This document provides information on hypertension (high blood pressure), including its types, classification, pathophysiology, diagnosis, and treatment. It discusses the mosaic theory of hypertension and factors involved in fluid volume regulation. It outlines the clinical presentation of hypertension and diagnostic evaluation. Finally, it provides details on non-pharmacological and pharmacological treatment approaches for hypertension, describing specific drug classes like diuretics, beta-blockers, ACE inhibitors, and others.

1. Prepared By
Dr.K.Sivasakthi Pharm D
Assistant Professor
HYPERTENSION

2. Persistent elevation of arterial blood pressure
Types:
Primary or essential or idiopathic(80-95%)
(no identifical causes)
Secondary (10%)
Identifical causes
Renal disease,renal vascular hypertension, cushing
syndrome, primary hyperaldosteronism

4. Adult Blood Pressure
Classification

5. pathophysiology
 Blood Pressure = Cardiac Output X Total
Peripheral Vascular Resistance (TPR)
 Altering any of the factors on the right side of the
blood pressure equation results in a change in
blood pressure

9. Mosaic theory
 Mosaic theory centers around the fact that multiple factors,
rather than one factor alone, are responsible for sustaining
hypertension. The interactions among the sympathetic nervous
system, renin–angiotensin–aldosterone system, and potential
defects in sodium transport within and outside the cell may all
play a role in long-term hypertension. Additional factors
contributing to the development include genetics, endothelial
dysfunction, and neurovascular anomalies.

10. Fluid volume regulation.
 Increased fluid volume increases venous system
distention
affecting cardiac output and tissue perfusion. These
changes alter vascular resistance,
increasing the blood pressure.

12. CLINICAL PRESENTATION
 Patients with uncomplicated primary hypertension are usually
asymptomaticinitially.
 Patients with secondary hypertension may complain of
symptoms suggestive of the underlying disorder.
1. Patients with pheochromocytoma may have a history of
paroxysmal headaches, sweating, tachycardia, palpitations,
and orthostatic hypotension.
2. In primary aldosteronism, hypokalemic symptoms of muscle
cramps and weakness may be present.
3. Patients with hypertension secondary to Cushing’s syndrome
may complain of weight gain, polyuria, edema, menstrual
irregularities, recurrent acne, or muscular weakness

13. DIAGNOSIS
 Frequently, the only sign of primary hypertension on physical examination
is elevated BP. The diagnosis of hypertension should be based on the average
of two or more readings taken at each of two or more clinical encounters.
 As hypertension progresses, signs of end-organ damage begin to appear,
chiefly related to pathologic changes in the eye, brain, heart, kidneys, and
peripheral blood vessels.
 The funduscopic examination may reveal arteriolar narrowing,focal
arteriolar narrowing, arteriovenous nicking, and retinal hemorrhages,
exudates, and infarcts. The presence of papilledema indicates hypertensive
emergency requiring rapid treatment.

14.  Cardiopulmonary examination may reveal an abnormal
heart rate or rhythm, left ventricular (LV) hypertrophy, third
and fourth heart sounds, and rales.
 Peripheral vascular examination can detect evidence of
atherosclerosis, which may present as aortic or abdominal
bruits, distended veins, diminished or absent peripheral
pulses, or lower extremity edema.
 Patients with Cushing’s syndrome may have the classic
physical features of moon face, buffalo hump, hirsutism,
and abdominal striae.

15. NON
PHARMACOGICAL
TREATMENT

17. PHARMACOLOGICAL
TREATMENT
 Diuretics.
 Beta-blockers.
 ACE inhibitors.
 Angiotensin II receptor blockers.
 Calcium channel blockers.
 Alpha blockers.
 Alpha-2 Receptor Agonists.
 Combined alpha and beta-blockers.
 vasodilators

19. DIURETICS
Thiazide diuretics
 JNC-7 recommends initiating therapy with a low dose (12.5 mg)
of hydrochlorothiazide [Microzide®]),
 increasing the dose if necessary, and not exceeding a dose of 50
mg of hydrochlorothiazide or its equivalent.

