7. • ARBs antagonise the action of angiotensin II in a highly selective manner
at the angiotensin II AT1-receptor.
• Angiotensin II receptors are subclassified into AT1 and AT2
receptors.
• The AT1-receptor mediates all the classical effects of angiotensin II e.g.
vasoconstriction, aldosterone release, sympathetic activation and other
potentially harmful effects on the cardiovascular system.
• The functional role of the AT2-receptor is less well understood but
broadly this receptor mediates effects opposite to the AT1- receptor.
Pabitra Thapa, Sr. Product Manager, MPD
8. • Because many tissues contain enzymic pathways capable of
converting angiotensin I to angiotensin II independent of angiotensin
converting enzyme (ACE),
• there are theoretical advantages in blocking the renin-angiotensin
system via the AT1- receptor compared with ACE inhibition.
Pabitra Thapa, Sr. Product Manager, MPD
9. Dose
• 40 mg/day PO initially; titrated to 20-80 mg/day PO,
depending on response;
Pabitra Thapa, Sr. Product Manager, MPD
13. Long Half Life
• Of the commercially available ARBs, telmisartan has the
longest half-life of about 24 h.
• This suggests that telmisartan have a long duration of
action, thus ensuring blood pressure control throughout the
once-daily dosing interval.
Pabitra Thapa, Sr. Product Manager, MPD
14. Not a Pro Drug
• Another feature that distinguishes Telmisartan from
the ARBs candesartan cilexetil, losartan, and
olmesartan is that it is not a prodrug;
• Thus antihypertensive potency is related to the
activity of the parent compound
Pabitra Thapa, Sr. Product Manager, MPD
15. Circadian Rythm
• In general, hypertensive and normotensive
individuals exhibit a similar circadian variation
in blood pressure, levels being highest during
the daytime and lowest in the middle of the
night
Pabitra Thapa, Sr. Product Manager, MPD
17. • Elevated blood pressure in the early morning is associated with increased
cardiovascular risk.
• It is crucial that antihypertensive medication controls blood pressure to
minimize this risk at this time.
• All antihypertensives given OD in the morning may not fulfil this requirement
and may place the patient at increased risk.
• The ARB with the longest half-life is telmisartan.
• Its potential to reduce blood pressure in the risky early morning hours has been
demonstrated in numerous clinical studies using ABPM.
Pabitra Thapa, Sr. Product Manager, MPD
18. Lipophilicity and Vd
• Another feature distinguishing telmisartan from other ARBs is its
high lipophilicity .
• This enhances tissue penetration, intracellular absorption and
bioavailability.
• The high lipophilicity is reflected in the high volume of distribution
of approximately 500 L .
• The high lipophilicity of telmisartan, in comparison with losartan,
may confer vascular protection
Pabitra Thapa, Sr. Product Manager, MPD
19. Other Advantages of Telmisartan
• Antihypertensive action begins in 3 hrs and maintained for
24 hrs. It might takes 4 weeks for its optimal action.
• No liver enzyme (CYP) are involved in metabolism of
telmisartan so no drug interaction ( for those drugs
metabolised by CYP)
Pabitra Thapa, Sr. Product Manager, MPD
20. Peroxisome Proliferator-Activated Receptors
(PPARs)
• PPARs comprise three subtypes, namely
PPARα, PPARγ, and PPARβ/δ
• Among the three subtypes, PPARγ is the most studied nuclear
receptor and is involved in the control of energy balance,
glucose and lipid homeostasis.
Pabitra Thapa, Sr. Product Manager, MPD
21. PPARs Agonist
• Thiazolidinediones: Rosiglitazone, Pioglitazone
• Despite the beneficial effects of thiazolidinediones on the heart, they
are also associated with several adverse effects, including cardiac
dysfunction and ventricular fibrillation.
Pabitra Thapa, Sr. Product Manager, MPD
22. • Full PPARγ agonists are associated with a number of side
effects, including weight gain, fluid retention (edema), and
cardiac toxicity.
• The first approved drug from the thiazolidinedione class was
Troglitazone, which was withdrawn from the market in
2000 owing to its fatal hepatotoxicity.
• Other thiazolidinediones are also associated with adverse
effects, including weight gain (adiposity), increased rate of
bone fracture, anemia, and hepatic damage
Pabitra Thapa, Sr. Product Manager, MPD
23. Rosiglitazone
• Rosiglitazone is associated with granulomatous hepatitis.
• increase cardiovascular risk.
• Hypertension, myocardial ischemia, heart failure, upper
respiratory tract infection, and diarrhea were also reported
with rosiglitazone use.
