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					Hypertension
                    A CASE
Mr. Ahmed is a 42 years old male referred from •
local health center as he was noted to have BP
of 180/110 for the last two months. Apart of
occasional headache there was no other
complains. He is a non-smoker and never
consumed alcohol, his past medical history is
only significant for allergic rhinitis. His father died
years ago but he is not sure what was the cause
of his death; his mother still alive and well, apart
of mild DM on diet control. He has 3 brothers
44,45,46 years respectively, the eldest brother is
hypertensive
                Definition
Hypertension is chronically elevated systolic
and/or diastolic BP 140 systolic /90
diastolic mm Hg under satisfactory
conditions of measurements. And
confirmed by repeated accurate
measurements over a period of time.
                  Our Patient
Mr. Ahmed is a 42 years old male referred from
local health center as he was noted to have BP
of 180/110 for the last two months. Apart of
occasional headache there was no other
complains. He is a non-smoker and never
consumed alcohol, his past medical history is
only significant for allergic rhinitis. His father died
years ago but he is not sure what was the cause
of his death; his mother still alive and well, apart
of mild DM on diet control. He has 3 brothers
44,45,46 years respectively, the eldest brother is
hypertensive
          Why is it important?
1-Silent killer and long life disease
- IN OMAN
In 1994 national survey
Screened 4239 persons >20
23.7%--- 25.4% male & 22.2% female
- In UK rule of halves!!
2- Complication of hypertension
-Sustained hypertension is associated with accelerated
atheromatous disease of the blood vessels
-Cerebrovascular disease
Thromboembolic
Intra cranial bleed
TIA
-Cardiovascular disease
Myocardial infarction
Heart failure
Coronary artery disease
Renal failure
Vascular disease… Aortic dissection.
Accelerated / malignant hypertension.
3-Concomitant disease
                 Our Patient
Mr. Ahmed is a 42 years old male referred from
local health center as he was noted to have BP
of 180/110 for the last two months. Apart of
occasional headache there was no other
complains. He is a non-smoker and never
consumed alcohol, his past medical history is
only significant for allergic rhinitis. His father
died years ago but he is not sure what was the
cause of his death; his mother still alive and well,
apart of mild DM on diet control. He has 3
brothers 44,45,46 years respectively, the eldest
brother is hypertensive
Classification
                  Our Patient
Mr. Ahmed is a 42 years old male referred from
local health center as he was noted to have BP
of 180/110 for the last two months. Apart of
occasional headache there was no other
complains. He is a non-smoker and never
consumed alcohol, his past medical history is
only significant for allergic rhinitis. His father died
years ago but he is not sure what was the cause
of his death; his mother still alive and well, apart
of mild DM on diet control. He has 3 brothers
44,45,46 years respectively, the eldest brother is
hypertensive
              Classification
1-HTN with   no CVS risks / target organ
damage
2-HTN with   CVS risks
3-HTN with   target organ damage
4-HTN with   CVS risks & target organ
damage
      Aetiology of Hypertension
Primary – 90-95% of cases – also termed
“essential” or “idiopathic”
Specific underlying??
environmental and genetic factors contribute.
  Modifiable and non-modifiable risk factors •
•Age & gender                      •Obesity
•Genetic factors                   •Sedentary
                                   life style
                                   •Salt intake
                                   •Alcohol
                                   •Stress
                                   •Smoking
                Our Patient
Mr. Ahmed is a 42 years old male referred from
local health center as he was noted to have
BP of 180/110 for the last two months. Apart of
occasional headache there was no other
complains. He is a non-smoker and never
consumed alcohol, his past medical history is
only significant for allergic rhinitis. His father
died years ago but he is not sure what was the
cause of his death; his mother still alive and
well, apart of mild DM on diet control. He has
3 brothers 44,45,46 years respectively, the
eldest brother is hypertensive
Secondary – about 5% of cases (specific
disease or abnormality leading to sodium
retention or peripheral vasoconstriction)
-Renal or renovascular disease
-Endocrine disease
-Coarctation of the aorta
-Iatrogenic (Drugs)
          Making the diagnosis
-HTN occasionally causes headache but other wise is
symptomless.
-Diagnosis made at routine examination (accident) or
when complication arise.
-Importance of EDUCATION and REGULAR CHECK UP
especially for elderly individuals.

