ANTIHYPERTENSIVE DRUGS By Dr Meherunisa Professor CIMS Hospital

ANTIHYPERTENSIVE DRUGS By: Dr Meherunisa Professor CIMS& Hospital 1

� Calcium channel blockers: Dihydropyridine: Nifedipine, nicardipine Phenylalkylamines: Verapamil Benzothiazepines: Diltiazem 2

Calcium channel blockers: It inhibits cellular influx of Ca, which is responsible for muscle contraction. Calcium channel blockers protect tissue by inhibiting entrance of Ca into cardiac & smooth muscle cells of coronary & systemic arterial beds. All Ca channel blockers are vasodilators that ultimately cause dilation of coronary & peripheral arteries, reduce heart rate. 20

� α-1 adrenergic receptors antagonist: �Decrease the peripheral vascular resistance & lower the arterial blood pressure by causing relaxation of both arterial & venous smooth muscle � Examples: Prazosin Doxazosin Terazosin 4

� α-2 adrenergic receptor agonist: Clonidine acts centrally to produce inhibition of sympathetic vasomotor centers. 5

� Miscellaneous α-methyl dopa Neuronal blockers (bretylium, guanethidine) � Bretylium 6

#Rauwolfia and derivatives (reserpine, deserpidine) reserpine 7

#Ganglionic blockers (guanadrel, mecamylamine) Guanadrel 8

#Non specific vasodilator (hydralazine, minoxidil) Hydralazine minoxidil 9

� Recent anti-hypertensive drugs AT 1 ANTAGONIST � Olmesartan minoxidil � Azilsartan minoxidil 10

� Serotonin receptor antagonist Ketanserin: At higher conc. it inhibits α-1 adrenergic receptors. 11

� Endothelin receptor antagonist E. g. , ambrisentan, sitasenten, bosentan, darusentan. � Ambrisentan � Darusenten 12

ET-1 is a more potent vasoconstrictor than angiotensin II and has high affinity for the ETA receptor subtype which mediates the vasoconstriction characteristics of the Endothelin. 13

� Protein Kinase C inhibitors Staurosporin(antibiotic); it is a natural product isolated in 1977 from bacterium “streptomyces staurosporeus”. 14

� CALCIUM CHANNEL BLOCKER Cilnidipine Azelnidine Clevidipine 15

� BUCINDOLOL Non-selective β-blocker and weak αblocker. Mild vasodilator. 16

� CHYMASE INHIBITORS Chymase inhibitors may be useful for preventing cardiovascular diseases and fibrosis via inhibition of angiotensin II formation and transforming growth factor-beta activation. E. g. , SPF-32629 A 17

� PROSTACYCLINE ANALOGUE M/C: -Direct vasodilation of pulmonary and systemic arterial beds; also inhibits platelet aggregation. E. g. , Treprostinil 18

� CONTRAINDICATIONS Antihypertensive drugs are contraindicated in patients with known hypersensitivity to the individual drug ACEIs: Contraindicated in patients with impaired renal function, congestive heart failure, salt or volume depletion, bilateral stenosis, or angioedema, also during pregnancy or lactation Use of the ACEIs and the angiotensin II receptor blockers during the second and third trimester of pregnancy is contraindicated because may cause fetal and neonatal injury or death 19

� SYNTHESIS OF NIFEDIPINE Claisen schmidt condensation 20

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