Term
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Definition
| Elevated arterial pressure |
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Term
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Definition
| Elevated total peripheral vascular resistance (R), which constitutes an elevated pressure load on the heart |
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Term
| Essential/Idiopathic/Primary hypertension |
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Definition
HTN of unknown etiology, accounting for over 90% of all cases |
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Term
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Definition
Produced by definable causes such as renal arterial stenosis, adrenomedullary tumors, hyperaldosteronism, Cushing's syndrome, aortic coarctation, and orthers, accounting for less tan 10% of all cases |
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Term
Threshold BP withOUT Diabetes or Renal Impairment |
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Definition
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Term
Threshold BP WITH Diabetes or Renal Impairment |
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Definition
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Term
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Definition
Elevated R (peripheral vascular resistance) P = Q x R Increase R; increases P; decreases Q Increase R = elevated workload on the heart (pressure load) = concentric cardiac ventricular hypertrophy |
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Term
| Contributing Factors leading to Elevated R |
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Definition
- Abnormally elevated arteriolar smooth muscle tone
- Abnormal growth of arterioles and proliferation of connective tissue
- Inbalance of vasoconstricting, vasodilating, and growth-influencing factors from vascular smooth muscle, endothelium, neurons, and blood
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Term
| Hemodynamic and structural consequences of Elevated R |
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Definition
- Without cardiac compensation, increased arterial pressure and decreased CO
- Progressive cardiac hypertrophy with abnormal structure of cardiomyocytes and conective tissue
- Early cardiac compensation
- Increased incidence of progressive coronary artery disease
- Mismatch between oxygen supply to the heart and oxygen demand in the heart
- Later cardiac decompensation and increased risk of CHF
- Increased risk of structural and functional damage in the kidney and renal failure
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Term
| Possible contributors to pathogenesis of essential HTN |
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Definition
- Defect in vascular smooth muscle leading to hypersensitivity to sodium
- Unknown ouabain-like substance causing Na-dependent HTN
- Renal malfunction leadig to abnormal renal function curves
- Abnormal functioning of the endocrine and local renin-angiotensin-aldosterone systems
- Abnormal activity of or responsiveness to the sympathoadrenal system
- Defect in vascular endothelium leading to imbalance in production or activities of vasoconstricting, vasodilating, and growth-influencing substances
- Abnormal expression of genes in arteriolar endothelium, arteriolar smooth muscle, neurons, or kidney
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Term
| Major strategies and goals in the pharmacologic tx of HTN |
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Definition
- RELAXATOIN OF ARTERIOLAR SMOOTH MUSCLE
- Reversal of arteriolar hypertrophy
- Depletion of body Na
- Reversal of cardiac ventricular hypertrophy
- Correction of impairment in renal function and improvement in renal hemodynamics
- Improvement in coronary, renal, and systemic vascular endothelial function and integrity
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Term
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Definition
| CO insufficient to meet metabolic demands of perfused tissues, including the heart itself |
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Term
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Definition
| CAD (#1) and Cardiac ischemia or nonfatal MI and related tachyarrhythmias, longstanding HTN (#2), ventricular hypertrophy, valvular defects, and mutations in genes coding for specific contractile and other proteins in cardiac myocytes |
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Term
Causes of HTN: Less common |
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Definition
| viral and bacterial infections, hormonal imbalances such as hyperthyroidism, pregnancy, congenital heart defects, non-infarction and non-ischemia related tacharrhythmias and anemias |
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Term
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Definition
| Low cardiac output due to diminished contractile function of the ventricle during systole |
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Term
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Definition
| Low cardiac output due to decreased diastolic ventricular volume |
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Term
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Definition
| maintenance of adequate CO at rest, at the expense of elevated diastolic ventricular volume or pressure or both |
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Term
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Definition
| CO at rest is insufficient to meet blood flow requirements of the rest of the body, in spite of the elevated ventricular volume and pressure |
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Term
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Definition
| Low cardiac output and consequences (systemic organ ischemia) |
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Term
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Definition
| Elevated ventricular diastolic pressure or volume (back up fluid in lung) |
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Term
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Definition
