Heart Failure (edited) Flashcards
1
Q
What causes HF?
A
HF is most commonly caused Reduced ability of the heart to eject blood, known AD low-output heart failure
2
Q
Types of heart failure?
A
HF with Reduced ejection fraction (HFrEF)/Systolic dysfunction - impaired ability to eject blood during systole
HF with preserved ejection fraction (HFpEF)/ Diastolic dysfunction - impaired ventricular relaxation and filling during diastole
3
Q
What characterizes systolic dysfxn of HF?
A
Left ventricle ejection fraction < 40%
HFrEF
4
Q
What characterizes mixed dysfxn of HF?
A
mid-range reduction of EF (40-49%)
mixed diastolic and systolic dysfunction
5
Q
What sometimes xterizes diastolic HF?
A
HF with preserved EF (HFpEF)
EF 50-54%
Normal EF is 55-70%
6
Q
T/F? HF is one of the most important conditions to include lifestyle counseling and the requirements for strict medication adherence?
A
True
7
Q
What does Ischemic cardiomyopathy result from?
A
Ischemic=from decreased blood supply
From myocardial damage sustained during an acute myocardial infarction, resulting in loss of contractile function
8
Q
What does Non-Ischemic cardiomyopathy encompass?
A
A variety of conditions that ultimately increase the workload of cardiomyocytes, accelerating cell death and lead to a thin-walled dilated left ventricle with reduced contractile function
long standing HTN valvular disease excessive alcohol illicit drugs congenital heart defects viral infections diabetes cardiotoxic drugs chest radiation
9
Q
What are the most common causes of HF in North America?
A
myocardial infarction
And
HTN
10
Q
List drugs that cause or worsen HF
A
DI NATION
Dipeptidyl peptidase 4 inhibitors (DPP-4 ———-inhibitors)
–alogliptin, sitagliptin
Immunosuppressants (TNF inhibitors)
–etanercept, rituximab and interferons
Nondihydropyridine CCBs
–diltiazem and verapamil (specifically in ————systolic HF)
Antiarrhythmics (avoid class I agents in HF)
–amiodarone and dofetilide have LESS risk of —worsening HF
Thiazolidinediones (increase risk of edema)
Itraconazole
Oncology Agents (anthracyclines-doxorubicin, —daunorubicin)
NSAIDs (all including celecoxib)
11
Q
What’s cardiac output? (CO)
A
Vol of blood (in L) pumped by the heart in 1 min
It’s a fxn of HR and stroke vol.
CO = HR x SV
12
Q
What’s stroke vol?
A
Amt of blood ejected from the left ventricle during 1 cardiac cycle (one heartbeat)
13
Q
What determines stroke volume?
A
SV is determined by vol of blood in ventricle (preload), the resistance to forward flow in arterial vessels (afterload), and how hard the ventricle squeezes during systole (contractility)
So, SV is determine by preload, afterload and contractility
14
Q
What’s preload?
A
Volume of blood in the ventricle
15
Q
What’s afterload?
A
Resistance to forward flow in the arterial vessels
16
Q
What’s contractility?
A
How hard the ventricle squeezes during systole
17
Q
What’s cardiac index?
A
CO/BSA
It relates the CO to the size of the patient
18
Q
HF is a progressive syndrome, what does that mean?
A
During low CO state (main problem in HFrEF), neurohormones try to compensate by increasing volume, or increasing force or speed of contractions
may temporarily increase CO
BUT chronic neurohormonal activation causes damage to myocytes and produces changes in size, composition and shape of heart CARDIAC REMODELING
19
Q
One of the ways the heart tries to compensate during HF is by activating RAAS? Implication of this?
A
In response to low CO, neurohormones are released to compensate by increasing volume of blood, or increasing force or speed of heart contraction
RAAS results in Ang II which causes VASOCONSTRICTION as well as Ang II stimulates the adrenal gland to release aldosterone which increases NA and H20 retention, K excretion. Ang II also stimulates adrenal release of vasopressin which cause vasoconstriction and water retention
20
Q
What other compensation by the heart increases HR and contractility? (T4 augmenting CO)
A
Sympathetic (adrenergic) activation
SNS activation results in NE and EPI release which causes increased HR and contractility (+ inotrope) and vasoconstriction
21
Q
While the RAAS activation in HF is useful (maintains BP and adequate perfusion), what’s not so good abt it?