20. ACTIONS
Antihypertensive effects are produced by directly dilating the
arterioles and reducing the total fluid volume.
Thiazide diuretics increase the following:
(a) Urinary excretion of sodium and water by inhibiting sodium
and chloride reabsorption in the distal convoluted (renal)
tubules
(b) Urinary excretion of potassium and, to a lesser extent,
bicarbonate

21. Precautions and monitoring
effects
(a) Potassium ion (K) depletion may require
supplementation, increased dietary intake, or the use of a
potassium-sparing diuretic, such as spironolactone
(b) Uric acid retention may occur; this is potentially
significant in patients who are predisposed to gout and
related disorders.
(c) Blood glucose levels may increase, which may be
significant in patients with diabetes.
(d) Calcium levels may increase because of the potential for
retaining calcium ions.
(e) Patients with known allergies to sulfa-type drugs should
be questioned to determine the significance of the allergy.

22. (f) Hyperlipidemia, including hyper triglyceridemia,
hypercholesterolemia, increased low-density lipoprotein
(LDL) cholesterol, and decreased high-density lipoprotein
(HDL) cholesterol, must be evaluated routinely to prevent
an added risk for coronary artery disease.
(g) Other common effects include fatigue, headache,
palpitations, rash, vertigo, and transitory impotence.

23. (h) Fluid losses must be evaluated and monitored to prevent
dehydration, postural hypotension, and even hypovolemic
shock.
(i) Alterations in fluids and electrolytes (e.g., hypokalemia,
hypomagnesemia,hypercalcemia) may predispose patients
to cardiac irritability, with a resultant increase in cardiac
arrhythmias. ECG is performed routinely to detect and
prevent the development of life-threatening arrhythmias

24. Usual effective doses
 Chlorothiazide : 250 to 500 mg daily or twice daily
 Chlorthalidone : 12.5 to 25 mg daily
 Hydrochlorothiazide :12.5 to 50 mg daily
 Indapamide : 1.25 to 5.0 mg daily
 Methyclothiazide : 2.5 to 5.0 mg daily
 Metolazone : 2.5 to 5.0 mg daily

25. LOOP (HIGH-CEILING) DIURETICS
Indications
 These agents are indicated when patients are unable to
tolerate thiazides, experience a loss of thiazide
effectiveness, or have impaired renal function (clearance 30
mL/min).

26. Actions
 Loop diuretics act primarily in the ascending loop of Henle;
hence, they are called “loop” diuretics. By acting within the
loop of Henle, they decrease sodium reabsorption.
 Their action is more intense but of shorter duration (1 to 4
hrs) than that of the thiazides;

27. Precautions and monitoring
effects
 Loop diuretics have the same effects as thiazides
(a) Loop diuretics have a complex influence on renal
hemodynamics; thus, patients must be monitored closely
for signs of hypovolemia.
(b) Because these agents should be used cautiously in
patients with episodic or chronic renal impairment, BUN
and serum creatinine levels should be checked routinely.
(c) Transient deafness has been reported. If the patient is
taking a potentially ototoxic drug (e.g., anaminoglycoside
antibiotic), another class of diuretic (e.g., a thiazide
diuretic) should be substituted.

28. Usual effective doses
 Bumetanide (Various): 0.5 to 2.0 mg daily
 Ethacrynic acid (Edecrin®): 25 to 100 mg daily
 Furosemide (Lasix®): 20 to 80 mg daily
 Torsemide (Demadex®): 2.5 to 10 mg daily

29. Potassium-sparing diuretics
Indications
 Spironolactone (aldactone®), amiloride (various),
And triamterene (dyrenium®)—are indicated for patients in
whom potassium loss is significant and supplementation is not
feasible. These agents are often used in combination with a
thiazide diuretic because they potentiate the effects of the
thiazide while minimizing potassium loss.
 These agents have been used in hypertension and have an
increased level of use in the treatment of HF

30. Actions
 Potassium-sparing diuretics achieve their diuretic effects
differently and less potently than the thiazides and loop
diuretics. Their most pertinent shared feature is that they
promote potassium retention.

31. Precautions and monitoring effects
(a) Potassium-sparing diuretics should be avoided in patients with acute
renal failure and used with caution in patients with impaired renal
function (monitor serum creatinine) because they can retain
potassium.
(b) Triamterene (Dyrenium®) should not be used in patients with a
history of kidney stones or hepatic disease.
(c) Hyperkalemia is a major risk, requiring routine monitoring of serum
electrolytes.
 BUN and serum creatinine levels should be checked routinely to
signal incipient excess potassium retention and impaired renal
function.

