Transcript isolated systolic hypertension

Blood pressure variation in the left ventricle (Blue line) & aorta (Red line) showing the
cyclic variations of systolic and diastolic pressure
Cushing
Syndrome
Cushing
Syndrome
 11β-hydroxysteroid dehydrogenase enzyme
 mineralocorticoid
 BP &
  K+
vasogenic edema
Metabolic
Syndrome
nephrosclerosis
o Sedentary lifestyle
o Obesity
o Insulin resistance
o Metabolic syndrome
o Aging
o Alcohol
o Vitamin-D deficiency
o Low birth-weight
o Family history
o Genetic
o Na+ sensitivity
o Sympathetic overactivity
o Renin overactivity
DASH diet:
(dietary approaches to
stop hypertension)
Rich in fruits &
vegetables and low-fat
or fat-free dairy foods.
Systolic
pressure
Diastolic pressure
mmHg
mmHg
90–119
60–79
Pre-hypertension
120–139
80–89
Stage 1
140–159
90–99
Stage 2
≥160
≥100
Isolated systolic HT
≥140
<90
Classification of
Hypertension
Normal
UK Hypertension Guidelines
Starting
Treatment
threshold
Group
Treatment
Target
>160/100
All those with such persisting readings >160/100.
<140/90
>140/90
Have established cardiovascular disease,
or Have  C.V. Risk (>20% per 10 years),
or Have evidence end-organ damage without D.M.,
or Ch. renal dis., without Macroalbuminuria (or D.M.)
<140/90
>130/80
Type-2 Diabetes alone.
<130/80
>135/85
Type-1 Diabetes alone.
<130/80
>130/80
Type-1 or 2 Diabetes with microalbuminuria.
Type-1 or 2 Diabetes with renal, eye or CV damage.
<130/80
>130/80
Chronic renal disease with Macroalbuminuria.
<125/75
DIABETIC HYPERTENSION
Diabetic Nephropathy with (Microalbuminuria)
 ACEIs / ARBs.
Diabetic Nephropathy with (Macroalbuminuria)
 ARBs / ACEIs.
Diabetic Hypertension without Nephropathy
 ACEIs / ARBs +/- Thiazide +/- CCBs.
CHRONIC RENAL DISEASE
Definition: [ GFR  60 ml / min / 1.73 m2
(= serum creatinine  1.5 mg / dL  or 1.3 mg / dL )]

[Albuminuria  300 mg/day (macroalbuminuria)].
Treatment Goal: Aggressive BP Lowering  125/75
Compelling Drug: ACEIs or ARBs (Diabetic or non-Diabetic Nephropathy).
N.B. GFR (serum creatinine) up to 35% from baseline is acceptable ,
And is NOT a reason to withhold treatment unless hyperkalemia develops.
In Advanced Renal Disease:
[= GFR  30 ml / min / 1.73 m2 (serum creatinine 2.5 - 3mg / dL)]:
Increasing dose of loop diuretic is usually needed with ARBs or ACEIs)
HEART FAILURE
Asymptomatic HF  ACEIs / ARBs + BBs.
Advanced HF
 ACEIs / ARBs + BBs + Diuretic.
CEREBRO-VASCULAR STROKE
Risks & Benefits of ACUTE Lowering of BP DURING acute CV
Stroke are still unclear.
Control of BP at intermediate levels (approximately 160/100
mmHg) is appropriate until condition is stabilized or improved.
Stroke rates are lowered better by ACEIs / ARBs + Thiazide.
ISCHEMIC HEART DISEASE
Asymptomatic Angina: BBs or CCBs
Symptomatic Angina: ACE-Is / ARBs
(ARBs in Patients can’t tolerate ACE-Is)
Acute MI (elevated ST segment): ACE-Is / ARBs + BBs
(ARBs in Patients can’t tolerate ACE-Is)
N.B. CCBs if given there should be extreme cautious to avoid
heart failure.
Compelling
Indications Diuretic
Heart failure

