Adrenergic antagonist drug

 Scheme of Renin-angitensin-aldosterone system

 

ACE inhibitor drug list

• Captopril
• Enalapril
• Lisinopril
• Fosinopril
• Ramipril
• Quinapril
  
• Benzpril
• Moexipril 
•   Perindopril  

Mechanism of action of ACE inhibitors

ACE inhibitors acts by blocking ther action of angiotensin converting enzyme (ACE), which cleaves angiotensin I to potent vasoconstrictor angiotensin II, by reducing circulating angiotensin II levels, ACE inhibitors decrease aldosterone secretion from adrenal medulla, also these drugs reduce the rate of bradykinin inactivation. 

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Pharmacological actions of ACE inhibitors on the heart

ACE inhibitors reduce cardiac workload by reduction of preload (venous return), afterload (peripheral vascular resistance) and blood pressure by reducing plasma volume by blunting angiotensin II mediated aldosterone secretion.

Indication of ACE inhibitors

ACE inhibitors have a considerable value in the treatment of such diseases as heart failure (ACE inhibitors has significantly reduce mortality and morbidity associated with heart failure),

hypertension (these drugs are considered first line treatment in hypertension) , nephropathy associated with diabetes mellitus (due to nephroprotective properties of ACE inhibitors) , proteinuria in patients with CKD is also an indication for the use of ACE inhibitors(proven effects on reducing proteinuria), ischemic stroke, stable angina and patients who had suffered of myocardial infarction.

Pharmacokinetics of ACE inhibitors

All ACE inhibitors are incompletely absorbed following oral administration.The presence of food reduce absorption (should be taken on an empty stomach).

 

Except for captopril, all other ACE inhibitors are prodrugs require activation by hydrolysis via hepatic enzyme.

 

Renal elimination of the active moiety is important for most ACE inhibitors with exception of fosinopril (heptic excretion).

Adverse effects of ACE inhibitors

The most common adverse effect of ACE inhibitors is the dry cough (may lead to incompliance of the patients and replacing ACE inhibitors by ARBs), adverse effects also include skin rash, postural hypotension , bitter taste, angioedema, hyperkalemia and renal insufficiency.

 

 

Nephroprotective actions of ACE inhibitors

ACE inhibitors have shown nephroprotective properties on the long term, which is related to angiotensin reducing effects on the renal arteries.

 

ACE inhibitors cause vasodilatation of efferent renal artery, resulting in decreased intraglomerular pressure.

 

On the short term ACE inhibitors may decrease renal function because of reduced glomerular filtration as a result of reduced glomerular pressure, but on the long term ACE inhibitors protect the kidney because increased glomerular pressure for long period leads to renal damage and kidney injury with time.

When to stop ACE inhibitors?

If the glomerular filtration rate (GFR) has reduced by 70% of the baseline measurement stop ACE inhibitors.

 Drug interactions of ACE inhibitors

Most common drug interactions of ACE inhibitors include NSAIDs and potassium supplements.

·         NSAIDs: both ACE inhibitors and NSAIDs cause potassium retention in the body so both drugs should not be used together because of increased risk of hyperkalemia.

 

·         Potassium supplements and salts: because ACE inhibitors can rise potassium blood levels, so avoid the use of potassium supplements or potassium salts in conjunction with ACE inhibitors.

Concomitant use of ACE inhibitors and potassium sparing diuretics

The concomitant use of these drugs could be indicated for some patients such as patients with resistant hypertension and patients with proteinuria (spironolactone reduce proteinuria when combined with ACE inhibitors), but when these drugs combined with each other close monitoring of potassium levels should be done to avoid occurrence of serious hyperkalemia.