
                 Can’t control
         In most of the patients of hypertension
         Two drugs are required for adequate control
         More so if the initial BP is 20/10 above the goal
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                   TODAY’S PARADIGM




            Gone are the days of monotherapy
            It is the era of combination therapy
                       Why is it so?



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                      CVD Risk Factors



           What are the so called CHD risk factors ?

           What are known as CHD risk equivalents ?

           What is Framingham risk score ?




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                  Global Risk Profile and HT




                          25)




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Dr.Sarma@works
                 HT combined with other CHD RF




        Framingham offspring study, subjects aged 17 – 84
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                     CVD Risk Factors


         What are the so called CHD risk factors ?
           List discussed in previous slide
         What are known as CHD risk equivalents ?
           DM, PVD, CVA, Nephropathy, Retinopathy
         What is Framingham 10 CHD risk estimate ?
           10 year CHD risk estimate based on age,
           sex, smoking, TC, HDL, SBP, Rx. for HT
                                      see the program
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                    Target Organ Damage



           Why is there TOD in HT ?

           What are the organs targeted for damage ?

           What is the basis of TOD ?

           What tests we need to do to assess HT ?

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              Diseases Attributable to Hypertension


                                                                       Stroke
              Coronary heart disease
                                                      Heart failure
                                                                             Cerebral hemorrhage
   Myocardial infarction

       Left ventricular
        hypertrophy                                  Hypertension             Chronic kidney failure


                                                                                 Hypertensive
       Aortic aneurysm                                                          encephalopathy
                                                               Retinopathy
                        Peripheral vascular disease                                      All
                                                                                       Vascular
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Adapted from: Arch Intern Med 1996; 156:1926-1935.
                 Target Organ Damage (TOD)


        • Heart
               Left ventricular hypertrophy (LVH)
               Angina or prior myocardial infarction (CHD)
               Prior Coronary revascularization PTCA or CABG
               Heart failure (Systolic / Diastolic dysfunction)
        • Brain
               CVA Stroke or Transient Ischemic Attack (TIA)
        • Kidney : Chronic kidney disease and CRF
        • Vessels : Peripheral arterial disease PVD
        • Eyes : Hypertensive Retinopathy
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                  Atherosclerosis – Time line




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                 Endothelial NO Balance




                       NO


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                 Target Organ Damage - Assessment


            Routine Tests
            • Electrocardiogram, Echocardiography (desirable)
            • Urinalysis for proteinuria, Microalbuminuria
            • Blood glucose (F and PP), and Hematocrit
            • Serum Na and K, Creatinine or GFR, Calcium
            • Lipid Profile complete, Eye examination, ABI
            Optional tests
            • X-Ray Chest PA
            • 24 hr. urine albumin excretion or ACR
            • More extensive testing is not generally indicated
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                   Target Organ Damage


        Why is there TOD in HT ?
          It is a disease of blood vessels.
        What are the organs targeted for damage ?
          Heart, brain, kidney, eye, peripheral vessel
        What is the basis of TOD ?
          ED, Arterial stiffness and Atherosclerosis
        What tests we need to do to assess TOD ?
          List discussed
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                     Paradigm Shift in HT Therapy


                 It is not just ↓B.P.   TODAY we must strive to
                 1. Alter the modifiable risk factors
                 2. Keep the SBP < 140 and DBP < 90
                 3. Prevent or halt or reduce TOD –
                     • LVH, CHD, CHF, CVA, CRF, PVD & Retino.
                 4. Prevent or control DM (as HT + DM is hazardous)
                 5. Prevent or control Dyslipidemia (Endothelial Dysf.)
                 6. Reduce morbidity and mortality
                 7. Improve QUALY – Quality Adjusted Life Years
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                     Target Organ Damage



        What is single most imp. predictor of CHD, HF, Death ?

        What time course of HT to LVH to LVF to death ?

        Can LVH be regressed at all ?

        Will drugs help to regress LVH and ↓TOD ?

        How important is Micro-albuminuria ?

www.drsarma.in                                                   42
                 Normal weight 350 to 450 g

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            Transverse Section of HEART - LVH




                    10 mm                  25 mm




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Dr.Sarma@works                                     44
              Echocardiography of Heart - LVH




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Dr.Sarma@works                                  45
            ECG and Left Ventricular Hypertrophy




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                 Chest PA view of Heart - LVH




                                 C/T ratio > 50%


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                 Progression of HT to LVH to HF




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                               Survival Rate HT + LVH v/s NT + LVH

                    1.00                                    Source : Am Hear J, 2000; 140 (6) : 848-856.


                    0.99


                                                                                Nomotensive-No LVH
                    0.98
Portion Surviving




                    0.97                                                        Hypertensive-No LVH

                    0.96                                                        Normotensive-LVH

                    0.95



                    0.94                                                        Hypertensive-LVH

                    0.93
                           0    2   4   6     8     10     12     14      16      18

                                        Survival Time (Years)
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                       Can LVH be reduced at all ??


                   0
                 -10
                 -20
                 -30
                 -40
                 -50
                 -60
                 -70
                 -80
                 -90
                          D       A       B       C      A+D

                       LVH is the Single Most important predictor
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                         Will Treatment Help ??

