Vasodilators in Cardiovascular Pharmacology PDF

█ Vaso odilators Classiffication Arte erio-dilato ors: Nifedipine – Hyddralazine – Minoxid dil – Diazoxxide – TThey dilate a ↓↓ BP (→ ↓ afterlo...

█ Vaso odilators Classiffication Arte erio-dilato ors: Nifedipine – Hyddralazine – Minoxid dil – Diazoxxide – TThey dilate a ↓↓ BP (→ ↓ afterlo e arteries and oad) – TThey are used u in sevvere system mic hypertension. Ven nodilators: Nitrates – TThey dilate eins →↓ ven e mainly ve n (→ ↓ preload) nous return – TThey are used u in acuute pulmonnary edema. Mix xed dilatorrs: Sodium m nitropru sside – Prrazosin – ACEIs A – Trrimetapha an – TThey ↓ pre eload & afte erload so tthey are us sed in CHF F. Genera al conside erations  Vassodilators relax r ular smootth ms and ↓ peripheral resistannce. vascu  Theey usually cause reflex sympaathetic stiimulation (e.g. reflexex tachycardia) so theyy can be combined c with w beta-b blockers.  Theey usually cause sa alt and wwater rete ention (du ue to refleex stimula ation of aldo osterone reelease) so they shou uld be combined withh diureticss.  Thee use of vasodilators v s is declin ning as a result of newer mo odalities, such s as ACEEIs and CCCBs, which h are more e effective with w fewerr adverse eeffects. Hydralazine  It is a direcct arterio olodilator by uncle ear mec chanism.  It iis used in severe e hyperte ension an nd rd hyppertension in pregna ancy (3 c choice aftter α-mmethyldopa a and nifed dipine).  It is usually combine ed with d diuretics to couunteract sa alt and waater retenttion, and β- blocckers to counteract c reflex tachhycardia.  It m may cause systemic lupus eryythematos sis (SLEE)-like syyndrome especiallyy in slo ow aceetylators. Th he patient develops mild form of arthritis, renal imp pairment, and a skin rashh that usua ally disappe ear upon sttopping of the drug. Minox xidil  It iss a direct arteriolodilator byy opening g K+ channels → hyyperpolarizzation → rela axation of the t vascula ar smooth ms. 160  It is given orally for chronic hypertension but its use as antihypertensive is declining; however, it should be combined with diuretics and β-blockers.  It was found to stimulate hair growth (hypertrichosis) (by unclear mechanism), so it is now used topically to prevent hair loss in both males and females. Diazoxide  Structurally related to thiazides but it is not diuretic  It is a direct arteriolodilator by opening K+ channels → hyperpolarization → relaxation of the vascular smooth ms.  It is given parenterally in hypertensive emergencies but its use is declining. Sodium nitroprusside  It liberates nitric oxide (NO) → ↑ cGMP → dilatation of both arteries and veins → ↓ both preload and afterload.  It is given by i.v. infusion in hypertensive emergencies and acute heart failure because it has rapid action  It can be converted to cyanide and thiocyanate. The accumulation of cyanide and risk of toxicity are minimized by concomitant administration of sodium thiosulfate (see angina) or hydroxocobalamin (vitamin B12).  Sodium nitroprusside in aqueous solution is sensitive to light and must be made up fresh before each administration and covered with opaque foil. Fenoldopam  It stimulates peripheral dopamine (D1) receptors in renal and mesenteric arteries, leading to VD and decrease peripheral resistance.  It is used parenterally as a rapid-acting vasodilator to treat emergency hypertension in hospitalized patients. █ Endothelin-1 receptor antagonists  Endothelin-1 is 21 amino acid peptide. It is the predominant endothelin secreted by the vascular endothelium. It is elevated in patients with pulmonary hypertension and coronary artery disease.  It acts on two types of receptors, ETA and ETB. ETA receptors is the main subtype in smooth ms and mediates VC and vascular smooth ms hypertrophy.  Bosentan is orally active nonselective blocker of ETA and ETB receptors, while ambrisentan is a selective ETA blocker.  Both drugs are approved for treatment of primary pulmonary hypertension. 161  █ Specialized vasodilators Drugs used for erectile dysfunction: Sildenafil, tadalafil  These drugs inhibit phosphodiesterase (PDE) type 5 the enzyme responsible for breakdown of cGMP in erectile tissue (and lung) → ↑ cGMP → VD of the corpus cavernosum.  They are very effective for treatment of erectile dysfunction in men. The effect of the drug appears after 30 min of oral administration and lasts for 4-5 hours.  Sildenafil is also approved for treatment of pulmonary hypertension.  Side effects include blue discloration of vision, headache, and optic neuropathy.  These drugs are contraindicated in patients taking nitrates or nicorandil for treatment of angina because nitrates also act by ↑ cGMP leading to severe VD, hypotension, and reflex tachycardia → aggravation of angina and development of arrhythmia. ▌Choice of the antihypertensive drugs: Clinical condition Best choice Starting therapy for non-complicated Patient 55 years old: CCBs If not adequate, add thiazide or beta blockers. Hypertension of pregnancy α-methyldopa Labetalol – Nifedipine - Hydralazine Hypertension in a diabetic patient with ACE inhibitors diabetic nephropathy (proteinuria) Hypertension with chronic kidney disease S. creatinine 3 mg/dl: CCBs Hypertension with CHF ACE inhibitors - diuretics Hypertension with bronchial asthma CCBs Hypertension with angina CCBs - beta-blockers Hypertension with thyrotoxicosis, Beta-blockers sympathetic overactivity, arrhythmia, or, HOCM Hypertension with BPH α1 blockers Primary pulmonary hypertension Endothelin receptor antagonists 162