This document discusses hypertension, including its definition, diagnosis, classification, etiology, and treatment. It defines hypertension as persistently elevated blood pressure and notes it is usually diagnosed based on repeated blood pressure measurements. Treatment includes several classes of antihypertensive drugs like diuretics, beta blockers, calcium channel blockers, ACE inhibitors, and ARBs. The document provides details on representative drugs in each class and their mechanisms and side effects.

2. HYPERTENSION
• “Hypertension is defined as persistently
elevated arterial blood pressure (BP)”.
• Hypertension is the most common
cardiovascular disease.
• According to some studies, 60–80% of both
men and women will develop hypertension by
age 80.
• Sustained arterial hypertension damages
blood vessels in kidney, heart, and brain and
leads to renal failure, coronary disease, heart
failure, stroke, and dementia.

3. DIAGNOSIS
• The diagnosis of hypertension is based on
repeated, reproducible measurements of
elevated blood pressure.
• Diagnosis of hypertension depends on
measurement of blood pressure and not on
symptoms reported by the patient.
• Risk factors include smoking, metabolic
syndrome; e.g. obesity, Hyperlipidemia,
diabetes and a family history of cardiovascular
disease.

4. Classification of hypertension on the
basis of B.P.
Classification Systolic
(mm Hg)
Diastolic
(mm Hg)
Normal <120 <80
Pre-Hypertension 120–139 80–89
Stage 1 Hypertension 140–159 90–99
Stage 2 Hypertension ≥160 ≥100

5. Etiology of Hypertension
• A specific cause of hypertension can be
established in only 10–15% of patients, called
Secondary hypertension.
• Secondary hypertension is usually caused by
chronic kidney disease (CKD) or Reno-vascular
disease.
• Other conditions are Cushing syndrome,
Hyperparathyroidism, Pheochromocytoma,
Hyperthyroidism.

6. Etiology of Hypertension
• Some drugs that may increase BP include
Corticosteroids, Estrogens, Non-steroidal anti-
inflammatory drugs (NSAIDs), Amphetamines.
• Primary or Essential Hypertension has no
specific cause.
• Factors which contribute in development of
Primary Hypertension includes; Humoral
Disturbance, CNS Disturbance or high Na
intake.

7. ANTI HYPERTENSIVE DRUGS
Anti-Hypertensive drugs includes:
• A = ACE Inhibitors, ARBs, Alpha Blockers
• B = Beta Blockers
• C = Ca Channel Blockers
• D = Diuretics
• E = etc

8. ANTIHYPERTENSIVE DRUGS
1.DIURETICS
• which lower blood pressure by depleting the
body of sodium and reducing blood volume.
• Initially, diuretics reduce blood pressure by
reducing blood volume and cardiac output,
peripheral vascular resistance may increase.
• Diuretics are effective in lowering B.P. by 10–
15 mmHg in most patients.

9. DIURETICS
• Diuretics alone often provide adequate
treatment for mild or moderate essential
hypertension.
• Thiazide diuretics are appropriate for most
patients with mild or moderate hypertension
and normal renal and cardiac function.
• Most powerful diuretics are Loop Diuretics
e.g. Furosemide, are used in severe
Hypertension.

10. DIURETICS
• Potassium-sparing diuretics are useful both to
avoid excessive potassium depletion and to
enhance the natriuretic effects of other
diuretics.
 ADVERSE EFFECTS:
• In the treatment of hypertension, the most
common adverse effect of diuretics (except for
potassium-sparing diuretics) is potassium
depletion.

11. 2. β-RECEPTOR BLOCKING AGENTS
• Propranolol; was the first β blocker to be
effective in hypertension and IHD.
• Propranolol (Non Selective) has now been
largely replaced by Cardioselective β blockers
such as metoprolol and atenolol.
• All β-adrenoceptor blocking agents are useful
for lowering blood pressure in mild to
moderate hypertension.

12. PROPRANOLOL
• Beta blockers have been shown to reduce
mortality after a myocardial infarction and
some also reduce mortality in patients with
heart failure.
• Propranolol decreases blood pressure
primarily as a result of a decrease in cardiac
output.
• Propranolol inhibits the stimulation of rennin
production by catecholamines (mediated by
β 1 receptors).

13. PROPRANOLOL
• The most important ADVERSE EFFECTS of the
β-blocking action occur in patients with
Bradicardia or cardiac conduction disease,
asthma and diabetes.
• When Propranolol is discontinued after
prolonged regular use some patients
experience a withdrawal syndrome,
manifested by nervousness, tachycardia &
increased blood pressure.

14. METOPROLOL & ATENOLOL
• Metoprolol and Atenolol, which are
Cardioselective, are the most widely used β
blockers in the treatment of hypertension.
• Cardioselectivity may be advantageous in
treating hypertensive patients who also suffer
from asthma, diabetes, or peripheral vascular
disease.
• Metoprolol is extensively metabolized by
CYP2D6 with high first pass metabolism.

15. • The drug has a relatively short half-life of 4–6
hours.
• Sustained-release Metoprolol is effective in
reducing mortality from heart failure
hypertension.
• ATENOLOL is not extensively metabolized and is
excreted primarily in the urine with a half-life of 6
hours.
• Recent studies have found Atenolol less effective
than Metoprolol in preventing the hypertension.
• Possible reason is once daily dose is not enough
to maintain the plasma conc. Of drug,

16. β-RECEPTOR BLOCKING AGENTS
• Betaxolol and Bisoprolol are β 1 -selective
blockers that are primarily metabolized in the
liver but have long half-lives.
• Because of relatively long half-lives, these
drugs can be administered once daily.
• Betaxolol at 10 mg/day and Bisoprolol at 5
mg/day.
• Increases in dosage to obtain a satisfactory
therapeutic effect.

