Antihypertensives PDF

Antihypertensives Hypertension Affects large percentage If not managed almost every organ system affected Damaging to : kidneys, heart , blood vessels, Increases risk of : Stroke, CHF, MI kidney failure etc Risk elevated in Diabetics and those with cardiovascular risk fact...

Antihypertensives Hypertension Affects large percentage If not managed almost every organ system affected Damaging to : kidneys, heart , blood vessels, Increases risk of : Stroke, CHF, MI kidney failure etc Risk elevated in Diabetics and those with cardiovascular risk factors Adequate control will reduce likelihood Compliance issues Normal BP is now considered < 120/80 Goal in HTN : to maintain below 140/90 and perhaps lower in high risk groups ( Diabetics, Kidney disease or CV risk factors) Mild HTN can often be controlled by monotherapy Stepwise approach otherwise Physiology of BP Regulation RAA Baroreceptors Increased Firing Inhibits SNS Vasodilation and lowered HR Decreased Firing SNS more active TPR increase and HR ( Reflex Tachycardia) Antihypertensive Mechanisms Drug Categories Diuretics Sympathetic agents Direct Vasodilators Drugs affecting RAA system Calcium channel blockers  Diuretics Lower blood volume and cardiac output Thiazides and loop diuretics also lower peripheral resistance They restore normal volume with reductions in resistance over time Loop diuretics act quickly to lower volume even in the presence of reduced renal function Pressure drop of 10-15 mm Hg Monotherapy often for mild to moderate HTN Often used in combination for severe HTN Vasodilators and sympathetic agents over time lead to sodium retention Diuretics reduce this Potassium losses problematic Will increase risk of digoxin toxicity Caution in arrhythmias Magnesium loss, glucose and uric acid elevation, lipid abnormalities  Sympathetic agents Alpha receptor blockers Beta receptor blockers Alpha 2 agonists Selectivity may vary, and so too will side effects Central acting agents cause sedation, sleep disturbances confusion Compensatory mechanisms may offset benefits sodium retention etc , often combined with diuretic  Central acting agents Alpha Methyldopa (aldomet) is prototype Prodrug metabolized to alpha methyl norepinephrine Clonidine ( Catapress) also Main action is alpha 2 agonist Reduction of sympathetic outflow Side effects/toxicity Postural hypotension Sedation Often decline with time Mental depression and changes Nightmares, vertigo, reduced mental concentration Dry mouth and life threatening withdrawal syndrome (clonidine) Adrenoreceptor blocking drugs Beta receptor blockers Would like selectivity for Beta 1 over Beta 2 Beneficial in mild to moderate heart failure Rational choice for reducing BP in these patients Reduce cardiac output and Renin levels Problem in bradycardic patients , asthmatics , Raynaud’s syndrome ( Beta 2 effects) Drugs vary , some are nonspecific and also act on alpha receptors Must be tapered Beta 1 selective Most are safe and effective ( atenolol and metoprolol are used widely and can be taken orally) Metoprolol (Toprol, Lopressor) is prototype Atenolol (Tenormin) Esmolol ( short acting) Hypertensive emergencies especially when tachycardic, and rapid control of vent rate in A fib Although all beta blockers are best avoided in asthmatics, Beta 1 selective agents would be the most advantageous ( selectivity is dose dependent )  B1=B2 Propranolol (Inderal) is the prototype Also Nadolol, Pindolol , Timolol Reduces cardiac output Cardiac effects and RAA blockade Contraindicated in asthmatics Alpha and beta blockade Labetolol (Trandate) and Carvedilol (Coreg) Carvedilol useful in heart failure Reduce afterload and heart work Beta1 and NO Nevibulol (Bystolic)  Beta blockers as a class are widely used More effective in Caucasians than African Americans Wise choice for HTN with coexisting conditions they treat Migraines, tachyarrhythmias, heart failure, angina Most are orally active Should be avoided in asthmatics Adverse effects include: Depression lethargy, hypotension, elevated triglycerides and reduction in HDL Can be problematic in diabetics May mask signs of hypoglycemia Should not be stopped abruptly Withdrawal syndrome that can be life threatening TAPER  Selective Alpha1 blockers Prazosin(minipress) prototype Doxazosin (Cardura) and terazosin (Hytrin) also Orthostatic hypotension, dizziness upon standing , headache, reflex tachycardia Resolves with time Non selective alpha blockers Phentolamine and Phenoxybenzamine Main use is pheochromocytoma  Drugs affecting RAA system