diagnosis assessment prevention of hypertension

1. HYPERTENSION

2. Definition
 Hypertension can be defined as a disorder
of CVS where in there is a persistent
elevation of arterial blood pressure to an
extent where clinical benefit is obtained
from lowering of blood pressure
 Diagnosis is confirmed when the average
of 2 or more systolic blood pressure is
>140mm Hg or diastolic blood pressure is
≥90mm Hg or (normal being 120/80mm
Hg)

3. CLASSIFICATION
JNC VII (Joint national committee
classification)
Class Systolic
blood
pressure
(mm Hg)
Diastolic blood
pressure
(mm Hg)
Normal <120 <80
Pre Hypertensive 120-139 80-89
Stage I HT 140-159 90-99
Stage II HT ≥160 ≥100

4. Etiology
1. Primary/essential (90-95%)
2. Secondary (5-10%)
3. Medication/Drug induced Hypertension
Primary (Unknown cause)
 Age->55 males and >65females
 Genetics
 Environmental stress
 Sodium intake
 Alcohol
 Weight
 Race
 Smoking
 Sedentary lifestyle
 Diabetes mellitus
 Dyslipidaemia

5. Contd..
Secondary(specific cause)
 Renovascular disease (renal artery stenosis)
 Endocrine disorders:
Pheochromocytoma, Cushings syndrome, Primary
aldosteronism, thyrotoxicosis, myxoedema
 Drug induced: NSAIDs, oral corticosteroids,
antidepressants, appetite stimulants, erythropoetin
 Sleep apnea
 Chronic kidney disease
 Preclampsia (prior to pregnancy)
 Stress

6. Contd..
Drug induced Hypertension
Medications
 Oral contraceptives
 Steroids
 Appetite suppressants
 Tricyclic anti depressants
 Cyclosporine
 NSAIDs

7. Regulation of Blood Pressure
 The mean Blood Pressure is the
product of cardiac output and total
peripheral resistance
 In most Hypertensive individuals,
cardiac output is not increased and
high BP arises as a result of
increased total peripheral resistance
caused by constriction of small
arterioles

8. Contd..
Control of Blood Pressure is regulated
by a number of homeostatic reflexes
to provide blood pressure
Homeostasis
 Sympathetic Nervous System
 Renin-Angiotensin Aldosterone System
 Fluid volume regulation
 Mosaic Theory

9. Sympathetic Nervous System
Baroreceptors in the carotids and aortic arch
Respond to changes in BP
Vasodilation Vasoconstriction
Constricted
Contractile Force
Heart Rate
Peripheral Resistance
Cardiac Output

10. Renin Angiotensin Aldosterone System
Decreased Renal Perfusion
Pressure in Afferent Arterioles
Release of Renin from
Juxtaglomerular cells
Angiotensinogen
Angiotensin
Stimulates
Aldosterone release
Increased Na reabsorption
Fluid Volume

11. Fluid Volume Regulation
Increased Fluid Volume
Venous System Distension and Venous Return
Alter Vascular Resistance
Cardiac Output
Blood Pressure

12. Mosaic Theory
 It states that multiple factors are
responsible for sustaining hypertension
rather than one factor alone
 Interactions between the sympathetic
nervous system, Renin Angiotensin-
Aldosterone system and potential defects
in sodium transport within and outside
the cell all play a role in long term
Hypertension

13. Complications of Hypertension
 Cardiac effects
 Renal effects
 Cerebral effects
 Retinal effects

14. Cardiac Effects
 Left ventricular hypertrophy compensates for
the increased cardiac workload
 Signs and symptoms of heart failure occur and
the increased oxygen requirements of the
enlarged heart may produce Angina Pectoris
 Hypertension can also be caused by
accelerated atherosclerosis. Atheromatous
lesions in the coronary arteries lead to
decreased blood flow resulting in Angina
Pectoris
 Myocardial infarction and sudden death may
occur

15. Renal Effects
Accelerated Atherosclerosis
Oxygen supply
Renal Parenchymal Damage
Decreased filtration capability
Azotemia

16. Contd..
Atherosclerosis
Blood flow to renal arterioles
Nephrosclerosis
Renal failure

17. Cerebral Effects
Decreased blood flow, oxygen supply
and weakened blood vessel walls
Transient Ischemic attacks, Cerebral
thromboses and development of
Aneurysms with Hemorrhage

