Irbesartan for control of Hypertension Valentina Forni Gregoire Wuerzner Menno Pruijm Michel Burnier Service of Nephrology and Hypertension Department of Medicine Centre ID: 816448
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Slide1
Long-term use and tolerability of
Irbesartan
for control of
Hypertension
Slide2Valentina
Forni, Gregoire Wuerzner, Menno Pruijm, Michel Burnier
Service of Nephrology and Hypertension, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Reported by:
DR. MARVIN JINO S. BUGNA
Slide3OBJECTIVE
To determine the pharmacokinetic and pharmacodynamics characteristic of ARBs and Irbesartan when used as an oral monotherapy or combination therapy in essential hypertension, diabetic nephropathy and cardiac disease.
Slide4Hypertension
Hypertension is sustained elevation of BP Systolic blood pressure 140 mm Hg Diastolic blood pressure 90 mm Hg
Slide5Hypertension
Types1. PRIMARY (Essential)Chronic high blood pressure without a source or associated with any other disease.Most common form of hypertension2. SECONDARYElevation of blood pressure associated with another disease such as kidney disease
Slide6BP
Classification
SBP mmHg
DBP mmHg
Normal
< 120 and
< 80
Pre-hypertension*
120-139 or
80-89
Stage 1 Hypertension
140-159 or
90-99
Stage 2 Hypertension
>
160 or
>
100
*newly recognized, requiring
lifestyle modifications
Slide7Risk Factors for Primary Hypertension
Genetic or Family HistoryAge (>55 for men; >65 for women)AlcoholCigarette smokingDiabetes mellitusElevate serum lipidsExcess dietary sodiumObesityEthnicitySedentary lifestyle
Socioeconomic statusStress
Slide8Clinical Manifestations
Frequently asymptomatic until severe and target organ disease has ocurred.Fatigue, reduced activity toleranceDizzinessPalpitations, anginaDyspnea
Slide9Complications
Thickening of heart muscleIncrease workload of the heartMay lead to other conditions such as:Heart attackStrokeRenal failureNephrosclerosis
Retinal damage
Slide10HYPERTENSION
Gangrene of the Lower Extremities
Heart Failure
Left Ventricular Hypertrophy
Myocardial Infarction
Coronary Heart Disease
Aortic Aneurym
Blindness
Chronic Kidney Failure
Stroke
Preeclampsia/Eclampsia
Cerebral Hemorrhage
Hypertensive encephalopathy
Adapted from Dustan HP et al. Arch Intern Med. 1996; 156: 1926-1935
Slide11RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
Slide12Angiotensin Receptor Blockers
Drugs that block the action of angiotensin II, permitting the blood vessels to relax and dilate lowering the blood pressure.
Slide13Mechanism of Action
The final active messenger of the renin-angiotensin pathway is Angiotensin II.Angiotensin II binds to AT1 receptors to cause vasoconstriction and fluid retention, both of which lead to an increase in blood pressure. The angiotensin II receptor blockers lower blood pressure by blocking the AT1 receptors.
Slide14Essential Hypertension
Heart FailureCardiovascular preventionNephropathyLosartanx
xSymptomatic NYHA II-IIIXDecrease stroke risk in LVHXHypertensive, Type II diabetics (Increase creatinine
and/or albuminuria >300 mg/day)
Valsartan
x
x
Symptomatic
NYHA II-III
X
Asymptomatic if recent MI and LVEF < 40%
Candesartan
x
X
If
LVEF < 40%
Slide15Essential Hypertension
Heart FailureCardiovascular preventionNephropathyIRBESARTAN
xXHypertensive, type II diabetics (Increase in creatinine
and/or albuminuria >30mg/day)
Olmesartan
x
Telmisartan
x
X
Decrease
MI and stroke risk in high CV risk and/or diabetic patients with target organ damage
Eprosartan
x
Slide16IRBESARTAN
Used on monotherapy in the treatment of HYPERTENSION but can be combined with other antihypertensive if needed. It is also used to slow the progression of kidney disease in patients with
Hypertension and Type 2 Diabetes.The usual starting dosage is 150 mg once daily and can be uptitrated to 300 mg once daily (maintenance dose)
Slide17IRBESARTAN
Pharmacologyan imidazole derivate with a bipentyl-tetrazole side chain.Does not require biotransformation Has a high affinity for the AT1 receptor in human vascular smooth muscles.Absolute average bioavailability (60-80%), the highest in its class, and is not affected by food intake.
Slide18Drug Interactions
Pharmacokinetic profile is not affected by Nifedipine, warfarin, simvastatin, tolbutamide, hydrochlorothiazide, or magnesium-aluminum hydroxide.It does not alter the steady-state pharmacokinetics of digoxin.When combined with COX-2 inhibitor with normal renal function,
it does not affect renal hemodynamics and renal salt handling.
Slide19Therapeutic efficacy
Randomized active controlled or placebo-controlled trials up to 3 months duration. Irbesartan in monotherapy is found to be very effective in lowering both systolic and diastolic blood pressure. It is effective in producing a sustained 24 hour blood pressure control. Irbesartan was at least effective as losartan, more effective than valsartan, but less effective than
olmesartan at reducing diastolic blood pressure.
Slide20Efficacy in hypertension when combined with other drugs
Two placebo controlled studies in patients with mild-to-moderate hypertension showed that Irbesartan 150mg + hydrochlorothiazide 12.5mg reduced blood pressure more effectively than placebo or either drug alone.
Slide21Efficacy in hypertension when combined with other drugs
Progressive uptitration to high dose Irbesartan-hydrochlorothiazide 300/25mg once daily lead to substantial reductions in systolic blood pressure (-23.0 + 13.3 mmHg, P< 0.001), between baseline and week 18.It allowed systolic blood pressure goals to be attained in
75% of patients.
Slide22Efficacy in diabetic nephropathy and cardiac disease
Irbesartan improved microalbuminuria in normotensive subgroup of diabetic patients with early stage microalbuminuric nephropathy.It significantly reduced QT and corrected QT interval dispersion with a reduction in the risk of arrhythmias in cardiac disease
.A dosage of 150-300 mg once daily was found to induce greater left ventricular mass index regression.
Slide23Slide24Irbesartan
is an effective antihypertensive drug in variety of mild – to – moderate hypertensive population.It is found to be effective on patients with diabetes, obesity, renal insufficiency and cardiovascular disease. Its slows the progression of early stage and late stage renal disease in hypertensive patients with type 2 diabetes
and reduces the risks of heart failure episodesCONCLUSION
Slide25Promotes regression of left ventricular mass
in patients with hypertension and left ventricular hypertrophy. Prevents recurrence of arrhythmia in patients with persistent atrial fibrillation when added to classical antiarrhythmic therapy. Treatment with Irbesartan in hypertensive patients with type 2 diabetes and nephropathy resulted in improved life expectancy and appeared to be
cost-saving and scores well for patient acceptation and adherence rates.CONCLUSION
Slide26