moxocard 1 cme update
TRANSCRIPT
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Essential hypertension is a serious concern amongstcardiovascular diseases because of its widespread prevalenceand association with other co-morbidities and mortality.
In emerging nations like India, essential hypertension hastaken shape of a sinister entity threatening to affect large
populations.
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2. Mancia G et al. J Hum Hypertens 1997;11(suppl 1):S3-S8., 3. Goldstein DS. Hypertension 1981;3:48-52.,4. Julius S, Valentini M. Blood Press 1998;7(suppl 3):5-13
In humans, plasma norepinephrine levels in hypertensive patientsare significantly higher than in normotensive controls (p
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Sympathetic overactivity
Sympatheticoveractivity may
be a central
feature linking
hypertensionwith other
components of
the metabolic
syndrome
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5. Scherrer U et al. Circulation 1994;89:2634-2640., 6. Landsberg L. Cardiovasc Risk Factors 1993;3:153-158
Raised BMI is associated
with an increased rate of
sympathetic nerve
discharge in skeletal
muscle5
There is a correlation
between BMI, body fat
distribution and urinary
norepinephrine excretion6
Link with obesity
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7. Jamerson KA et al. Hypertension 1993;21:618-623., 8. Huggett RJ et al. Circulation 2003;108:3097-3101.,9. Valensi P et al. ESC 2004 (www.solvaycardio.com)
Sympathetic activation is a major component of
insulin resistance in clinical experiments7and in
humans with type 2 diabetes8
Cardiac autonomic dysfunction occurs in:
- 30-50% of patients with diabetes
- 40% of obese patients without diabetes9
Link with insulin resistance and diabetes
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10. Ritz E et al. Blood Press 1998;7(suppl 3):14-19., 11. Haczynski J et al. J Clin Basic Cardiol 2001;4:61-65.,12. Lanfranchi A et al. Blood Press 1998;7(suppl 3):40-45
Sympathetic overactivity is also
implicated in:
- renal disease10
- left ventricular hypertrophy11
- congestive heart failure12
Link with other risk factors
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The classic centrally acting antihypertensive drugs (clonidine,
methyldopa, guanfacine) stimulate pre- or postsynaptic alpha2-
adrenoceptors, mainly in the NTS, reduce sympathetic efferentation,
decrease TPR and heart rate, and thereby systolic (SBP) and diastolic
(DBP) blood pressure.
Unfavourable effects of these drugs (dry mouth, decreased alertness,
sleepiness, sedation, impotence, constipation) limited their use, so these
agents are not considered as first-line antihypertensive drugs.
Drugs/therapeutic agents acting on
sympathetic nervous system: Sympatholytics:
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-Adrenoreceptor antagonists are effective antihypertensive agents,but there are concerns about their safety profile. In the ALLHAT trial,the -blocker (doxazosin) arm was stopped prematurely because of anincreased risk of cardiovascular events, particularly heart failure.
Similarly, -blockers are effective in obesity-associated hypertensionbut do result in reduced energy expenditure leading to a small weightgain.
In a recent large-scale trial (POISE study group) of over 8,000 patientsundergoing noncardiac surgery, the use of the perioperative -blockermetoprolol was found to reduce the incidence of MI, but increased therisk of strokes and death in the 30 days after the operation.
Sympatholytics continue
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Rationale for moxonidine
15. Hamilton CA. In: van Zwieten PA et al (eds). The I1Imidazoline Receptor Agonist Moxonidine. 2nd Ed,London: Roy Soc Med,1996:7-30., 16. Ernsberger PR et al. J Cardiovasc Pharmacol 1992;20(suppl 4):S1-S10
Moxonidine binds selectively and with high affinity to I1-
receptors in the RVLM16
thus reducing peripheral sympathetic activity
Sympathetic tone is regulated centrally in therostral ventrolateral medulla (RVLM)15
This region contains imidazoline I1-receptors and
a2-adrenoceptors which regulate sympatheticactivity
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Moxonidine versus active comparators
Moxonidine has been found to be similarlyeffective to other first-line antihypertensive
agents in reducing blood pressure including:
Diuretics (hydrochlorothiazide - HCTZ)
Beta-blockers (atenolol)
ACE inhibitors (captopril and enalapril)
Calcium-channel blockers (nifedipine)
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Highlights
Effective when used as monotherapy
An effective adjunct to other first-line
therapies such as diuretics and ACE-inhibitors
Linear dose-response effect allows dose titration
Improves glucose metabolism / insulin resistance
Neutral effect on the lipid profile
Renal protective effect
Lowers peripheral arterial resistance without significant effects on cardiac output
Relatively little affinity for a2-receptors in the brainstem (adverse events such as
sedation and dry mouth are infrequently reported during prolonged therapy)
Low potential for drug interactions
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Thank you
Managing Hypertension at the Source