Diversity in Hypertension

1 9 Diversity in Hypertension 5 2554 Ballroom B-C 23 1 5 2554 Theme Diversity in Hypertension calcium channel blockers, beta-blockers, diuretics, angiotensin converting enzyme inhibitors angiotensin receptor blockers angiotensin converting enzyme inhibitors angiotensin receptor blockers direct renin inhibitor Breakfast luncheon symposium breakfast luncheon lecture.

2 2 9 - . - . Breakfast Symposium ( ) Blood Pressure Achieving Using Single Pill, Cost Effective & Good Compliance .. (Moderator) - .. - . Diversity of calcium channel Blockers in Hypertension : Are all CCBs the same? .. - . Diversity of Beta-Blockers in Hypertension : Are all beta-blockers the same? .. - . Coffee break . Diversity of Diuretics in Hypertension : Are all diuretics the same? .. (Moderator) . Luncheon lecture ( ( ) The Power of RAAS Blockade in Hypertension Management .. (Moderator) . Diversity of Renin Angiotensin Aldosterone System Blockade in Hypertension : ACEI and ARB: Class versus Individual effects?)

3 ACEI/ARB combinations: Should we use them or not? . Where is the place of DRI in Hypertension ? .. (Moderator) .. Coffee break 3 Diversity of calcium channel Blockers in Hypertension : Are All CCBs The Same ? Peera Buranakitjaroen, , * *Division of Hypertension , Department of Medicine, Siriraj Hospital. calcium channel blockers (CCB) is one of the most potent antihypertensive drug. There are 2 types, long lasting type (L type) and transient type (T type). At this moment, only L type CCBs are available for clinical use. According to World Health Organization classification, only class A CCBs which exert antihypertensive effect consist of 3 types type 1 phenylalkylamine verapamil, type 2 benzothiazepine diltiazem and type 3 dihydropyridine (DHP) nifedipine, felodipine, amlodipine etc. Each type of CCB has totally different molecular structure and act at different sites at the calcium channel on the cell membrane of smooth mucle cells to inhibit influx of Ca++ prevent vascular constriction.

4 Non-DHP CCBs (verapamil and diltiazem) are less vasoselective but exert cardiac nodal inhibition to slow heart rate, while DHP-CCBs are more vasoselective with minimal effect on the heart. CCB had been shown to be as effective as angiotension converting enzyme inhibitor/angiotensin receptor blocker in left ventricular hypertrophy regression. CCB had been shown to prevent stroke better, but caused more heart failure than conventional antihypertensive drugs (diuretic+ beta-blocker). There are several DHP-CCBs available for clinical use. They have different pharmacokinetic, trough to peak ratio and only some of them have beneficial effect on renal microcirculation. Non-DHP CCB diltiazem was shown to have antiproteinuric effect. On the contrary verapamil was not able to prevent microalbuminuria in type II diabetic patients in BENEDICT (BErgamo NEphrologic DIabetes Complication Trial).

5 Only certain types of DHP-CCBs efonidipine, manidipine and lercanidipine have antiproteinuric effect by dilating efferent arteriole. Meta-analyses showed that short-acting nifedipine caused more cardiovascular events than control group, while long-acting ones did not. Nifedipine GITS was safe to use in stable angina patients (ACTION-A Coronary disease Trial Investigation Outcome with Nifedipine GITS). Long acting CCBs were shown to decrease CV events in high CV risk patients when compared with placebo nitrendipine in SYST-EUR (Systolic Hypertension -Europe) and amlodipine in PREVENT (Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial) etc. DHP-CCB either alone or combination with other antihypertensive drug exhibited better CV prevention than other drug classes amlodipine vs lisinopril in ALLHAT (Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial), amlodipine perindopril vs atenolol bendroflumethiazide in ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm) and benazepril+ amlodipine vs hydrochlorothiazide+benazepril in ACCOMPLISH trial (Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension trial) etc.

6 4 .. Beta-adrenergic antagonists Beta blockers -blockers .. 1958 beta blocker dichloroisoproterenol Sir James W. Black .. 1962 (cardiac arrhythmias), epinephrine adrenaline (angina pectoris) beta blockers block catecholamines (epinephrine adrenaline) norepinephrine noradrenaline -adrenergic receptors (sympathetic nervous system) Beta receptor 1, 2 and 3 receptors 1-adrenergic receptors 2-adrenergic receptors 3-adrenergic receptors beta-blocker beta-receptor receptor partial agonist intrinsic sympathomimetic full agonist beta-receptor beta1 receptor membrane stabilizing effect propranolol, metoprolol.

7 Nadolol beta-blocker renin-angiotensin rennin beta-blocker beta2 receptor beta-blocker aqueous humor beta-blocker lipolysis glycogenolysis glucagon reserve beta-blocker VLDL HDL-cholesterol LDL cholesterol HDL LDL-cholesterol Diversity of Beta-Blockers in Hypertension : Are all beta-blockers the same?

8 5 1-3 Propranolol first pass metabolism bioavailability hepatic extraction Propranolol 2-5 propranolol metoprolol Pindolol atenolol nadolol 1. angina pectoris supraventricular ventricular arrhythmias (acute myocardial infarction) redistribution anti-arrhythmic 2.

9 Hyperthyroidism sympathetic migraine propranolol, timolol metoprolol block craniovascular beta receptor vasodilation ( migraine pain vasodilation cranial vessels) propranolol sympathetic open-angle glaucoma timolol butatoxol aqueous humor ciliary body beta-blocker Beta-blockers 2 non-selective blockers 1 2 receptors selective 1 blockers cardioselective beta-blockers receptor intrinsic sympathetic activity Nonselective beta-adrenergic antagonists Propranolol beta blocker beta1 beta2-receptor intrinsic sympathomimetic activity 6 Propranolol first pass

10 Metabolism 20% bioavailability propranolol beta-receptor 4-hydroxypropranolol 4 2 Nadolol nonselective beta-blocker membrane stabilizing intrinsic sympathomimetic activity Timolol nonselective beta-blocker membrane stabilizing intrinsic sympathomimetic activity glaucoma Labetalol competitive antagonist alpha1 beta-receptors receptors Selective beta1-adrenergic antagonists beta1-receptor receptor NE b agonists Metoprolol Atenolol intrinsic sympathomimetic activity Atenolol Atenolol metoprolol Esmolol membrane stabilizing activity intrinsic sympathomimetic activity beta-receptor Acebutolol intrinsic sympathomimetic activity 7 beta blocker