                  0

                 -10

                 -20

                 -30

                 -40

                 -50

                 -60
                       CHF     CVA        LVH       CVD        CHD

                         Combined results of 17 RCTs ( n = 48,000)
www.drsarma.in                   Hebert 1993, Moser 1996             51
   Value of excellent vs. good blood pressure control in NIDDM
                                                       (144/82 vs. 154/87mmHg)



                                     40
                                                  Less tight control
          Patients With Events (%)



                                                  Tight control
                                     30


                                     20


                                     10


                                     0
                                          0   1       2     3   4    5     6     7    8
                                          9          Years From Randomisation




                                      Reduction in risk with tight control 32% (95% CI 6% to 51%) (P=0.019)

UKPDS, BMJ 1998;317:703-713.
    MAU as a Predictor of Morbidity and Mortality



                               Retinopathy


                  LVH
                              Diabetes                Nephropathy

                                 +
                                MAU                    Non-fatal
                 All-cause                          cardiovascular
                 mortality                             disease
                             Peripheral/autonom
                               ic neuropathy



                                     Parving HH. J Hypertens 1996;14 Suppl 2:S89-S94.

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       Definitions of abnormalities in albuminuria

                         24 hour
                                           Timed collection    Spot collection
    Category             collection
                                           (g/min)            (g/mg Cr)
                         (mg/24h)

    Normal               < 30              < 20                < 30

    Microalbuminuria     30-299            20-199              30-299

    Clinical (macro)
                          300              200                300
    albuminuria
    Because of variability in urinary albumin excretion, 2 of 3 specimens over
    3-6 mon should be abnormal before considering diagnostic threshold positive
    False positive: exercise < 24 hours, fever, CHF, marked hyperglycemia,
    marked HTN, pyuria and hematuria.

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                      Relative Importance of MAU


                            10.02
                 10



                  8
                                           6.52
                  6

   CHD Odds
     Ratio        4
                                                          3.20
                                                                          2.32
                  2



                  0
                       Microalbuminuria   Smoking    Hypertension      Cholesterol


                                                    Eastman RC, Keen H. Lancet 1997;350 Suppl 1:29-32.

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                     Target Organ Damage


        What is single most imp. predictor of CHD, HF, Death ?
            LVH – LV mass index
        What is the time course of HT to LVH to LVF to death ?
            The chart is explained
        Can LVH be regressed at all ?
            Very much Yes. Diuretics and ACEi are the best
        Will drugs help to regress ↓TOD ?
            Yes. All TOD regresses; LVF and CVA most
        How important is Micro-albuminuria ?
            The most important prognostic indicator of TOD
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                 Clinical Signs of LV Dysfunction


     Hypotension                   Soft S1
     Pulsus alternans              Paradoxically split S2
     Trigeminy, Bigeminy           S3 gallop
     Reduced volume of carotid     S4 impaired LV compliance)
     LV apical                     Mitral regurgitation
     Enlargement/displacement
                                   Pulmonary congestion rales
     Sustained heave of apex –
     Change in heart sounds

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                       Ankle-Brachial Index



       Resting and post exercise SBP in ankle and arm.
            1. Normal ABI > 1 (Ankle BP more than the arm BP)
            2. ABI < 0.9 has 95% sensitivity for angiographic PVD
            3. ABI of 0.5- 0.84 correlates with claudication
            4. ABI < 0.5 indicates advanced ischemia




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                     Dippers & Non Dippers




        What is this pattern in HT – Dippers and Non-dippers ?

        What is its significance and clinical relevance ?




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                                                         Dippers & Non Dippers

                                                              Systolic Blood Pressure
                                           160
         Systolic Blood Pressure (mm Hg)




                                           150



                                           140
                                                                                                          Non - dippers

                                           130

                                                                                                          Dippers
                                           120



                                           110
                                                 6   8   10   12   14   16   18   20   22   24   2   4
                                                          24 hours clock time

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                                                         Dippers & Non Dippers

                                                              Diastolic Blood Pressure
                                           100
        Diastolic Blood Pressure (mm Hg)




                                           90

                                                                                                          Non - dippers


                                           80
                                                                                                          Dippers



                                           70
                                                 6   8   10   12   14   16   18   20   22   24   2   4
                                                          24 hours clock time
                                                                                  Yonsei, Med J, Vol 43, No 3: 2002
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                         Dippers & Non Dippers



      1. Less than 10% circadian variation in SBP and DBP
      2. Essential hypertension patients are – usually ‘Dippers’
      3. Non dippers are Dx. by ABPM – They are usually
           1. Secondary HT cases
           2.    More end organ damage
           3.    More LVH
           4.    More responsive to salt restriction
           5.    Diabetics are non dippers
           6.    Diuretics convert a non dipper to dipper
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     Ambulatory Blood Pressure Monitoring - ABPM
1.   24 hour B.P monitoring (every 15 minutes)
2.   Today - 24 hour B.P. control is essential
3.   Identifies dippers and non-dippers
4.   Excludes white coat hypertension




                                                   63
                 Pulse wave velocity – Arterial Stiffness




                         Systole                      Diastole



                                   PulseTrace PCA




                                    Sphygmocor

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                     What is MOST essential ??


                  Not that ‘my drug is superior to yours’
                  Not that ‘this trial is better than that’
                  Nor ‘this combination is better than that’
                  But to get AS MANY PEOPLE as we
                   can to goal SBP < 140 & DBP < 90
                  And prevent or halt TOD.
                  Of course, tailor the treatment as per
                   individual patient’s co-morbidities.

