Normal Blood Pressure Blood Pressure of < 140/ 90 Blood Pressure of 130 to 139/ 85 to 89 should be closely watched High Blood Pressure Blood Pressure > 140/ 90 How can I tell if I have High Blood Pressure? Usually NO SYMPTOMS! “The Silent Killer” May have: Headache, Blurry vision, Chest Pain, Frequent urination at night Definition: These are the drugs used to lower BP in hypertension Types of Hypertension: 1. Primary/ Essential / Idiopathic: Definite cause is unknown Characterized by - BP, normal CO, P.V.R. 2. Secondary Hypertension: Secondary to- Renal – Glomerulonephritis, pylonephritis etc Endocrine – Hyperaldosteronism, Cushing’s syndrome etc Vascular Diseases- renal artery disease etc.

1. Anti-hypertensive drugs
Umesh B. Mahajan,
Assistant Professor,
Department of Pharmacology,
R. C. Patel Institute of Pharmaceutical
Education and Research

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Hypertension
n Normal Blood Pressure
n Blood Pressure of < 140/ 90
n Blood Pressure of 130 to 139/ 85 to 89 should be
closely watched
n High Blood Pressure
n Blood Pressure > 140/ 90
n How can I tell if I have High Blood Pressure?
n Usually NO SYMPTOMS!
n “The Silent Killer”
n May have: Headache, Blurry vision, Chest Pain,
Frequent urination at night

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Anti-hypertensives
n Definition: These are the drugs used to lower BP in hypertension
n Types of Hypertension:
1. Primary/ Essential / Idiopathic:
Definite cause is unknown
Characterized by - BP, normal CO, P.V.R.
2. Secondary Hypertension:
Secondary to-
Renal – Glomerulonephritis, pylonephritis etc
Endocrine – Hyperaldosteronism, Cushing’s syndrome etc
Vascular Diseases- renal artery disease etc.

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Classification
1. ACE inhibitors:
Captopril, Enalapril, Lisinopril, Ramipril etc.
2. Angiotensin Antagonist:
Losartan, Candesartan, Irbesartan
3. Ca++ Chanel Blockers:
Verapamil, Diltiazem, Nifedipine, Amlodipine, Felodipine
4. Diuretics:
A) Thiazides: Hydrochlorothiazide, Chlorthalidone
B) High ceiling: Furosemide
C) K+ Sparing: Spironolactone, Amiloride
5. Beta Adrenergic Blockers:
Propranolol, Metaprolol, Atenolol etc.

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6. Beta + Alfa Adrenergic Blockers:
Labetalol, Carvedilol
7. Alfa Adrenergic Blockers:
Prazosin, Terazosin, Phentolamine
8. Central Sympatholytics:
Clonidine, Methyldopa
9. Vasodilators:
Hydralazine, Minoxidil, Sodium Nitropruside

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Angiotensinogen AI AII
Renin
arteries
kidneys
adrenal glands
Aldosterone
Na+ Na+
Drugs acting on the
renin-angiotensin system

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Drugs acting on the
renin-angiotensin system
Angiotensinogen AI AII
Renin
arteries
kidneys
adrenal glands
Aldosterone
ACE Inhibitors
AIIRA
Spironolactone

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n One of the first choice drugs in all grades of essential &
renovascular hypertension.
n Most patients requires relatively low doses (Enalapril 2.5-10
mg/day) which are well tolerated.
n ACE inhibitors – control hypertension in about 50%
n ACE inhibitors + Diuretic/Beta blocker – efficacy in about 90%
n ACE inhibitors + Diuretic – supraadditive effect
n Potential for improving renal blood flow- thus used in diabetic
nephropathy, left ventricular hypertrophy, CHF, angina and MI.
n Dry persistence cough is side effect- requires discontinuation of
ACE inhibitor.
ACE Inhibitors

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n Captopril
n In hypertensive subjects:
ü Captopril systemic arterial resistance, mean, systolic & diastolic
BP.
ü Dilatation & blood flow in renal, cerebral & coronary beds.
ü Captopril compliance of large arteries and thus contributes to
the systolic BP
ü Baroreceptors function is reset, response to posture & exercise are
not impaired.

