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Lecture 3: RAAS- Antihypertensives Flashcards

1
Q

Which commonly used drugs have been associated with the induction of HTN?

A

Oral contraceptives

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2
Q

Angiotensin II formed from RAAS is a potent _________.

A

Angiotensin II formed from RAAS is a potent vasoconstrictor.

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3
Q

Angiotensin II acts to increase what 2 things?

A

1) Total peripheral resistance
2) Extracellular fluid volume

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4
Q

What 3 things are stimulated by angiotensin II?

A
  1. Stimulates thirst
  2. Aldosterone secretion (causes retention of Na+)
  3. ADH secretion (retention of H2O)
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5
Q

What is the MOA of Captopril?

A
  • Competitive inhibitor of ACE
  • Prevents conversion of angiotensin I —> angiotensin II
  • Increases plasma renin and decreases aldosterone secretion = lower BP
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6
Q

Why is enalapril significant?

A

Is a prodrug, w/ active form being enalaprilat

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7
Q

What are ACE inhibitors used for clinically?

A
  • HTN, can combo w/ thiazide or loop diuretic
  • Acute HTN (urgency/emergency)
  • HF w/ reduced ejection fraction
  • Diabetic nephropathy
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8
Q

What are the adverse effects associated w/ ACE inhibitors?

Which AE is the reason most people stop taking the drug and what is a potentially deadly AE?

A
  • Cough = #1 reason people stop taking
  • Hypotension, HA, drowsiness
  • Angioedema = can be fatal
  • Loss of/altered taste
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9
Q

ACE inhibitor drugs have what suffix?

A

-pril

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10
Q

What is the MOA of the -sartans?

A

- Competitive nonpeptide angiotensin II receptor antagonist

  • Blocks the vasocontrictor and aldosterone-secreting effects
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11
Q

What is the clinical application of the -sartans (i.e., losartan)?

A
  • Diabetic nephropathy w/ ↑ Scr and proteinuria
  • HTN, alone or in combo
  • Heart failure if intolerant of ACE inhibitors
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12
Q

What is the big advantage of the -sartans for HTN and other clinical applications?

A

Doesn’t produce as much of a cough as the ACE inhibitors so is better tolerated

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13
Q

What is the significance of Valsartan and Candesartan?

A
  • Valsartan = is NOT a prodrug requring activation
  • Candesartan = has irreversible binding of the angiotensin II receptor
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14
Q

Which drug is often used in people w/ heart failure that are intolerant to ACE inhibitors (i.e., too much cough)?

A

Losartan

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15
Q

Which drug used for the tx of HTN is a direct renin inhibitor?

A

Aliskiren

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16
Q

What are the effects of Aliskiren?

A

Direct renin inhibitor –> blocks conversion of angiotensinogen to angiotensin I

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17
Q

What is the clinical application of Aliskiren?

How often is it used?

A
  • Tx of HTN, alone or in combo w/ others
  • New, expensive, no obvious benefits, some evidence of increased risk of AE’s
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18
Q

What are some of the AE’s associated w/ Aliskiren?

A
  • Skin rash
  • Diarrhea
  • >300% increase in creatine phosphokinase (1%)
  • Hyperkalemia, especially if combined or pt has renal dysf. or DM
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19
Q

You should NOT use a β-blocker, like propranolol, in patients with what 2 disorders?

A

1) Asthma
2) Diabetes

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20
Q

Which drugs work well in combo when treating an African American for HTN?

A
  • Diuretics and Ca2+ channel blockers
  • β-blockers, ACE inhibitors and ARBS work well when added to diuretic, but NOT as monotherapy
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21
Q

Which HTN drugs should not be given to sexually active girls?

A
  • ACE inhibitors
  • ARBs
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22
Q

Which drug used for HTN is contraindicated throughout pregnancy?

A

ACE inhibitors

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23
Q

What is the effect of drugs that interfer with Angiotensin II on pts with bilateral renal stenosis and pts with diabetes?

A
  • Can precipitate renal failure in pts w/ bilateral renal stenosis
  • Can help preserve renal function in diabetics
24
Q

What type of HTN is associated with unilateral renal artery stenosis?