-Objectives of assessing individual with high blood
pressure
-To confirm a persistent elevation of blood pressure.
-To asses the overall cardiovascular risk.
-To evaluate existing organ damage or concomitant disease
-To search for possible causes of the hypertension
  Crucial point when taking BP
-Patient seated for 5 minutes (relaxed)
-Patient seated, arm at heart level
-Full bladder or recent use of tobaccos or
caffeine (coffee) or tea.
-Remove tight clothing.
-Cuff should encircle 2/3 of arm > obese!!
-Lower mercury slowly
-BP high…. What should I do??
Give the patient 5-10 minutes to relax and re-measure
again.
The diagnosis should be made after three
measurements on at least two separate
occasions
Still HIGH
Take a comprehensive history, including risk
factors and ruling out a secondary cause of
HPT.
“White Coat” hypertension.
                      History
Risk factors
Features suggesting secondary causes
Age<25
Renal disease
Drugs
Sweating, headache, anxiety (pheochromocytoma)
End-organ
CVS: Orthpnea, chest pain, palpation, ankle swelling.
Brain: TIA, Vertigo, impared vision
           Physical examination
Full examination but focus in signs of
Secondary hypertension.
Features of Cushing’s syndrome
Abdominal bruits (RAS)
Femoral delay (Corc. Aorta)
Palpable kidneys (PS)
Organ damage
CVS:Apex (heave), S4, dependent odema, rales.
Eye: retinal changes
Neurological defects.
                     Lab test
The minimum
Urinalysis
Blood glucose
Serum urea, creatinine, Na and K.
ECG
Fasting serum cholesterol
Selected patients
Chest CXR
Echo
Renal ultrasound/angiography
Urinary catecholamine
The Therapeutic goals


        British Hypertension Society 2004 guidelines

          www.hyp.ac.uk/bhs/resources/guidelines.htm



  In diabetes mellitus, aim for >130/80 mmHg
  In non-diabetic, the treatment goal is 140/85 mmHg
  In proteinuria, aim for >125/75 mmHg
            Modifications
•   Weight reduction
•   Diet
•   Dietary sodium reduction
•   Physical activity
•   Cessation of Alcohol consumption
    Modification            Recommendation                     SBP
                                                             Reduction
    Weight reduction            BMI 18.5–24.9           5–20 mmHg/10 kg wt loss


Adopt DASH eating plan         - diet rich in fruits,         8–14 mmHg
                            vegetables, and low fat
                                 dairy products
                           - reduced saturated and
                                      total fat
Dietary sodium reduction     No more than 2.4 g               2–8 mmHg
                                sodium/day


    Physical activity      Regular aerobic physical           4–9 mmHg
                            activity > 30 min/day,
                            most days of the week
 Moderation of alcohol         No more than 2                 2–8 mmHg
    consumption            drinks/day in most men
                                     and
                           No more than 1 drink/day
                                  in women
     Major Anti-Hypertensive
             Drugs
•   Diuretics
•   β-blockers
•   Calcium channel blockers
•   ACE inhibitors & ARB
•   α1-adrenoceptor blockers
•   Centrally-acting adrenergic drugs
•   vasodilators
            Diuretics



Thiazides                   LOOP diuretics

            K-retaining diuretics
                    Thiazides
Action:
• inhibit reabsorption of Na & Cl in distal convoluted
  tubules, resulting in retention of water.
• Prototype: HYDROCHLOROTHIAZIDE
• (dose: 6.25-25 mg PO once daily)

Therapeutic indications:
• effective as ACE inhibitors & CCB in prevention of CHD &
  non-fatal MI in HTN.
• useful in combination therapy with ACEI & β-Blockers.
• Useful in the treatment of black or elderly patients &
  those with CRF.
Side-effects:
•    hypokalemia (in 70%) → cardiac arrhythmia
•    hyperglycaemia (in 10%)
•    hyperuricaemia (in 70%)
•    increase. LDL … high doses only.