32. Usual effective doses
 Amiloride: 5 to 10 mg daily
 Spironolactone (Aldactone): 25 to 100 mg daily and 400
mg daily to treat hyperaldosteronism
 Triamterene : 50 to 100 mg daily
 Eplerenone : 50 to 100 mg daily

33. Adrenergic beta blockers
Indications
 Beta Blockers are particularly effective in patients with
rapid resting heart rates (i.e., atrial fibrillation, paroxysmal
supraventricular tachycardia) or for those compelling
indications, such as heart failure, post-MI and high
coronary disease risk

35. Actions
 Stimulation of renin secretion is blocked.
 Cardiac contractility is decreased, thus diminishing cardiac
output.
 Sympathetic output is decreased centrally.
 Reduction in heart rate decreases cardiac output.
 Young ( 45 years) whites with high cardiac output, high
heart rate, and normal vascular resistance respond best to -
blocker therapy.

36. Precautions and monitoring
effects
 Patients must be monitored for signs and symptoms of cardiac
decompensation (i.e., reduction in cardiac output) owing to the fact that
decreased myocardial contractility can trigger compensatory mechanisms,
leading to HF
 ECGs should be monitored routinely because all beta-blockers can decrease
electrical conduction within the heart and cause bradyarrhythmias.
 Relative cardio selectivity is dose dependent and is lost as dosages are
increased. No beta-blocker is totally safe in patients with broncho spastic
disease—that is asthma and chronic obstructive pulmonary disease (COPD).

37. Usual effective doses
Metoprolol - 50 to 100 mg
Atenolol-25 to 100 mg
Labetalol -200 to 800 mg
Carvedilol-12.5 to 50 mg daily
Nebivolol -5 mg

38. Peripheral alpha 1-adrenergic
blockers
example,
 prazosin
 terazosin
 Doxazosin

39. Actions
 The alpha 1-blockers (indirect vasodilators) block the
peripheral postsynaptic 1-alpha adrenergic receptor,
causing vasodilation of both arteries and veins.
 The incidence of reflex tachycardia is lower with these
agents than with the vasodilator hydralazine(various).
 Recent studies have also shown that these agents have
no adverse effect on serum lipids and other cardiac risk
factors

40. Precautions and monitoring
effects
First-dose phenomenon
 A syncopal episode may occur within 30 to 90 mins of
the first dose; similarly associated are postural
hypotension, nausea, dizziness, headache,palpitations,
and sweating.
 To minimize these effects, the first dose should be
limited to a small dose (1 mg) and administered just
before bedtime.

41.  Additional adverse effects include diarrhea, weight gain,
peripheral edema, drymouth, urinary urgency,
constipation, and priapism.
 Doxazosin (Cardura®) in doses of 2 to 8 mg/day was one
of the treatment arms in the recent Antihypertensive and
Lipid-Lowering Treatment to Prevent Heart Attack Trial
(ALLHAT), and the treatment was discontinued
prematurely owing to an apparent 25% increase in the
incidence of combined cardiovascular disease outcomes
than patients in the control group receiving the diuretic
chlorthalidone. The added risk for HF, stroke, and
coronary heart disease were the major outcomes affected
in the doxazosin arm.

42. Usual effective doses
 Prazosin (Minipress®): 2 to 20 mg
 Terazosin (Hytrin®): 1 to 20 mg
 Doxazosin (Cardura®): 1 to 16 mg

43. Centrally active -agonists

44. Precautions and monitoring
effects
(i) orthostatic hypotension,
(ii) fluid accumulation (in the absence of a diuretic), and
rebound hypertension on abrupt withdrawal.
(iii) Sedation is a common finding upon initiating therapy and
when increasing doses; however, the sedative effect
usually decreases with continued therapy.
(iv) Fever and other flu-like symptoms occasionally occur
and may represent hepatic dysfunction, which should be
monitored by liver function tests.

45. v. A positive Coombs test develops in 25% of patients
with chronic use ( 6 months).Less than 1% of these
patients develop a hemolytic anemia. (Red blood
cells,hemoglobin, and blood count indices should be
checked.) The anemia is reversible by discontinuing
the drug.
vi. Other effects include dry mouth, subtly decreased
mental activity, sleep disturbances, depression,
impotence, and lactation in either gender.

46. ACE inhibitors
Indications
 first-line alternatives for treating hypertension in patients
unable to tolerate thiazides or beta blockers.
 JNC-7 recommendations have identified specific patient
populations that have compelling indications—such as
diabetes mellitus, post-MI, high coronary disease risk,
chronic kidney disease, and recurrent stroke prevention—
for which the ACE inhibitors are indicated in the treatment
of hypertension or pre hypertension.