A
Na and water retention => edema
Excess fluid causes body to be congested and the classic sx of “congestive” HF is seen
22
Q
General HF S/Sx
A
Dyspnea (SOB)
Cough
Fatigue, Weakness
Reduction of exercise capacity
23
Q
Labs to distinguish between cardiac causes of SOB or other issues
A
Increased BNP (B-type Natriuretic Peptide): normal < 100 pg/ml
Increased NT-proBNP (N-terminal pro B-type Natriuretic Peptide) normal < 300 pg/ml
24
Q
S/sx of left-sided HF?
A
Orthopnea-SOB when laying flat
S3 gallop-abnormal heart sound
hypo perfusion-renal impairment, cool extremities
Bibasilar rales-crackling lung sounds
Paroxysmal nocturnal dyspnea (PND) or nocturnal cough and SOB
25
S/sx of right-sided HF?
Peripheral edema
Ascites
Jugular venous distention (JVD)
Hepatojugular reflux (HJR)-neck vein distends when pressure put on abdomen
Hepatomegaly-enlarged liver due to fluid congestion
26
What's the use of the staging system of HF?
| ACC/AHA
Help practitioners optimize mgt of pts in order to slow the development of sx
A-at risk for HF w/o structure disease or symptoms
B-structural disease w/o S/SX
C-structural disease w/ current or prior HF Sx
D-adv structural disease w/ Sx despite rest and maximal Tx
27
Whats another type of classification system used in HF?
New York Heart Association functional class (NYHA)
Important prognostic indicator for HF pts
28
What's the equivalent of ACC/AHA Staging System A to NYHA functional class?
No corresponding category
29
What's the equivalent of ACC/AHA Staging System B to NYHA functional class?
```
NYHA functional class I
(structure disease but no Sx)-no limitation
```
30
What's the equivalent of ACC/AHA Staging System C to NYHA functional class?
NYHA functional class I, II, III
I-no limitation
II-slight limitation
III-marked limitation
31
What's the equivalent of ACC/AHA Staging System D to NYHA functional class?
```
NYHA functional class IV
IV-can't do physical activity w/o Sx OR Sx at rest
```
32
Non-pharmacologic therapy for HF?
Monitor and document body weight DAILY
Notify provider of HF sx worsens or when weight increases
- --2-4 lbs in 1 day or
- --3-5 lbs in 1week)
Sodium restriction in stage A & B
< 1500 mg/d
Daily MVTE
Fluid restrictions in stage D or hyponatremia
---1.5-2L/d
BMI < 30 preferred
Exercise recommended for pts who can
33
What's the appropriate sodium restriction for HF pts?
< 1500 mg/d
34
What OTC med is reasonable to be used as adjunctive therapy in pts with NYHA class II - IV to reduce mortality and CV hospitalizations?
Omega-3 polyunsaturated fatty acid (PUFA)
35
What meds should be avoided in HF?
Products contains ephedra (ma huang) or ephedrine and stimulants such as decongests
NSAIDs, including COX-2 inhibitors (due to risk of renal insufficiency and fluid retention)
36
What alt med has may improve HF symptoms
Hawthorn and coenzyme Q10
37
What meds are the cornerstones of HF therapy?
Diuretics to control fluid volume
+
Angiotensin antagonist (ACE-I or ARBs or ARNI)
+
Beta blockers (to delay the progression of cardiac dysfunction and improve survival)
+
Aldosterone Receptor Antagonists (ARA)
These combo should be used in everyone with HF, who doesn't have a CI or intolerance to their use
38
Which of the cornerstones of HF therapy improves survival rate?
Beta blockers, ACEi or ARB or ARA or ARNI
39
What type of diuretic is more commonly used in HF?
Loop diuretics
40
MOA of loop diuretics?
They increase excretion of NA, K, Cl, Mg, Ca, and H20
=Block NA and Cl reabsorption in THICK ASCENDING LIMB OF LOOP OF HENLE =>
Do not alter survival, but decrease fluid volume making it easier for heart to pump AND help control symptoms
lowest dose effective should be used w/ care not to over-diurese (=hypoTN or renal impair)
Can use in combo w/thiazide (metolazone, etc) if loop response is poor
41
What's excreted by loop diuretics in HF?