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                 Morbidity and Mortality in HT


        Most of the morbidity and mortality of HT is due to
         LVH – LV diastolic and systolic dysfunction
         Increased risk of Coronary Artery Disease
         Increased risk of Cerebral Vascular Disease
         Hypertensive heart failure
         Chronic Renal Disease of hypertension
         Hypertensive vascular damage

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                 The correct Approach to HT

        • Are all patients screened for hypertension?
  Step1 • Are all hypertensives correctly identified?

        • Are they evaluated for co-morbidities/TOD?
 Step 2 • Are they assessed for CHD risk factors?

        • Are the correct drug combinations prescribed?
 Step 3 • What is the compliance for medicines & f/u?

        • Is the goal B.P. achieved and maintained?
 Step 4 • Are there any complications/ side effects?
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                 So, What is new in Hypertension ?


 1. High B.P recorded is only a clinical marker disease
 2. HT is a multi-organ disease, often asymptomatic
 3. Not to consider in isolation- Must look for ‘Co-Thieves’
 4. Today’s goal BP is 140/90 – It will sure be less tomorrow
 5. It matters to attain goal; matters more how it is attained
 6. In DM, CKD, IHD the cut off values are 10 mm less
 7. Remember rule of ½ in HT– Adequate control only in 7%
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         What is new in Hypertension - continued


8. ↑ SBP is more important than ↑ DBP; Often ignored it is !
9. Wide pulse pressure (SBP-DBP) signifies arterial damage
10. Day’s of monotherapy have gone; Combined Rx replaces
11. All HT must be screened for CHD risk factors & addressed
12. Target organ damage (TOD) must be investigated and Rx.
13. LVH is the single most predictor of mortality and morbidity
14. ABI, MAU, ABPM, PWV etc., identify high risk cases early
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70                 Dr.Sarma@works
                       Lifestyle Modification



             1. Life style modification is the sheet anchor
                in the management Hypertension.

             2. This surely reduces the number of drugs
                used and their dosage in controlling HT.

             3. Any drug treatment has value only when
                coupled with Life style modification.


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Dr.Sarma@works
                          Lifestyle Modification


      Modification                         Approximate BP reduction
                                                   (range)

      Weight reduction                       5–20 mm/10 kg wt loss

      Adopt DASH eating plan                      8–14 mmHg

      Dietary sodium reduction                     2–8 mmHg

      Physical activity                            4–9 mmHg

      Abstinence from alcohol                      2–4 mmHg

                 All put together reduce BP by 20 to 55 mmHg
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                 What to choose from the ocean

                      16 different classes of drugs
                      117 approved molecules as on date
                      Innumerable drug combinations
                  No significant change in the
                     Over 1800 clinical trials of repute
                     Five international societies on control
                 proportion of HT under HT
                      Seven JNC guidelines so far
                      Multiple target organs damage
                      Many co-morbidities
                      Varied outcomes of interest
                      Cost constraints
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                 Many avoidable HT deaths !


        On April 12, 1945, US President Franklin D. Roosevelt
        died of cerebral hemorrhage, a consequence of HT. It
        was a devastating illness for him.
        By current standards, President Roosevelt’s death was
        unnecessary. President Roosevelt was never treated
        with Anti-hypertensive drugs.
        Modern treatment would have controlled his BP and
        prolonged his life.
                                     Arch Int Med, Sept, 23,1996
         . . . so also of many others!
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            The Many Faces of HT Therapy Today



                                          Enalapril
                                          Lisinopril
                                          Ramipril
                                          Quinapril
                                          Perindopril
                  Hypertension




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                 Which drug should we prescribe ?



                  Choice must be tailored to individual
                   patient
                  Should be rational and as per approved
                   guidelines
                  Only class1 evidence based medications
                   to be used
                  Suitable to patients’ purse
                  Can never be arbitrary


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                 Physicians’ Bias in HT

 Isolated SHT is often dubbed as ‘aging factor’

 To consider HT is only in the ‘ARM’ and not in the body

 No concept of ‘pulse pressure’ – Not seeing the whole

 Worry about side effects – Need to watch, not to worry

 OK, some control is achieved – why attain goal BP ?

 Not insisting on compliance with drugs and assessments

 Pressure from patients – B.P. How much ? How much ?

 Concentrating on the pill and not on the ill – TLC forgotten
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                 Anti Hypertensive drug classes




                           The
                        A, B, C, D
                        approach


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                 Anti Hypertensive drug classes

              ACEi – Angiotensin converting enzyme
                 inhibitors – Enalapril- let us call them ‘A’
              ARB – Angiotensin Receptor Blockers –
                 Losartan - Let us call them also as ‘A’
              BB – Beta Receptor Blockers – Metoprolol,
                 Carveidilol, Atenelol - let us call them ‘B’
              CCB – Calcium channel blockers – Amlodepine
                 Verapamil, Diltiazem - let us call them ‘C’
              Diuretics – Hydrochlor Thiaz.- Furosemide,
                 Spiranolactone - let us call them ‘ D ’
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                      AB/CD Rule – HT Treatment


     (AB/CD = ACEi, Beta-blocker               Ca++-blocker, Diuretic)
                                     AGE

   Younger (< 55)                     Renin                       Older (> 55)
   High Renin HT                                                 Low Renin HT

 I ACEi            BB        III                III            CCB        Diuretic I

          II       A+B      A+B+D             D+C+A            D + C II
           Resistant HT /   IV: Add / substitute alpha blocker
           Intolerance      V: Re-consider 20 causes  trial of spironolactone

www.drsarma.in                      Dickerson et al. Lancet 353:2008-11;1999      81
                         The A B C D classes

