Antihypertensive drugs

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Classification of antihypertensive drugs:


According to mode of action antihypertensive drugs are classify as 

given below:

Centrally acting antihypertensive drugs.
Peripheral nervous system acting antihypertensive drugs.
Calcium Channel Blockers (CCB).
Diuretics.
Angiotensin Converting Enzyme (ACE) Inhibitors.
Angiotensin-II Antagonists.
Direct vasodilation.




Centrally acting Antihypertensive drugs


Ex: Clonidine, Methyldopa.

Mechanism of Action of methyldopa:

Methyldopa  a prodrug  that exhibit its antihypertensive action via an active metabolite (α -methynorepinephrine).

Act on central α2A receptors to decrease sympathetic outflow – fall in BP.



Peripheral nervous system acting antihypertensive drugs


      1. ß-adrenergic blockers:

a.      Non selective: Propranolol (others: nadolol, timolol, pindolol, labetolol)
b.      Cardioselective: Metoprolol (others: atenolol, esmolol, betaxolol)  
 
Mechanism of Action of Propranolol :

1.      Reduce Cardiac Output (CO)
2.      Inhibits renin release & Angiotensin-II & aldosterone production, and lower peripheral resistance.
3.      Decrease adrenergic outflow from the CNS.

Note: Renin is a proteolytic enzyme and also called angiotensinogenase It is produced by juxtaglomerular cells of kidney. It is secreted in response to:

Decrease in arterial blood pressure 
Decrease Na+ in macula densa
Increased sympathetic nervous activity

2     2. α – adrenergic blockers:

           Ex: Prazosin, terazosin, doxazosin, phenoxybenzamine and phentolamine.


Mechanism of Action of Prazosin: 

Blocking of alpha adrenergic receptors in smooth muscles, vasodilatation & finally decrease BP.


Calcium Channel Blockers (CCB).


Ex: Verapamil, diltiazem, nifedipine, felodipine, amlodipine, nimodipine etc.

Mechanism of Action of CCB:

Blocks influx of Ca++ in smooth muscle cells – relaxation of SMCs – decrease BP.


Diuretics.


Ex: Thiazides: Hydrochlorothiazide.
High ceiling: Furosemide.
K+ sparing: Spironolactone.

Mechanism of Action of Diuretics:
Acts on Kidneys to increase excretion of Na and H2O – decrease in blood volume – decreased BP


Angiotensin Converting Enzyme (ACE) Inhibitors


EX: Captopril, lisinopril., enalapril, ramipril and fosinopril.

Mechanism of Action of (ACE):

Inhibit synthesis of Angiotensin II – decrease in peripheral resistance and blood volume.


Angiotensin-II Antagonists


Ex: Losartan, candesartan, valsartan and telmisartan

Mechanism of Action of (AT- II-A):

Angiotensin- II:

formed from angiotensin I in a reaction catalyzed byangiotensin converting enzyme (ACE, kininase II)], is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. 

Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues, (e.g., vascularsmooth muscle, adrenal gland). There is also an AT2 receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. 

Both losartan and its principal active metabolite do not exhibit any partial agonist activity at the AT1 receptor and have much greater affinity (about 1000-fold) for the AT1 receptor than for the AT2 receptor. In vitro binding studies indicate that losartan is a reversible, competitive inhibitor of the AT1 receptor. The active metabolite is 10 to 40 times more potent by weight than losartan and appears to be a reversible, non-competitive inhibitor of the AT1 receptor.



Direct vasodilation

Ex: Minoxidil

Mechanism of Action:

 Orally administered minoxidil lowers blood pressure by relaxing vascular smooth muscle through the action of its sulphated metabolite, minoxidil sulphate, as an opener of sarcolemmal KATP channels.



If you have any  opinion Please, comments ...

Data accumulated & compiled by:
Dewan Pavel (M. PHARM)
       Mundipharma (Bangladesh) Pvt. Ltd.
       Officer, Quality Assurance.



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