Contraindication:
•    gout
•    patients receiving lithium
•    Should be avoided in hypertensive diabetics or patients with
     hyperlipidemia

    NB. Thiazides are ineffective if GFR<30ml/min
                 K-retaining diuretics
                 (spironolactone, amiloride)
Action:
•   spironolactone inhibits the aldosterone-mediated reabsorption of Na &
    secreation of k.
•   amiloride blocks Na cannels in distal tubules
•   Dose: spironolactone → 12.5-200 mg/d PO
          amiloride → 5-20 mg/d PO

Therapuetic indication:
•   drug of choice in HTN due to primary aldosteronism
•   limit K loss in patient treated with thiazides

Side-effects:
•   sexual dysfunction
•   painful gynecomastia
                    LOOP diuretics
Action:
•   block Na/K/Cl co-transport in thick ascending loop of Henle, resulting
    in retention of Na, Cl & water.
•   Prototype: frusemide
•   (dose : 20-160 mg/d PO/IV/ IM)

Therapuetic indication:
•   no role in routine management of HTN except in patients with impaired
    renal function or heart failure.

Side-effect: (rare)
•   interstitial nephritis of kidney
•   ototoxicity
•   acute hypovolemia
                        β-
                     blockers
Classes:
• non-selective agents act on β1/ β2
(propranolol).

• cardio-selective act on β1
(metoprolol,atenolol,acebutolol,bisprolol).
selectivity lost at high doses

• drugs act on β/α1blockers
(labetalol,carvidilol).
                        Mechanism of action
Therapuetic indications:
•   cardioselective (atenolol) in hyertensive patient with CHD.
•   (labetolol) used in treatment of malignant HTN.

• useful in treatment of:
atrial tachyarrythmia/fibrillation.
Dose:
•   Atenolol :25-100 mg PO once daily
•   Metoprolol: 50-200 mg PO once daily
•   Propranolol: 40-160 mg PO twice daily
•   Labetalol: 20-30 mg IV over 2 min followed by 40-80mg at
    10-min intervals
Side-effects:
• contraction of smooth muscles (bronchospasm,
  Raynaud’s phenomenon).
• 2nd & 3rd degree heart block.
• penetration of CNS ( depression & nightmares ).
• tiredness & fatigue.
• inc. in triglycerides & dec. HDL cholesterols.
• type II DM… 15%
Contraindication:
• asthma & other forms of reactive airway disease.
• heart block.
• Depression.
          Calcium channel
              blockers
Action:
• Block openings of voltage-gated (L-type) Ca
  channels thereby prevent Ca entry into:
  cardiac muscles → dec cardiac contractility
  vascular smooth muscles → vasodilatation

Classes:
 dihydropyridine (nifidipine,felodipine, amlodipine)
  act on vascular smooth muscles.
 non- dihydropyridine (verapamil,diltiazem) act on
  cardiac muscle cells.
Therapeutic indication:
• dihydropyridine CCB are as effective as ACEI & diuretics
  in dec. overall cardiovascular & cerebrovascular
  accidents.


• excellent outcomes in elderly diabetic patients & isolated
  systolic HTN.