                     D                                   A
                  Diuretics                         ACEI, ARB

                    Ca channelBlockers
                    DIURETICS
                    ACEI and ARB
                    βBlockers
                                     D A
                              First and Best Useful
                              Fourth Best Choice
                              Second Choice,Choice
                              Good third Choice
                                     B C            D, A
                              Can be combined with A, B, C
                              Can be combined with A, D
                              Can be combined with D, B, C
                              Can be combined with


                     B                                   C
                 β-Blockers                        Ca-Blockers


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                       A B C D – some brand names

            Thiazide diuretics –
             Hydrochlorothiazide - Aquazide, Hydride, Xenia
             Chlorthalidone – Hythalton, Loop diuretic – Frusemide
            Potassium sparing
             Triamterene, Amiloride, Spironalactone (Aldo anta)
            Beta blockers
                 Selective – Metoprolol, Metoprolol XL, Atenelol
                 Combined alpha and beta blockers – Carveidilol, Labetolol
            ACEI – Enalapril, Ramipril, Lisinopril, Quinapril, Perindopril
            ARB – Losartan, Valsratan, Candesartan, Irbesartan
            CCB – Nefedipine, Amlodipine, Varapamil, Diltiazem
            Alpha Blokers – Prazocin, Doxizocin, Terazocin, Tamsulocin
www.drsarma.in                                                                83
                 Hypertension – Why Combinations ?


     If goal BP is not achieved by a single drug in full dose

     Then adding another agent will help achieve the goal BP

     Two agents sometimes nullify each others side effects

     Fixed dose combinations will reduce the no. of tablets

     Once daily formulations are good for compliance

     Sustained release or LA formulations for 24 h BP control

     If three drugs can’t achieve goal BP – Resistant HT

www.drsarma.in                                                   84
                 Drug Combinations




Dr.Sarma@works                       85
        Hypertension – Rational Drug Combinations


                 ACEI and ARB = A              Diuretics = D – Rank 1
                 Beta Blockers = B             ACEI and ARB = A – Rank 2
                 Calcium Channel (CCB) = C     Beta Blockers = B – Rank 3
                 Diuretics Drugs= D            CCB = C – Rank 4


          D and A combination is excellent -   Ramace H, Losar H, Enace D
          D and B combination next -           Betaloc H, Atecard D, Tenoric
          D and C combination sixth -          Amlogaurd H, Stamlo D
          A and B combination Third -          Losar A, Cardif Beta
          A and C combination fourth -         Amlopres L, Hipril A, Amlo LS
          B and C combination fifth -          Amlo AT, Amlobet, Beta Nicardia

www.drsarma.in                                                                   86
                  Some Irrational Combinations


    Beta blockers + Beta1 stimulants -   Rebound HT, Paradoxical BP ↑
    Beta blockers + Vepapamil -          Extreme bradycardia, HB, CHF
    Thiazide + Furesemide       -        Potential volume ↓ and K ↓
    CCB + Thiazide    -                  No RCTs to support the additive
    Prazocin + Beta blocker -            They nullify the effects of each other
    Verapamil / Dilzem + Nefidepine -    No rationale (cardiac actions contridic)
    Beta blocker + ACEI                  Not for HT alone, Good for CHF, MI, IHD
    Sub clinical doses of two drugs      Try one drug in good dosage, then add
    Two drugs of same class -            No rationale (like Enalapril + Ramipril)
                                         (Atenelol + Metoprolol, Nefidepine + Amlo)



www.drsarma.in                                                                        87
 DIURETIC                 I am ‘D’ for DIURETIC
                             KNOW ME WELL


                  My Good aspects
                     Fluid depletion, Na washout, Low cost
                     Improve CHF, Systolic function, Ca saving
                     Reduce LVH, Morbidity & Mortality
                  My Bad aspects
                     Potassium washout, ↑ in Uric acid, ↑ Ca
                     Adverse on Lipids, Glucose control
                  Don’t use me in
                     Gout, Hypokalaemia
                     Dyslipedemia, Uncontrolled DM
www.drsarma.in                                                   88
 ACEI, ARB                     KNOW ACEI and
                         I am ‘A’ for ME WELL ARB


                  My Good aspects
                     Improve Diastolic function, Systolic function
                     Control Proteinuria, Very favourable in DM
                     Improve Coronary Ischemia, Good on Lipids
                     Reduce LVH, Morbidity & Mortality
                  My Bad aspects
                     Bradykinin accumulation, Angio-edema
                     ↑ Serum K , ↓ GFR
                  Don’t use me in
                        Pregnancy, Creatinine is > 3 mg%, ↑ K 5.0 meq
                        Bilateral Renal Artery Stenosis, Angio-edema
www.drsarma.in                                                          89
  β Blocker              I am ‘B’ for βBlocker
                            KNOW ME WELL


             My Good aspects
               ↓Heart rate, ↓Forceof contraction, ↓Conduction
               ↓Myocardial O2 demand, Improve Ischemia
                Improve QUALY in CHD, Useful in CHF, Migraine
             My Bad aspects
                Constrict peripheral vessels, Bradycardia
                Unfavourable on Lipids, Glucose
             Don’t use me in
                Bradycardia, Conduction defects, Caution in CHF
                Prinzmetal Angina, MSD, PVD, BA, COPD, Dys lipid
                   Pheochromocytoma, Chronic smokers
www.drsarma.in                                                     90
                        for Ca channel
 Ca+ Blockers I am ‘C’ KNOW ME WELLBlocker


