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Chapter 47: Drugs for HTN

QuestionAnswer
When should treatment of HTN be initiated in adults over 60? when SBP >150mmHg or DBP >90mmHg
When should treatment of HTN be initiated in adults under 60? when SBP >140 mmHg and/or DBP >90 mmHg
Two categories of HTN: 1. Primary HTN: aka essential HTN; most common 2. Secondary HTN: less than 10%
Define primary HTN: HTN that has no identifiable cause; a chronic, progressive disorder; pt's will have a gradual rise in BP over the rest of their lives. Can be successfully treated, but cannot eliminate the underlying pathology.
Define secondary HTN: An elevation of BP brought on by an identifiable primary cause. Some individuals may be cured, but if not then it can be managed with the same drugs used for primary HTN.
Prolonged HTN can cause: MI, HF, angina pectoris, kidney disease, and stroke. The higher the BP the greater the risk. Among 40 to 70 y/o risk of CVD is doubled for each 20 mmHg increase in SBP or each 10 mmHG increase in DBP beginning at 115/75 to 185/155
What are two ways to manage chronic HTN? 1. Lifestyle modification 2. Drug therapy
What are some lifestyle modifications? Sodium restriction, The DASH (Dietary Approaches to Stop HTN) diet, alcohol restriction, aerobic exercise, smoking cessation, weight loss, maintenance of K+ and Ca++ intake.
Prototype Drugs: Diuretics 1/4First-line therapy for HTN b/c they reduce reduction of blood volume and arterial resistance.Furosemide: reserved when thiazides don't work and there is a low GFR. 1. Diuretics: Hydrochlorothiazide, chlorthalidone: 2. Loop Diuretics: Furosemide 3. Potassium-sparing: Spironolactone
Prototype Drugs: Beta-blockers 2/4 2. Beta-Adrenergic Blockers [Propranolol, Metoprolol] -
Prototype Drugs: Inhibitors of RAAS:3/4 3. Inhibitors of RAAS: - Captopril (ACE Inhibitor) - Losartan (angriotensin II receptor blocker) - Aliskiren (direct renin inhibitor) - Eplerenone (aldosterone antagonist).
Prototype Drugs: Calcium Channel Blockers 4/4 4. Calcium Channel Blockers: Verapamil and Nifedipine
What are the systems that help regulate BP? 1. SNS: baroreceptors 2. RAAS: Renin 3. Kidneys: blood volume
What is the first-line drugs for HTN? Thiazide diuretics (hydrochlorothiazide, chlorthalidone). They reduce BP by two mechanisms: reduction of blood volume and reduction of arterial resistance.
Drug-Drug interactions: Potassium-sparing diuretics Do not mix potassium-sparing diuretics with potassium supplements, ACE inhibitors, angiotensin II receptor blockers, or aldosterone antagonists, all of which promote hyperkalemia.
Define Sympatholytics (Antiadrenergic Drugs) Drugs that suppress the influence of SNS on the heart, blood vessels, etc. These drugs are widely used for HTN.
5 subcategories of Antiadrenergic Drugs: 1. Beta blockers 2. Alpha1 blockers 3. Alpha/beta blockers 4. Centrally acting alpha2 agonists 5. Adrenergic neuron blockers
Beta-Adrenergic Blockers: Actions 1/3 1. Blockade of cardiac beta 1 receptors decreases HR and contractility, causing CO to decline. 2. Suppress reflex tachycardia caused by vasodilators.
Beta-Adrenergic Blockers: Actions 2/3 3. Blockade of beta1 receptors on juxtaglomerular cells of kidney reduces release of renin, reducing angiotensin II-mediated vasoconstriction and aldosterone-mediated volume expansion.
Beta-Adrenergic Blockers: Actions 3/3 4. Long-term use reduces peripheral vascular resistance- by a mechanism unknown
Adverse effects of Beta-Blockers Bradycardia, decreased AV conduction, reduced contractility. Should not be used with pt's that have sick sinus syndrome or 2nd/3rd degree AV block, and must be used carefully with pt's that have HF.
Adverse effects of Beta-Blockers Continued Can promote bronchoconstriction and should be avoided with asthma pt's. Masks signs of hypoglycemia. Depression, insomnia, bizarre dreams, and sexual dysfunction.
Alpha 1 Blockers [Doxazosin, Terazosin]
Therapeutic uses of Alpha1 Blockers: Prevents stimulation of alpha 1 receptors on arterioles and veins, preventing sympathetically mediated vasoconstriction.The result: reduces both peripheral resistance and venous return to the heart. Not recommended for first-line therapy for HTN.
Alpha1 Blocker SE: Orthostatic hypotension; Patients taking doxazosin experienced 25% more cardiovascular events and 2x as likely to be hosptilized for HF.
Alpha/Beta Blockers: Carvedilol and Labetalol: (1) Promotes dilation of arterioles and veins by blocking alpha1 (2) Reduces HR and contractility by blocking cardia beta1 receptors. (3)Suppresses release of renin by blocking beta1 receptors on jux cells
Alpha/Beta Blocker Adverse Effects Like other nonselective beta blockers, can exacerbate bradycardia, AV heart block, and asthma; Blockade of venous alpha1 receptors can produce postural hypotension
Centrally Acting Alpha2 Agonists [Clonodine, methyldopa] Act w/i brainstem to suppress sympathetic overflow to the heart and blood vessels. The result is vasodilation and reduced CO, both hep lower BP.
Centrally Acting Alpha2 Agonists Adverse Effects: Dry mouth, sedation. Clonodine can cause severe rebound hypertension is Tx is abruptly discontinued. Methyldopa: hemolytic anemia and liver disorders
Adrenergic Neuron Blockers: [Reserpine] drops CO and BP. Adverse reactions: depletes serootnin and catecholamines causing deep emotional depression. Not a preferred drug for HTN
Drugs for HTN: 1. Diuretics 2. Beta-Arenergic Blockers 3. Inhibitors of the RAAS 4. CCB's
Drugs for Hypertensive emergencies: Sodium nitroprusside Fenoldopam Labetalol Diazoxide Clevidipine
Drugs for hypertensive disorders in pregnancy Chronic hypertension and pregnancy ACE inhibitors, ARBs, and DRIs are contraindicated during pregnancy Most other antihypertensives can be continued during pregnancy Preeclampsia and eclampsia Hydralazine Magnesium sulfate (anticonvulsant)
Drugs that suppress the RAAS: 1. ACE Inhibitors 2. Angiotensin II Receptor Blockers 3. Direct Renin Inhibitors 3. Aldosterone Antagonists
ACE Inhibitors: [Captopril, Enalapril] Lowers BP by preventing formation of angiotensin II, thereby preventing angio. II-mediated vasoconstriction and aldosterone-mediated volume expansion
ACE Adverse effects: Persistent cough, first-dose hypotension, angioedema, and hyperkalemia (secondary to suppression of aldosterone release). Can cause serious fetal harm.
Angiotensin II Receptor Blockers: ARBs lower BP by blocking the action of angiotensin II-mediated vasoconstriction and release of aldosterone. Adverse effects: can cause fetal harm; Angioedema.
Direct Renin Inhibitors: [Aliskiren] Act directly on renin to inhibit conversion of angiotensinogen into angiotensin I. Can suppress the entire RAAS.
 

 



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