Therapeutic use:Guanethidine reduces CO due to bradycardia and relaxation of capacitance vessels.Long-term use leads to reduced PVR.Clinically used for outpatient treatment of severe hypertension.Guanethidine is highly basic and cannot enter brain.Therefore there is no CNS adverse effects seen in many other antihypertensive agents. Adverse effects and toxicity: (1)Sodium and water retention are often seen. (2)Postural hypotension and decreased blood flow to heart and brain. (3)Delayed ejaculation in men.Increased GI motility and diarrhea. (4)Supersensitivity of effector cells(smooth muscle)occurs following long-term use,reminiscent of surgical sympathectomy.Therefore it cannot be used with some over-the-counter cold medicine that contain sympathomimetic agent.Not suitable for patients with pheochromocytoma. (5)Not to be used together with drugs that act on Uptake 1,such as TCA. Direct vasodilators Mechanism of action:These agents relax smooth muscle of arterioles and some also work on veins.They stabilize membrane potential at resting level by opening K*channel(hydralazine,minoxidil,diazoxide),or increase cellular cyclic GMP level which leads to smooth muscle relaxation(sodium nitroprusside). EXTERNAL ELASTIC MEMBRANE VESSELS OF AOVENTITIA TUNICA ADVENTITA INTEAEMDRAN ARTERY RCULAR MUSCLES UNICA INTIMA TUNICA INTIMA CIRCULAR MUSCLES- VEIN FAT CELLS、 1515 Therapeutic use: Guanethidine reduces CO due to bradycardia and relaxation of capacitance vessels. Long-term use leads to reduced PVR. Clinically used for outpatient treatment of severe hypertension. Guanethidine is highly basic and cannot enter brain. Therefore there is no CNS adverse effects seen in many other antihypertensive agents. Adverse effects and toxicity: (1) Sodium and water retention are often seen. (2) Postural hypotension and decreased blood flow to heart and brain. (3) Delayed ejaculation in men. Increased GI motility and diarrhea. (4) Supersensitivity of effector cells (smooth muscle) occurs following long-term use, reminiscent of surgical sympathectomy. Therefore it cannot be used with some over-the-counter cold medicine that contain sympathomimetic agent. Not suitable for patients with pheochromocytoma. (5) Not to be used together with drugs that act on Uptake 1, such as TCA. Direct vasodilators Mechanism of action: These agents relax smooth muscle of arterioles and some also work on veins. They stabilize membrane potential at resting level by opening K+ channel (hydralazine, minoxidil, diazoxide), or increase cellular cyclic GMP level which leads to smooth muscle relaxation (sodium nitroprusside)