48. ACTIONS
(1) These agents inhibit the conversion of angiotensin I (a
weak vasoconstrictor) to angiotensin II (a potent
vasoconstrictor), which decreases the availability of
angiotensin II.
(2) ACE inhibitors indirectly inhibit fluid volume increases
when interfering with angiotensin II by inhibiting
angiotensin II–stimulated release of aldosterone, which
promotes sodium and water retention. The net effect
appears to be a decrease in fluid volume, along with
peripheral vasodilation.

49. Significant interactions
 The antihypertensive effect of ACE inhibitors may
be diminished by NSAIDs (e.g., over the counter
forms of ibuprofen).
 Potassium-sparing diuretics increase serum
potassium levels when used with ACE inhibitors,
and potassium levels need to be closely
monitored in these patients.

50. Precautions and monitoring
effects
(1) Neutropenia is rare but serious; there is an increased incidence in
patients with renal insufficiency or autoimmune disease.
(2) Proteinuria occurs, particularly in patients with a history of renal
disease. Urinary proteins should be monitored regularly.
(3) Serum potassium levels should be monitored regularly for
hyperkalemia. The mechanism of action tends to increase potassium
levels somewhat. Patients with renal impairment are at increased risk.

51. (4) Renal insufficiency can occur in patients with predisposing factors, such as
renal stenosis, and when ACE inhibitors are administered with thiazide
diuretics. Renal function should be monitored (e.g., through monitoring levels
of serum creatinine and BUN).
(5) A dry cough may occur but disappears within a few days after the ACE
inhibitor is discontinued.
All ACE inhibitors have the potential to cause this side effect, but switching
to an alternative agent may improve the symptoms.
(6) Other untoward effects include rashes, an altered sense of taste (dysgeusia),
vertigo, headache, fatigue, first-dose hypotension, and minor gastrointestinal
disturbances.

52. Usual effective dose
Captopril
 12.5 to 25 mg dose three times daily
 increased to a usual daily dose of 25 to 100 mg in two or
three doses.
Enalapril
 5 mg daily, with a usual daily dose of 5 to 40 mg in one
to two doses.
Lisinopril
 daily dose and adjusted to a usual daily dose of 10 to 40
mg

53. Angiotensin II type I receptor antagonists
Indications
 fastest growing groups of drugs for the treatment of
hypertension.
Actions
 This class of drugs works by blocking the binding of
angiotensin II to the angiotensin II receptors. By blocking
the receptor site, these agents inhibit the vasoconstrictor
effects of angiotensin II while also preventing the release
of aldosterone from the adrenal glands.
 These two properties of angiotensin II have been shown to
be important causes for developing hypertension.
Clinically, angiotensin receptor blockers appear to be

54. Precautions and monitoring
effects
(1) When used alone, hyperkalemia has not been reported to be severe enough
to require stopping its use. However, as in patients receiving ACE inhibitors,
potassium levels need to be monitored closely in those with compromised
renal function.
(2) Similar to ACE inhibitors, declining renal function or acute renal failure
will result in elevated serum potassium levels, owing to the kidneys inability
to excrete potassium. BUN and serum creatinine levels should be monitored
to prevent the development of hyperkalemia.

55. Usual effective dose
 Candesartan: 8 to 32 mg in one to two doses
 Eprosartan : 400 to 800 mg in one to two doses
 Irbesartan : 150 to 300 mg in one dose
 Losartan : 25 to 100 mg in one to two doses
 Olmesartan : 20 to 40 mg in one dose
 Telmisartan: 20 to 80 mg in one dose
 Valsartan : 80 to 320 mg in one to two doses
 Azilsartan : 80 mg daily in one dose

56. Calcium-channel blockers
Indications
 The calcium-channel blockers are considered alternative
drugs for the initial treatment of hypertension in select
patient populations that are unable to take –beta
blockers, such as patients with a high coronary disease
risk or diabetes mellitus who also have bronchospastic
disease or Raynaud disease.

57. Actions
Calcium-channel blockers inhibit the influx of calcium
through slow channels in vascular smooth muscle and
cause relaxation. Low- renin hypertensive, black, and
elderly patients respond well to these agents.

58. Significant interactions
 Beta blockers, when used with calcium-channel
blockers, may have an additive effect on inducing HF
and bradycardia.
 Electrical conduction to the AV node may be further
depressed when patients are given agents such as
verapamil or diltiazem along with beta -blockers.

