Use of Ace Inhibitors for Treatment of Hypertension Essay Example for Free

Use of Ace Inhibitors for Treatment of Hypertension Essay The prevalence of hypertension globally has sparked much research on medications and ways to cure it. Although there are varieties of medications available in the market to control hypertension, there are still none that can actually cure it. Until the time a drug to cure hypertension emerges, hypertension will be controlled by the use of antihypertensive drugs. Among the few well known classes of antihypertensive drugs is a group of angiotensin converting enzyme inhibitors or ACE inhibitors. ACE inhibitors are a fairly recent addition to the antihypertensive drug class and have been widely used since then due to its many potential benefits. ACE inhibitors are indicated for many conditions which include hypertension, prevention and treatment of cardiovascular disorders, and prevention of nephropathy in diabetes mellitus. When used in hypertension, it is done so in combination with diuretics with fairly good results. (Merck, 2003)   Ã‚  Ã‚  Ã‚  Ã‚   The use of ACE inhibitors is especially useful for congestive heart failure patients. Therefore, it is indicated in cases where hypertension exists in correlation with congestive heart failure. There has been a significant decrease in the overall morbidity and mortality rates of patients suffering from both the conditions when using ACE inhibitors.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   The mode of action of these drugs is many fold, and for that reason very effective in the treatment of hypertension. For instance, it acts on the vascular system to reduce vascular pressure, which allows for less arterial pressure, combined with more venous capacity, thus immediately reducing the blood pressure. Alongside, it increases cardiac output and cardiac index and stroke volume. The main function of the ACE inhibitors, however, is the inhibition of the ACE enzyme, which is responsible for increased vascular pressure, ventricular remodeling, production of aldosterone and vasopressin respectively. (Katzung, 2004)   Ã‚  Ã‚  Ã‚  Ã‚   Such drugs however, require careful dosage regimes based on extensive studying of the case, as there are many side effects associated with these drugs. The most common of these include hypotension, due to the vasodilator effect of the drugs.(Merck, 2003)   The second most common problem is the development of persistent cough in such patients, which leads to reduction in patient compliance. The bid and tid dosage regimes also reduce the patients’ compliance. Due to its renal effects, ACE inhibitors must be used carefully in cases where damage to the kidney is expected or the kidneys are functionally impaired. For example, in patients with renal artery stenosis, the use of these drugs can lead to renal impairment. The prevention of release of aldosterone caused by these drugs impairs excretion of potassium in the body, which can lead to hyperkalemia. Increased levels can also lead to the development of angioedema, which can be life threatening. ACE inhibitors are also contraindicated in patients who are pregnant as it is teratogenic in nature. (Kaplan and Rose, 2007)   Ã‚  Ã‚  Ã‚   Due to the mode of activity of these drugs, the ACE inhibitors become contraindicated in cases of history of angioedemas or renal artery stenosis, compromised renal functioning capacities, aortic valve stenosis and in patients suffering from hypovolumia. (Klabunde, 2007)   Ã‚  Ã‚  Ã‚  Ã‚   Many drugs now belong to this category, however, the paper will discuss three of these, captopril, enalapril and lisinopril.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Captopril main mode of action lies in the suppression of the renin-angiotensin-aldosterone system. By inhibiting the ACE inhibitor, angiotensin I is prevented from converting into angiotensin II.   Captopril enjoys universal attention due to the fact that it is the first ACE inhibitor introduced. Its mode of action and its effect were considered a breakthrough at the time of its conception. Its action is two fold. Firstly, it helps in dilating the vessels, thereby helping reduce blood pressure. Secondly, it has shown very good performance in the cases of myocardial infarction and congestive heart failure. And thirdly, it has shown good results in the prevention of diabetic nephropathy. (www.rxlist.com)   Ã‚  Ã‚  Ã‚   There is very little difference in the working of all the ACE drugs, however, captopril differs in this respect due to its shorter duration of action and increased chances of adverse effects.   