17. Labetalol, Carvedilol & Nebivolol
• These drugs have both β-blocking and
vasodilating effects.
• Nebivolol is a β 1 -selective blocker with
vasodilating properties.
• D-Nebivolol has highly selective β 1 blocking
effects, while L-isomer causes vasodilation.
• The vasodilating effect may be due to an
increase in endothelial release of nitric oxide
via induction of endothelial nitric oxide
synthase.

18. 3. CALCIUM CHANNEL BLOCKERS
• Calcium channel blockers (CCB) also reduce
peripheral resistance and blood pressure.
• The mechanism of action in hypertension is
“inhibition of calcium influx into arterial
smooth muscle cells”.
• Verapamil, Diltiazem and Dihydropyridines
family ( Amlodipine, Felodipine, Nicardipine,
Nifedipine.) are all equally effective in
lowering B.P.

19. 3. CALCIUM CHANNEL BLOCKERS
• Verapamil has the greatest depressant effect
on the heart and may decrease heart rate and
cardiac output.
• Some studies shows an increased risk of
myocardial infarction or mortality in patients
receiving short acting Nifedipine for
hypertension.
• It is therefore recommended that short-acting
oral Dihydropyridines NOT be used for
hypertension.

20. • Nifedipine and the other Dihydropyridines
agents are more selective as vasodilators and
have less cardiac depressant effect.
• Sustained-release calcium blockers with long
half-lives provide smoother B.P. control and
are more appropriate for treatment of chronic
hypertension.
• IV Nicardipine and Clevidipine are available for
the treatment of hypertension when oral
therapy is not feasible.
• Parenteral Verapamil and Diltiazem can also
be used for the same indication.

21. 4. ANGIOTENSIN-CONVERTING
ENZYME (ACE) INHIBITORS
• Captopril and other drugs in this class inhibit
the converting enzyme peptidyl dipeptidase
that hydrolyzes Angiotensin I to Angiotensin II
and inactivates bradykinin, a potent
vasodilator.
• Enalapril is an oral prodrug that is converted
by hydrolysis to Enalaprilat, with effects
similar to those of Captopril.
• Enalaprilat itself is available only for I.V. use,
primarily for hypertensive emergencies.

22. • Lisinopril is a lysine derivative of Enalaprilat.
• Benazepril, Fosinopril, Moexipril, Perindopril,
Quinapril, Ramipril, and Trandolapril are other
long acting members of the class.
• All are prodrugs, like Enalapril, and are converted
to the active agents primarily in the liver.
• ACE inhibitors have a particularly useful role in
treating patients with chronic kidney disease
because they diminish Proteinuria and stabilize
renal function.

23. • This effect is particularly valuable in diabetes, and
these drugs are now recommended in diabetes
even in the absence of hypertension.
TOXICITY
• Severe hypotension can occur after initial doses
of any ACE inhibitor.
• ACE inhibitors cause acute renal failure,
hyperkalemia, dry cough sometimes
accompanied by wheezing, and Angioedema.
• ACE inhibitors are contraindicated during the
second and third trimesters of pregnancy
because of the risk of fetal hypotension and renal
failure.

24. 5.ANGIOTENSIN RECEPTOR BLOCKING
AGENTS
• Losartan and Valsartan were the first
marketed blockers of the angiotensin II type 1
(AT 1 ) receptor.
• Candesartan, Eprosartan, Irbisartan,
Telmisartan, and Olmesartan are also
available.
• They have no effect on bradykinin metabolism
and are therefore more selective blockers of
Angiotensin effects than ACE inhibitors.

25. • ARBs provide benefits similar to those of ACE
inhibitors in patients with heart failure and
chronic kidney disease.
• The adverse effects are similar to those
described for ACE inhibitors, including the
hazard of use during pregnancy.
• Cough and Angioedema can occur but are less
common with ARBs than with ACE inhibitors.

26. 6.HYDRALAZINE
• Hydralazine, a hydrazine derivative, dilates
arterioles but not veins.
• The benefits of combination therapy are now
recognized, and Hydralazine may be used
more effectively, particularly in severe
hypertension.
• Hydralazine is well absorbed and rapidly
metabolized by the liver during the first pass,
so that bioavailability is low.

27. • The half-life of Hydralazine ranges from 1.5 to
3 hours, but vascular effects persist longer
than do blood concentrations, possibly due to
avid binding to vascular tissue.
• The most common adverse effects of
Hydralazine are headache, nausea, anorexia,
palpitations, sweating, and flushing.

28. 7.SODIUM NITROPRUSSIDE
• Sodium nitroprusside is a powerful
parenterally administered vasodilator that is
used in treating hypertensive emergencies.
• Nitroprusside dilates both arterial and venous
vessels, resulting in reduced peripheral
vascular resistance and venous return.
• The action occurs as a result of activation of
Guanylyl Cyclase, either via release of nitric
oxide or by direct stimulation of the enzyme.
The result is increased intracellular cGMP,
which relaxes vascular smooth muscle.

29. • Nitroprusside is a complex of iron, cyanide
groups, and a nitroso moiety.
• It is rapidly metabolized by uptake into red
blood cells with liberation of cyanide. Cyanide
in turn is metabolized by the mitochondrial
enzyme in the presence of a sulfur donor, to
the less toxic thiocyanate. Thiocyanate is
distributed in extracellular fluid and slowly
eliminated by the kidney.

30. • Nitroprusside rapidly lowers blood pressure,
and its effects disappear within 1–10 minutes
after discontinuation.
• The drug is given by intravenous infusion.
• Sodium nitroprusside in aqueous solution is
sensitive to light and must therefore be made
up fresh before each administration and
covered with opaque foil.