Final Exam Flashcards
1
Q
Major pathophysiological characteristics of asthma
A
airway narrowing & inflammation mostly in medium-sized bronchi
airway hyperresponsiveness
Th2 cell response
2
Q
Th2 high inflammation asthma
A
early onset allergic asthma, adult-onset eosinophilic nonallergic asthma, & exercised-induced
respond well to inhaled corticosteroids (ICS), monoclonal antibodies to IgE, and Th2-targeted therapeutics
3
Q
adult-onset eosinophilic nonallergic asthma
A
chronic sinusitis, nasal polyps, exacerbated by aspirin
high eosinophils in sputum & blood
tx= ICD & IL-5 monoclonal antibodies
4
Q
nonallergic, Th2 low asthma
A
severe adult onset
high neutrophils in sputum
triggered by= URI, pollution, smoke. Obesity worsens
*Poor response to ICS
5
Q
preferred method of measuring expiratory flow to dx asthma > 5 y/o
A
spirometry (* may be normal if asx)
peak expiratory flow can be used if needed
6
Q
3 things to measure asthma control
A
freq/severity of sx
use of SABA
impact on life (restricting activity? impacting sleep?)
7
Q
non-pharm interventions for asthma sx control
A
no smoking
physical activity; warm up & take SABA 5-20 min before
occupational exposure
stop NSAIDs if worsen sx
beta blocker to cardioselective
allergens
weight loss, avoid sulfites (beer, wine, shrimp, dried fruit)
vaccinations (flu, covid)
emotions
weather
outdoor pollen/allergens ***all patients w/ asthma tested for allergens
8
Q
long term/maintenance med classes for asthma
A
inhaled corticosteroids (ICS)
inhaled long-acting beta agonists (LABA)
oral leukotriene receptor antagonists (LTRA)
inhaled long acting muscarinic antagonists (LAMA)
biologic agents
9
Q
quick relief meds for asthma
A
short acting beta agonist (SABA)
ICS-formoterol (steroid + LABA)
short acting muscarinic antagonist (SAMA)
short bursts of systemic corticosteroids
10
Q
theophylline’s place in asthma/COPD therapy & why fallen out of favor?
A
higher risk of SE and not recommended; weak efficacy.
nausea and other gastrointestinal disturbances, cardiac arrhythmias, and CNS excitation, leading to a narrow therapeutic window.
11
Q
who qualifies for ICS tx in asthma
A
all people w/ persistent asthma at least 2 days each month
12
Q
ICS dosing considerations
A
flat dose-response curve
smoking decreases response
2 weeks of therapy needed to see significant clinical effects
13
Q
ICS adverse effects & interactions
A
oral candidiasis
cough
dysphonia
pneumonia in high dose
long term- decreased BMD, adrenal suppression
genetic variant causes wide range of response to ICS
interaction= cushings & adrenal insufficiency when potent inhibitors of CYP3A4 (ritonavir, itraconazole, ketoconazole) with high dose ICS so avoid
14
Q
last line for asthma tx
A
systemic corticosteroids when all other add on tx options have been expended
assess barriers to asthma control before adding
15
Q
when are LABAs (long acting inhaled beta 2 agonists) used for asthma & ex
A
acts as bronchodilator
add-on maintenance not controlled on ICS alone
as effective as doubling ICS dose or adding LTRA
**black box= NEVER used alone w/o ICS bc risk exacerbations/death
ex- salmeterol, formoterol, vilanterol
16
Q
LAMAs (long acting muscarinic antagonists)
mech. of action, indication, SE, ex (w/ onset/duration)
A
mechanism of action: inhibit acetylcholine effect on muscarinic receptors in airways and protect against cholinergic mediated bronchoconstriction
indication: uncontrolled asthma, already taking ICS or ICS & LABA
SE=(think anticholinergic) urinary retention, dry mouth, HA, URI
ex: tiotropium bromide; onset 30 min x24 hr; umeclidinium
17
Q
LTRA (leukotriene receptor antagonists)
mech. of action, indication, SE & interactions
A
mech. of action= anti-inflammatory that either inhibit 5-lipoxygenase or antagonize leukotriene D4 effects. Oral med so convenient but significantly less effective than ICS
indication= steroid sparing; *beneficial for asthma + allergic rhinitis, aspirin sensitivity, exercise-induced bronchospasm