                  My Good aspects
                     Vasodilatory, Suitable in elderly, Low cost
                     Anti arrhythmic (Verapamil), ↑Coronary BF (Diltz)
                     Neutral on lipidemia, Vasospastic Angina
                  My Bad aspects
                     Fluid retention, Impair failing heart
                     Adverse on Glucose control , Pedal edema ? Rx.
                  Don’t use me in
                     Tachycardia, arrhythmias, CHF,
                      Uncontrolled DM, Volume overload
www.drsarma.in                                                           91
                  ABCD Compare & Contrast

  Parameter       Diuretic    ACEi, ARB   βblocker      Ca+ Blocker
  Ischemia        No effect   Improves    Improves      Negative
  LVH, LVF        Improves    Improves    Improves*     Negative
  CV Mortality    Improves    Improves    Improves      Increases
  Heart rate      No effect   No effect   Bradycardia   Tachycardia
  Use in DM       Negative    Excellent   Negative      Negative
  Lipid effects   Negative    Excellent   Negative      Neutral
  Fluid & Na      Enhances    No effect   Vasoconstr.   Vasodilatory
  K ex / bronchi Enhances     No effect   Bronchospa    No effect
  UA / Conduct. ↑ Uric acid   No effect   ↓conduction   No effect
www.drsarma.in                                                         92
                 Which drug in each class




www.drsarma.in                              93
                 Persistence with hypertensive therapy




www.drsarma.in                                           94
                      Hypertension
                  Case specific approach

                 some selected case scenarios



www.drsarma.in                                  95
                   Case specific approach


      Case 1     Pre Hypertension   TLC, No Drug     Yearly F/u


      Case 2     Stage 1 HT         Single Drug     D or D + A


      Case 3     Stage 2 HT          Two Drugs      D + A, D + B


      Case 4     HT + Tachycardia   Beta blockers    Not CCB

                 HT + Bradycardia
      Case 5                         CCB, ACEi        Not BB
                 Heart Blocks BBB
www.drsarma.in                                                     96
                   Case specific approach


      Case 1     Pre Hypertension   TLC, No Drug     Yearly F/u


      Case 2     Stage 1 HT         Single Drug     D or D + A


      Case 3     Stage 2 HT          Two Drugs      D + A, D + B


      Case 4     HT + Tachycardia   Beta blockers    Not CCB

                 HT + Bradycardia
      Case 5                         CCB, ACEi        Not BB
                 Heart Blocks BBB
www.drsarma.in                                                     97
                   Case specific approach


      Case 1     Pre Hypertension   TLC, No Drug     Yearly F/u


      Case 2     Stage 1 HT         Single Drug     D or D + A


      Case 3     Stage 2 HT          Two Drugs      D + A, D + B


      Case 4     HT + Tachycardia   Beta blockers    Not CCB

                 HT + Bradycardia
      Case 5                         CCB, ACEi        Not BB
                 Heart Blocks BBB
www.drsarma.in                                                     98
                   Case specific approach


      Case 1     Pre Hypertension   TLC, No Drug     Yearly F/u


      Case 2     Stage 1 HT         Single Drug     D or D + A


      Case 3     Stage 2 HT          Two Drugs      D + A, D + B


      Case 4     HT + Tachycardia   Beta blockers    Not CCB

                 HT + Bradycardia
      Case 5                         CCB, ACEi        Not BB
                 Heart Blocks BBB
www.drsarma.in                                                     99
                   Case specific approach


      Case 1     Pre Hypertension   TLC, No Drug     Yearly F/u


      Case 2     Stage 1 HT         Single Drug     D or D + A


      Case 3     Stage 2 HT          Two Drugs      D + A, D + B


      Case 4     HT + Tachycardia   Beta blockers    Not CCB

                 HT + Bradycardia
      Case 5                         CCB, ACEi        Not BB
                 Heart Blocks BBB
www.drsarma.in                                                     100
                   Case specific approach

      Case 1     Pre Hypertension   TLC, No Drug     Yearly F/u


      Case 2     Stage 1 HT         Single Drug     D or D + A


      Case 3     Stage 2 HT          Two Drugs      D + A, D + B


      Case 4     HT + Tachycardia   Beta blockers    Not CCB

                 HT + Bradycardia
      Case 5                         CCB, ACEi        Not BB
                 Heart Blocks BBB
www.drsarma.in                                                     101
                   Case specific approach

      Case 6     HT + CHD Risk F    ACEi (Perindo)   BB (Meto)

      Case 7     HT + IHD (No MI)     BB + ACEi      B+A+D

                                     BB (Car) +      Aldactone
      Case 8     HT + MI or (RVP)
                                     ACEi, ARB       Diltiazem

      Case 9     HT + PZM Angina     CCB, α bloc      Not BB

                                    ARB Losartan
     Case 10 HT + Diast. Dys                         BB - Meto
                                    ACE Ramipril

     Case 11 HT + Sys Dys             ACEi + D       A+ D+ B
www.drsarma.in                                                   102
                   Case specific approach

      Case 6     HT + CHD Risk F    ACEi (Perindo)   BB (Meto)

      Case 7     HT + IHD (No MI)     BB + ACEi      B+A+D

                                     BB (Car) +      Aldactone
      Case 8     HT + MI or (RVP)
                                     ACEi, ARB       Diltiazem

      Case 9     HT + PZM Angina     CCB, α bloc      Not BB

                                    ARB Losartan
     Case 10 HT + Diast. Dys                         BB - Meto
                                    ACE Ramipril