Post-MI
High CAD risk
Diabetes


Chronic kidney
disease
Recurrent
stroke
prevention

ßB
ACEI
ARB















CCB
AA



AA, aldosterone antagonist; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II-receptor blocker; βB, ß-blocker; CCB,
calcium channel blocker; MI, myocardial infarction;
CAD, coronary artery disease.
JAMA. 2004;289(19):2560-2572.
The Use of Diuretics
Require Electrolyte &
Acid-base Balance
Monitoring
Osmotic
mannitol
glucose
CAI
acetazolamide
HCT
chlortalidone
furosemide
spironolactone
Adverse Effect
Type of Diuretics
Example
Hypovolemia
Loop Diuretic
Thiazide
Lasix
Hypotension
HCT  25 mg/day Thirst
 GFR
Hypokalemia
Loop Diuretic
Thiazide
Carbonic Anhydrase Inhibitor
Lasix
Muscle weakness
HCT  25 mg/day Cardiac arrhythmia
Acetazolamide
Hyperkalemia
Potassium Sparing Diuretics
Spironolactone
Hyponatremia
Loop Diuretic
Thiazide
Lasix
Neurological
HCT  25 mg/day manifestations
Metabolic Alkalosis
Loop Diuretic
Thiazide
Lasix
CNS manifestations
HCT  25 mg/day Cardiac arrhythmia
Metabolic Acidosis
Potassium Sparing Diuretics
Amilorides –
triamterene
Acetazolamide
muscle weakness
neurological symptoms
seizures
Decrease Ca++ Excretion Thiazide
HCT
Prevents Osteoporosis
Prevents Renal calculi
Hyperuricemia
Lasix
Gout
CAI
Loop Diuretic
Clinical Effect
Muscle Cramps
Cardiac arrhythmia
α-adrenergic receptors are present in the smooth muscles
e.g. prostate, arteries & veins.
α1 -adrenergic stimulation  smooth muscles contraction
 vasoconstriction.
α1-adrenergic blockers  Relaxing vascular smooth muscles
 vasodilatation
  vascular resistance
 hypotension.
α1-adrenergic blockers  Relaxing prostate & U.B. neck.
Other minor effects:
Relaxing cardiac muscle   COP  hypotension.
Side effects:
o Relaxing cardiac muscle  Heart Failure.
o
 obesity
o Dryness of mouth
o Weak antihypertensive
β-adrenergic Receptors Location:
o β1-adrenergic receptors mainly in : Heart & kidneys.
o β2-adrenergic receptors mainly in : Smooth muscles,
Liver & Sk. Muscles.
o β3-adrenergic receptors : Fat cells.
Stimulation of β-adrenergic Receptors:
o β1 : +ve Chronotropic on heart muscle.
+ve Inotropic on heart muscle.
Renin Release   BP.
o β2 : Bronchodilation.
Vasodilatation.
Affect Glycogen Breakdown in Liver & Skeletal muscles
o β3 : Lipolysis.
Blocking of β-adrenergic Receptors By β-blockers :
o β1 :  Stress & Physical exertion effect on heart muscle.
  HR &  Cardiac contractility force.
  Renin Release   BP.
o β2 : Bronchospasm  induces asthma
Vasospasm   BP.
o β3 : Diabetogenic.
o Cardio-protection after MI


o Management of cardiac arrhythmias


o Antihypertensive. 

