Important points about Antihypertensive drugs

1. ANTIHYPERTENSIVE DRUGS

2. • Most common CVS condition.
• Persistent and sustained increased BP has
damaging effect on heart, brain, kidney, eye •
Types:
– Primary/essential: No specific cause (95% of
cases).
– Secondary hypertension: Due to specific
disease or drug (5% of cases)

4. I. Drugs acting on the sympathetic nervous system
1) Beta-adrenoceptor antagonists (b -blockers)
2) Alpha-Adrenoceptor Antagonists (a-blockers)
3) Centrally Acting Sympatholytics (a2-Adrenoceptor Agonists)
4) Adrenergic Neuron Blockers
5) Ganglion Blockers
II. Drugs affecting the renin-angiotensin system
1) Angiotensin-converting enzyme (ACE) inhibitors
2) Angiotensin Receptor Antagonists
III. Diuretics
IV. Calcium Channel Antagonists
V. Potassium Channel Activators
VI. Others
ANTIHYPERTENSIVE DRUGS

5. II. Drugs affecting the renin-
angiotensin system

6. 1) Angiotensin-converting enzyme (ACE)
inhibitors
Examples: Captopril, Enalapril
Mechanisms of action
n Competitive inhibition of ACE reduces generation of
angiotensin II and consequently reduces the release
of aldosterone. Reduced tissue concentrations of
angiotensin II leads to arterial and, to a lesser extent,
venous dilation.
n ACE also degrades vasodilator kinins. Increased
kinins in the vascular wall may contribute to the
hypotensive actions of ACE inhibitors.

8. Uses of ACE Inhibitors:
Ø Treatment of hypertension
Ø Treatment of heart failure
Ø Diabetic nephropathy
Adverse effects
Ø Dry cough & angioedema caused by accumulation of
kinins in the lung,
Ø postural hypotension,
Ø disturbance of taste,
Ø rashes

9. 2) Angiotensin Receptor Antagonists
Example: Losartan
Mechanism of action
n The angiotensin receptor antagonists are selective for the
AT1 receptor subtype, which is found in the heart, blood
vessels, kidney, adrenal cortex, lung and brain.
Advantages of Losartan: Rare incidence of dry cough
and angioedema
Adverse effects: Headache, fatigue

10. IV. Calcium Channel Antagonists

11. IV. Calcium Channel Antagonists
Examples: Nifedipine, Amlodepine, Diltiazem
M.O.A.:
The Ca2+ channel antagonists (Ca2+ antagonists)
lower blood pressure principally by arterial
vasodilation.
Clinical Uses:
Ø Treatment of hypertension
Ø Prevention and treatment of supraventricular
arrhythmias

12. V. Potassium Channel Activators

13. V. Potassium Channel Activators
Example: Minoxidil
Mechanism of action
n Minoxidil activates cell membrane potassium channels
leading to potassium accumulation in the cell and
hyperpolarization of the cell membrane.
Unwanted effects
n Arterial vasodilatation produces flushing and
headache.
n The reflex sympathetic nervous system response to
vasodilatation causes tachycardia and palpitation.
n Hirsutism; therefore rarely used for women.

14. VI. Others

15. 1) Hydralazine
Mechanism of action
v It may activate guanylate cyclase leading to the intracellular
production of cGMP.
v This produces relaxation by a mechanism similar to that of
organic nitrates.
Pharmacokinetics
v Hydralazine is metabolized in liver by N-acetylation.
Adverse effects
v Arterial vasodilation and reflex sympathetic activation.
v A systemic lupus erythematosus-like syndrome, which is
more common in slow acetylators.

16. 2) Nitroprusside
Mechanism of action
n Nitroprusside is a nitro vasodilator with a
mechanism of action similar to that of organic
nitrates
n It produces dilation of arterioles and veins,
reducing both peripheral resistance and
venous return.
n Its use is limited to the emergency
management of some hypertensive states.

17. Pharmacokinetics
n Metabolism to cyanide within red blood cells terminates
its effect.
n The cyanide is partly bound in the erythrocyte.
n Free cyanide is converted in the liver to less toxic
thiocyanate.
Adverse effects
n Confusion
n Weakness and nausea caused by thiocyanate accumulation