Water
Sodium
Potassium
Chloride
Magnesium
Calcium
42
Whys the lowest effective dose of loop used in HF?
They haven't been shown to alter the survival of HF pts, don't want to over diurese and cause hypotension or renal failure
43
List loop diuretics used in HF?
Furosemide (Lasix)
Bumetanide (Bumex)
Torsemide (Demadex)
Ethacrynic Acid (Edecrin)
44
Whats the brand name of Furosemide (loop used in HF)?
Lasix
45
Whats the oral loop dose equivalency of Furosemide (Lasix)?
40mg
Bum 1 torse 20 furo 40 etha 50
46
Whats the oral loop dose equivalency of Bumetanide?
1mg
Bum 1 torse 20 furo 40 etha 50
47
Whats the oral loop dose equivalency of Torsemide (Dermadex)?
20mg
Bum 1 torse 20 furo 40 etha 50
48
Whats the oral loop dose equivalency of Ethacrynic acid (Edecrin)?
50mg
Bum 1 torse 20 furo 40 etha 50
49
What's warning associated with loops use?
Sulfa allergy
50
Which loop is the sulfa allergy warning not applicable to?
Ethacrynic acid (Edecrin)
51
SEs of loop?
Hypokalemia
Orthostatic hypotension
Decreased Na, Mg, Cl, Ca (different than thiazides which increase Ca)
Metabolic alkalosis
Hyperuricemia (increased uric acid)
Hyperglycemia
Increased TGs, TC
Photosensitivity
Ototoxicity (more with Ethacrynic acid), including hearing loss, tinnitus and vertigo
52
Monitoring for loops?
BP
Hearing with high doses of rapid IV admin
Renal fxn (SCr, BUN)
Electrolytes
Fluid status (in's and out's, weight)
hearing w/ high doses or rapid IV admin
53
Which loops are light-sensitive (stored in Amber bottles)?
furosemide and Bumetanide
IV admixtures do not require light protection
STORE furosemide inj. at ROOM temp-crystallizes
54
What's the furosemide IV to PO ratio?
1:2
| Furosemide 20mg IV = Furosemide 40mg PO
55
Diuretics such as loops and lithium?
May decrease lithium renal clearance and increase risk of lithium toxicity
56
MOA of ACE-I?
Block conversion of angiotensin I to angiotensin II by inhibiting the ACE
=decrease vasoconstriction and decrease aldosterone secretion
57
MOA of ARBs?
They block angiotensin II receptor AT1, which is responsible for vasoconstriction, aldosterone stimulating and re-modeling effects of angiotensin II
58
Is triple combo of ACE-I/ARB/aldosterone receptor antagonist recommended? Why/why not?
ACEi + ARB has been shown to decrease HF hospitalizations
BUT it is more common to combine ACEi+ARA OR ARB+ARA
ACEi+ARB+ARA is NOT recommended due to higher hyperkalemia or renal risks
59
List ACE-I agents in HF guidelines
Captopril (Capoten)
Enalapril (Vasotec)
Enalaprilat (vasotec IV)
Fosinopril
Lisinopril (Prinivil, Zestril)
Perindopril (Aceon)
Quinapril (Accupril)
Ramipril (Altace)
Trandolapril (Mavik)
60
What's the brand name of Enalapril (ACE-I)?
Vasotec
61
What's the brand name of Lisinopril (ACE-I)?
Prinivil
Zestril
62
What's the brand name of Quinapril (ACE-I)?
Accupril
63
What's the brand name of Ramipril (ACE-I)?
Altace
64
Howz Captopril (Capoten) taken?
1 hr B4 meals
65
Black box warning of ACE-I?
D/c as soon as pregnancy is detected
66
CI to ACE-I use?
Angioedema Hx
Bilateral renal artery stenosis
Use within 36 hr of neprilysin inhibitor (Entresto)
NOTE: ARBs do NOT have wash out warning for ENTRESTO
67
SEs to ACE-I and ARBs use?
Cough (not for ARB, only ACE-I SE)
Hyperkalemia
Angioedema (less with ARB than ACEi)
--d/c drug immediately and drug is then CI
Hypotension
68
Which ACE-I has more SEs? What are they?
Captopril (Capoten)
Taste perversion
Rash
69
Monitoring parameters of ACE-I and ARBs?