Side Effects of β-blockers :
o Bronchospasm & dyspnea.
o Diabetogenic Risk:
Other Side Effects of β-blockers :
oHyperkalemia.
o Erectile dysfunction.
o Bradicardia, heart failure, heart block.
o Hypotension, orthostatic hypotension.
o Tremors.
o Insomnia 
Mode of Action:
Disrupt the calcium ions (Ca+2) transport at calcium channels:
o In vascular smooth muscles
o In cardiac muscle
o In cardiac muscle
INDICATIONS:
o Hypertension
o Atrial flutter & AF
o Angina
o Headache.
o Flushing.
o Lower limb edema
o Direct Bradycardia.
o Reflex Tachicardia:
o At high doses CCBs block the effect of insulin.
Glomerular Corpuscle
Afferent arteriole
macula densa
Juxta glomerular cells
Efferent arteriole
Distal convoluted tubule
Urinary chamber
Bowman’s capsule
Basement membrane Podocytes
Proximal convoluted
tubule
Urinary excretion:
Fluid & electrolyte filtration from capillary
side to urinary side through the basement
membrane & podocytes to the urinary
chamber of the glomerulus.
water
retention
Blood Blood
Blood
Direct Na+ H2O retention
water
retention
Blood Blood
Blood
Direct Na+ H2O retention
water
retention
Blood Blood
Blood
Direct Na+ H2O retention
water
retention
Blood Blood
Blood
Direct Na+ H2O retention
Chronic
hypertension
with chronic
renal disease
Intraglomerular Pressure
High
Chronic
hypertension
with normal
renal function
Normal
Magdi El-Shalakany
Low
60
80
100
120
140
160
Mean Arterial Pressure (mm Hg)
180
smooth
muscle
cells
1.
2.
3.
4.
5.
•
•
•
6.
1.
2.
3.
4.
5.
BP
 IGP
 Renal t. injury
 GFR
Bradykinin S.E:
Persist Dry Cough
Inflammation symp
Angio-edema
Tolerance
Hypertension
 IGP
Renal Hyperfiltration
Renal Tissue injury
Structural & Morphological
Changes :
• Mesangial tissue expansion
• Basement membrane thickening
• Podocyte pedicles’ detachment
• Intraglomerular Fibrosis
Degradation
1. Hypertension
2. Left Ventricular remodeling  (CHF)
3.  IGP
4. Renal Hyper-filtration
5. Renal Tissue injury  Chronic renal disease
6. Structural & Morphological Changes :
o Mesangial tissue expansion
o Basement membrane thickening
o Podocytes pedicles’ detachment
o Intraglomerular Fibrosis
1.
2.
3.
4.
5.
BP
 sympathetic tone   peripheral resistance
 Na+ & water retention   blood volume
 sympathetic tone   HR
 COP &  Heart work load & O2 consumption
1.
2.
3.
4.
Hypertension
Heart Failure
Angina
Post myocardial infarction
6.  Intra-Glomerular Pressure (IGP)
7.  Renal Hyper-filtration
8.  Renal Tissue injury
9. Improve functional & structural renal condition
10.Structural & Morphological Changes
11. micro & macro-albuminuria
5. Diabetic Nephropathy
6. Chronic renal disease
1. Bradykinin & inflammatory related S.E:
o Persistent Dry Cough
o Angio-edema
o Rash
o Inflammation-related Pain
2.  GFR   Creatinine Clearance Rate (Ccr or C C)   serum
Creatinine
 GFR (serum creatinine) up to 35% from baseline is acceptable & is
NOT a reason to withhold treatment unless hyperkalemia develops.
3. Hyperkalemia
4. Metallic Taste (sulfhydryl part in Captopril molecule)
1. Renal artery stenosis (bilateral)
2. Renal artery stenosis (Unilateral)
3. Impaired renal function (ACE-Is may GFR).
4. Aortic valve stenosis or cardiac outflow obstruction (ACE-I  COP).
5. Hypovolemia or dehydration (ACE-Is diuresis ( fluid volume)
&  BP).
6. Pregnancy (category D)
1.
2.
3.
4.
5.
•
•
•
6.
1.
2.
3.
4.
5.
BP
 IGP
 Renal t. injury
 GFR  C Cr
Bradykinin S.E:
Persist Dry Cough
Inflammatory symptoms
Angio-edema
Tolerance
Hypertension
 IGP
Renal Hyperfiltration
Renal Tissue injury
Structural & Morphological
Changes :
• Mesangial tissue expansion
• Basement membrane thickening
• Podocyte pedicles’ detachment
• Intraglomerular Fibrosis
Degradation
1. No Bradykinin & inflammatory related S.E:
o
o
o
o
Persistent Dry Cough
Angio-edema
Rash
Inflammation-related Pain
2. ARBs prevent excessive  GFR   Creatinine Clearance
Rate which  serum creatinine.
It Keeps the Drop in GFR & C cr (if occur)  35% from baseline which
is acceptable & So No Need to Withhold treatment.
3. No Decline of Anti-Hypertensive Effect
4. No Metallic Taste (sulfhydryl part in Captopril molecule)
CCBs
Diuretics
β-blockers
ACE-Is/ARBs
ACE-Is/ARBs
CCBs
ACE-Is/ARBs
CCBs
β-blockers
α-blockers
Diuretics
ACE-Is/ARBs
Diuretics
-blockers
AT1-receptor
blockers
-blockers
Calcium
antagonists
ACE inhibitors
ESH Guidelines. J Hypertens. 2007;25:1105-1087.
ESH= European Society of Hypertension
o CRD = Chronic Renal Disease.
o GFR = Glomerular Filtration Rate.
o BUN = Blood Urea Nitrogen = Uremia = Azotemia.
o ESRD = End Stage Renal Disease
(= Need for Dialysis or Kidney Transplant)
o Plasma concentrations of creatinine and urea (BUN = Blood
Urea Nitrogen) are used to measure renal function.
o Creatinine clearance rate (CCr or CrCl): “A measure for GFR”.
o BUN and serum creatinine will not be raised  normal
Until 60% of total kidney function is lost.
o Creatinine clearance (CCr or CrCl) is then more accurate to
measure suspected renal disease.
o Proteinuria (elevated level of protein (albumin) in urine) :
It is an important Prognostic marker for renal disease.
o Albumin level  30 mg/24 hr urine
is diagnostic for chronic kidney disease
o Microalbuminuria is a level of 30-300 mg/24 hr urine;
(can not be detected by usual urine dipstick methods).
o Macroalbuminuria is a level  300 mg/24 hr urine.
1. In patients  50 yr : SBP ( 140 mmHg)
is much more important Risk Factor for CVD than DBP.
2. CVD Risk doubles with each increment of 20/10 mmHg
(above normal).
3. Pre-hypertensive patients (SBP 120-139 / DBP 80-89)
Require Lifestyle modifications to CV Risk.
4. Thiazide diuretic is drug of First choice
for most patients with uncomplicated hypertension.
5. Certain Risk conditions are Compelling Indications
For Other Anti-hypertensive Agents
(e.g. ACE-Is , ARBs , CCBs , BBs …. etc)
6. Most hypertensive patients will require 2 or more
antihypertensive agents to Achieve Treatment Goals:
(  140/90 mmHg, or  130/80 mmHg for Diabetic or Chronic
Renal disease patients )
7. If BP is  20/10 mmHg above Goal, consider additional
agent therapy, one of which should be thiazide.
8. Empathy & Motivating Patients are very important to reach
Treatment Goal.
9. Responsible Physician’s Judgment remains paramount in
the presence of these guidelines.
e.g. women with child-bearing potential.
e.g. those who have symptomatic angina
or who have had myocardial infarction.