SE = **black box warning serious mental health SE for montelukast; neuropysch SE (sleep disorder, aggression, suicide)
hepatotoxicity (zileuton & zafirlukast)
CYP 2C9 metabolism= drug interactions
18
Q
biologic agents for asthma indication & action
A
poor sx control despite all recommendations
target Th2 inflammation to reduce steroid use, fewer exacerbations, improved lung function
19
Q
anti-IgE monoclonal antibody for asthma
action, indication, SE, ex
A
omalizumab
action= inhibits binding of IgE to receptors on mast cells & basophils that decreases inflammation & allergic response
indication= mod-severe asthma, not controlled on ICS, positive skin test or reactivity to aeroallergens & high IgE
SE= injection site reaction, anaphylaxis rare but possible so *monitor x2 hours x3 months then reduce to 30 min. *rx epinephrine
20
Q
IL-5 & IL-5R antagonist monoclonal antibody
indication, action, SE, ex
A
indication= severe exacerbations, high eosinophils
action= prevention of eosinophils
ex= mepolizumab, reslizumab, benralizumab
SE= nasopharyngitis, HA, hypersensitivity, worse asthma, URI. Long term effects unknown
21
Q
IL-4 receptor alpha antagonist monoclonal antibody
indication, action, SE, ex
A
dupilumab
high IgE and eosinophil count
inhibit IL-4 and IL-13 signaling in Th2 inflammation
SE= injection site pain, transient blood eosinophilia
22
Q
macrolides & asthma
indication, action, ex
A
azithromycin 500mg 3x/week decreases asthma sx
uncontrolled medium-high dose ICS/LABA
benefits from anti-inflammatory NOT antimicrobial properties
tx x6 months
23
Q
SABAs for asthma
indication, action, use, SE, ex
A
action= reverse acute airway obstruction d/t bronchoconstriction & block early-phase response to antigen in asthma exacerbation. Increase mucociliary clearance and stabilize mast cell membranes. PRN only, not scheduled
onset < 5 min, lasts 4-6 hours
indication= asthma exacerbation; use with ICS
use= 4-10 puffs Q20 min up to 1 hour in severe acute exacerbation. Shouldn’t have repeated use over 1-2 days
SE= use without ICS increases risk of death, reduced lung function, urgent healthcare!
tachycardia, tremor, hypokalemia
24
Q
ICS (budesonide)-formoterol
A
low dose ICS-formoterol as maintenance and reliever therapy (MART) is recommended for all adolescents and adults (80/4.5 mcg); maxium dose of formoterol 72 mcg
25
I.C.E
ICE= inhaler technique, compliance, environment
evaluate at every step of asthma control
26
when can asthma severity be determined
severity can only be determined once asthma is controlled and the individual is utilizing their lowest effective dose
27
short-acting muscarinic antagonists (SAMA)
onset/duration, indication
ipratropium bromide (MDI or neb)
onset 15 min, lasts 4-8 hrs
add to SABA in mod-severe exacerbation in ED only
28
tx if acute asthma doesn't respond to SABA
systemic corticosteroids
oral route > IV in acute asthma
5-7 days, no taper needed
29
tx chronic asthma, sx < 2/month
PRN low dose budesonide/formoterol or low dose ICS when SABA taken
30
tx asthma sx > or = 2 sx/month
low dose ICD w/ SABA PRN or PRN low dose ICS/formoterol
31
asthma sx most days or waking up d/t asthma at least 1x/week tx
low dose ICD/formoterol as controller & reliever or low dose ICD/LABA with PRN SABA or medium dose ICS with SABA
32
tx daily sx, waking up w/ sx 1x/week or more or FEV1 < 65%
high dose ICD w/ PRN SABA +- oral steroid burst or medium dose ICS/formoterol daily and PRN +- oral steroid burst
33
well-controlled, partly controlled and uncontrolled asthma
Sx in 1 month: daytime asthma sx > 2x/week, nighttime waking d/t asthma, reliever needed > 2x/week, activity limitation d/t asthma
well controlled= yes to NONE of the sx listed
partly controlled= yes to 1-2 of sx
uncontrolled= yes to 3-4 of sx
34
risk factors asthma exacerbations
uncontrolled sx
freq. use SABA
inadequate ICS
low FEV1 (esp. if < 60% predicted)
major psych/socioeconomic problems
exposures to smoke, allergens
comorbid: obesity, rhinosinusitis, food allergy
sputum/blood eosinophilia, elevated FeNO
pregnancy