     Case 11 HT + Sys Dys             ACEi + D       A+ D+ B
www.drsarma.in                                                   103
                   Case specific approach

      Case 6     HT + CHD Risk F    ACEi (Perindo)   BB (Meto)

      Case 7     HT + IHD (No MI)     BB + ACEi      B+A+D

                                     BB (Car) +      Aldactone
      Case 8     HT + MI or (RVP)
                                     ACEi, ARB       Diltiazem

      Case 9     HT + PZM Angina     CCB, α bloc      Not BB

                                    ARB Losartan
     Case 10 HT + Diast. Dys                         BB - Meto
                                    ACE Ramipril

     Case 11 HT + Sys Dys             ACEi + D       A+ D+ B
www.drsarma.in                                                   104
                   Case specific approach

      Case 6     HT + CHD Risk f    ACEi (Perindo)   BB (Meto)

      Case 7     HT + IHD (No MI)     BB + ACEi      B+A+D

                                     BB (Car) +      Aldactone
      Case 8     HT + MI or (RVP)
                                     ACEi, ARB       Diltiazem

      Case 9     HT + PZM Angina     CCB, α bloc      Not BB

                                    ARB Losartan
     Case 10 HT + Diast. Dys                         BB - Meto
                                    ACE Ramipril

     Case 11 HT + Sys Dys             ACEi + D       A+ D+ B
www.drsarma.in                                                   105
                   Case specific approach

      Case 6     HT + CHD Risk F    ACEi (Perindo)   BB (Meto)

      Case 7     HT + IHD (No MI)     BB + ACEi      B+A+D

                                     BB (Car) +      Aldactone
      Case 8     HT + MI or (RVP)
                                     ACEi, ARB       Diltiazem

      Case 9     HT + PZM Angina     CCB, α bloc      Not BB

                                    ARB Losartan
     Case 10 HT + Diast. Dys                         BB - Meto
                                    ACE Ramipril

     Case 11 HT + Sys Dys             ACEi + D       A+ D+ B
www.drsarma.in                                                   106
                   Case specific approach

      Case 6     HT + CHD Risk F    ACEi (Perindo)   BB (Meto)

      Case 7     HT + IHD (No MI)     BB + ACEi      B+A+D

                                     BB (Car) +      Aldactone
      Case 8     HT + MI or (RVP)
                                     ACEi, ARB       Diltiazem

      Case 9     HT + PZM Angina     CCB, α bloc      Not BB

                                    ARB Losartan
     Case 10 HT + Diast. Dys                         BB - Meto
                                    ACE Ramipril

     Case 11 HT + Sys Dys             ACEi + D       A+ D+ B
www.drsarma.in                                                   107
                   Case specific approach

      Case 6     HT + CHD Risk F    ACEi (Perindo)   BB (Meto)

      Case 7     HT + IHD (No MI)     BB + ACEi      B+A+D

                                     BB (Car) +      Aldactone
      Case 8     HT + MI or (RVP)
                                     ACEi, ARB       Diltiazem

      Case 9     HT + PZM Angina     CCB, α bloc      Not BB

                                    ARB Losartan
     Case 10 HT + Diast. Dys                         BB - Meto
                                    ACE Ramipril

     Case 11 HT + Sys Dys             ACEi + D       A+ D+ B
www.drsarma.in                                                   108
                 Case specific approach

                                 Diu - Fru. Sp.   Not CCB,
     Case 12 HT + CHF
                                 + ARB / ACEi      α bloc

     Case 13 HT + DM (No DK)      ARB, ACEi       Not D, C

                                                  Not CCB,
     Case 14 HT + DM+ DKD        MD, HYZ, D
                                                  ACEi, ARB

     Case 15 HT + Dys lipidem.    ACEi, CCB       Not BB, D

     Case 16 HT + BA / COPD       ACEi / ARB       Not BB

     Case 17 HT + PVD / smoker CCB, ACEi, HZ       Not BB
www.drsarma.in                                                109
                 Case specific approach

                                 Diu - Fru. Sp.   Not CCB,
     Case 12 HT + CHF
                                 + ARB / ACEi      α bloc

     Case 13 HT + DM (No DK)      ARB, ACEi       Not D, C

                                                  Not CCB,
     Case 14 HT + DM+ DKD        MD, HYZ, D
                                                  ACEi, ARB

     Case 15 HT + Dys lipidem.    ACEi, CCB       Not BB, D

     Case 16 HT + BA / COPD       ACEi / ARB       Not BB

     Case 17 HT + PVD / smoker CCB, ACEi, HZ       Not BB
www.drsarma.in                                                110
                 Case specific approach

                                 Diu - Fru. Sp.   Not CCB,
     Case 12 HT + CHF
                                 + ARB / ACEi      α bloc

     Case 13 HT + DM (No DK)      ARB, ACEi       Not D, C

                                                  Not CCB,
     Case 14 HT + DM+ DKD        MD, HYZ, D
                                                  ACEi, ARB

     Case 15 HT + Dys lipidem.    ACEi, CCB       Not BB, D

     Case 16 HT + BA / COPD       ACEi / ARB       Not BB

     Case 17 HT + PVD / smoker CCB, ACEi, HZ       Not BB
www.drsarma.in                                                111
                 Case specific approach

                                 Diu - Fru. Sp.   Not CCB,
     Case 12 HT + CHF
                                 + ARB / ACEi      α bloc

