ZESTRIL ® Lisinopril

ZESTRIL ® is a lisinopril based drug

THERAPEUTIC GROUP: Antihypertensives - ACE inhibitors not associated

IndicationsAction mechanismStudies and clinical effectiveness Usage and dosage instructionsWarnings Pregnancy and lactationInteractionsContraindicationsUndesirable effects

Directions ZESTRIL ® Lisinopril

ZESTRIL ® is used both in monotherapy and in combination therapy in the treatment of high blood pressure.

ZESTRIL ® is also used in the treatment of symptomatic heart failure and in the short-term treatment (for about 6 weeks) of hemodynamically stable post-infarcted patients.

As with other ACE inhibitors, ZESTRIL ® is also used to treat some diabetic complications, such as diabetic nephropathy and hypertension.

Mechanism of action ZESTRIL ® Lisinopril

ZESTRIL ® administered orally, allows the absorption of its active ingredient lisinopril at the gastrointestinal level. The maximum plasma peak, however, is recorded only 7 hours after its intake. Both the time necessary to reach the maximum blood concentrations and the bioavailability of the active principle are in any case subject to enormous interindividual variability, determining for this reason also a modest variability of therapeutic efficacy.

The antihypertensive effect of lisinopril seems to be associated mainly with its inhibitory action on the angiotensin I converting enzyme, which manifests itself with a decrease in angiontensin II levels and with the consequent reduction both in the contraction of vascular smooth muscle cells, and of the blood concentration of aldosterone, both factors responsible for the increase in blood pressure. Although the aforementioned action seems to be the most validated one, emerging hypotheses are evaluating the ability of ACE inhibitors to inhibit the enzyme kininase II, responsible for the degradation of bradykinin, a vasodilatory molecule. This mechanism could justify the therapeutic efficacy of these molecules also in the treatment of low renin hypertension.

Several studies also show that lisinopril can prevent the incidence of cardiovascular diseases, reducing morbidity and mortality, while at the same time playing a protective role against complications of diabetic disease, in particular microalbuminuria.

After its action, with a half-life estimated at about 12 and a half hours, lisinopril is excreted unchanged through the urine.

Studies carried out and clinical efficacy

1 LISINOPRIL IN THE METABOLIC SYNDROME

Given the presence of biological effects other than antihypertensive action alone, it was decided to test the drug lisinopril in the treatment of a complex condition such as the metabolic syndrome, a pathology characterized by hypertension, impaired fasting glucose, altered lipidemic profile, overweight and obesity, the all inevitably associated with a high cardiovascular risk. The administration of lisinopril as monotherapy for about 12 weeks, guaranteed not only a significant drop in blood pressure, but also a marked improvement in glucose metabolism, which resulted in a reduction in post prandial glycaemia and insulinemia.

2. THE EFFECTIVENESS OF LISINOPRIL IN THE CONTROL OF MICROALBUMINURIA

Lisinopril is known to be a particularly effective drug in the treatment of arterial hypertension, guaranteeing an average drop in blood pressure of about 15/18 mmHg in 4/8 weeks of treatment. The study in question, however, also evaluates another activity, namely the ability to counteract the microalbuminuria associated with hypertension. Unlike other antihypertensive drugs with similar therapeutic efficacy, lisinopril can significantly reduce microalbuminuria in hypertensive patients.

3. LISINOPRIL IN ASSOCIATED THERAPY

The COSMOS study shows how the administration of lisinopril, in combination therapy with beta blockers, may be more effective than monotherapy in reducing arterial pressure and reporting the values of systolic and diastolic pressure in the normal range. The results, also derived from clinical practice, show a tolerability of the combined treatment equal to that observed in single-drug therapy.