hx intubation or tx ICU for asthma
1+ severe exacerbations in past 12 months
35
intermittent asthma characteristics and tx
infrequent trigger exposure (ex. exercise induced); still have chronic inflammation
preferred tx: ICS/formoterol PRN or PRN SABA w/ low dose ICS. Can use SABA alone but increased risk of severe exacerbations
36
tx for moderate persistent asthma
single maintenance and reliever therapy (SMART) of ICS/formoterol (both control & reliever)
addition of LAMA, biologic agents, and/or oral steroids may be considered if unable to control on SMART alone
37
what is step up asthma therapy mean
control-based tx, meds adjusted in continuous cycle w/ assessment, tx, review
f/u 1-3 months after change to regimen
always assess adherence and technique
38
when to step down asthma therapy
monitor Q3-12 months, step down once control maintained x3 months
gradual decrease; if too quick can increase risk of serious exacerbation even if sx are still controlled
*taper down ICS dose by 25%-50% at 3 month intervals
complete d/c of ICS not recommended
39
for asthma exacerbations, what to do if adherence to ICS is a problem
increase ICS dose during acute exacerbations
40
what to do if worsening asthma sx persist x48 hr
add oral steroid
41
parts of asthma self management action plan
corticosteroid rx for exacerbation PRN
PEF (daily in am or when sx worsen) for mod/severe persistent asthma w/ poor perception or unexplained response
42
PEF asthma plan
personal best PEF over 2-3 week period when receiving optimal tx
subsequent are compared to personal best
80-100% of personal best means therapy acceptable
50-79% of personal best means impending exacerbation
< 50% of personal best means medical alert, use PRN immediately, steroids, go to ER
PEF alone not used to determine severity of airflow limitation bc poor technique or inflammation of small airways in severe exacerbation that PEF can't detect
43
Dx of COPD
Spirometry is required to make a clinical diagnosis of COPD. The presence of a post-
bronchodilator FEV1/FVC < 0.70 confirms the presence of persistent airflow limitation
and of COPD
44
genetic factor in COPD
rare hereditary deficiency of alpha 1 antitrypsin (AAT) can cause premature/accelerate emphysema
45
COPD patho
repeated exposure to noxious particles/gas= chronic inflammation= patho change central/peripheral airways, lung parenchyma, pulmonary vasculature= obstruction. Imbalance proteases & antiproteases in lungs and oxidative stress
46
do all smokers develop COPD
no but all have inflammation
47
difference between asthma & COPD inflammation
asthma= inflammation from eosinophils and mast cells
COPD= inflammation from neutrophils, macrophages, CD8+ T lymphocytes. Some w/ COPD have eosinophils & respond better to bronchodilators & corticosteroids, may indicate co asthma
48
GOLD category of severity COPD based on FEV1
GOLD 1 mild= 80% predicted or greater
GOLD 2 moderate- 50% to 79% predicted
GOLD 3 severe= 30% to 49% predicted
GOLD 4 very severe= less than 30% predicted
49
what to use for COPD sx assessment
CAT
score of 10 or more need inhaled long acing bronchodilators
50
COPD treatment domain grades
A= low risk, less sx, GOLD 1-2, <= 1 exacerbation/year, mMRC 0-1, CAT < 10
B= low risk, more sx, GOLD 1-2, <= 1 exacerbation/year, mMRC >= 2, CAT >= 10
C= high risk, less sx, GOLD 3-4, >= 2 exacerbations/year, mMRC 0-1, CAT < 10
D= high risk, more sx, GOLD 3-4, >= 2 exacerbations/year, mMRC >= 2, CAT >= 10
51
what's the only intervention proven to slow decline of FEV1 & slow COPD progression
smoking cessation
no meds shown to modify progressive decline in lung function or prolong survival
52
considered 1st line tx COPD (though GOLD doesn't distinguish)
LAMA (long acting anticholingergics)
53
recommended labs COPD
CBC (elevated hct > 55% d/t polycythemia)
AAT level
ABGs if pulse ox < 92%
54
how to address smoking cessation in COPD
encourage every visit; "5 As" :
Ask: identify/document tobacco use status
Advise: strongly urge to quit
Assess: Is user willing to attempt to quit?