BP
Potassium
Renal fxn
S/sx of HF
70
List ARBs agents in HF guidelines
Candesartan (Atacand)
Losartan (Cozaar)
Valsartan (Diovan)
71
Which of the ARBs has shown benefit in clinical trials but no FDA indication for use in HF?
Losartan (Cozaar)
72
What's the brand name of Losartan (ARB)?
Cozaar
73
What's the brand name of Valsartan (ARB)?
Diovan
74
Black box warning, CI, SEs, Monitoring Parameters same as ACE?
Same as ACE-I
75
Which electrolyte is typically increased in ACE-I and ARBs use?
Potassium (Hyperkalemia)
76
MOA of bb in HF?
Bb antagonize the effects of catecholamines, esp norepinephrine
77
Both BB and ACE-I/ARBs reduce mortality and morbidity, but what's the difference btw them?
BB don't have a class effect, only Carvedilol, Metoprolol Succinate ext-release and Bisoprolol
ACE-I/ARBs have a class effect
78
List BB used in HF?
Carvedilol
Metoprolol Succinate extended-release
Bisoprolol
79
Which BB should be absolutely avoided?
BB with intrinsic sympathomimetic activity (ISA)
80
List the selective BB used in HF
Bisoprolol (Zebeta)
Metoprolol Succinate ext-release (Toprol XL)
81
What's the brand name of Metoprolol Succinate ext-release (selective BB)?
Toprol XL
82
List non-selective BB used in HF
Carvedilol (Coreg, Coreg CR)
83
What's the brand name of Carvedilol (non-selective BB)?
Coreg
84
SE of selective BB (Bisoprolol and Toprol XL)?
Reduced HR
Hypotension
Fatigue
Dizziness
Depression
increase TG
85
Monitoring of selective BB (Bisoprolol and Toprol XL)?
HR
BP (titrate Q 2 wks, reduce dose if HR < 55 BPM)
S/Sx of HF
weight gain & edema (esp Carvedilol)
86
How do u d/c BB?
Must taper
87
Are IV doses of selective BB (Bisoprolol and Toprol XL) equivalent to oral doses?
IV doses are NOT equivalent to PO doses (IV is usually lower)
88
How do u take Carvedilol (Coreg, Coreg CR) - no selective BB?
Take Carvedilol - all forms -'with food
89
Which DM sx are NOT masked by BB?
Sweating (Diaphoresis)
And
Hunger
90
Which ARAs is non-selective?
Spironolactone-also blocks androgen (endocrine SE)
91
Which ARAs is selective? Benefits?
Eplerenone (Inspra)
Doesn't exhibit endocrine SE
92
MOA of ARAs?
They compete with aldosterone (a mineralocorticoid) at receptor sites in DISTAL CONVOLUTED TUBULE and COLLECTING DUCTS
93
When ARAs used in pts with HF?
```
Decreases morbidity and mortality
should be added to Standard therapy NYHA class II-IV pts
```
94
What's the brand name of Spironolactone (ARAs)?
Aldactone
95
CI of Aldosterone Receptor Antagonists (ARAs)?
Renal impairment (CrCl < 30mL/min)
Anuria
Hyperkalemia
Addison's disease or other diseases that ---------increase K
96
SEs of ARAs?
Hyperkalemia
Increased SCr
Dizziness
Spironolactone: Gynecomastia and breast tenderness impotence, irregular menses, amenorrhea
Eplerenone: Increase TG
97
Which SE is unique to Spironolactone?
Gynecomastia and breast tenderness impotence and menses irregularities
98
Monitoring of ARAs?
Check K B4 starting and freq thereafter
---Do not start in HF if K>5 or eGFR<30
BP
SCr/BUN
S/Sx of HF
99
How do u minimize risk of hyperkalemia in pts treated with aldosterone blockers?
Don't start if K > 5 mEq/L
CrCl<30 or SCr >2 in women or >2.5 in men
Use low doses, start low
Don't use w/NSAIDs-can cause increase K as well as decrease antihypertensive effect
Monitor freq
Counsel pt about increased risk of dehydration (due to vomiting, diarrhea or reduced fluid intake)
100
What's Hydralazine?
A direct arterial vasodilator which reduces afterload
101
What's Nitrates?
Nitrates are venous vasodilators and reduce preload by increasing nitric oxide availability
102
What's the role of Hydralazine/Nitrate (combo) in HF?
