Pharm: Rx of HF and HTN Flashcards Preview

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Flashcards in Pharm: Rx of HF and HTN Deck (25):

Blocking the renin-angiotensin system 1

-Angiotensinogen converted to angiotensin I by renin
-Kidneys release renin from 2 inputs: lack of kidney perfusion (decreased BP) or B-stimulation of kidney from cardiac center (due to decreased BP)
-Angiotensin I converted to angiotensin II by ACE (secreted by the lungs)
-Angiotensin II binds to receptors causing vasoconstriction of both arteries and veins


Blocking the renin-angiotensin system 2

-Angiotensin also leads to aldosterone secretion from adrenals, and aldosterone stimulates Na/H2O reabsorption from kidneys, increasing blood volume
-Together, the increased blood volume (increases preload) and the increased resistance (increased after load) leads to elevated blood pressure and more work for the heart


Goals of CHF Rx

-To reduce work done by the heart while maintaining/increasing SV
-Reducing work means decreasing preload and after load


ACE inhibitors 1

-All end in "pril": benazopril, captopril, enalopril, lisinopril
-Blocking ACE leads to a block in the angiotensin pathway and thus no increase in TPR or blood volume
-By reducing preload (lower EDV b/c decreased blood volume) ACEIs shift the point on the volume-function curve to the left, down the same curve
-By reducing after load (decreasing TPR) ACEIs shift the curve up


ACE inhibitors 2

-Therefore, overall, ACEIs cause a up and to the left shift of the point on volume-function curves
-May also block detrimental myocardial remodeling
-Side effects of ACEIs: dry cough, b/c blocking ACE also blocks the metabolism of bradykinin, which then builds up in the lungs and cause coughing/edema. Postural hypotension occasionally


Angiotensin receptor blockers (ARBs)

-All end in "artan": losartan
-Blocks angiotensin II from binding to its receptors in adrenal cortex and vascular beds
-Thus blocks the action, but not formation of angiotensin II and has the same effects on volume-function curves as ACEIs (up and to the left)
-Minimal side effects b/c they do not block the metabolism of bradykinin


Renin antagonists

-Ex: aliskiren
-Block the action of renin in converting angiotensinogen to angiotensin I
-Have the same overall effect as ARBs and ACEIs in moving the volume function curve up and to the left
-Also minimal side effects since it does not block metabolism of bradykinin


Aldosterone antagonists 1

-Aldosterone causes reabsorption of Na in exchange for excretion of K (works @ collecting duct)
-Aldosterone antagonists allows Na to be reabsorbed (and thus H2O) but prevents the excretion of K (K sparing diuretic)
-This causes blood volume to fall and thus reduces preload and relieves edema


Aldosterone antagonists 2

-Since only preload is falling these drugs only move the point on a volume-function curve to the left on the same curve
-May also prevent cardiac remodeling
-Ex: eplerenone and spironolactone
-Side effects: only spironolactone has major side effects, since its a sex hormone it binds to steroid nuclear receptors and cause gynecomastia (breasts in males) and menstrual irregularities in females


Diruetics for CHF

-All diuretics cause hypotension, some work @ loop of henle (loop diuretics) others work on proximal tubule
-Loop diuretics: furosemide, bumetanide (block Na, Cl, H2O reabsorption)
-Proximal tubule: metolazone (blocks Na, H2O reabsorption)
-Since blood volume/EDV are lowered these drugs lower only preload, thus moving the V-F curve point to the left on a single curve
-These drugs also reduce edema
-Side effects: hypokalemia (unless K-sparing diuretic) for loop diuretics


BBs for CHF

-Metoprolol and carvedilol are always used in CHF, but the mechanism is not understood (may prevent remodeling and block upregulated B receptors)
-Side effects: worsening cardiac failure
-Withdrawal from BBs must be slow since B-receptors have been unregulated
-BBs are always given in part b/c they are the only way to block the cardiac reflex


Vasodilators for CHF

-Nitrates (isorbide dinitrate) are direct vasodilators that dilate veins only via NO
-Since they only dilate veins they reduce EDV and shift the point on the V-F curve to the left
-Hydralazine is a dilator of arteries, therefore it decreases after load instead of preload and moves the VF point up to the next curve
-Nitroprusside is a dilator of both arteries and veins, meaning it decreases both after load and preload and moves the VF point up and to the left
-Side effects: hypotension, tachycardia, headache
-Contraindicated: if pt is taking phosphodiesterase inhibitors (viagra) b/c there can be severe hypotension


Inotropic agents for CHF: dopamine and dobutamine

-All inotropic agents increase intracellular Ca thus increasing force of contraction of the heart
-Dopamine: causes vasodilation at low doses, at medium doses it stimulates cardiac contractility
-At high doses it causes vasoconstriction, thus must keep doses low
-Dobutamine: stimulates B1 receptors on heart and dilates blood vessels so overall it has positive inotropic effects (does not elevate O2 demand)