| Low CO and elevated LEFT ventricular diastolic pressure or volume, usually associated with pulmonary congestion and edema |
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Term
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Definition
| Elevated RIGHT ventricular diastolic pressure or volume, usually associated with systmic fluid retention and peripheral edema |
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Term
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Definition
MOST COMMON Low CO associated with systolic or diastolic dysfunction related to the more common causes descried above |
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Term
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Definition
RARE Insufficient organ perfusion in spite of an elevated CO, usually associated with the less common causes described above |
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Term
| Involvement of ventricular hypertrophy |
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Definition
| pathologic hypertrophy is distinguished from physiologic hypertrophy of exercise mainly by the microvascular blood suppl in the myocardium; sufficient in physiologic hypertorphy, abnormal and insufficient in pathologic hypertorphy |
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Term
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Definition
involve the left ventricle and septum MOST COMMON |
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Term
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Definition
Right ventricle LESS COMMON |
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Term
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Definition
| Uniform wall thickening with decreased diastolic volume, usually of the left ventricle and septum and caused by, or associated with, elevated pressure loading |
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Term
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Definition
| ventricular wall thickening with increased diastolic volume, usually caused by or associated with elevated volume loading |
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Term
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Definition
| dyspnea (exertional or nocturnal breating difficulty), orthopnea (recumbent breathing diffculty, fatigue and exercise intolerance, abd pain and hepatomegaly, mental dysfunction, elevated central venous pressure and vein engorgement, pulmonary edema and rales, peripheral edema, weight los, and oliguria |
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Term
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Definition
Diastolic: Concentric Systolic: Eccentric |
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Term
| Left Ventricular Contractility |
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Definition
D: Normal or above normal S: Below Normal |
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Term
| Diastolic Left Ventricular Volume |
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Definition
D: Below Normal S: Above Normal |
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Term
| Left Ventricular Diastolic Compliance |
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Definition
D: Below Normal S: Above Normal |
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Term
| Diastolic Left Ventricular Pressure |
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Definition
D: Above Normal S: Above Normal |
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Term
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Definition
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Term
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Definition
D: Below Normal S: Below Normal |
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Term
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Definition
D: Below Normal S: Below Normal |
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Term
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Definition
HTN & CHF: decreased TPR inhibition of renin action some sodium depletion partial reversal of LVH |
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Term
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Definition
HTN & CHF: decreased TPR Sodium depletion volume depletion (HTN: minor, CHF: major) |
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Term
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Definition
HTN & CHF: decreased renin secretion partial reversal of LVH moderate reduction in TPR HTN: reductions in cardiac contractility CHF: reductions in HR |
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Term
Renin Inhibitor Aliskiren (FDA approved) Enalkiren, remikiren, zankiren |
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Definition
- work upstream to directly inhibit ability of renin to convert angiotensinogen to angiotensin I
- inhibit endocrine and local RAS
- block prorenin from activating prorenin receptors
- AE: HA, dizziness, and diarrhea
- CI in pregnancy
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Term
ACE Inh. & ARBs Clinical Efficacy in HTN & CHF |
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Definition
- decreased pressure load reduction (decreased TPR) due to reduced levels of ang II (constrictor) and increased bradkinin (only ACE)
- beneficial cardiac and vascular remodeling
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Term
ACE Inh & ARBs Clinical Efficacy in CHF |
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Definition
| volume load reduction due to mild diuresis (natriuresis) secondary to deminished ang II induced aldosterone secretion, dialation of large veins |
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Term
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Definition
hyperkalemia exacerbation of impared renal function angioedema characteristic cough |
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Term
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Definition
hyperkalemia exacerbation of impaired renal function |
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Term
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Definition
| HCTZ, chlorothiazide, bendroflumethiazide |
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Term
