Adrenergic antagonist drug

   We will talk about hypertension drugs and their groups, and for more details about this disease, how it occurs and how to prevent it, click here

Diuretics

β-blockers

· They are block β-adrenoceptor in the heart thus decrease cardiac output thus decrease BP.

· Propranolol and Nadolol are a non-selective β-blocker.

· Metoprolol, Atenolol, Esmolol, Bisoprolol and Nebivolol are selective β1- blockers. (All β-blockers should be gradually tapered off).

· Carvedilol, Metoprolol and Bisoprolol are only B-blockers may be used in congestive heart failure (CHF).

· Nebivolol induce releases of nitric oxide and causes VD.

· Esmolol is an ultra-short-acting, half-life about 10 minutes.

· Acebutolol, Pindolol, Celiprolol, Oxprenolol and Penbutolol are partial agonists, i.e., β-blocker with some intrinsic sympathomimetic activity (ISA).

· Labetalol and Carvedilol are a non-selective β-blocker and selective α1- blocker

ACE Inhibitors

· Angiotensin-Converting Enzyme Inhibitors such as:

Captopril. Isinopril, Enalapril, Fosinopril, Perindoprll and Ramipril. ·

      · ACE inhibitors are first-line drugs for hypertensive patients with diabetes, chronic kidney disease, & patients with coronary artery disease

·  The hypotensive activity of ACE inhibitors, due to;

1)   Blocks the conversion of angiotensin I to angiotensin II.

2)   Inhibits the degradation of bradykinin cause VD via NO release.

·   Avoid other drugs that increase K+ level e.g. ARBS, Aliskiren and K+ sparing.

·   ACEIs may develop dry persistence cough and angioedema; due to increase levels of bradykinin and substance Persistent

·   Can be treated by:

1)   Iron supplements (an inhibitor of NO synthase)

2)   NSAIDS (e.g. aspirin).

·   ACEIs are contraindicated with pregnancy; increase risk of fetal malformation.

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ARBs

· Angiotensin II Receptor Blockers:

Losartan, Valsartan, Candesartan & Irbesartan.

· ARBS have a similar uses and precautions to ACE inhibitors, but less in cough.

Direct Renin Inhibitors

· Aliskiren is the first and only drug available.

· It is act by binding to active site of renin

· decreasing plasma renin activity thus inhibiting conversion of angiotensinogen to angiotensin I.

· Has a similar uses and precautions but Angioedema and cough; less common.

· Most common side effects: Diarrhea, Gl symptoms and rash, headache and dizziness.

α-blockers

· Prazosin, Doxazosin and Terazosin are selective competitive α1 receptors blockers.

· Acts by blocking α1-adrenoceptors on vascular smooth muscle thus make VD thus decrease PVR thus decrease BP.

· Used mainly in men with hypertension and benign prostatic hyperplasia (BPH).

· Most common side effects are first-dose orthostatic hypotension (Initial syncope attack or first-dose phenomenon)

Calcium Channel Blockers (CCBS)

                    I.  Dihydropyridines:

· Nifedipine (is the prototype), Amlodipine, Felodipine, Isradipine, Lacidipine, Nicardipine, Lercanidipine and Nitrendipine

· have a much greater affinity for vascular calcium channels than for calcium channels in the heart.

                  II.  non-dihydropyridines:

· Verapamil a CCB that is a class IV anti-arrhythmia agent, much effects on cardiac CC.

· Diltiazem affects both cardiac and vascular smooth muscle.

· Side effects: Verapamil; First-degree atrioventricular block and constipation.

· Dihydropyridines S.E: Dizziness, headache, fatigue and peripheral

Centrally Acting Sympathetic Inhibitors

· Clonidine is an α2 agonist (centrally and peripherally) that is used for the treatment of hypertension.

· It decreases blood pressure by;

1) Stimulate presynaptic α2 receptors: decrease Presynaptic Ca+2 thus decrease NE release.

2) Stimulate central α2 receptors: decrease Sympathetic vasomotor centers thus decrease Sympathetic outflow thus decrease NE release thus decrease renin release.

3) Stimulate l1: (Imidazoline) receptor: Sympatho-inhibitory action.

· Clonidine therapy should be gradually tapered off; Clonidine suppresses sympathetic outflow, but sudden discontinuation can cause rebound hypertension (life-threating hypertensive crisis) due to a rebound in sympathetic outflow.

· Methyldopa is an a agonist that has both central and peripheral effects.

· It decreases blood pressure by:

1) Methyldopa is converted into the false transmitter called: alpha-methyl-norepinephrine, in the CNS thus the false transmitter is central α2- agonist thus decrease sympathetic outflow thus decrease NE release thus decrease renin release.

2) It is a competitive inhibitor of dopa-decarboxylase enzyme which converts L- dopa into dopamine.

· Dopamine is a precursor for NE and subsequently epinephrine.

· Mainly used for management of hypertension in pregnancy (category B).

Peripherally Acting Sympathetic Inhibitors

· Guanethidine and Reserpine acts by reduces the release of catecholamines, such as NE.

· Trimethaphan used in emergency, while Mecamylamine used in moderate hypertension.

Vasodilators

· Hydralazine is a direct vasodilator (arterioles but not veins).

· Uses: Severe hypertension, with nitrates for CHF in African American, and in HTN in pregnancy.

· Sodium Nitroprusside is a powerful short acting that is used in emergency.

· Fenoldopam is an agonist of peripheral dopamine D1 receptors that is used in emergency.

References

1. Medscape
2. PubMed
3. drugbank
4. pharmaguide
5. WebMD