A

Angiotensin II-dependent HTN

25
How can reducing salt help hypertension?
limits fluid retention increases Na-retaining receptors --\> drugs work better too
26
What were the first drugs though of to control htn? AEs?
alpha blockers **phentolamine** --\> short half life, long hypotensive episodes, orthostatic hypoT, tachycardia and arrhythmias **phenoxybenzamine** --\> non-competitive antagonist; similar to phentolamine + miosis
27
When phentolamine and phenoxybenzamine didn't work to control htn, what was the next class of drugs created and how did they work?
28
What is clonidine?
**alpha-2** adrenergic **agonist** that can cross the BBB --\> reduces overall sympathetic tone Used to tx htn, ADHD, tourettes IV admin causes transient incr in BP AE: drowsiness, xerostomia, \*rebound htn if dose is missed\*
29
What is alpha-methyldopa's MOA and its use?
alpha-2 receptor agonist drug of choice for gestational htn can cause positive coombs test and SLE-like sx
30
What is hexamethonium's MOA, use, and AEs?
blocks nicotinic receptors of both SNS and PSNS used to lower BP, best if inj 3-4x/day AEs from disruptions of PSNS and SNS: PSNS --\> higher resting HR and BP and opposite of SLUDGEM SNS --\> difficult to maintain CO/BP when upright
31
MOA, use and AEs of reserpine
MOA: blocks VMAT so NE can't get into synaptic vesicles oldest/least effect sympatholytic AEs: crosses BBB --\> severe depression/suicidal ideation
32
MOA, use, and AEs of guanethidine
displaces NE from synaptic vesicles --\> lowers CO, TPR, RBF, and GFR used for tx of htn beginnning in 1960 AEs: severe orthostatic hypotension BP slowly increases during day
33
Why are beta-blockers contraindicated if there is peripheral vascular dz?
cause cold extremities, esp in infants
34
What is the difference btw atenelol and metoprolol?
both selective B1 blockers metoprolol has a shorter half-life than atenelol but available in XR, more lipid soluble, so more likely to cause adverse CNS effects
35
What is bisoprolol noted for?
has highest beta1-selectivity
36
What does phenylephrine do and how does it affect BP?
alpha1 agonist raises blood pressure substantially
37
Why aren't beta blockers used as the first choice tx for HTN?
doesn't prevent MI, HF, or death as well as other therapies significan't higher incidence of stroke than other therapies
38
How do ACE inh affect GFR?
decreases GFR by decreasing resistance in efferent arterioles this means serum creatinine increases even though ACEIs preserve kidny fxn in hyperfiltering diabetics \<30% incr likely ok
39
What is significant about valsartan?
not a prodrug
40
What are the off-label uses of nifedipine (2)?
hypertensive emergency in pregnancy pulmonary htn
41
What are the AEs of nifedipine?
flushing, peripheral edema, headache palpitations gingival hyperplasia
42
Why is amlodipine so widely used for HTN?
long 1/2 life of 30-50 hrs
43
What is hydralazine?
direct vasodilator of arterioles exact mechanism unknown \*used for htn in pregnancy can cause drug-induced lupus-like syn
44
What are the 3 direct vasodilators to know, and what vessels do they work on?
hydralazine - arterioles nitroprusside - venous and arterioles monoxidil - arterioles
45
What is the use of nitroprusside?
directly dilates veins and arterioles used for management of htn crisis and HF half life is only abt 2 min, can be used to dial up or down bp fast
46
How does the blockade of RAS affect bilateral renal A stenosis?
reduced arterial pressure only after volume depletion may lower GFR
47
What does plasma renin look like in bilateral and unilateral renal stenosis?
bilateral - normal or low unilateral - elevated
48
Do you perform renal revascularization in pts w/ renal A stenosis or atherosclerotic dz?
from ASTRAL and CORAL trials: restoring vessel patency fails to materially recover kidney fxn no better than ACEIs and statins
49
What are primary agents to tx htn?
thiazide diuretics ACE inhibitors ARBs CCBs
50
What are secondary agents to tx htn?
loop diuretics K+ sparing diuretics beta blockers direct renin inhibitors alpha-1 blockers central alpha-2 agonists direct vasodilators
51
What is your first line tx for htn w/ stable ischemic heart dz?
beta blockers --\> if goal not met add dihydropyridine CCBs, thiazide diuretics, and or MRAs as needed
52
How do you tx htn in pts w/ chronic kidney dz?
if no albuminuria - usual first line meds if albuminuria --\> ACE inhibitors or ARBs if intolerant
53
What do you do if a pt has an ischemic stroke and high BP, but doesn't qualify for thrombolysis?
BP 220/110 or less --\> htn tx within first 48-72 hrs is ineffective to prevent death, only tx after neurological stability BP over 220/110 --\> lower BP 155 during first 24 hrs
54
What do you do if someone had a stroke more than 72 hrs ago and is stable neurologically but has htn?
initiate hypertensive tx unless 140/90 or below and not previously hypertensive
55
How do you treat htn in black adults?
initial tx should include a thiazide diuretic or CCB 2+ agents are recommended bc usually AAs have decreased renin - need diff drug than ACEIs and ARBs
56
What drugs are used to tx htn in pregnancy?
alpha-methyldopa difedipine labetalol (never ACEIs, ARBs, or direct renin inh)

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