18. Retinal Effects
Decreased Blood flow+Retinal vascular
sclerosis+Increased arteriolar pressure with
the appearance of exudates and Hemorrhage
Visual Defects (Blurred
vision, spots, blindness)

19. Evaluation of Hypertensive Patients
Three main criteria
 Medical History
 Physical examination
 Laboratory tests

20. Medical History
 Family history of Hypertension and
Hypertensive complications
 History of cardiovascular, cerebrovascular
or renal diseases or diabetes mellitus
 Duration and level of Blood Pressure
evaluation
 Effectiveness and side effects of previous
drug treatment
 Medication history of drugs that elevate
BP
 Lifestyle and health habits: Smoking,
alcohol, sodium intake, caffeine, exercise
or emotional stress

21. Physical Examination
 Two or more BP measurements with
patient supine or seated and standing
 Verification of BP in the contralateral arm
 Height and weight with calculation of
body mass index or measurement of
waist circumference
 Fundoscopic examination for arteriolar
narrowing, arteriovenous compression,
hemmorhage, exudates and papilloedema

22. Contd..
 Neck examination for carotid bruits,
distended veins and enlarged thyroid
 Cardiac examination for increased heart
rate, size, murmurs, arrhythmias
 Abdominal examinations for bruits,
enlarged kidneys, aortic dilation
 Extremity examination for oedema,
femoral bruits and decreased or absent
pulses
 Neurologic assessment

23. Laboratory Tests
 Hb and Haematocrit
 Urinalysis- Urinary albumin/creatinine
ratio
 Serum potassium
 Serum Creatinine or estimated glomerular
filtration rate
 Serum uric acid
 Serum calcium
 Fasting lipid panel
 Fasting plasma glucose
 Electrocardiogram

24. Diagnosis
 Hypertension is not diagnosed on an initial
reading rather it is confirmed after two or
more properly measured readings
 Various diagnostic tests are recommended
before initiating the therapy
 ECG, Blood glucose, Haemoglobin,
Haematocrit, complete urinalysis, Serum
Potassium and Creatinine, Liver function
tests, Calcium and Magnesium,
Glycosylated Haemoglobin, Fasting lipid
panel(9-12hr fast) which includes test for
LDL, HDL and triglycerides
 Optional tests include Urinary albumin
excretion or albumin/creatinine ratio

25. Treatment
Goals of Drug Therapy
 The goal of Antihypertensive therapy is to reduce
cardiovascular and renal morbidity and mortality
 Reducing BP to less than 140/90mm Hg is
associated with a decrease in the risk of
cardiovascular disease
 In patients with Hypertension and comorbidities
(diabetes or renal disease), the BP goal endorsed
by JNC, American Diabetes Association, The
National Kidney Foundation and the Canadian
Hypertensive Society is less than 130/80mm Hg
 The American College of Physicians goal for
systolic BP is slightly higher at 135mm Hg

26. Principles of Antihypertensive Therapy
Guidelines as indicated in JNC-VI and
WHO can be summarised as follows
1. Except for advanced stage Hypertension,
start with a single most appropriate drug
2. Initiate therapy at low dose, if needed
increase dose moderately. Thiazide dose
should not be>12.5-25mg/day unless
specifically mandated
3. If only partial response, add a drug from
another complimentary class or change
to low dose combination

27. Contd..
4. If no response, change to a drug from
another class or low dose combination
from other classes
5. One ingredient of the combination
should generally be a thiazide
6. In case of side effect to the initially
chosen drug, either substitute with drug
of another class or reduce dose and add
a drug from another class

28. Pharmacological Treatment
1 Diuretics Thiazides: Hydrochlorthiazide,Xipamide
Thiazide like: Indapamide,Chlorthalidone
Loop: Furosemide, Bumetamide, Torsemide
Pot sparing: Amiloride, Spironolactone
CAI: Acetazolamide
2 Beta
Blockers
Selective: Atenolol, Betaxolol, Timolol,
Propranolol, Metoprolol
Combined: Carvedilol, Labetolol
3 ACE
Inhibitors
Captopril, Enalapril, Fosinopril, Lisinopril
4 Angiotensin
II receptor
blockers
Losartan, Valsartan, Candesartan