Assist: use counceling/pharm to help pt willing to quit
Arrange: scheduled f/u preferably within first week of quit date
55
pulmonary rehab
within 2 weeks of hospitalization
2x/week x6-8 weeks
max tolerated load or interval & strength training, education, self management interventions aimed at behavior change
56
when O2 in COPD
stable COPD with PsO2 <= 55 mm Hg, or O2 sat <= 88%, or evidence pulmonary HTN/edema d/t HF/polycythemia
ABGs after 60-90 days
57
Mainstay tx for symptomatic COPD
bronchodilators PRN or scheduled
increase FEV1, reduce sx, reduce freq/severity exacerbations/hospital, improve exercise tol., pulmonary rehab efficacy, and health status
58
adverse effects SABA & LABA
dose related
palpitations, tachycardia, cough, hypokalemia, sleep disturbance, tremor
59
ex antimuscarinics
ipratropium, tiotropium, aclidinium, glycopyrrolate
promote bronchodilation, decrease mucus
not one better than other
60
LABA or LAMA mod-very severe COPD
LAMA more effective at reducing exacerbations/hospital, fewer adverse effects
61
methylxanthine/theophylline & COPD
limited use d/t narrow therapeutic index, drug interact, questionable efficacy, adverse effects
reserved for those who cant use inhaled meds or still sx after appropriate bronchodilators
62
methylxanthine/theophylline interractions/adverse effects
interacts (through CYP450) with age, tobacco smoke (induce metabolism & increase clearance), and marijuana
SE: HA, heartburn, insomnia, tachycardia, palpitations, tremor
Dose-related= n/v, seizures, arryhthmias
63
tx COPD group a
few sx, low exacerbation risk
bronchodilator (SABA)
64
tx COPD group b
more sx, low exacerbation risk
LABA or LAMA
65
tx COPD group c
few sx, high exacerbation risk
LAMA
66
tx COPD group D
more sx, high exacerbation risk
LAMA or LAMA + LABA or ICS + LABA
67
when to use ICS in COPD
mod-very severe COPD w/ increased exacerbation risk, not controlled by first line (LAMA)
prevents exacerbations when high serum eosinophils
*monotherapy not recommended. Combine with LABA
68
phosphodiesterase-4 (PDE-4) inhibitor in COPD
Roflumilast (oral)
reduce inflammation
severe-very severe COPD associated w/ bronchitis & h/o exacerbations
little effect on sx/quality of life
SE: diarrhea, nausea, weight loss, HA, insomnia, low appetite, abdominal pain, neuropsych effects
*avoid in underweight & depression
69
med with pneumonia risk COPD
ICS
70
combination therapy COPD
when not responding to monotherapy
LAMA/LABA preferred
triple LAMA/LABA/ICS reduce mortality in severe-very severe
71
vaccines for COPD
annual flu
PPSV23 regardless of age
PCV13 > 65 and/or comorbidities/immunocompromised/smoker
72
tx for all AAT deficient COPD pt
alpha 1 augmentation therapy
73
other pharm meds for COPD
N-acetylcysteine= mucolytic
*prophylaxis w/ macrolides (azithromycin); greatest benefits in smokers
anti-interleukin-5 monoclonal antibodies (mepolizumab) with triple therapy
vitamin D if low levels
beta blockers for cardioprotection
chinese medicines when added to standard regimen
74
meds for COPD exacerbation
*SABA with or w/o ipratropium is standard
d/c LAMA if using ipratropium d/t anticholinergic effects
systemic corticosteroids esp w/ high serum eosinophils
75
ABX in COPD exacerbation
use when increased sputum purulence & volume or increased dyspnea or all, or patients who need mechanical vent.
76
"other" tx COPD exacerbation
thromboprophylaxis
fluids
higher risk of repeat exacerbation or cardio event after exacerbation
77
what's allergic rhinitis (AR) and other term used to describe d/t common concurrent sx
allergen-induced IgE mediated inflammatory condition of the lining of the nose and upper respiratory tract
aka allergic rhinoconjunctivitis d/t ocular sx
78
4 approaches to tx for AR (allergic rhinitis)
avoidance of allergen triggers
patient/caregiver education
pharmacotherapy
immunotherapy
79
goals of tx of AR (since NO "cure")
min. freq/severity of sx
prevent comorbid disorders (ex asthma)
improve QOL
improve work/school performance/attendance
min. adverse effects of tx
80
non-pharm. tx AR
*avoid triggers
nasal saline
81
first line and second line tx AR
#1: intranasal corticosteroids for mod-severe persistent and oral antihistamines for mild intermittent
2 (sometime first in certain pt): oral decongestants, intranasal mast cell stabilizer (cromolyn), intranasal antimuscarinic (ipratropium) and intranasal saline irrigation
82
why intranasal steroid for AR tx
anti-inflammatory most effective to treat nasal congestion (inflammation in late phase AR)
recommended as MONOTHERAPY vs combo w/ antihist. initially
83
INCS examples, onset, duration, administration
not one better than the other
fluticasone, budesonide, ciclesonide, mometasone, triamcinolone
onset 3-4 hr but up to 12 hr so use regularly. Max fax can be delayed 14 days
if severe nasal congestion IN may not be effective d/t limited exposure to nasal mucosa
84
INCS admin technique and SE
head down, spray lateral away from septum to prevent septum irritation & med down esophagus
SE: dryness irritation, burning, mild epistaxis, RARE nasal septum perforation
systemic SE concern: adrenal suppression, osteoporosis, ocular effects
85
INCS admin technique and SE
head down, spray lateral away from septum to prevent septum irritation & med down esophagus
SE: dryness irritation, burning, mild epistaxis, RARE nasal septum perforation
systemic SE concern: adrenal suppression, osteoporosis, ocular effects
86
antihistamines for AR
histamine 1 (H1) receptors; inverse agonists
little effect on nasal congestion
onset 1-2 hours for oral 15 min nasal
first & second generation oral
IN are second generation, need rx, anti-inflammatory effects: azelastine and olopatadine, SE bitter taste.