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Definition
indapamide chlorthalidone metolazone quinethazone |
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Term
Thiazide/Thiazide like Diuretics Clinical efficacy in HTN/CHF |
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Definition
deminished pressure load secondary to Na depletion resulting in vasodialation |
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Term
Thiazide/Thiazide-like Diuretics Clinical Efficacy in CHF |
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Definition
| persistent volume load reduction due to enhanced excretion of Na and water (diuresis) leading to ECF volume contraction and deminished venous return |
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Term
| Thiazide/Thiazide-like diuretics SE |
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Definition
REACTIVE INCREASES IN RENIN, ANG II, & ALD Hypokalemia hyponatremia hypochloremia, hypomagnesmia, hyperuricemia, hypercalcemia, hyperglycemia, glucose intolerance, metabolic alkalosis, decreased secretion of uric acid, adverse serum lipid profile, sexual impotence |
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Term
| Thiazide/Thiazide-like D/D Int |
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Definition
| Quinidine, Digitalis, Droperiodl, Levomethadyl: increased risk of hypokalemia and cardiac arrhythmias (QT prolongation & torsades de pointe) |
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Term
| Loop (high-ceiling) Diuretics |
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Definition
furosemide ethacynic acid bumetanide torsemide |
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Term
Loop Diuretics Actions for clinical efficacy |
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Definition
| Similar to those of thiazide group but stronger maximal diuretic effect |
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Term
Loop Diuretics Important AE |
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Definition
Similar to those of thiazides except potentially MORE SEVERE HYPOcalcemia Ototoxicity |
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Term
Loop Diuretics Important D/D Int |
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Definition
Similar to those of thiazides but potentially more severe Blunted diuretic response by NSAIDs Enhancement of ototoxicity by AMG |
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Term
Antialdosterone (K-sparing) Diuretics Na Channel Inh |
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Definition
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Term
Antialdosterone Diuretics Aldosterone receptor antagonists |
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Definition
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Term
Antialdosterone Diuretics Actions responsible for Clinical Efficacy |
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Definition
All Agents: Diuresis that is weaker than that of either the thiazide or loop diuretics Ald. receptor antagonists: promotion of beneficial vascular and cardiac remodeling |
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Term
Antialdosterone Diuretics AE |
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Definition
HYPERkalemia megaloblastosis in cirrhosis (triamterene |
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Term
Antialdosterone Diuretics D/D Int |
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Definition
Exacerbation of HYPERkalemia with ACE Inh or K supplements bone marrow suppresion with MTX |
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Term
Beta Blockers Non-selective |
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Definition
propranolol madolol timolol etc |
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Term
Beta Blockers Beta-1 Selective |
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Definition
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Term
Beta Blockers With alpha blocking activity |
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Definition
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Term
Beta Blockers With intrinsic sympathomimetic activity (ISA; partial agonsim) |
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Definition
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Term
Beta Blockers Clinical Activity in HTN/CHF |
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Definition
- reduction in sympathoadrenal-dependedt renin production by the kidney leading to moderate reduction in pressure loading
- beneficial cardiac remodeling
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Term
Beta Blockers Clinical Efficacy in CHF |
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Definition
| decreased myocardial oxygen demand through reductions in HR and moderate reductions in PVR and cardiac contractility |
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Term
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Definition
BRONCHOCONSTRICTION severe bradycardia, AV block, exercise intolerance, promotion of hperkalemia in exercise, cardiodepression, adverse lipid profiles, delayed recovery from hypoglycemia in diabetes, and rebound HTN, tachycardia, and angina with rapid D/C of tx |
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Term
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Definition
- Augmentation of the pressor effects of Epinepherine
- antihypertensive actions blunted by NSAIDs
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Term
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Definition
prazosin terazosin doxazosin |
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Term
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Definition
| decreased total peripheral vascular resistance and BP |
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Term
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Definition
TACHYCARDIA INCREASED RENIN, ANG II, & ALD ...due to reflex activation of sympathoadrenal system rapid fall in BP and orthostatic HTN with first dose |
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Term
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Definition
- reversal of pressor action of Epi to a depressor action, enhancement of Epi-induced tachycardia