This intensity of side effects potentiated further research, the result of which was the introduction of enalapril in the market, and still further drugs subsequently. Regardless of the drug, the ACE inhibitors generally take several weeks of administration to give full effectiveness and results. When used with thiazide diuretics, the results achieved are even more.(Merck, 2003)   Ã‚  Ã‚  Ã‚   Captopril is administered one hour before meals to achieve maximum peak volume concentration, which is reached within an hour of ingestion of drug. Initial dosage may be as low as 25 mg bid or tid, and gradually can be increased to double dose bid or tid. The addition of thiazide diuretics is usually carried out when using captopril alone at 50 mg alone does not sufficiently control blood pressure.(Katzung, 2004) This range can be increased to 150 mg per day, provided the use of a thiazide diuretic is also carried out. The administration of drug results in the lowering of blood pressure within one hour. Renal blood flow is increased; however, the GFR remains unchanged. When used with digitalis, captopril shows good efficacy in the treatment of congestive heart failure. Its use has been very favorable in patients who had previously suffered from myocardial infarction, or those with left ventricular dysfunction. In case of LVD and CHF or MI, the usual starting dose is 50 mg target dose. (Kaplan and Rose, 2007)   Ã‚  Ã‚     Captopril has shown to increase the risk of developing neutropenia and agranulocytosis and therefore, full blood picture is mandatory for patients using captopril for a prolonged period. Also, since mode of elimination from the body is through the kidneys, the use of captopril becomes contraindicated or at least under observation in cases of renal impairment or dysfunction. (Katzung, 2004)   Ã‚  Ã‚  Ã‚  Ã‚   Enalapril is the second drug introduced in the ACE inhibitor series. The main reason for its production was to eliminate the problems seen with the use of captopril. As in captopril, the drug utilizes the renin-angiotensin-aldosterone system. Production of enalapril involved changing the molecular constitution of captopril, and therefore, the final result was the first dicarboxylate- containing ACE inhibitor, or enalaprilat. However, this modification limited the use of this drug as intravenous injection only. Further modifications in this structure led to the oral form by the name enalapril. (www.rxlist.com)   Ã‚  Ã‚  Ã‚   Enalapril works by converting itself through hydrolysis into enalaprilat in the body. Enalaprilat then inhibits the ACE enzyme. The peak serum levels are reached within an hour of administration of the drug. As opposed to captopril, enalapril absorption is independent of gastric contents; rather it is dependant on the urinary recovery. In hypertensive patients, the dosage of enalapril results in both supine and standing but not orthostatic hypotension. This effect is not seen in case of captopril. The antihypertensive activity becomes visible within one hour of administration of the drug. This effect then remains for around 24 hours. Similar to captopril, enalapril shows improved hypertensive control when administered with a thiazide diuretic. it is also indicated for cases suffering from heart failure, and asymptomatic left ventricular dysfunction. (Kaplan and Rose, 2007)   Ã‚  Ã‚  Ã‚  Ã‚   Unlike captopril, which can be administered simultaneously with a preceding diuretic, enalapril can only be started after cessation of the diuretic after two to three days. This is essential to minimize the risk of developing hypotension. If this is not possible a test dose of 2.5 mg is given for at least two hours under observation, and the drug administered accordingly. The usual dosage regime may vary from 10 to 40 mg per day, and that is if the patient is not on a diuretic. Dose adjustment becomes necessary for patients who have impaired renal function, which may require reduction of the dose to almost half of the average 5 mg. this dosage is amenable to changes based on the blood pressure response seen. (www.rxlist.com)   Ã‚  Ã‚  Ã‚  Ã‚   Enalapril is highly favored over captopril as it has lesser side effects than its predecessor. It has a well toleration response, and