Method of use and dosage

ZESTRIL ® 5/10/20 mg lisinopril anhydrous tablets:

for the treatment of arterial hypertension, the initial dose must be formulated by the doctor based on the severity of the pathology, the objective sought and the possible concomitant administration of other drugs with an antihypertensive effect, such as diuretics. Usually, the initial dosage is in the range 5/10 mg per day, but is doubled within the second / fourth week in the maintenance phase. In any case, the intake of ZESTRIL must be limited once a day at the same time.
for the treatment of heart failure, generally the administration of ZESTRIL ® is used in synergy with other drugs active on the cardiovascular system, such as diuretics, digitalis or beta-blockers. The correct combination, therefore the relative dosage, must be established by the doctor on the basis of the extent of the pathology.
for the treatment of diabetes complications, it is usually used the administration of 20mg a day of ZESTRIL, constantly monitoring the blood pressure levels;
the treatment of myocardial infarction is usually a hospital therapy, which as such is appropriately established after a careful evaluation of cardiac and vascular function.

IN ANY CASE, BEFORE TAKING ZESTRIL ® Lisinopril - THE REQUIREMENT AND CHECK OF YOUR DOCTOR IS NECESSARY.

Warnings ZESTRIL ® Lisinopril

The administration of ZESTRIL ® especially in the initial phase of treatment, can be associated with symptomatic and transient hypotension, decidedly more frequent in patients with impaired cardiac function, hypovolemia or under therapy with diuretics and antihypertensive drugs. In this case it would be necessary to review the dosage and constantly monitor the blood pressure levels.

The same caution in the correct dosage formulation should be maintained for elderly patients and in all cases of reduced renal function, in which, given the renal elimination of lisinopril, variations in the normal pharmacokinetics could occur, with strengthening of the biological effects of the principle active.

Furthermore, in particular categories of patients at risk (affected by renal artery stenosis, immunosuppression, renal insufficiency) it would be appropriate to monitor blood urea and creatinine levels and the number of blood granulocytes.

Additional precautions would be necessary in the case of use by patients subjected to concomitant therapy with potassium-sparing diuretics or potassium salt supplements and hypoglycemic drugs, for which blood concentrations of potassium and glucose should be monitored, respectively.

ACE inhibitor therapy may also be associated with facial angioedema, resulting in breathing difficulties; in such circumstances the immediate suspension of the drug and the implementation of the practices necessary to avoid suffocation should be provided. This side effect appears to be statistically more frequent in patients of African ethnicity, in which the therapeutic efficacy of ACE inhibitors is decidedly reduced.

Therapy with antihypertensive drugs in general, and that with ACE inhibitors in particular, could lead to a decrease in the patient's perceptive and reactive capacities, making the driving of vehicles and the use of machinery dangerous.

PREGNANCY AND BREASTFEEDING

The use of ZESTRIL ® is severely contraindicated during pregnancy, given the presence of numerous studies showing the teratogenic and fetal-toxic action of ACE inhibitors.

If taken during breastfeeding, it should be discontinued, given the neonatal toxic potential of this pharmaceutical category.

Interactions

ZESTRIL ®, like other ACE inhibitor drugs, can interact with a wide range of active ingredients, with consequent alteration of the normal therapeutic efficacy. More precisely, the antihypertensive effect of lisinopril can be enhanced by the concomitant administration of various types of antihypertensive drugs, tricyclic antidepressants, antipsychotics, anesthetics and diuretics.

In addition to the antihypertensive effect, potassium-sparing diuretics could significantly increase the blood concentrations of this element, increasing the risk to the patient's health.

The antihypertensive effect, on the other hand, could be reduced by the concomitant administration of non-steroidal anti-inflammatory drugs.

Several studies show that ZESTRIL ® could help the functionality of hypoglycemic drugs, resulting in significant and potentially dangerous glycemic drops, if not properly planned.

Contraindications ZESTRIL ® Lisinopril

ZESTRIL ® is contraindicated in case of hypersensitivity to one of its components, in case of hereditary angioedema or associated with previous pharmacological treatments with ACE inhibitors, in case of severe impairment of renal function and during the period of pregnancy and lactation.

Undesirable effects - Side effects

ZESTRIL ® appears to be well tolerated by most patients, although adverse drug reactions are described in the literature. Generally, the most common side effects are also transient and clinically irrelevant; they include dizziness, headache, hypotension, dry cough, diarrhea and vomiting. In addition to these, there are other undesirable effects of greater importance, but decidedly more rare, such as the alteration of renal function, skin rash, erythema and angioedema (in cases of hypersensitivity), rhinitis, alterations in cardiovascular function, hypoglycemia, neutropenia and hyperkalemia .