• Owing to its cardiovascular side effects and adverse effects
on the lipid profile, rosiglitazone was banned in India
in 2010. Pabitra Thapa, Sr. Product Manager, MPD
24. Pioglitazone
• A/E weight gain, precipitation of heart failure, peripheral edema,
and an increase in bone fractures.
• Nephrotoxicity, Hepatotoxicity, Cardiotoxicity, and
Hematological disorders.
New PPARγ ligands with increased therapeutic efficacy and
reduced adverse effects are needed.
Partial PPARγ modulators are one of the promising
classes in this regard
Pabitra Thapa, Sr. Product Manager, MPD
25. PPARγ partial agonists
• PPARγ partial agonists selectively modify the expression of
genes needed only for insulin sensitization without
activating the genes responsible for weight gain and edema.
• This makes partial PPARγ agonists preferable to full
agonists.
• The partial PPARγ agonist balaglitazone
Pabitra Thapa, Sr. Product Manager, MPD
26. PPARγ partial agonists
PPARγ partial activation may have an important endothelial
defensive action through activating eNOS,
generating nitric oxide (NO)
enhancing NO bioavailability,
reducing oxidative stress, and preventing the adhesion cascade
and vascular inflammation.
Pabitra Thapa, Sr. Product Manager, MPD
27. • Partial PPARγ agonists may offer beneficial
effects for the management of type II DM
(T2DM) with attenuated adverse effects
such as fluid retention and cardiac
hypertrophy
Pabitra Thapa, Sr. Product Manager, MPD
28. Telmisartan as partial PPARγ-agonistic
• As telmisartan is reported to have
partial PPARγ-agonistic effect, the
drug can regulate glucose and lipid
metabolism, and improve insulin
resistance.
Pabitra Thapa, Sr. Product Manager, MPD
29. Telmisartan as partial PPARγ-agonistic
suppression of reactive oxygen species and an agonistic effect on PPARγ.
increase serum adiponectin and improved both oxidative stress and insulin
resistance in type 2 diabetic patients.
in diabetic patients with hypertension, telmisartan increased high-molecular-weight
adiponectin levels and improved insulin resistance, through partial PPARγ
activation.
Adiponectin, through binding to its receptors, mediates the insulin-sensitizing
effect, which is important in DM patients
Pabitra Thapa, Sr. Product Manager, MPD
30. Adiponectin
• Adiponectin is a hormone our adipose (fat)
tissue releases that helps with insulin sensitivity
and inflammation.
• Low levels of adiponectin are associated with
several conditions, including obesity, Type 2
diabetes and atherosclerosis
Pabitra Thapa, Sr. Product Manager, MPD
31. Telmisarta as partial PPARγ-agonistic
The partial PPARγ-agonistic activity and angiotensin receptor
blockade activity of telmisartan have been shown to have multiple
clinical benefits,
including anti-diabetic (insulin resistance) and cardiovascular effects,
stroke
and ultimately mitigating the burden of cerebrovascular and
cardiovascular disease
Pabitra Thapa, Sr. Product Manager, MPD
32. • In addition, telmisartan is reported to have
PPARα and PPARδ agonist activity.
• ideal alternative dual-purpose medication
for patients with T2DM, hypertension and
other cardiovascular disorders.
Pabitra Thapa, Sr. Product Manager, MPD
38. Positioning(Communication)
Long Half life -24 hrs, long duration of action, thus ensuring blood pressure
control throughout the once-daily dosing interval.
Reduce blood pressure in the risky early morning hours has been demonstrated in
numerous clinical studies using ABPM.
The high lipophilicity of telmisartan, in comparison with losartan, may confer
vascular protection
No liver enzyme (CYP) are involved in metabolism of telmisartan so no drug
interaction ( for those drugs metabolised by CYP)
effectively and safely reduces proteinuria in chronic kidney disease patients
Pabitra Thapa, Sr. Product Manager, MPD
39. Partial PPARγ-agonistic &increase serum
adiponectin
• Telmisartan as partial PPARγ-agonistic, increase serum
adiponectin , so have advantage over other
antihypertensive drugs in Diabetes and hyperlipidemia
• Antihypertensive with antidiabetic effects
Pabitra Thapa, Sr. Product Manager, MPD
large myocardial infarction and subsequent chronic heart failure- sympathetic activation
Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. These natural processes respond primarily to light and dark and affect most living things
Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. These natural processes respond primarily to light and dark and affect most living things
Ambulatory Blood Pressure Monitoring (ABPM) is a diagnostic test to determine the presence of hypertension by taking measurements during normal daily activities, over a span of 24 consecutive hours. It helps to diagnose as well as monitor high blood pressure, usually defined as a systolic pressure of 140 mm Hg or more and a diastolic pressure of 90 mm Hg or more.