• diltiazem & verpamil (without β-blockers) in treatment of
  angina.
Dose:
•   Diltiazem: 120-540 mg PO once daily
•   Verapamil: 120-480 mg PO once daily
•   Nifedipine: 30-120mg PO once daily
•   Amlodipine: 2.5-10 mg PO once daily

Side-effects:
•   Headache
•   Flushing
•   Ankle oedema
•   Constipation

contraindication:
• verapamil in LVD & heart block
      ACEI


• Mechanism of Action
Therapeutic indication:
• hypertensive patients with diabetes nephropathy.
• left venticular dysfunction
• after MI
Dosage:
• captopril …25-150 mg/day
• lisinopril … 5-80 mg/day
• ramipril … 2.5-20mg/daily
Side-effects:
• dry cough …(10-20)%
• hyperkalemia (<2%)

Contraindication:
• bilateral renl artery stenosis
• hyperkalemia (if K>5.6mmol/l)
• pregnancy
                      ARB
                (Angiotensin II Antagonists)
• Drug name: Losartan ,Valsartan
• Mechanism of action: vasodilation & block aldosterone
  secretion (similar to ACEI)
Therapeutic indication:
• indicated in patients intolerant to ACEI
Dose:
• losartan … 25-100 mg PO once or twice daily
• valsartan … 80 mg/d PO; may increase to 160 mg/d if
  needed
Side effects:
• hyperkalaemia

Contraindication:
• same as ACEI
             Alpha1-adrenergic
                 blockers
(Prazosin & Terazosin)
Action:
•   Selectively block postsynaptic alpha1-adrenergic receptors. Dilate
    arterioles and veins, thus lowering blood pressure.

Therapeutic indication:
•   Prazosin treats HTN with prostatic hypertrophy
Dose:
•   Prazosin 1-40 mg PO twice daily
•   Terazosin: 1-20 mg PO once daily
Side–effects:
• reflex tachycardia & 1st dose syncope
Contraindicated in renal incontinence.
     Centrally acting agents
mechanism of action:
A- stimulation of α-adrenergic receptor in CNS lowers
   central sympethatic outflow.
B- stimulation of pre-synaptic α-receptor causes feedback
   inhibition of norepinephrine release from peripheral
  sympethatic nerve terminal.

  1- ↓ HR
  2- ↓ CO
  3- ↓ PR
Drugs:
• Methyldopa .. 250 mg PO once/twice daily
• Clonidine .. 0.2-1.2 mg PO twice daily


Therapuetic indication:
• rarely indicated in routine of HTN management
• α-methyldopa is drug of choice for chronic HTN in
  pregnancy.
Side effects:
• 1- sedation
• 2- dry mouth
• 3- depression
• 4- excessive bradycardia (not used with beta blockers)
• 5- orthostatic hypotension
• 6- (α-methyldopa): autoimmune haemolytic anaemia,
  pyrexia, hepatitis
• 7- rebound hypertension if clonidine discontinued
  abruptly
        Direct vasodilators
Mechanism of action:
• Tow drugs: Minoxidil – hydralazine - open
  vascular ATP-sensitive potassium
  channels.


Therapeutic indicates:
• Hydralazine: drug of choice for pre-eclampsia
  (HTN in pregnancy).
• minoxidil: main indication in HTN with chronic
  renal failure.
Dose:
• Hydralazine: 10-20 mg/dose IV/IM q4-6h

• Minoxidil: 5 mg PO once daily
Side-efects:
• hypotension & reflex tachycardia
• peripheral oedema
• minoxidil causes hirsuitism
Thiazide
Diuretics
                           Na, H 2O retention




                             Blood volume



            PR              Cardiac output




                 Decrease in BP
β-Adrenocepter
   blockers




                   Activation
           β1-Adrenocepters on heart
                                                     Cardiac output


                                                         PR


                                                                       Decrease
                 Renin                                Angiotensin II      in
                                                                         BP

                                       Aldosterone


            Na, H 2O retention                        Blood volume
  Angiotensinogen
(α2 -globulin in blood)

                                               Output of sympathetic
                                                  Nervous system



                                               Vasodilation of vascular
                                                                    SM
                ACE                                                       ↓ BP
Angiotensin I             ↓ Angiotensin
                               II               Retention of Na & H2o
 (inactive)