the adverse effects are very mild in nature. Patients may complain of fatigue, asthenia, diarrhea and nausea, headache and dizziness, cough and skin rash. These symptoms can be present with varying degrees according to the reason why the drug is being administered. For example in heart cases, it can also lead to syncope symptoms and some differences in the special sensory perceptions. Angioedema is perhaps the most serious side effect of enalapril, with severity seen more in blacks than in non-black populations. This can be very fatal should laryngeal angioedema ensue. Initial doses can lead to fall of blood pressure and hypotension, which must be monitored very closely. Hyperkalemia, increase in blood urea nitrogen and serum creatinin levels, and decrease in hematocrit and hemoglobin can also be seen. Liver enzymes can also become elevated. (Merck manual, 2003)   Ã‚  Ã‚  Ã‚  Ã‚   The effects of enalapril were much improved and effective with lesser side effects when compared to captopril, however, the speed of effect was still high in the case of captopril. The third drug to get introduced in the series of ACE inhibitors became lisinopril. The drug was important as it was the first hydrophilic ACE inhibitor introduces, with longer half life and penetration in the tissue. The drug remains the same even after excretion from the body, and is indicated for all the conditions mentioned above for which ACE inhibitors are introduced. While captopril and enalapril were made for bid and tid dosages, lisinopril, due to its longer half life, is generally administered once a day, helping aid patient compliance.   Ã‚  Ã‚  Ã‚  Ã‚   The mode of action is similar to its sister drugs, that is the drug acts by inhibiting the ACE enzyme. The peak serum concentration of this drug however, is reached after 7 hours, compared to one hour of both captopril and enalapril. When used for hypertension, it results in the reduction of both standing and supine hypertension, with â€Å"no compensatory tachycardia†(Rx list, 2007)   Ã‚  Ã‚  Ã‚  Ã‚   The dosage of lisinopril is given according to the drug history of the patient. Patients with no use of diuretics are given 10 mg per day as initial dose. This can be increased from 20 to 40 mg as the case may need. In diuretic using patients, the protocol for the administration of lisinopril is the same as for enalapril. The diuretic is stopped two to three days prior to the administration of lisinopril, and observed for signs of hypotension. Dosage is then adjusted according to the body response of the patient. This drug should not be given along with any potassium supplements as it can lead to hyperkalemia. Renal status similarly, addresses the dosage of the drug, with 10 mg as standard for normal kidney function, 5 mg for moderate to severe renal impairment, and 2.5 mg or so for dialysis patients after proper observation and blood pressure response. (Klabubde, 2007)   Ã‚  Ã‚  Ã‚   Side effects of lisinopril are not so different from the side effects seen in the case of enalapril and captopril. However, cough becomes the primary side effect of this drug along with fatigue and asthenia etc. In all cases of ACE inhibitors, the side effects must be monitored closely and managed accordingly should the need arise. (ACE Inhibitors, 2004)   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   In conclusion, the introduction of ACE inhibitors has been a welcome addition in the antihypertensive drug family and is now used widely due to its excellent prognosis in patients with concurrent heart conditions. Its use with thiazide diuretics has been widely documented and further studies will help in the introduction of much improved brands of ACE inhibitors. References ACE inhibitor drugs. Site last accessed on August 5, 2007 from www.rxlist.com ACE inhibitors, 2004. Site last accessed on August 5, 2007 from http://www.chfpatients.com/ace_old.htm Norman A Kaplan and Burton D Rose, 2007. ACE inhibitors in the Treatment of Hypertension. Site last accessed on August 5, 2007 from http://patients.uptodate.com/topic.asp?file=hyperten/10107#1 Richard E. Klabunde, 2007. Angiotensin Converting Enzyme Inhibitors. Site last accessed on August 5, 2007 from http://cvpharmacology.com/vasodilator/ACE.htm Bertram G. Katzung, 2004. Basic and Clinical Pharmacology, ninth edition. The Merck Manual of Medical Information. Second Home Edition. Section III, Heart and Blood Vessel Disorders.