     Case 13 HT + DM (No DK)      ARB, ACEi       Not D, C

                                                  Not CCB,
     Case 14 HT + DM+ DKD        MD, HYZ, D
                                                  ACEi, ARB

     Case 15 HT + Dys lipidem.    ACEi, CCB       Not BB, D

     Case 16 HT + BA / COPD       ACEi / ARB       Not BB

     Case 17 HT + PVD / smoker CCB, ACEi, HZ       Not BB
www.drsarma.in                                                112
                 Case specific approach

                                 Diu - Fru. Sp.   Not CCB,
     Case 12 HT + CHF
                                 + ARB / ACEi      α bloc

     Case 13 HT + DM (No DK)      ARB, ACEi       Not D, C

                                                  Not CCB,
     Case 14 HT + DM+ DKD        MD, HYZ, D
                                                  ACEi, ARB

     Case 15 HT + Dys lipidem.    ACEi, CCB       Not BB, D

     Case 16 HT + BA / COPD       ACEi / ARB       Not BB

     Case 17 HT + PVD / smoker CCB, ACEi, HZ       Not BB
www.drsarma.in                                                113
                 Case specific approach

                                 Diu - Fru. Sp.   Not CCB,
     Case 12 HT + CHF
                                 + ARB / ACEi      α bloc

     Case 13 HT + DM (No DK)      ARB, ACEi       Not D, C

                                                  Not CCB,
     Case 14 HT + DM+ DKD        MD, HYZ, D
                                                  ACEi, ARB

     Case 15 HT + Dys lipidem.    ACEi, CCB       Not BB, D

     Case 16 HT + BA / COPD       ACEi / ARB       Not BB

     Case 17 HT + PVD / smoker CCB, ACEi, HZ       Not BB
www.drsarma.in                                                114
                 Case specific approach

                                 Diu - Fru. Sp.   Not CCB,
     Case 12 HT + CHF
                                 + ARB / ACEi      α bloc

     Case 13 HT + DM (No DK)      ARB, ACEi       Not D, C

                                                  Not CCB,
     Case 14 HT + DM+ DKD        MD, HYZ, D
                                                  ACEi, ARB

     Case 15 HT + Dys lipidem.    ACEi, CCB       Not BB, D

     Case 16 HT + BA / COPD       ACEi / ARB       Not BB

     Case 17 HT + PVD / smoker CCB, ACEi, HZ       Not BB
www.drsarma.in                                                115
                 Case specific approach

     Case 18 HT + BPH          α bloc, Tamsu    Not BB

                                α bloc, HZ,
     Case 19 HT + ED                            Not BB
                                ACEi /CCB
                                               Not ACEi,
     Case 20 HT + Pregnancy    MD, HYZ, CCB
                                                or ARB

     Case 21 HT + Gout, ↑ UA    ACEi, CCB       Not D

                                Indap, Amlo,
     Case 22 ISH                                Not BB
                                  Enalapril
                                                 Cough
     Case 23 HT + Cough         ACEi cough
                                                remedy
www.drsarma.in                                             116
                 Case specific approach

     Case 18 HT + BPH          α bloc, Tamsu    Not BB

                                α bloc, HZ,
     Case 19 HT + ED                            Not BB
                                ACEi /CCB
                                               Not ACEi,
     Case 20 HT + Pregnancy    MD, HYZ, CCB
                                                or ARB

     Case 21 HT + Gout, ↑ UA    ACEi, CCB       Not D

                                Indap, Amlo,
     Case 22 ISH                                Not BB
                                  Enalapril
                                                 Cough
     Case 23 HT + Cough         ACEi cough
                                                remedy
www.drsarma.in                                             117
                 Case specific approach

     Case 18 HT + BPH          α bloc, Tamsu    Not BB

                                α bloc, HZ,
     Case 19 HT + ED                            Not BB
                                ACEi /CCB
                                               Not ACEi,
     Case 20 HT + Pregnancy    MD, HYZ, CCB
                                                or ARB

     Case 21 HT + Gout, ↑ UA    ACEi, CCB       Not D

                                Indap, Amlo,
     Case 22 ISH                                Not BB
                                  Enalapril
                                                 Cough
     Case 23 HT + Cough         ACEi cough
                                                remedy
www.drsarma.in                                             118
                 Case specific approach

     Case 18 HT + BPH          α bloc, Tamsu    Not BB

                                α bloc, HZ,
     Case 19 HT + ED                            Not BB
                                ACEi /CCB
                                               Not ACEi,
     Case 20 HT + Pregnancy    MD, HYZ, CCB
                                                or ARB

     Case 21 HT + Gout, ↑ UA    ACEi, CCB       Not D

                                Indap, Amlo,
     Case 22 ISH                                Not BB
                                  Enalapril
                                                 Cough
     Case 23 HT + Cough         ACEi cough
                                                remedy
www.drsarma.in                                             119
                 Case specific approach

     Case 18 HT + BPH          α bloc, Tamsu    Not BB

                                α bloc, HZ,
     Case 19 HT + ED                            Not BB
                                ACEi /CCB
                                               Not ACEi,
     Case 20 HT + Pregnancy    MD, HYZ, CCB
                                                or ARB

     Case 21 HT + Gout, ↑ UA    ACEi, CCB       Not D

                                Indap, Amlo,
     Case 22 ISH - SBP > 140                    Not BB
                                  Enalapril
                                                 Cough
     Case 23 HT + Cough         ACEi cough
                                                remedy
www.drsarma.in                                             120
                 Case specific approach