Alternative therapy for pts who can't tolerate ACE-I or ARBs due to poor renal function, angioedema, or hyperkalemia
Standard therapy in black pts with class III or IV who are symptomatic despite optimal treatment with ACEi and BB
Though individually beneficial for other indication alone, they do not affect HF outcomes if not both used
103
What's the brand name of Hydralazine/Nitrate (combo) in HF?
BiDil
104
What's the brand name of Isosorbide mononitrate in HF?
Monoket- denitrate used in trial but mononitrate is used in practice
105
CI to using BiDil (Isosorbide dinitrate/hydralazine), Hydralazine, Monoket (Isosorbide mononitrate)?
mitral valve rheumatic heart disease, CAD
106
SE to using BiDil (Isosorbide dinitrate/hydralazine)?
Headache
Hypotension
dizzy/lightheaed
flushing
DILE
107
Monitoring of BiDil (Isosorbide dinitrate/hydralazine), Hydralazine, Monoket (Isosorbide mononitrate)?
HR
BP
S/Sx of HF
ANA
108
SE unique to Hydralazine? (Gen. SE include headache, rare lupus-like syndrome)
Headache
Hypotension
Reflux tachycardia
Palpitations
Fluid Retention
Peripheral Neuritis
DILE
109
SE of Monoket (Isosorbide mononitrate)?
Headache
Dizziness/ Lightheadedness
Flushing
Hypotension
Tachyphylaxis (need 10-12 hr nitrate free interval)
Syncope
110
MOA of Digoxin?
Inhibits the Na/K ATPase pump => positive INOTROPIC effect (increased in CO)
+
Exerts a parasympathetic effect which provides a negative CHRONOTROPIC effect (decreased HR)
111
Role of digoxin?
Added in pts who remain symptomatic despite receiving standard therapy, including ACE-I or ARB and BB.
112
Effects of digoxin in HF?
Shown to improve sx, exercise tolerance and QOL
Shown to reduce hospitalizations for HF
But, doesn't improve survival of HF pts
113
What should be considered b4 dosing digoxin?
Pts renal fxn
Body size
Age
Gender
T4, lower dose for renal insufficiency, smaller, older, female
114
What's the brand name of Digoxin?
Lanoxin DigiTek Digox
115
Usual dose of digoxin in HF?
0.125-0.25mg daily
LD not used in HF
116
Therapeutic range for digoxin in HF?
0.5-0.9 ng/ml (higher range for A.Fib)
117
What's the antidote for Digoxin?
DigiFab
118
What increases the risk of digoxin toxicity?
Hypokalemia (K < 3.5 mEq/L)
Hypomagnesemia
Hypercalcemia
119
Why's potassium oral supplementation necessary in HF?
Bcuz many HF drugs waste K
120
What's the most commonly used potassium oral supplementation in HF?
Potassium chloride (KCl)
121
When should K levels be checked?
Baseline
Any change in diuretic, ACE-I, ARBs or ARAs dose
When a pt's renal fxn changes
122
What deficiency aggravates hypokalemia? What should be done?
Mg deficiency aggravates hypokalemia
Check Mg levels and correct prior to correcting K levels
123
What's the usual range of K? Exception?
3.5-5 mEq/L
In pts using Digoxin: 4-5 mEq/L
124
Do all pts require K supplement?
No! Some, esp those in class I and II, are able to get their K from food e.g.
Banana, potatoes, orange juice, beans, dark leafy greens, apricots, peaches, avocados, white mushrooms and some varieties of fish
125
What's the brand name of Potassium chloride?
K-Tab, Klor-Com, Klor-Con M10; M15; M20, Micro-K; 10 etc
126
How should Micro-K capsules be used?
Capsules may be opened and contents sprinkled on a spoonful of applesauce or pudding and immediately swallowed w/o chewing
127
How should Klor-Con, K-Tab be used?
Swallow whole, don't crush, cut, chew, or suck on tablet
128
How should Kor-Con M be used?
Swallow whole, don't crush, chew or suck on tablet
Tablet may be cut in half and swallowed separately or dissolve the whole tab in 4 oz of water -stir for 2 minutes- drink immediately
129
What's acute decompensated HF?
