It covers about the antihypertensives classification, structures and mechanism of action and uses

1. MEDICINAL CHEMISTRY II
B. Pharmacy III/IV (First sem.)
DR. K. PURNA NAGASREE
M.PHARM. (BITS, PILANI), PH.D., PDF (DST, WOSA)
ANTI HYPETENSIVES

2. ANTI
HYPETENSIVES
Timolol, Captopril, Lisinopril,
Enalapril, Benazepril
hydrochloride, Quinapril
hydrochloride,
Methyldopate hydrochloride,*
Clonidine hydrochloride,
Guanethidine monosulphate,
Guanabenz acetate,
Sodium nitroprusside,
Diazoxide, Minoxidil,
Reserpine, Hydralazine
hydrochloride

3. ANTIHYPETENSIVES
Antihypertensives are defined as the drugs that are used
to decrease the elevated blood pressure (hypertension)
 Hypertension
It is one of the common cardiovascular disorders and it
is a state of the body in which the systolic blood
pressure (BP) is 150 mm Hg or more and diastolic BP is
95 mm Hg or more.

4. PRIMARY HYPERTENSION
 It is other wise known as essential hypertension. It is
characterized by the following:
 Elevation of diastolic BP
 Normal cardiac output
 An increase in peripheral resistance
SECONDARY HYPERTENSION
Factors causing secondary hypertension are as follows:
 Acute or chronic renal disease
 Hyperaldosteronism
 Cushing’s syndrome
 Acromegaly
 Pheochromocytoma
 Oral contraceptives, steroids, estrogen, and sympathomimetics

5. CLASSIFICATION
 I. Diuretics
a. Thiazides
b. Loop diuretics
c. Potassium-sparing diuretics
 II. Drugs acting on sympathetic system
a. Centrally acting drugs
i. Clonidine ii. α-Methyl dopa iii. Guanabenz
b. Catacholamine depletors
Reserpine

6. CLASSIFICATION
c. Adrenergic blockers
i. ß-adrenergic blockers - Timolol
ii. alpha-Aderenergic blockers
iii. Mixed alpha and ß blockers (non selective)
iv. Imidazoline receptor agonist
d. Aderenergic neuron blockers
Guanethidine
e. Ganglion blockers
i. Quaternary ammonium compounds
ii. Secondary amines
iii. Tertirary amines

7. CLASSIFICATION
 III. Calcium channel blockers
 IV. Drugs acting on renin-angiotensin system
a. Drugs that block renin release—Propranolol
b. Drugs that inhibit angiotensin II—Saralasin
c. Drugs that inhibit angiotensin II receptors
d. Drugs that inhibit aldosterone—Spironolactone
e. ACE inhibitors
i. Sulphahydryl containing ACE inhibitors – Captopril
ii. Dicarboxylate containing ACE inhibitors- Enalapril,
Lisinopril, quinapril HCl, Benazepril HCl

8. CLASSIFICATION
 V. Va s o d i l a t o r s
i. Hydralazine
ii. Diazoxide
iii. Minoxidil
iv. Sodium Nitroprusside

9.  When the heart's ventricles squeeze to move blood forward, this is known
as systole. Diastole, on the other hand, is when the ventricles relax and
fill with blood.

10. II. Drugs acting on sympathetic
system
a. Centrally acting drugs
Clonidine

11. α-Methyl
dopa
II. Drugs acting on sympathetic system
a. Centrally acting drugs

12. Guanabenz
II. Drugs acting on sympathetic system
a. Centrally acting drugs

13. II. Drugs acting on sympathetic system
b. Catacholamine depletors
Reserpine

14. II. Drugs acting on sympathetic system
c. Adrenergic blockers
i. ß-adrenergic blockers
Timolol

15. II. Drugs acting on
sympathetic system
d. Aderenergic neuron blockers
i. Guanethidine

16. IV. Drugs acting on renin-angiotensin
system e. ACE inhibitors
i. Sulphahydryl containing ACE inhibitors
CaptoprilIt is a white or almost white
crystalline powder and it
dissolves in dilute sodium
hydroxide and potassium
hydroxide solution.
It is also soluble in water,
methylene chloride, and methanol.
The first orally effective ACE
inhibitor to have been marketed,
Used in treatment of hypertension,
heart failure, left ventricular
dysfunction, and postmyocardial
infarction.

