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Classifications ‡ Primary (essential) hypertension ‡ high blood p pressure ressure with no obvious underlying un nderlying medical...

Classifications ‡ Primary (essential) hypertension ‡ high blood p pressure ressure with no obvious underlying un nderlying medical medical cause. ‡ 90-95% of cases ‡ Secondary hypertension ‡ caused d by other cconditions onditioons that thaat affect affect thee kidneys, kidneys, arteries, arteriees, heart or endocrine system. endoccrine system m.  ANTI-HYPERTENSIVE AGENTS 1. Diuretics 2. Sympathoplegic agents (B-blockers, alpha1 blockers, alpha2 agonists) 3. Calcium Channel Blockers 4. Direct vasodilators 5. Agents that block production or action of angiotensin (ACEi, ARBs) BASIC ASIC & CLINICAL PHARMACOLOGY - 12th Ed. NATRIURETICS ʹ Increase Na excretion SITE EXAMPLE S/E THIAZIDE Distal Convulated Convullated d ͻBendroflumethiazide ͻBenddrofflumethhiazidde -Hyponatremia -H Hyponatremia -mild to Tubule (Naturetin) -Hypokalemiaa moderate HTN ͻChlorothiazide (Diuril) -Hypercalcemia -Hyperc calcemia - CHF ͻTrichlorome ͻT Trichlorome (Diurese) (Diureese) -Hyperuricemia -Hy yperuricemia - Liver /Renal ͻ,d;Hydrodiuril) ͻ,d;;Hydroddiuril) -Hyperglycemiaa Disease ͻHydroflume ͻHydroflum me (Saluron) -Hyperlipidemia -Hyperlip pid demia - D. insipidus LOOP TThick hick Ascending Ascend ding -Furosemidee ((Lasix) Lasix) --Ototoxixity Ototoxixity LLoop oop of Henle -Torsemide (Demodex) -Hyperuricemia -Hyperuriceemia -Bumethanide -B Bumethanide (Bumex) (Bumeex) -Decrease -Decre ease magnesemiaa -Ethacrynide -Ethac crynidee (Edecrin) (Edecrinn) -Hypokalemia -H Hypokalemia -Metabolic alkalosis allkalosis K-SPARRING LLate ate Distal Tubule -Spironolacttone (Alda -Spironolactone (Aldactone actone -Hyp -Hyperkalemia perkalemia Collecting lecting Tubule -Eplenerone & Coll -Eplenerone(Inspra) e(Inspra) --Menstrual Menstrual abnorm abnormalities malities -Amiloride(Midamor) -Amiloride(MMidamor) -Gynecomastia -G Gynecomasttia -Triamterene (Dyrenium (Dyrenium) m) AQUARETICS ʹ Increase water excretion SITE EXAMPLE S/E S /E OSMOTIC Proximal Tubule Tubulle -Mannitol -Dehydration -Dehydrration AGENTS & Descending -Glycerin.-Isosorbide -G Glycerin.-Isosorb bide -Hypernatremia -Hyypernatremia Loop of -Urea Henle He enle CARBONIC Proximal Pr roximal Tubule -Brinzolamide -B Brinzolam mide (Azo (Azopt) opt) -GI upset up pset ANHYDRASE -Acetazolamide -Acettazola amide (D (Diqmox) Diqmox) -Urinary -U Urinary infrequency infreque ency INHIBITOR NHIBITOR -Methazolamide -Methazol lamide -Metabolic a acidosis cidosis (Neptazone) (Neptazone e) -Renal -Renaal ccalculi alculi -Dorzolamide -Dorzolami ide -Drowsiness -D Drowsiness Vasodilators - Relax smooth muscle, Ļ TPR - Reflex stimulation of heart - used with Diuretic or Beta blocker ORAL, LONG TERM HTN - Minoxidil ʹ Hirsutism - Hydralazine ʹ SLE PARENTERAL, HTN EMERGENCY - Sodium nitroprusside - Diazoxide - Fenoldopam CALCIUM CHANNEL BLOCKER - highly protein bound - Large volume of distribution Verapamil - 5.5 L/kg Diltiazem - 5.3 L/kg Nifedipine - 0.8 L/kg Clinical Manifestation ͻ Hypotension- peripheral vasodilation ͻƌĂĚLJĐĂƌĚŝĂ- AV & SA node block ACE INHIBITORS - ͞-WZ/>͟ - Potent vasodilator Use: HTN, CHF, diabetic nephropathy Use: tx. Mild to moderate HTN ADR: *Anorexia *Hyperkalemia *Polyuria *Oliguria *idiosyncratic dry cough ARBs - ͞-sartan͟ - used alone or in combination combinatiion therapy -Ļ cough & angioedema Examples: Candesartan - Atacard® Atacard® - C/I pregnancy nancy = fetal abnormalities C//I to pregn abnorm malities Irbesartan - Avapro® Avapro® - assoc. asssoc. w/ fetal abnormalities abnormaalities & death Losartan - Cozaar® Coozaar® Telmisartan - Micardis® Episartan - Teveten® Tevetten® Olmesartan ʹ Benecar® ® Valsartan V alsartan - Diovan® ALPHA2 AGONISTS Ļ sym pathetic outflow Anti-HTN axn = stimulate a2 adrenoceptor & (-) release of catecholamines Ex. Methyldopa (Aldomet®) Clonidine (Catapres®) Guanabenz Guanfacine  Adrenoceptor antagonists a. BETA BLOCKERS ʹ ͞K>K>͟ b. Alpha-1 blockers ͞-zosin͟ Use: HTN & BPH Syncope ʹ in 1st time adm of alpha1- blocker 1st dose phenomenon mgt of syncope: dose should be small and at bed time. BASIC & CLINICAL PHARMACOLOGY - 12th Ed. GANGLION-BLOCKING AGENTS Mecamylamine Trimethaphan (quaternary amine) - oral -Short acting - w/ CNS effect - IV infusion - lacks CNS effects - polar MOA: competitively block nicotinic cholinoceptors in post ganglionic neurons A/E: Sympathoplegic *Orthostatic hypotension *Erectile dysfunction Parasympathoplegic *Constipation *blurred vision *Urinary retention *dry mouth