        ACE inhibitors
                               ↓ Aldosterone
                                production
                                               Levels of bradykinin
         FOLLOW UP
At follow up 4 weeks later his BP
 was 160/100. His investigation
 results turned to all normal
 except for high fasting blood
 sugar (8.6 mmol/l ). He told you
 that he developed 2 wheezy
 attacks which required
 nebulized salbutamol.
          In brief
After 4 weeks , the patient has :
 BP 160/100 ► still high
 FBS (8.6 mmol/l) ► diabetic
 Other investigations ------- Normal
 2 wheezy attacks , required nebulized
  salbutamol ► airway narrowing?
• How the result of his high blood
  sugar affect your subsequent
  choice of his antihypertensive
  medications ? Why ?


• What class of antihypertensive
  drug would be the most
  appropriate in this condition?
 Hypertension and diabetes

• It has been shown that CVD risk is elevated
  in people with diabetes at every level
  increase in BP.
• In diabetics –Treatment goal BP 130/80
• In non-diabetics- Treatment goal BP 140/85
 * It has been shown that hypertensive
  patients with diabetes are at risk of
  developing renal abnormalities(diabetic
  nephropathy).
• The presence of concomitant
  disease should influence
  selection of antihypertensive
  drugs because two diseases
  may benefit from a single
  drug.
• In hypertensive patients with
  diabetes, ACE inhibitors have
  been shown to provide greater
  benefit in reducing the risk of
  progression of nephropathy than
  equal blood pressure reduction
  achieved with other drugs.

      DO YOU KNOW HOW??
The benefit of ACE inhibitors in
 the kidney may result from :

1- Improved intrarenal hemodynamics.
2- Decreased glomerular efferent
  arteriolar resistance.
3- Reduction of intraglomerular
  capillary pressure.
* What are the precautions to be
taken to the use of ACE inhibitors?
• Should be used with particular care in patients with
  impaired renal function or renal artery stenosis ►
  Reduce the filtration pressure in the glomeruli and
  precipitate renal failure.

• Caution in valvular stenosis, or severe congestive
  heart failure.

• Caution in Hyperkalemia,Hyponatremia and
  hypovolaemia

• Caution in severe COPD and cor pulmonade.


* ELECTROLYTES AND CREATININE SHOULD BE
CHECKED BEORE AND 1-2 WEEKS AFTER
COMANCING THERAPY.
 * What are the contraindications to the
         use of ACE Inhibitors?

1- Hypersensitivity to ACE inhibitors.
2- Renovascular disases( Bilateral renal
   artery stenosis).
3- History of angioedema.

* Other contraindication ► Pregnancy.
 * What is the cause of wheezy attacks?
            This May be due to :
1- Allergy rhinitis.
2- As side effect of 1st medication
    (B-blocker ► Bronchospasm)
3- Infection precipitated by diabetes.
  * What other side effects you look for
   regarding the use of ACE inhibitors?

- Hypotension , especially with 1ST DOSE.
- Dry cough.
- Taste disturbance.
- Hyperkalemia.
- Renal impairment.
- Urticaria and angioneurotic oedema.
- Rarely: proteinuria,leukopaenia,fatigue,throat
          discomfort.
- Drug fever.
   FOLLOW UP AND MONITORING

• The patient should be seen after 2 weeks and
  then after 2-3 months.
• Review medications and possible adverse
  effects
• Review cardiac signs, BP, HR, rhythm, new
  murmur, JVP, edema ,..
• Blood sugar should be checked
• ELECTROLYTES AND CREATININE SHOULD
  BE CHECKED
• A more detailed clinical examination should
  be performed.
• Patient education.
A&E Case
Mr. Ahmed hasn't been to your clinic
  for more than a 1 year ,you are
  the SHO on call and you were
  called to see Mr. Ahmed in the
  A&E department complaining of
  blurring of vision, headache and
  vomiting, his BP was found to be
  220/130 mm Hg. clinically has S4
  and papillodema.
S4:
produced by atrial contraction against stiff
hypertrophied ventricle is seen in:
Systemic hypertension
Scarring following MI
etc
papilloedema
PC:
  blurring of vision, headache and vomiting.