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ü Antihypertensive effects are seen in all varieties of hypertension
but most marked in patients with renovascular hypertension.
ü Effects are potentiated by concurrent use of diuretics.
ü Secretion of aldosterone is reduced but not seriously lowered.
n In CHF subjects:
ü As a result of peripheral arterial resistance – it afterload
ü Nitriuresis Aldosterone secretion
Expanded volume of bloodVasomotor tone
Venous return to the heart Preload

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n MOA of captopril
Competitive inhibition of conversion of AT-I to AT-II.
ü Thus it prevents:
ü A) The effect (AT-II)
ü B) Stimulation of aldosterone synthesis
ü ACE metabolizes Bradykinin
n ADME:
[ Rapidly absorbed from gut (Bioavailability of about 65%).
[ Cleared from body by renal excretion.
n Adverse effects:
? Generally well tolerated.
? Skin rashes, headache, GI disturbances, dry cough etc.

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n Preparation & dosage:
• Available as Tab of 25, 50, 10 mg.
• Initial starting dose adults is 12.5 mg, BD.
• Can be increased up to 50 mg BD
n Therapeutic uses:
n Hypertension:
Ø Useful in all types including malignant hypertension, When
combined with diuretic it can reduce hypokalemia,
hypercholesterolemia, hyperglycemia etc.
Ø It can be combined with any class of antihypertensive.
n Chronic CHF
n Diabetic nephropathy
n Acute MI

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n Enalapril
n It is the congener of captopril, has similar actions to those of
captopril & same precautions apply to its use.
n It differs from captopril:
Ø Enalapril (prodrug) Enalaprilat (active metabolite)
Ø Food does not interfere with its absorption.
Ø It is more potent than captopril.
Ø Its action is slower but long lasting.
Ø Hypotension & renal insufficiency are common with enalapril.
Ø Less liable to cause taste disturbances.

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Angiotensin Antagonists
n Losartan
Ø It acts as a selective angiotensin-II receptor antagonist and it
decreases peripheral vascular resistance.
Ø It lacks ADR of ACE inhibitors like cough.
Ø Given orally it is well absorbed and partly metabolized to more
active metabolite.
Ø It can causes skin rashes & neuropsychiatric disturbances such as
insomnia, confusion, nightmares etc.
Ø It is an expensive drug.
n Valsartan, Irbesartan & Candesartan are newer analogues of
Losartan

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Ca++ Channel Blockers
n These are first line antihypertensive drugs.
n They lower BP by PVR
n The onset of action is quick. Long acting preparations requires
once daily dose only.
n Monotherapy is effective in about 50% patients.
n Do not compromise hemodynamics.
n No sedation or other CNS effects.
n Not contraindicated in asthma.
n Do not impaired renal function.
n No harmful effect on lipid profile, uric acid level & electrolyte
balance.

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Diuretics
n Diuretics have been the standard anti-hypertensive drugs over
the past 4 decades.
n They Don’t lower BP in normotensives.
n Thiazides (Chlorthalidone)
n These are diuretics of choice in uncomplicated hypertension.
n MOA of thiazides:
Ø Diuresis reduces plasma & e.c.f. volume about 15%
decreased C.O.
Ø Thiazides are mild antihypertensive - average fall in BP is 10
mm/hg.
Ø They are effective alone in 30% cases but potentiates all the
antihypertensives.

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n High ceiling diuretics (Furosemide)
Ø Prototype of this class is a strong diuretic.
Ø Furosemide is a weaker antihypertensive than thiazides.
Ø The T.P.R. is not reduced and are more liable to cause fluid &
electrolyte imbalance.
Ø They are indicated in hypertension only when it is complicated
by: Chronic renal failure and coexisting CHF.
n Desirable properties of Diuretics as Antihypertensives:
Ø Once day dosing.
Ø No fluid retention & no tolerance.
Ø Low incidence of postural hypotension and relative freedom from
side effect.
Ø Low cost.