59. Precautions and monitoring
effects
(1) Diltiazem and verapamil must be used with extreme
caution or not at all in patients with conductive
disturbances involving the SA or AV node, such as second-
or third-degree AV block, sick sinus syndrome, and digitalis
toxicity.
(2) Nifedipine use has been associated with flushing,
headache, and peripheral edema; the patient may find these
troubles and thus may become noncompliant. Using the
sustained-release product, once daily has been shown to
effectively reduce these effects.
(3) Verapamil use has been associated with a significant
degree of constipation, which must be treated to prevent
stool straining and noncompliance

60. Usual effective dose
 Amlodipine : 2.5 to 10 mg in one dose
 Isradipine : 2.5 to 10 mg in one to two doses
 Felodipine : 2.5 to 20 mg in one dose
 Nicardipine : 60 to 120 mg as an extended-release product
twice daily
 Nisoldipine : 10 to 40 mg in one dose
 Clevidipine : Intravenous administration only; as 1 to 2
mg/hr, doubled at 90-second intervals up to target blood
pressure goal.

61. Vasodilators
 These drugs are used as second-line agents.
 Vasodilators directly relax peripheral vascular smooth
muscle—arterial, venous, or both.

62. Hydralazine
Actions
 Hydralazine directly relaxes arterioles, decreasing systemic
vascular resistance.
 It is also used intravenously or intramuscularly in managing
hypertensive crisis.
Usual daily dose - 25 to 100 mg.

63. Precautions And Monitoring
Effects
 Hydralazine triggers compensatory reactions that
counteract its antihypertensive effects, it is most useful
when combined with a beta -blocker, central alpha -
agonist, or diuretic as a latter-step agent.
 Reflex tachycardia is common and should be considered
before initiating therapy.
 Hydralazine may induce angina, especially in patients with
coronary artery disease and those not receiving a beta-
blocker.

64.  Drug-induced systemic lupus
erythematosus (SLE) may occur.
 Baseline and serial complete blood counts
(CBCs) with antinuclear antibody titers
should be followed routinely to detect SLE.
 Slow acetylators of this drug have an
increased incidence of SLE. Their risk
maybe reduced by administering doses of
200 mg/day.
 Fatigue, malaise, low-grade fever, and joint
aches may signal SLE.

65.  Other adverse effects may include headache, peripheral
neuropathy, nausea, vomiting, fluid retention, and
postural hypotension.

66. Nitroprusside
Actions
 A direct-acting peripheral dilator, this agent has potent effects on both the
arterial and venous systems. It is usually used only in short-term emergency
treatment of acute hypertensive crisis, when a rapid effect is required.
 Onset of action is almost instantaneous and is maximal in 1 to 2 mins.
 Nitroprusside is administered intravenously with continuous blood pressure
monitoring.
Usual dose - 0.3 to 10 mcg/kg/min as a continuous intravenous infusion

67. Precautions and monitoring
effects
 To prevent acute hypotensive episodes, initial doses should be very low,
followed by slow titration upward until the desired effect is achieved.
(a) Once the solution is prepared, it should be protected from light. Color
changes are a signal that replacement is needed.
(b) Thiocyanate toxicity may develop with long-term treatment—particularly
in patients with reduced renal activity—but can be treated with
hemodialysis. Symptoms may include fatigue, anorexia, disorientation,
nausea, psychotic behavior, or muscle spasms.
(c) Cyanide toxicity can occur (rarely) with long-term, high-dose
administration. It may present as altered consciousness, convulsions,
tachypnea , or even coma.

68. Renin Inhibitors
Indications
 Aliskiren (Tekturna®) is the first of this new class of drugs recently approved
by the FDA for the treatment of hypertension.
Actions
 Unlike ACE inhibitors and ARBs, aliskiren works directly on the enzyme
renin, to reduce the eventual production of angiotensin II.

69. Usual effective dose
 Aliskiren (Tekturna®) is available in 150 and 300 mg
tablets.
 The usual starting dose is 150 mg daily, and for those who
do not respond the dose can be increased to 300 mg daily.
 Doses greater than 300 mg have not been shown to offer
additional blood pressure lowering effects.

70. Significant interactions
 Furosemide serum levels have been reported to be reduced
significantly when administered in patients receiving
aliskiren. This might result in a diminished pharmacologic
effect from furosemide.

71. Precautions and monitoring
effects
 diabetic patients receiving both ACE inhibitors or ARBs in
combination with aliskiren, close monitoring of serum
electrolytes and renal function is required due to an
increased frequency of elevated serum potassium levels.

73. Reference
 Comprehensive Pharmacy Review 8th editsion- Leon
Shargel
 Text Book Of Pharmacotherapy- T. Dipiro