HPC:
  HTN for more than one year.

O/E:
 BP : 220/130 mm Hg.
 S4
  papillodema.
What is your diagnosis?
Malignant hypertension: sever elevation in
BP resulting in target organs damage with
the presence of papilloedema
Accelerated hypertension: is a recent
significant increase over baseline blood
pressure that is associated with target
organs damage but without papilledema.
Hypertensive encephalopathy :is a
group of symptoms present in severe
hypertension: headache, vomiting, visual
disturbance, mental status changes,
seizure, and retinopathy with papilledema
Our diagnosis:



   Malignant hypertension with
evidence    of hypertensive
encephalopathy
Pathophysiology:

Normal : 60-120 mm Hg.
Hypertensive: 110-180 mm Hg
hydrostatic leakage across the capillaries
within CNS
arteriolar damage and necrosis occur.
generalized vasodilatation, cerebral edema,
and papilledema.
Other causes of hypertensive
encephalopathy
1.Renal:Chronic renal parenchymal
disease,Acute glomerulonephritis,
Pheochromocytoma
Renovascular hypertension
2.CVS: Collagen vascular disease,
Vasculitis
3. NS: Head trauma, Encephalitis,
meningitis, Autonomic hyperactivity
4.Withdrawal from hypertensive agents (eg,
)clonidine)
Is it hypertensive urgency or
emergency?
Hypertensive emergencies:are
characterized by severe elevations in BP
complicated by evidences of ongoing vital
TOD .

They require:
BP reduction within minutes or hours (not
necessarily to normal) to prevent further
TOD
Hypertensive urgency:
Sever hypertension with no evidence of ongoing
processes of TOD.
Rarely requires emergency treatment.
Goal is reduction in BP to ≤ 160/110-100 over 24-
48 hours with oral therapy.
Rest in quiet environment & loop diuretic (20-40mg
furosemide) then additional agents: blocker,
CCB, -agonist.
How can you manage
Mr.Ahmed?
1.admitted ICU
2. continuous cardiac monitoring
   with invasive BP monitoring
   frequent assessment of neurologic status.
   Assess urine output.
3.IV medications.
4. The initial goal of therapy :
 to reduce MABP by 25% (within minutes to
1 hour)
 then if stable, to 160/100–110 mmHg within
the next 2–6 hours.
                                           •
NOTE:
Excessive falls in pressure that
may precipitate renal,
cerebral, or coronary
ischemia should be avoided
What are the potential
consequences if he isn’t treated
quickly?
One year survival is less than 20%
Patient could have :
1.Cerebral edema and hemorrhage .
2.Rapidly progressive RF.
3.Cardiac complications: ( HF,MI dissecting
aortic aneurysm)
What are the futher investigations
that should be done in our
patient?
Urinanalysis
Blood gloucose
Glycated Hg
RFT
Lipid profile
Chest X-ray
What will be the suitable drugs
at this stage?
Proper antihypertension medications:

Hypoglycemic medications
Others: statin
       aspirin
What advice should be given to
him to emphasize compliance?
References:
1.Hypertensive Encephalopathy, Ryan C Chang, MD.
www,emedicine.com accessed on 9th October 2006.
2.Malignant hypertension, John D Bisognano,www.emedicine.com
accessed on 9th October 2006.
3. Hypertensive Heart Disease , Kamran Riaz,
www,emedicine.com accessed on 9th October 2006.
4. Hypertension , Sat Sharma, www,emedicine.com accessed on
9th October 2006.
5. Ramsay LE, Williams B, Johnston DG, MacGregor GA, Poston
L, Potter JF, et al. Guidelines for management of hypertension:
report of the third working party of the British Hypertension
Society, 1999. J Hum Hypertens 1999; 13: 569-592
6.Harrisons principlee of internal medicine,14th edition,the
McGraw compaies, 1998

				
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