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n K+ sparing diuretics (Spironolactone/ amiloride)
Ø They lowers BP only slightly and are used only in conjugation
with thiazide diuretics.

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β-Adrenergic Blockers
Ø They are mild Anti-hypertensives, do not significantly lower
BP in normotensives.
Ø Their hypotensive response is well sustained
Ø All β -blockers irrespective of associated properties, exert
similar antihypertensive effect.
Ø They are contraindicated in cardiac, and peripheral vascular
diseases.
Ø These are the best choice drugs due to:
Ø Absence of postural hypotension, salt & water retention, low
incidences of side effects, low cost & once day administration.

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α + β Adrenergic blockers
n Labetalol:
Ø It is combined α & β blocker.
Ø Acts faster than pure β- blocker.
Ø Reduces T.P.R.
Ø Side effects of both α & β blocker occur with it.
n Carvedilol:
Ø It is nonselective β + selective α1 blocker.
Ø It produces vasodilatation, has antioxidant & free radical
scavenging activity.
Ø Side effects are similar to labetalol, liver enzyme may rise in
some patients.

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n Prazosin:
Ø This prototype of α1 dilates resistance vessels, reduction in
T.P.R. and BP.
Ø Renal blood flow & GFR are maintained.
Ø CVS refluxes are not impaired by the chronic therapy, but
postural hypotension occurs in the beginning.
Ø For this reason prazosin is always started at low dose (0.5 mg)
given at bed time and gradually increase with twice daily
administration (Max. 10 mg BD).
Ø Oral dose produce peak fall in BP after 4-5 hr. & effect lasts
for nearly 12 hrs.
α-Adrenergic blockers

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Ø Generally well tolerated at higher doses.
Ø Postural hypotension, headache, drowsiness, dry mouth,
weakness, nasal blockade, blurred vision and rash.
Ø Prazosin is potent antihypertensive with many desirable features
but is not used as first choice drug because of fluid retention &
gradual development of tolerance on monotherapy.
Ø Terazosin and Doxazosin are long acting congeners of prazosin
with similar properties and once daily dosing.

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n Clonidine:
Ø Decreases sympathetic outflow and causes fall in BP &
bradycardia
Ø It decline plasma level of NA
Ø Clonidine is well absorbed orally
Ø Peak occurs in 2-4 hrs. Plasma half life is 8-12 hrs. Effect of single
dose lasts for 6-24 hrs.
Central Sympatholytics

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n Adverse effects of clonidine:
Ø Side effects are relatively common & disturbing.
Ø Sedation, mental depression, disturbed sleep, dryness of mouth,
nose & eyes
Ø Salt & water retention, bradycardia.
Ø Postural hypotension.
Ø When doses of clonidine are missed – Alarming rise in BP,
tachycardia, restlessness, headache, nausea, vomiting etc.
Ø Regular schedule for drug administration must be maintained to
prevent withdrawal syndrome.
n Use:
Hypertension, effective & cheap, combined with diuretics.

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Vasodilators
n Hydralazine:
Ø It is directly acting vasodilator which reduces t.p.r.
Ø It increases the caliber of blood vessels.
Ø It causes grater reduction of diastolic than systolic BP.
Ø Hydralazine is well absorbed orally. Peak occurs in 1-2 hrs and is
subjected to first pass metabolism in liver.
Ø Plasma half life is 1-2 hrs but effect lasts up to 12 hrs.

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n Adverse Effects:
Ø Facial flushing, headache, dizziness, nasal stuffiness, fluid
retention, edema.
Ø Postural hypotension is not prominent
n Uses:
Ø Hydralazine is used in moderate to severe hypertension not
controlled by the first line drugs.
Ø Usually low doses are added to diuretics & β-blockers already
being administered.
Ø It is one of the preferred antihypertensive during pregnancy.

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