- exaggerated first-dose phenomenon with beta-blockers
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Term
Ca Channel Blockers Phenylalkylamines |
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Definition
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Term
Ca Channel Blockers Benzothiazepines |
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Definition
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Term
Ca Channel Blockers Dihydropyridines |
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Definition
nifedipine amlodipine feldipine |
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Term
Ca Channel Blockers Diarylaminopropylamine ether |
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Definition
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Term
Ca Channel Blockers Clinical Effects |
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Definition
| decreased total peripheral vascular resistance and BP |
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Term
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Definition
| reflex increase in sympathetic drive, excessive HYPOtension, cardiodepresion, AV Block |
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Term
Ca Channel Blockers D/D Int |
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Definition
Beta Blockers/Bupivacaine: severe AV block, bradycardia, cardiodepression Digitalis: enhancement of toxicity Hypokalemic drugs: life-threatening arrhythmias |
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Term
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Definition
| hydralazine, minoxidil, nitrovasodilators |
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Term
Other vasodilators Clinical Efficacy in HTN/CHF |
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Definition
| relaxation of vascular smooth muscle, reducing vascular resistance in BP, reducing pressure load and improving CO in CHF |
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Term
Other vasodilators Clinical Efficacy in CHF |
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Definition
| Dilation of veins (nitrates), decreasing volume loading and venous return |
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Term
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Definition
Reflex tachycardia and fluid retention Nitrates: severe HA, tolerance |
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Term
| Centrally acting sympatholytic agents |
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Definition
clonidine (primary drug) methyldopa (prodrug) guanabenz (Wytensin) guanfacine |
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Term
Centrally acting sympatholytic agents Clinical Efficacy |
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Definition
| partial agonist on alpha-2 receptors on neurons in the brain, decreasing efferent sympathetic nerve activity, antagonizing sympathoadrenal-dependent vasoconstriction, lowering HR, and decreasing renin production |
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Term
Centrally acting sympatholytic agents AE |
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Definition
All agents: sedation, xerostomia, depression, decreased libido, withdrawal syndrome, rebound HTN (less w/ methyldopa) Methyldopa: hyperprolactinemia w/ or w/out gynecomastia, hepatotoxicity, hemolytic anemia |
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Term
Centrally acting sympatholytic agents D/D Int |
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Definition
Ca Channel Blockers, adenosine, Beta blockers: potentiation of AV block TCA: decreased efficacy Beta blockers: exaggereated withdrawal syndrome |
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Term
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Definition
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Term
Digitalis glycosides Clinically efficacy |
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Definition
Positive inotropy: increased ventricular muscle contractile force, improving CO Bradycardia, through stimulation of vagus nerve, which decreases oxygen demand |
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Term
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Definition
| Proarrhythmia (commonly AV block with atrial or ventricular tachycardias), peripheral vasoconstriction which would add to the elevated pressure load in CHF |
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Term
Digitalis glycosides D/D Int |
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Definition
| Thiazide/Loop Diuretics/Quinidine: enhanced risk of arrhythmias |
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Term
Dobutamine (Dobutrex) Clinical Efficacy & AE |
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Definition
Beta agonist with a positive inotropic activity but minimal tachycardia AE: tachycardia, HTN in high doses |
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Term
Inamrinone/Milrinone Clinical Efficacy & AE |
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Definition
positive inotropy combined with peripheral vasodilation, both secondary to inhibition of specific cAMP-dependent phosphodiesterases, leading to increase in CO AE: tachycardia, thrombocytopenia (inamrinone) |
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Term
| Drug Treatment Targets for HTN |
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Definition
- Vascular defect and pathologic vascular remodeling
- elevated arteriolar constriction and VR (pressure loading)
- Assicaited LVH and pathologic cardiac remodeling
- Elevated O2 demand to heart (high resting HR, elevated pressure laoding, abnormal coronary vascular dynamics related to LVH)
- Impaired renal function
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Term
| Targets in Treatment of CHF |
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Definition
- Contraction defect and pathologic ventricular remodeling
- low EF, SV, CO
- high diastolic ventricular volume and pressure
- pulmonary congestion, systemic fluid retention, peripheral edema
- elevated O2 demand on heart
- diminised O2 supply to heart
- poor systemic organ perfusion
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