17. ii. Dicarboxylate containing ACE
inhibitors
Benazepril HCl

18. Enalapril
 It is a white or almost white, crystalline powder, and it dissolves
in dilute solutions of alkali hydroxides, sparingly soluble in
water, freely soluble in methanol, but insoluble in methylene
chloride.
 A prodrug is converted to the active ACE inhibitor, enalaprilat.
 Used in the treatment of hypertension, heart failure, and
asymptomatic left ventricular dysfunction.
 It produces well to excellent responses in patients with
Essential hypertension.
1-[N -1-Carboxy-3-phenyl propyl]-L-alanyl]-l-proline-1-ethyl ester

19. Lisinopril
 It is a white or almost white crystalline powder, and is
insoluble in acetone and in ethanol, soluble in water,
but sparingly soluble in methanol.
 It is used in the treatment of renovascular
hypertension, essential, malignant hypertension, and
also for ventricular congestive heart failure.
1-[N-1-Carboxy-3-phenyl propyl]-L-lysyl]-l-proline

20. Qu i napr i l
 It exists as white crystals.
 It is used as an antihypertensive agent and is
also used in the treatment of congestive heart
failure. Quinaprilate is the active form
2-[2-[[1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-3,4-dihydro-1H-
isoquinoline-3-carboxylic acid; hydrochloride

21. Benazepril
 It exists as a white crystalline powder that is soluble
in water, ethanol, or methanol.
 It is beneficial for patients with congestive heart
failure.
2-[-3-[[1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-2-oxo-4,5-dihydro-3H-1-
benzazepin-1-yl]acetic acid

22. Mechanism of action
 Angiotensionogen
 Angiotensin I
 Angiotensin II
 Vasoconstriction and sodium retention
 Hypertension
 Bradykinin, Substance P
 Angio oedema, dry cough

23. V. Va s o d i l a t o r s
i. Hydralazine
 It is a white or almost white crystalline powder, which
is slightly soluble in methylene chloride, but soluble in
water and slightly soluble in alcohol.
 The side effects are tachycardia and palpitations may
Precipitate attacks of angina pectoris.
 It is used in the treatment of moderate to severe
hypertension.

24. iii. Minoxidil
It is a white or almost white crystalline powder, which is slightly
soluble in water, soluble in methanol and in propylene glycol.
Minoxidil, which is a piperidino pyrimidine derivative directly
relaxes arteriolar smooth muscle, and is indicated for patients
with severe hypertension, who do not respond to other drugs.
It is used as the last line of therapy to treat moderate to severe
essential hypertension.
A side effect is excessive hair growth. Consequently, the drug is
used topically to restore hair Growth in androgenic alopecia and
alopecia areata.

25. ii. Diazoxide
It is a white or almost white and fine crystalline powder that is
soluble in dilute solutions of alkali hydroxides, in
dimethylformamide, slightly soluble in alcohol, but insoluble in
water.
A potent vasodilator, it can be used intravenously as a
hypotensive drug in acute hypertensive crisis.
It is also used as antihyperglycemic agent.

26. Mechanism of action
 Diazoxide is a benzothiadiazine derivate with antihypertensive
and hyperglycemic activities.
 Diazoxide increases membrane permeability to potassium ions
in vascular smooth muscle, thereby stabilizing the membrane
action potential and preventing vascular smooth muscle
contraction; this results in peripheral vasodilatation and
decreases in peripheral vascular resistance.
 This agent also inhibits insulin release by interacting with ATP-
sensitive potassium channels of pancreatic islet beta-cells.

27. iv. Sodium Nitroprusside
It is a reddish-brown powder or crystals, freely soluble in water,
but slightly soluble in alcohol.
A potent directly acting peripheral vasodilator, this drug has an
immediate onset of effect and short duration of action, therefore,
it is effective in treating hypertensive emergencies
Side effects of this drug include significant hypotension and
cyanide or thiocyanate toxicity. MOA similar to nitro vasodilators