Remix education
pharmacystudy material

Anti-hypertensive Agents (Med Chem:- 2) Notes Download


A condition in which the blood pressure of systemic artery increases beyond the
normal pressure is known as hypertension. Therefore to deliver blood to tissues, the
heart works harder to overcome the increased systemic pressure. This increased
systemic arterial pressure puts strain on heart and other arteries, thus resulting in high
blood pressure. Based on the degree of severity, hypertension can be graded as:
1) Mild: Diastole up to 104 mmHg,
2) Moderate: Diastole105-114 mmHg, and
3) Severe: Diastole more than 115 mmHg.
Therapy for hypertensive patients aims at reducing the increased blood pressure.
This is accomplished by administration of drugs from different classes; treatment
is often given in the form of a combination of several agents. If left untreated, it
would result in end organ damage, an increased risk for MI and stroke.
6.1.2. Classification
Antihypertensive drugs are classified as follows:
1) Diuretics
i) Thiazides: Hydrochlorothiazide, Chlorthalidone, and Indapamide.
ii) Loop Diuretics: Furosemide, Bumetanide, and Torsemide.
iii) Potassium Sparing Diuretics: Spironolactone, Amiloride, and Triamterene.
2) Angiotensin Converting Enzyme Inhibitors: Captopril, Enalapril, Lisinopril,
Ramipril, Perindopril, Fosinopril, Trandolapril, Quinapril, and Benazepril.
3) Angiotensin II Receptor Antagonists: Losartan, Candesartan, Valsartan,
Eprosartan, and Irbesartan.
4) Ganglion Blockers: Trimethaphan.
5) Adrenergic Drugs
i) Centrally Acting Drugs: Clonidine, Methyldopa, Guanabenz, &Guanfacine.
ii) Adrenergic Neuron Blockers: Guanethidine and Reserpine.
iii) Sympatholytics (Adrenergic Receptor Blockers)
a) -Blockers: Prazosin, Terazosin, Doxazin, Phenoxybenzamine, and
b) -Blockers: Propranolol, Atenolol, Esmolol, and Metoprolol.
c)  & -Blockers: Labetalol and Carvedilol.
6) Calcium Channel Blockers: Verapamil, Nifedipine, Nicardipine,
Nimodipine, Amlodipine, and Felodipine.

7) Vasodilators
i) Arteriolar Dilators: Hydralazine, Minoxidil, and Diazoxide.
ii) Arteriolar and Venular Dilators: Sodium nitroprusside.
6.1.3. Mechanism of Action
Anti-hypertensive drugs involve the following mechanisms:
1) Diuretics: These drugs are secreted into the u rine by the proximal tubule
cells. The three diuretic types used for treating hypertension are:
i) Thiazide Diuretics: These diuretics work initially by increasing urinary
sodium excretion by inhibiting the Na+
pump in the early segment of
the distal convoluted tubule. This causes an initial reduction in plasma
volume, which increases plasma renin activity and aldosterone.
Eventually, vascular resistance decreases by unknown mechanisms
because plasma volume approaches pre-treatment levels.
ii) Loop Diuretics: These diuretics act at the thick ascending loop of Henle
to prevent sodium and chloride reabsorption from urine. They have a
rapid onset of action compared to thiazide diuretics. Torsemide is the
longest-acting loop diuretic.
iii) Potassium-Sparing Diuretics: These diuretics decrease the excretion of
magnesium and potassium. Amiloride and triamterene inhibit the Na +

proton exchanger in the distal and collecting tubules. They block the
epithelial sodium transport chan nel. Spironolactone inhibits the Na +
exchanger affected by aldosterone, and it is particularly effective in
hyperaldosteronism. It is a potent non -selective aldosterone blocker that
also interacts with androgen and progesterone receptors.
Figure 6.1: ACE inhibitors block the conversion of angiotensin I
and angiotensin II via angiotensin converting enzyme, but do
not prevent the formation of angiotensin II via alternate
pathways. Angiotensin II Receptor Blockers (ARBs) work at the
receptor level to block the binding of angiotensin II to its Type 1
receptor (AT1
), which mediates all known pressor effects of
angiotensin II. (BK, Bradykinin)
Renin blockade
2) Angiotensin-Converting Enzyme (ACE) Inhibitors: These drugs slow
down the formation of angiotensin II, which reduces vascular resistance,
blood volume, and blood pressure. Renin enzyme is released by the kidneys
in response to reduced renal blood circulation or hypernatremia. This enzyme
acts in the plasma angiotensinogen to produce angiotensin I which is then
converted to angiotensin II, mostly in the lungs. Angiotensin II is a
vasoconstricting agent. It causes sodium retention via aldosterone re lease. In
adrenal gland, angiotensin II is converted to angiotensin III. Both of them
stimulate the release of aldosterone.
3) Angiotensin II Receptor Blockers (ARBs): These drugs inhibit the final
step of renin-angiotensin cascade, i.e., the interaction betw een angiotensin II
and the angiotensin II type 1 receptor (AT1) – which is thought to mediate all
effects of this hormone and some of its effects that promote atherosclerosis.
ARBs result in more complete antagonism of angiotensin II than ACE
inhibitors, b ecause angiotensin II can be produced by non -ACE pathways
(figure 6.1). ARBs do not cause elevations in bradykinin, which may be
responsible for the dry cough seen with ACE inhibitors.
4) -Blockers: These drugs decrease the cardiac output by blocking -
adrenergic receptors in the heart, resulting in negative chronotropic (heart
rate) and inotropic (contractility) effects. The -blockers also decrease renin
release from the kidney and are thought to decrease sympathetic outflow to
the periphery via central eff ect. Over -activity of the sympathetic nervous
system increases blood pressure by increasing cardiac output.
5) Calcium Channel Blockers: These drugs block or alter cell membrane
calcium flux. Dihydropyridine calcium channel blockers ( e.g., amlodipine,
felodipine, and nifedipine) lower the blood pressure via arteriolar and venous
vasodilation; non-dihydropyridine calcium channel blockers ( e.g., verapamil
and diltiazem) are less potent vasodilators and lower the blood pressure
through peripheral vasodilation and a negative inotropic effect.
6) Vasodilators: Available evidence suggests that a single mechanism does not
exist; instead various vasodilators act at different places in a series of
processes that couple excitation of vascular smooth muscle cells with
contraction. For example, the vasodilators known as calcium channel
antagonists block or limit the entry of calcium through voltage -dependent
channels in the membrane of vascular smooth muscle cells. In this way, the
calcium channel blockers limit the amount of free intracellular calcium
available to interact with smooth muscle contractile proteins. Other
vasodilators, such as diazoxide and minoxidil, cause dilation of blood
vessels by activating potassium channels in vascular smooth muscle. An
increase in potas sium conductance results in hyperpolarisation of the cell
membrane, which will cause relaxation of vascular smooth muscle.
Another group of drugs, called nitrovasodilators (e.g., nitroprusside)
activate soluble guanylate cy clase in vascular smooth muscle to increase the
intracellular levels of cGMP. This i ncrease in cGMP is associated with
vascular smooth muscle relaxation.

Subject:- Medicinal chemistry 2

Semester:- Sem 5

Course:- Bachelor of pharmacy