29. Contd…
5 Calcium Channel
Blockers
Non dihydropyridines: Diltiazem,
Verapamil
Dihydropyridines:
Amlodipine,Felodipine, Nicardipine
6 Peripheral alpha-1
receptor blockers
Doxazosin, Prazosin, Terazosin
7 Central alpha-2
receptor agonists
Clonidine, Guanfacine, Guanabenz
Methyldopa
8 Direct Vasodilators Hydralazine, Minoxidil
9 Adrenergic
Antagonists
Guanadrel, Guanethidine,
Reserpine

30. Diuretics
 MOA: Diuretics decrease BP by
causing diuresis, which results in
decreased plasma volume, stroke
volume and cardiac output
 During chronic therapy, their major
hemodynamic effect is reduction of
peripheral vascular resistance

31. Thiazide Diuretics
 MOA: Thiazide diuretics work by increasing
the urinary excretion of sodium and
chloride in equal amounts
 They inhibit the re absorption of sodium
and chloride in the thick ascending limb of
the loop of henle and the early distal
tubules
 They also increase potassium and HCO3
excretion and decrease calcium excretion
and uric acid retention
 Thiazide diuretics are the preferred agents
to reduce BP unless there are compelling or
specific indications for another drug
 Duration of action of the thiazides requires
a single daily dose to control BP

32. Contd..
Drugs Dose ADR
Chlorthalidone 12.5-
100mg qd
Hyperuricaemia, Hypokalemia,
Hypomagnesemia,
Hyponatremia,
Hyperglycemia,
Hypercalcaemia,
Hypercholesterolemia,
Hypertriglyceridemia,
Pancreatitis, rashes
Hydrochlorthiazide 12.5-
25mg qd
Same as above
Metolazone 2.5-5mg
qd
Same as above

33. Loop Diuretics
 MOA: Furosemide and Ethacrynic acid
inhibit the re absorption of sodium and
chloride not only in proximal and distal
tubules but also in the loop of henle

34. Contd..
Drugs Dose ADR
Bumetanide 0.5-5mg bd-td Dehydration,
circulatory collapse,
hypokalemia,
hyponatremia,
Hypomagnesemia,
Hyperglycemia,
metabolic alkalosis,
hyperuricaemia
Ethacrynic acid 25-100mg bd-td Same as above
(ototoxicity)
Furosemide 20-320mg qd Same as above

35. Potassium sparing diuretics
 MOA: These interfere with sodium
re absorption at the distal tubule,
thus decreasing potassium secretion

36. Contd..
Drugs Dose ADR
Amiloride 5-10mg bd-qd Hyperkalemia,
GI disturbances,
rashes
Spironolactone 12.5-100mg
bd-qd
Same as above
(Gynecomastia)
Triamterene 50-150mg bd-
qd
Same
(Nephrolithiasis)

37. Beta Blockers
Beta blockers
reduce BP by
blocking central
and peripheral
beta receptors
which results in
decreased cardiac
output and
sympathetic
outflow
Blockade of beta-I receptors on
the surface of juxtaglomerular
cells
Reduced Renin Release
Decreased
stimulation of the
Renin- Angiotensin
Aldosterone system

38. Contd..
 Beta-1 receptors are referred to as
cardioselective because they do not block
beta-2 receptors and therefore do not
stimulate bronchoconstriction (Metoprolol,
betaxolol, atenolol, acebutolol, bisoprolol)
 Partial beta receptor agonists like
Pindolol, Penbutolol, Carteolol and
acebutolol also reduce heart rate and
contractility during excessive sympathetic
outflow

39. Contd..
 Beta blockers also decrease sympathetic
activity involved with the progression of
heart failure (Carvedilol decreases
mortality in patients with heart failure)
 Dose of beta blockers should be tapered
gradually over 14 days to prevent
withdrawl symptoms which include
unstable angina, MI or even death in
patients with cardiovascular disease

40. Contd..
Drugs Dose ADR
Atenolol 25-100mg qd Fatigue, depression,
bradycardia, exercise
tolerance, CHF, bronchospasm,
Raynaud’s phenomenon,
insomnia, hallucinations, acute
mental disorder, impotence,
serum triglycerides, HDL
Bisoprolol 2.5-10mg
qd
Same as above
Timolol 10-60mg
bd
Same as above

41. Contd..
Metoprolol 50-100mg bd-qd Same as above
Propranolol 40-160mg bd
60-180mg bd
Same as above
Pindolol 10-40mg bd Same (less
resting
bradycardia and
lipid changes)
Acebutolol 200-600mg bd Same as above
Carvedilol 12.5-50mg bd Same but more
postural
hypotension,
bronchospasm

