moxocard 1 cme update

8/10/2019 Moxocard 1 CME Update

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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

moxocard 1 cme update

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