When pts experience episodes of worsening sx such as sudden wt gain, inability to lie flat w/o becoming SOB, decreasing functionality (eg, unable to perform their daily routine), increasing SOB and fatigue.
130
What does most ADHF pts present with?
Worsening congestion
131
When should BB be stopped in ADHF?
When hypotension or hypoperfusion is present
132
Howz congestion treated in ADHF?
Diuretics and possibly IV vasodilators
133
What's the inotrope of choice in HF pts with SBP < 90 mmHg?
Dopamine
134
How long should HF be on dopamine?
Inotropes (dopamine) are assoc. with worse outcomes and should be d/c once pt is stabilized
135
List vasodilators used in ADHF?
Nitroglycerin
Nitroprusside
Nesiritide
136
What must be monitored if ADHF pt is on vasodilators (NTG, nitroprusside and nesiritide)?
BP must be monitored closely
137
Howz NTG effective in ADHF?
It's more of a venous VD, esp at low doses; it's effective as an arterial VD at higher doses (doses should be titrated up)
138
In what cases is NTG preferred? Duration of tx?
In ADHF + active myocardial ischemia or uncontrolled HTN
Effectiveness may be limited after 2-3 days
139
What's Nitroprusside?
An equal arterial and venous VD at all doses
140
Effect of Nitroprusside metabolism?
Results in the formation of Thiocyanate and Cyanide (both of which can cause toxicity)
141
When's Nitroprusside preferred in ADHF?
In pts with uncontrolled HTN, but renal and hepatic fxn must be monitored closely
142
What's Nesiritide?
Recombinant B-type natriuretic peptide
143
Effect of Nesiritide (Natrecor)?
Both arterial and venous VD
144
What's the brand name of Nesiritide (VD used in ADHF)?
Natrecor
145
What's the brand name of Nitroprusside (VD used in ADHF)?
Nitropress
146
SE of Nesiritide (Natrecor)?
Hypotension
SCr
147
Monitoring of Nesiritide (Natrecor) and NTG?
BP
SCr
BUN
Urine output
148
CI to NTG and Nitroprusside (Nitropress) use?
SBP < 90mmHg
CI with PDE-5 inh
Increased intracranial pressure
149
Monitoring of Nitroprusside (Nitropress)?
BP
HR
BUN
Urine output
Thiocyanate/cyanide toxicity
Acid-base status
150
SEs of Nitroprusside (Nitropress)?
Hypotension
Headache
Tachycardia
Thiocyanate/cyanide toxicity (esp, in renal and hepatic impairment)
151
Storage of Nitroprusside (Nitropress)?
Need to protect infusion bag from light (cover with opaque material or aluminum foil)
152
What's indicates degradation of Nitroprusside (Nitropress) to cyanide?
A blue color solution
T4 don't use
153
What's the target dose of Carvedilol (Coreg) in HF?
IR: 25 mg bid
Or
50 mg bid (if pt > 85kg)
CR: 80mg daily.
154
What's the brand name of Eplerenone?
Inspra
155
What's heart failure (HF)?
HF is a syndrome where the heart is not able to supply sufficient blood flow (or cardiac output) to meet the metabolic needs of the body
156
Ivabradine
Corlander
Inhibits funny current (I f) in sinus node which reduces sinus rate and therefore HR reduction.
Reduces hospitalizations for HF but doesn't affect mortality
For class II-III w EF=<35% on all appropriate 1st line meds and still have resting HR>= 70 BPM
Warning: decrease Hr, brady, increase QT
157
ARNI
sacubitril/valsartan (Entresto
Box: Has ARB-D/C as soon as pregnancy detected
CI: Use w/ ACEi or ARB, angioedema hx
WARN: Angioedema, renal impair, hyperkalemia, hypotension
SE: Cough
MUST HAVE 36 HOUR WASHOUT of ACEi before starting ENTRESTO or WASHOUT entrust 36 HR before starting ACEi
158
HF meds that decrease lithium clearance
ACEi, ARB, ARNI, Diuretics
159
Cutting Toprol XL
Must use pill cutter and cut ONLY at score line
Swallow 1/2 tablet whole
Do NOT crush or chew
160
Avoid with Ivrabradine
Grapefruit Juice, St Johns Wort
161
Avoid with Bidil
PDE5 inhibitors DO NOT USE in these pts
as well as Riociguat
The combo can cause severe hypotension