42. ACE Inhibitors
 MOA: These exert an antihypertensive
effect by inhibiting ACE, which is
responsible for converting AgI to AgII, a
potent vasoconstrictor
 They also inhibit the degradation of
Bradykinin and increase the synthesis of
vasodilating PG’s
 Indicated as first line therapy in
Hypertensive patients who have
proteinuria

43. Contd..
Drugs Dose ADR
Captopril 25-100mg bd-td Cough, hypotension,
hyperkalemia, loss of taste,
leukopenia, angioedema,
neutropenia, agranulocytosis
Enalapril 2.5-40mg bd-qd Same as above
Lisinopril 10-40mg qd Same as above
Ramipril 2.5-20mg qd Same as above

44. Angiotensin II Receptor Blockers
 MOA: ARB’s block the vasoconstriction
and aldosterone secreting effects of AgII
by selectively blocking the binding of AgII
receptor found in many tissues
 Indicated for patients with hypertension,
nephropathy in type II diabetes, heart
failure and those who cannot tolerate the
side effects associated with ACE inhibitors

45. Contd..
Drugs Dose ADR
Losartan 25-100mg bd-
qd
Similar to
ACE inhibitors
but does not
cause cough,
angioedema,
hyperkalemia
Valsartan 80-320mg qd Same as
above
Candesartan 8-32mg qd Same as
above

46. Calcium Channel Blockers
 These inhibit the movement of calcium
ions across the cell membrane
 The effects on the CVS include depression
of mechanical contraction of myocardial
and smooth muscle and depression of
both impulse formation and conduction
velocity
 This results in muscle relaxation and
vasodilation

47. Contd..
 Common CCB’s such as Verapamil
and Diltiazem decrease heart rate
and slow cardiac conduction at the
AV node
 Dihydropyridines like Amlodipine,
Nifedipine are potent vasodilators
 Indicated for treating hypertension
associated with IHD

48. Contd..
Drugs Dose ADR
Diltiazem Hcl Tiazac:180-420mg qd
Diltia XT:120-480 mg qd
Cardizemla:120-540mg qd
Dizziness, headache,
edema, constipation,
lupus like rash,
conduction defects,
worsening of systolic
dysfunction, gingival
hyperplasia
Verapamil Hcl Isoptin SR:120-480mg qd
Covera HS:180-480mg qd
Same as above
Amlodipine 2.5-10mg qd Dizziness, headache,
rash, peripheral
oedema, flushing,
gingival hypertrophy

49. Contd..
Nicardipine 60-120mg bd Same as
amlodipine
Nifedipine 60-120mg bd Same as
amlodipine

50. Peripheral alpha receptor blockers
 MOA: They act peripherally by
dilating both arterioles and veins
causing relaxation of smooth
muscles
 Also cause a decrease in LDL and
cholesterol
 Effective in patients with benign
prostatic hypertrophy

51. Contd..
Drugs Dose ADR
Doxazosin 1-16mg qd Postural
hypotension,
lassitude, vivid
dreams, depression,
fluid retention,
weakness, priapism,
drowsiness
Prazosin 2-20mg bd-td Same as above
Terazosin 1-20mg bd-qd Same as above

52. Central alpha-2 receptor agonists
 MOA: These stimulate alpha-2 adrenergic
receptors in the brain resulting in
decreased sympathetic outflow, cardiac
output and peripheral resistance
 These may cause fluid retention and usually
used in combination with a diuretic
 Abrupt cessation of alpha-2 agonist therapy
may result in a compensatory increase in
the NE level which in turn raises BP. This
effect is called as Rebound Hypertension

53. Contd..
Drugs Dose ADR
Clonidine 0.1-0.8mg bd-td Sedation, dry
mouth,
bradycardia,
heart block
Guanabenz 4-64mg bd Same as above
Guanfacine 0.5-2.0mg qd Same as above
Methyldopa 250-1000mg bd Same as above
(autoimmune
disorders, colitis,
hepatitis,
hemolytic anemia

54. Direct Vasodilators
 MOA: These cause arteriolar smooth
muscle relaxation resulting in
reduced BP
 Are generally reserved for patients
with essential or severe
hypertension