     Case 18 HT + BPH          α bloc, Tamsu    Not BB

                                α bloc, HZ,
     Case 19 HT + ED                            Not BB
                                ACEi /CCB
                                               Not ACEi,
     Case 20 HT + Pregnancy    MD, HYZ, CCB
                                                or ARB

     Case 21 HT + Gout, ↑ UA    ACEi, CCB       Not D

                                Indap, Amlo,
     Case 22 ISH                                Not BB
                                  Enalapril
                                                 Cough
     Case 23 HT + Cough         ACEi cough
                                                remedy
www.drsarma.in                                             121
                 Case specific approach

     Case 18 HT + BPH          α bloc, Tamsu    Not BB

                                α bloc, HZ,
     Case 19 HT + ED                            Not BB
                                ACEi /CCB
                                               Not ACEi,
     Case 20 HT + Pregnancy    MD, HYZ, CCB
                                                or ARB

     Case 21 HT + Gout, ↑ UA    ACEi, CCB       Not D

                                Indap, Amlo,
     Case 22 ISH                                Not BB
                                  Enalapril
                                                 Cough
     Case 23 HT + Cough         ACEi cough
                                                remedy
www.drsarma.in                                             122
     Case 24                  Hypertension and cough



            Hypertensives may present with cough – watch out
                 1. Consider LVF as the cause of cough
                 2. Consider ACEI induced dry cough
                 3. Stop ACEI and give ARB or other agents
                 4. Check the composition of the cough remedy you give
                 5. Ephedrine, Pseudephedrine, should be avoided
                 6. Oral Beta agonists like Orciprenaline, Salbutamol,
                   Terbutaline the less used, the better.
                 7. Inhaled beta agonists, ICS are safe
                 8. Decongestants like phenyl propanolamine to be avoided

www.drsarma.in
                                                                            123
     Case 25        Secondary Hypertension – various causes



       Secondary HT       Usually Stage 2 - HT
                           Secondary causes will be present
                           May present in young individuals
       Treatment          Look for secondary cause and treat
                           Life style interventions must
                           Vigorous efforts required to control HT
                           Often two or even 3 drugs may be required
                           Resistant HT may be encountered
                           Anti HT drugs as per secondary cause

       Absolute contra    ACEI or ARB in bilateral renal artery stenosis


www.drsarma.in                                                              124
     Case 26     Secondary Hypertension in Pheochromocytoma


      Pheochromocytoma Usually Stage 2 HT, Episodic or Labile
                        Secondary adrenal medullay tumor
                        May present in young individuals
      Treatment        Surgical Ablation of the chromaffin tissue
                        HT needs to be controlled before surgery
                        Alpha blockers are the drugs of choice
                        Phentolamine, Phenoxybenzamine, Prazocin
                        Vigorous efforts required to control HT
                        Often two or even 3 drugs may be required
                        Resistant HT may be encountered
      Surgery          First reduce HT, then surgery

      Do not use         Beta blockers
www.drsarma.in                                                       125
     Case 27          Resistant Hypertension



      Resistant HT    Usually Stage 2 HT
                       May present in young individuals
                       May have secondary causes
      Reasons         Not taking medication (liers)
                       Improper BP measurement
                       Excessive Na intake, Inadequate diuretic Rx.
                       Full doses of drugs not employed
                       Drug interactions – NSAIDs, SMA, OCP, OTC
                       Herbal remedies, Excessive alcohol use
      Rationale       Identify the above and correct
                       Secondary causes to be searched for


www.drsarma.in                                                        126
     Case 29           Hypertensive emergencies



         HT emergency       Marked DBP elevation
                             Acute TOD present
         TOD Presentation   Encephalopathy, MI, ACS, Pul Edema,
                             Eclampsia, stroke, head trauma, life-
                             threatening arterial bleeding, or aortic
                             dissection
         Treatment          With TOD immediate admission to ICU
                             IV Nitroprusside, Diazoxide, Labetolol
                             Without TOD Combination of 2 or 3 drugs
                             Close monitoring
                             Life style modification not now – no time
         Do not use         No sublingual nefedipine,

www.drsarma.in                                                           127
     Case 30          Hypertensive with Acute CVA (Stoke)



        HT + CVA (Stroke)   Marked DBP elevation
                             May be SAH, ICH, Acute Brain Infarction
        Rationale           In acute setting, no consensus on
                             treatment of elevated BP
                             HT at time of an acute stroke associated
                             with increased risk of cerebral hemorrhage
                             and edema, increased mortality
                             After acute ischemic stroke, cerebral
                             auto regulation affected
                             Active treatment of BP in the first 7 days
                             could worsen symptoms
        Treatment           Recommendation not to start HT Rx.
                             before 7 to 10 days after ischemic stroke

www.drsarma.in
                                                                          128
                 Current Indications for Alpha Blockers



                 1. Hypertension with BPH
                 2. In Pheochromoytoma before surgery
                 3. In the treatment of Ergot over dose
                 4. Raynaud’s syndrome and PVD, TAO
                 5. Vasospastic (prinzemetal Angina)
                 6. Diabetic neuropathy
                 7. Hypertensive smokers
                 8. Hypertension with Dyslipidemia

                  First dose syncope and Postural Hypotension
                                How to avoid ?
www.drsarma.in                                                  129
                 Learning is a cyclical process




                 Each of these presentations
                 Thank You all
                   is a valuable learning
                      experience for me




www.drsarma.in                                    130