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Non-pharm therapy for HTN |
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Lose weight even w/o changing salt intake Salt intake works best for blacks Less alcohol More exercise |
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Saluresis causing dec. EABV = dec. TPR = dec. BP -20/-10 (2-4 wks) Activated RAAS but HR NC or slightly inc. Reverses LVH CO returns to pretreatment value |
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The antiHTN effect of thiazides occurs at ___. Inc. the dose above this value ___ |
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Small doses Doesn't cause a greater fall in BP but inc. incidence of metabolic issues |
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How does salt restriction work with HCTZ? |
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Modest salt restriction prevents the need for larger doses of HCTZ and limits the loss of K |
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Thiazides have no effect on BP in patients w/ ___ |
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Thiazides are routinely used to prevent/reverse ___ |
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Salt and water retention caused by other antiHTNs like arterial VD, a/B blockers, centrally-acting sympatholytics |
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Hypokalemia (from activated RAAS) = watch it w/ digoxin (hypokalemia causing) Inhibit insulin secretion causing hyperglycemia = don't give to diabetics! Hyperuricemia = may cause gout |
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Thiazide-induced hypokalemia can be lessened/prevented by: |
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Definition
Low doses of HCTZ + Na restriction Cotx w/ K-sparing diuretic like amiloride, triamterene, spironolactone Cotx w/ ACEI/ARB Cotx w/ B-blocker Cotx w/ K supplement |
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Prevents conversion of AngI to AngII as well as breakdown of bradykinin (aldosterone maintained by ACTH and plasma K) Reversal of AngII effects on collagen synthesis = inc. compliance of large arteries = dec. SBP Balanced VD = dec. TPR = dec. MAP (CO little changed) NC GFr + inc. RBF = dec. FF = no salt/water retention NC HR and baroreflex still in tact |
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HTN patients w/ HF/LVH/DM Patients w/ systolic dysfxn post MI |
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Prego category X!!! Angioedema *Dry cough (give ARB or aspirin) *Skin rash (dose-related) *Ageusia, dysgeusia First-dose hypotension esp. if already taking thiazide *Dec. glomerular pressure = renal insufficiency in pt w/ bilateral renal artery stenosis or stenosis of single kidney Hyperkalemia in pt on K-sparing diuretic or oral supplement *Fatigue, weakness, sexual dysfxn rare No hypokalemia, hyperglycemia, hyperuricemia |
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Block AT1-R = no AngII effects |
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If an additional fall in BP is desired on ARBs, add ___ |
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Small dose of HCTZ rather than inc. dose of ARB |
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Mild-moderate HTN Systolic HTN HTN in pt w/ asthma, DM, renal dysfxn, gout, hyperlipidemia Proteinuria in NIDDM (but ACEI/ARB better) |
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L-type Ca channel is found in vascular smooth muscle Depolarization causes them to open, allowing Ca to flow down its gradient This Ca activates calmodulin and triggers the release of stored Ca from the SR CCAs block L-type Ca channels in arterioles (don't block the SR channels!) VD = dec. TPR/DBP = dec. afterload Large arteries: inc. compliance = dec. SBP Baroreflex inc. in sympathetic activity CO maybe slightly inc. No salt/water retention b/c direct natriuretic effect at renal tubules NC RAAS |
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Pedal edema from dilation of precap. sphincters Paradoxical angina from dilating healthy arteries more than atherosclerotic ones thus causing ischemia in the latter areas Hypotension GERD |
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B-blockers are a cheap/effective way to manage HTN, but... |
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Definition
Dec. glomerular pressure = inc. FF = salt/water retention that limits antiHTN effect = pseudotolerance |
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In tx of HTN, B-blockers are combined w/ ___ |
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Thiazides to cause a further reduction in BP and prevent any salt/water retention that may occur in response to the fall in glomerular pressure |
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HTN drugs that don't cause salt/water retention |
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Diazoxide Labetalol Na nitroprusside |
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Block cardiac B1R = prevent symp stimulation = dec. HR Block a1R in vasculature = balanced VD = dec. TPR = dec. MAP = dec. preload and afterload Partial agonist at vascular a2R = active VD Dec. glomerular pressure = inc. FF = salt/water retention NC RAAS |
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Labetalol: HTN emergency effects |
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IV push = smooth effect = onset 2-4 min, peak 10-15, duration 2-4 hrs NC HR NC CO = cerebral/coronary/renal blood flows maintained Can use in preeclampsia |
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Orthostatic hypotension Headaches Fatigue Dec. sexual fxn |
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aMeDA: indications, effects |
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Pediatric and prego HTN Slow fall in BP prevents MI/CVA |
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Sedation Dry mouth Rebound HTN Fatigue, flu-like syndrome Pos. Coomb's Hepatitis |
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Clonidine: indications, MOA |
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Used w/ diuretic to tx mild/mod HTN Lipid soluble = enters brain Stim postsynaptic a2R in rostral ventrolateral medulla = inhibit symp outflow |
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Dec. glomerular pressure = inc. FF = salt/water retention = pseudotolerance RAAS suppressed |
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Sedation: can persist! Dry mouth Vivid dreams, restlessness, depression Orthostatic intolerance, bradycardia, slowed AV conduction Withdrawal syndrome |
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Diazoxide Hydralazine Minoxidil |
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Arterial VD for HTN: effects |
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Dec. TPR = dec. DBP = dec. afterload Baroreflex inc. in symp. activity -Inc. HR and dp/dt -Venoconstriction = inc. preload -Together = inc. CO (give w/ B-blocker to temper this otherwise feels like the heart is pounding, also prevents secondary hyperaldosteronism) -Inc. RAAS = salt/water retention |
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Arterial VD for HTN: indications |
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Definition
Patients w/ severe HTN resistant to combined tx w/ first line drugs Severe HTN: can't be used as single drugs b/c of tachycardia and inc. EABV Diazoxide: can be used to arrest labor in eclampsia |
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Minoxidil can also be used as... |
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Hydralazine has a ___ onset whereas minoxidil has a ___ onset. |
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Tachycardia, palpitations, angina Edema Hydralazine: SHIP! = fever, arthralgia, arthritis Diazoxide: hyperglycemia |
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Balanced VD! -Dec. TPR = dec. DBP = baroreflex inc. HR -Venodilation = dec. preload -NC CO Not given long enough to cause salt/water retention
If given to patients w/ CHF, balanced VD = inc. CO = hemodynamic saluresis |
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Na nitroprusside: pharmacokinetics |
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Definition
t1/2 = 30s = dose titration based on hemodynamic response Can only give to supine patients Must be in D5W covered w/ foil via slow IV |
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Na nitroprusside: indications |
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HTN emergencies Controlled hypotension during surgery Halt acute dissecting aortic aneurysm Inc. CO in CHF Dec. myocardial O2 demand post MI |
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Tachycardia, palpitations Thiocyanate intoxication: anorexia, nausia, delirium, hallucinations, psychosis, metabolic acidosis (counter w/ furosemide to improve renal fxn!) |
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The goal of antiHTN therapy is... |
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If patients have an inadequate response to a single agent... |
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Definition
Use a different class of first-line agents Then add second drug from another class of first-line agents Then add a third drug from another class of first-line agents |
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Systolic HTN a result of dec. arterial compliance = wide PP Tx w/ ACEI/ARB, DHP to inc. compliance |
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Drugs that cause salt/water retention |
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B-blockers a-blockers Clonidine Arterial VD |
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VD that NC CO = balanced VD |
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ACEI/ARBs Labetalol Centrally acting = aMeDA, clonidine Na nitroprusside DHPs not nifedipine |
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