55. Contd..
Drugs Dose ADR
Hydralazine 25-100mg bd Tachycardia,
aggravation of
angina, headache,
dizziness, fluid
retention, nasal
congestion, lupus
like syndrome,
dermatitis, drug
fever, hepatitis,
peripheral
neuropathy
Minoxidil 2.5-80mg bd-qd Same as above

56. Adrenergic Antagonists
 MOA: These inhibit the sympathetic
nervous system by depleting nor
epinephrine stores in the CNS which
decreases peripheral vascular
resistance thereby reducing BP

57. Contd..
Drugs Dose ADR
Guanadrel 10-75mg bd Postural hypotension,
diarrhea, weight gain,
syncope
Guanethidine 10-50mg qd Same as above
(greater incidence of
diarrhea)
Reserpine 0.1-0.25-0.5mg qd Nasal stiffness,
drowsiness, GI dist,
bradycardia,
nightmares with
doses, fluid retention,
depression, peptic
ulcer

58. BP>120/80
Lifestyle modifications
Not at goal BP(<140/90mm Hg or 130mm Hg for those
with diabetes or CKD
Initial drug choices
Hypertension
without CI
Hypertension with CI
Stage I HT
Systolic BP 140-159mmHg
Diastolic BP90-99mm Hg
Stage II HT
Systolic BP≥160mm
Hg or Diastolic BP
≥100mm Hg
Thiazide Diuretics for
most .May consider
ACEI, ARB, Beta
blockers, CCB or
combn
2 drug comb( usually
thiazide and ACEI or
ARB or Beta blocker or
CCB
Not at goal BP
Diuretics, ACEI, Beta
Blockers, ARB or
CCB as needed
Optimise dosages or
add additional drugs
until goal BP is
achieved. Consider
consultation with a
Physician

59. Hypertensive Emergency
 Also called as malignant hypertension and can be
defined as severe elevation in diastolic BP usually
>120mm Hg in the presence of target organ
damage
 The marked elevation in BP results in arteriolar
fibrinoid necrosis, endothelial damage, platelet
and fibrin deposition in the smooth muscle and
loss of autoregulatory function
 This results in end organ ischemia such as
encephalopathy, MI, unstable angina, pulmonary
oedema, eclampsia, stroke, intracranial
hemorrhage and arterial bleeding

60. Treatment
 The drug of choice to treat Hypertensive
emergencies depends on the clinical
situation
 Commomly used medications include
Nitroprusside, IV Nitroglycerine,
Diazoxide, Trimethapan, Labetalol and
Hydralazine
 In cases of Hypertensive urgency without
evidence of organ damage, the BP can be
reduced over 24 hours
 Fast acting oral agents such as Captopril
and Clonidine are commonly used

61. Monitoring Patient Response
 Patients should be followed at 1 month
intervals after the initiation of treatment
until the goal BP is attained
 Once the desired BP is attained, patients
should return for visits until the target BP
is achieved
 Serum creatinine and potassium levels
should be monitored once or twice a year
in patients taking antihypertensive
medications

62. Contd..
 Patients with stage I or stage II HT should
be scheduled for a follow-up visit 2 to 4
weeks after initiation of drug therapy or a
change in the drug regimen
 Patients with stage III or Hypertensive
urgency should be seen within 2 weeks
 Once BP returns to a normal range, the
patient should be monitored every 3 to 6
months

63. Non Pharmacological Treatment
Lifestyle modifications to manage
Hypertension
 Weight reduction: Maintain normal body
wt (BMI 18.5-24.9)
 Adopt DASH eating plan: Consume a diet
rich in fruits, vegetables and low fat dairy
products with a reduced content of a
saturated and total fat
 Dietary sodium retention: Reduce dietary
sodium intake to not more than
100meq/L(2.4g sodium or 6g Nacl)

64. Contd..
 Physical activity: Engage in regular
aerobic physical activity such as
brisk walking (at least 30 mins per
day)
 Moderation of alcohol consumption:
Limit consumption to not more than
2 drinks/day

65. REFERENCES
 Text Book of Clinical Pharmacy and
Therapeutics-Roger Walker
 Pharmacotherapeutics for Advance
Practice (Second Edition): Virginia Poole
Arcangelo
 Text Book of Therapeutics (Eighth Edition)
Eric T. Herfindal
 Pharmacotherapy- A Pathophysiologic
Approach (Third Edition): Joseph T. Dipiro