Inotropic agents for CHF: phosphodiesterase inhibitors

-Ex: inamrinone, milrinone
-Prevent the breakdown of cAMP, which activates more protein kinase to phosphorylate Ca channels
-W/ more phosphorylated Ca channels Ca levels rise in myocardial cells and the force of contraction is greater
-Side effects: long term use leads to decreased longevity
-NEVER use Ca-blocker in CHF



-Positive inotrope on the heart by blocking the Na/K ATPase, preventing Na from being pumped out of the cell
-As Na levels rise in the cell the Na/Ca exchanger (Na in Ca out) begins to fail b/c the Na concentration gradient is lost
-This leads to an increase of Ca in the cell and is transported to SR, released during systole and thus causes a greater contraction
-Side effects of digoxin: low therapeutic index (side effects @ low doses), hypokalemia, atrial fibrillation, tachycardia, premature ventricular contractions, seeing halos and yellow
-Do not combine w/ K-lowering diuretic


Order of Rx for CHF

-First is to restrict salt intake to lower BP, but first drugs are ACEIs (or ARBs) + BB
-If edema is present then aldosterone inhibitor and a diuretic is started
-If pt continues to have Sx then inotropes (digoxin first) are initiated


Factors to consider when Rxing HTN

-Severity of HTN
-Side effects
-Co-existing diseases


BBs in Rxing HTN

-Atenolol (hydrophilic), metoprolol and carvedilol (has A1 action) are all used
-Carvedilol is best for HTN b/c its A1 blocking action prevents cardiac reflex-induced vasoconstriction
-BBs work on the brain to control adrenergic output (lipid soluble only), on the heart to decrease chronotropic and inotropic activity, and on the kidney to prevent adrenergic stimulation and thus the secretion of renin
-BBs take a month to lower BP, so are usually 2nd drug added to a regimen and are mostly there to prevent cardiac reflex (carvedilol is best)


Things to remember about BBs

-Lipid soluble BBs cross the BBB and can cause nightmares and depression
-BBs decrease HDL and increase LDL
-Cause impotence in older males
-Contraindicated in PAD, since the potential B2 blockage would cause A1 to be unopposed leading to vasoconstriction and possible ischemia of limbs
-B2 blockage prevents epinephrine from binding to liver to stimulate glc release, thus when blood glc falls there is no compensation for low glc level
-BBs can cause problems in those w/ asthma
-African americans and the elderly respond less well to BBs


Diuretics 1

-Prevent Na reabsorption in the nephron to decrease H2O load and blood volume
-Thiazide diuretics (hydrochlorothiazide, good @ low doses) act on early segment of the distal tubule
-Side effects: hypokalemia, decreased Mg, increased uric acid (gout), can lead to elevated glc, TAGs, cholesterol
-Long term effect of thiazides: decreases SMC contraction due to lower Ca levels and thus dilation of arterioles


Diuretics 2

-Loop diuretics (furosemide): act on loop of henle
-K-sparing diuretics (triamterene, amiloride): act on distal tubule but can cause hyperkalemia
-Thiazides are best choice b/c they are effective @ low doses and have fewer side effects
-Diuretics are most effective in african americans and elderly (opposite to BBs)



-Lisinopril, enalapril, benazepril all used widely for HTN
-Side effect is still mainly the cough, w/ hypotension being a possible one (usually only in beginning of Rx)
-If hyperkalemia is a problem then add a loop diuretic
-Young and caucasians respond best to ACEIs (same as BBs)
-Blacks and elderly may require ACEIs and diuretics
-If ACEIs have too many side effects can use ARBs or RA instead (but don't give both since they share a common pathway)


Ca-blockers for HTN

-Not used in CHF but used in HTN: nifedipene, nicardipene, amlodipine, diltiazem, verapamil (best one)
-Work equally effective in everyone, best choice for those w/ PAD, asthma, or diabetes
-Primary action is vasodilation of arterioles (not veins), and diltiazem and verapamil both suppress inotropic and chronotropic activity of the heart


Direct vasodilators

-Hydralazine: dilates arteries but not veins (2nd or 3rd line drug)
-Unique side effect: Sx that look like SLE
-Nitroprusside: used in emergency hypertensive crises, dilates arteries and veins and used w/ BB to stop cardiac reflex



-Arteriolar dilator via opening K channels in smooth muscle and causing hyperpolarization leading to VSMC relaxation
-Is a 2nd or 3rd line drug
-Side effect: causes hair follicles to grow, may lead to hirsutism (unwanted hair)-rogaine