Pharm: Rx of HF and HTN Flashcards
1
Q
Blocking the renin-angiotensin system 1
A
- 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
2
Q
Blocking the renin-angiotensin system 2
A
- 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
3
Q
Goals of CHF Rx
A
- To reduce work done by the heart while maintaining/increasing SV
- Reducing work means decreasing preload and after load
4
Q
ACE inhibitors 1
A
- 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
5
Q
ACE inhibitors 2
A
- 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
6
Q
Angiotensin receptor blockers (ARBs)
A
- 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
7
Q
Renin antagonists
A
- 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
8
Q
Aldosterone antagonists 1
A
- 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
9
Q
Aldosterone antagonists 2
A
- 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
10
Q
Diruetics for CHF
A
- 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
11
Q
BBs for CHF
A
- 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
12
Q
Vasodilators for CHF
A
- 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
13
Q
Inotropic agents for CHF: dopamine and dobutamine
A
- 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)
14
Q
Inotropic agents for CHF: phosphodiesterase inhibitors
A
- 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
15
Q
Digoxin
A
- 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
