hypertesion

hypertesion

1. BP>= 140/90 mmHg

   • BP force exerted by blood on the arterial wall
     • systole= max
     • dyastole=min
     • PAM=PAD+[(PAS-PAD)/3]
       • DEPENDS OF
         • Cardiac Output= Heart Rate * Stroke Volume
           • SV
             • Contractility
               • INFLUENCED NY SNS and neurohumoral activity
             • preload
               • venous tone
               • intravascular volume
                 • water
                 • Na+ retention
                   • INFLUENCED BY SNS, ALD, ADH, natriuretic peptide
                 • decreased by diuretics : decrease CO: decrease BP
                   • mechanism: increase renal excretion of sodium and water: 1) inhibit Na+ reabsorption in proximal tubule 2) increase delivery of Na+ and H2O in distal tubule: coupled to an increase in K+ excretion
                     • Thiazides
                       • high oral availability and long duration of action
                       • treatment for patients with volume-based hypertension : primary renal disease.
                       • Vasodilation effect compensates volume depletion
                         • sustained decrease in BP
                     • Loop diuretics
                       • short duration (4-6hrs)
                       • treatment of mild or moderate hypertension
                         • If chronic kidney disease is advanced
                       • attenuated due to compensatory mechansim
                     • given as complementary treatment to correct drug induced kaliuresis... hypokalemia
                       • K+ sparing diuretics
                         • treatment of secondary hypertension caused by hyperaldosteronism
                           • ex: spinoralactone, aldosterone R antagonist
                   • attenuated by compensatory mechanism
                 • neurohumoral regulators
           • HR
             • INFLUENCED BY ANS and neurohumoral activity
           • reduced by
             • sympatholitic drugs
               • Beta adrenoreceptor antagonist
                 • ex: propanolol, metoprolol, atenolol, nebivolol
                 • mechanism: chronotropic effect *inothropic effect reduction of HR, SV, :. CO
                   • decreased vasomotor tone: decrease systemic vascular resistance
                     • kydney
                       • decrease secretion of renin :. decrease secretion of AngII
                 • associated with elevation of triglycerides levels and reduction of HDL
               • mixed alpha-beta antagonist
                 • ex: labetalol
                 • treatment of hypertensive emergencies
                 • mechanism: antagonizes alpha1 R , reduces systemic vascular resistance by vasodilation, reduction of BP.
                   • Advantage: no compensatory mechanism: not increased reflex of HR or CO due to Betha 1 R antagonist
               • Alpha 1 antagonist
                 • ex: prozosin, terazosin, doxasin
                 • Mechanism: inhibit peripheral vasomotor tone: reduce vasoconstriction: decreased systemic vascular resistance
               • Non-selective alpha antagonist
                 • ex: phenoxybentozamine, phentholamine
                 • treatment NOT EMPLOYED as long-term , excessive compensatory responses
                   • unopposed reflex tachycardia
                 • treatment of pheochromocytoma
               • central
                 • alpha 2 agonist
                   • ex: methyldopa, clonidine, guanabenz
                   • Mechanism: reduce sympathetic outflow from medulla, leading to decrease in HR, contractility and vasomotor tone
                 • ganglionic blockers
                   • ex: trimethaphan, hexamethonium
                   • mechanism: inhibit nicotine cholinergic activity at symphatetic ganglia, :. lower BP
                   • A combined reaction of SP and PS blockage can have adverse effects: constipation, blurred vision, sexual dysfunction, orsthostatic hypotension
         • Pheripheric vascular resistance
           • reduced by
             • vasodilators
               • mechanism: act on endothelial smooth muscle by blocking Ca+
                 • ex: verapamil, diltiazen, nifedipine, amlodipine.
                 • can act as arterial vasodilators, negative inotropes and/or negative chronothropes
                   • decrease contractility, heart rate and impulse conduction.
               • and opening metabotropc K channels.
                 • long treatment of hypertension
         • arteries´elasticity

2. Pharmacological Intervention

   • Decrease BP
     • Homeostatic compensatory response
       • Baroreceptor reflex: aortic arch and carotid sinus
         • Increase Sympathetic outflow
           • tachycardia
           • contractility
           • vasoconstriction
       • Decreased renal perfussion
         • increase release renin from juxtaglomerular cells , leading to vasoconstriction by ANGII
           • Increase secretion of aldosterone, leads to reabsorption of Na+ and H2O
             • Increased intravascular volume
               • Increase BP
           • Angiotensin inhibitors
             • ACE INHIBITORS
               • decrease systemic vascular resistance, decrease impedance to LV ejection, not aldosterone promotes natriuresis; decrease bradykinin inhibition
             • AT1 ANTAGONIST
               • LOSARTAN, VAlsartan, irbesatan.

3. REBOLLAR VILLASEÑOR TOQUIA MIRANDA

   • DR DAVID MÜLLER
     • MEDICAL PHARMACOLOGY