Antihypertensive drugs

By -


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.



Comments

Post a Comment

Popular posts from this blog

Cleaning Validation | Campaign Cleaning Validation (CCV)

By -
Image
When the product demand does not allow for a complete clean up after each batch, a campaign cleaning validation must be conducted.   A back to back cleaning is performed between batches in a campaign, and a complete cleaning at the end of a campaign. Sampling of the equipment is performed after the last batch in a campaign, and all test results must meet predetermined acceptance criteria as per campaign cleaning validation protocol.   Samples for residual active may be taken after back to back cleanings where possible, for information only . Microbiology samples may be taken after back to back cleanings in a campaign to ensure that there is no excessive microbial growth on the equipment.
Read more

Western blot | troubleshooting | samples turn yellow and precipitate

By -
Image
Why western Blot samples turn yellow and precipitate? Sample appears to be acidic. Bromophenol blue in the loading buffer turns to yellow at acidic pH (below 3). Try to adjust the pH by adding NaOH [ 1 ].  Reason for that is proteins may be getting degraded due to heat exposure. One researcher had the same problem and so instead of keeping samples at 95 ° c  he started warming at 60-65 °  C. So anyone can try it out and as [ 1 ] said check the pH as well of the loading dye [ 2] .  Heating a sample also changes pH. An altered pH is not only responsible to turn the sample color yellow, but may also precipitate the proteins. Keeping SDS containing samples in ice is another common mistake to see this precipitation [ 3 ].  Another researcher said that he has got to do more with the total protein concentration in the lysate. He faced the same problem of precipitation upon denaturation at 100 ° c . He added 1/10th volume of 10% SDS and then boiled. Protein did not precipitate. T
Read more

Blending | Effective Sampling During Process Validation | Optimize Sampling Location

By -
Image
Important of sampling during blending: Sampling plays a great role in achieving the accurate results of analysis. Sampling must and procedure must be defined in validation protocols and training should be provided to the concerned staff before the validation activities start. Samples are representative of the whole batch. So it should be handled and weight carefully because segregation may occur during weighing and transpiration. Sample quantity should not be more than the required and whole mass sample should be used in the analysis. Fig: Blending Machine Sampling for blend: Blends are tested for their homogeneity. Homogeneity of the blend is critical for the quality of the final product. The sample should be taken from at least 10 locations in the blender. The sampling location should be selected according to the difficulty of the blending. Ares of poor blending must be covered in sampling. Corners and discharged point must have sampling location.
Read more