Increased activity or deregulation of RAA system seems to be at play in many cases of essential hypertension. Angiotensin Receptor Blockers, ACE inhibitors, Renin Inhibitors In general ARBS and ACE inhibitors have similar efficacy and side effect profiles with minor differences ACE Inhibitors Captopril (Capoten) is the prototype Many others: Lisinopril (Zestril) enalapril (Vasotec), etc Very Effective at lowering blood pressure More effective in Caucasians Less effective responses in African Americans ( CCBs better choice) Decrease Peripheral resistance but do not cause reflex mechanisms Promote salt and water excretion Also increase bradykinin levels Responsible for side effect of dry cough and perhaps angioedema ACE inhibitors Preserve ventricular function and improve outcome in heart failure patients ( 5 year survival and slow disease progression) Most are prodrugs and require adequate liver function for their activity Captopril is not Most are excreted into urine Useful for treating HTN in diabetic nephropathy patients Stabilize renal function Side effects and interactions Hypotension May be severe in hypovolemic patients Renal failure (acute) in hypovolemic patients Hyperkalemia More likely in diabetes or renal insufficiency Often requires monitoring of levels Dry cough (often necessitates discontinuation) Contraindicated in pregnancy No potassium supplements or K sparing diuretics NSAIDS will offset benefits due to bradykinin blockade ARBs Losartan (Cozaar) Valsartan(Diovan), and many others Effects on bradykinin reduced Dry cough and angioedema less likely Side effects ,contraindications and actions similar to ACE inhibitors Contraindicated during pregnancy May be more effective than ACE inhibitors Renin inhibitors Aliskiren (Tekturna) Used for HTN either as monotherapy or in combination Inhibit the production of Angiotensin 1 and Angiotensin II Dry cough and angioedema less likely Adverse Effects Back pain, GI disturbances, allergies, headache, dizziness Hyperkalemia when combined with ACE inhibitors  Calcium channel blockers Well tolerated, relatively safe and effective drugs with many uses Also used for angina, migraines, etc Block calcium channels causing relaxation of vascular smooth muscle and reduction in rate and force of cardiac contraction Dihydropyridines have greater effects on vessels ( Vasodilate) Amlodipine( Norvasc) is the prototype Less effects on cardiac muscle Reflex tachycardia often and angioedema but newer agents have better profiles Amlodipine, Felodipine (Plendil) Contraindicated in tachyarrhythmias (dihydropyridines) Verapamil (Calan) most cardio selective Diltiazem (Cardizem) acts on cardiac and vascular smooth muscle Vasodilates, but reflex responses blunted  They are useful for reduction of mild to moderate HTN Can be used in asthmatics Can also be used in diabetics and beneficial for patients with angina and tachyarrhythmias (nondihydropyridines) May be a better choice for elderly and diabetics ( esp those with nephropathy) Less compensatory responses and side effects than direct vasodilators Constipation is a common S/E Caution in CHF especially Verapamil due to negative inotropic actions Verapamil should also be avoided in any type of AV nodal block Direct Vasodilators Hydralazine, Minoxidil (Rogaine, Loniten) Outpatient therapy Diazoxide (hyperstat), Nitroprusside (Nitropress) Parenteral , hypertensive emergencies Hydralazine (Apresoline) Acts directly on vascular smooth muscle Administered with a beta blocker and diuretic ( offset reflex tachycardia and sodium retention) Lupus like syndrome among other S/E Minoxidil (Loniten) More potent than hydralazine Somewhat selective for resistance vessels Taken orally to treat malignant HTN refractory to other Tx Reflex tachycardia and fluid retention necessitates blockade Hair growth (this is also known as Rogaine) Nitroprusside Lowers BP rapidly with short duration of action Used in hospital setting CN toxicity Increases NO levels Aldosterone receptor antagonists Eplerenone ( Inspra) Similar to sprironolactone with less endocrine side effects due to better specificity for the aldosterone receptor Hyperkalemia especially in diabetes or renal insufficiency Very useful if cause of HTN is elevated aldosterone Spironolactone (Aldactone) Treatment Algorithm Individualized approaches African Americans respond better to CCBs and thiazides and not well to ACE inhibitors or beta blockers Elderly patients respond better to ACE inhibitors, CCBs, and diuretics. Beta blockers and alpha blockers are less well tolerated