87
first vs second generation antihistamines
1st generation= 6 chemical classes from diphenhydramine > chlorpheniramine. do not routinely use d/t CNS & antimuscarinic SE (caution in elderly & w/ other meds with SE)
2nd generation= cetirizine, loratadine, acrivastine; less antimuscarinic SE. Not 1 superior to another
*need adjustment w/ renal impairment
* effective alone for mild or intermittent AR; preferred d/t fewer SE
88
what if on antihistamine for AR but persistent nasal congestion
add decongestant
maybe use oral w/ IN
or mod-sever seasonal AR use both INCS and IN antihistamine
89
oral decongestants
onset SE & contraindications
onset: oral 30 min, IN 5-10 min
SE: CNS or cardiovascular d/t SNS stimulation so HTN, insomnia, nervousness, irritability, anxiety, tremor, HA, hallucinations, decreased appetite
IN SE: persistent rebound congestion rhinitis medicamentosa ******only use x3 days*****
contraindicated (oral):
cardiac hx > use IN decongestant instead
BPH & other bladder outlet conditions can have increased urinary retention
DM
hypothyroidism
glaucoma esp closed angle
90
mast cell stabilizer for AR
cromolyn (OTC IN product)
less effective than INCAS, oral and IN antihistamines
helps early & late effects of AR
onset 4-7 days but not maximal until 2 weeks; can be PRN if episodic
well tolerated; burning sneezing bad taste nosebleed
FOUR times daily
****best in pediatric & pregnant with mild or intermittent sx
91
leukotriene receptor antagonist for AR
montelukast
For AR reserved for pt who can't tolerate/don't respond to first line tx
recommended over antihistamines in perennial AR
better for nasal congestion and rhinorrhea
SE: neuropsych, HA, GI, rash
92
antimuscarinic agent for AR
ipratropium IN spray
reserved for those whose rhinorrhea not controlled by other therapy
93
tx of AR in children
USE: second gen. antihistamine and/or INCS, montelukast chewable option, IN ipratropium in unresponsive > 5, *cromolyn mild or intermittent d/t excellent safety
avoid combo meds > unintentional OD
no first generation antihistamines
94
tx AR in pregnancy
USE: nasal saline, physical exercise, external nasal strip, 2nd gen. antihistamines generally safe, cromolyn safe but less efficacious
AVOID: oral decongestants, not a lot of data on fetal risk w/ INCS
95
BP value to start pharmacologic tx to lower BP if h/o CAD, DM or CKD, PCE score for CVD risk >= 10%, or greater than 65
SBP >= 130-140, DBP >= 80-90
for above 65 y/o SBP >= 130 warrants tx
96
when to start pharm. tx to lower BP in person w/o comorbid. or age >= 65
SBP >= 140 or DBP >= 90
97
how long to wait between each antihypertensive drug change
2 weeks for full effect
98
what class of med can be used at any stage of HTN if indicated
beta blocker
99
when to start TWO antihypertensive drugs for HTN
dual therapy for stage 2 HTN > 160/100
100
two med classes known to be more effective as initial antiHTN therapy in older people and blacks
thiazide and CCB
101
what population to try to avoid diuretic for HTN & what to use instead
younger patients to avoid long term exposure to metabolic side effects of diuretics
use CCB instead
also consider metabolic effects of beta blockers
102
what to avoid for HTN tx in advance CKD
potassium sparing diuretics (ex spironolactone); refer to specialist if > 3 drugs required at max dose
103
step care approach to initiation/titration of antihypertensive meds (1-4)
Step 1:
ACE or ARB
or
CCB or
thiazide diuretic
Step 2:
ACE or ARB plus
CCB or thiazide
Step 3:
ACE or ARB plus
CCB plus
thiazide
Step 4:
ACE or ARB plus
CCB plus
thiazide plus
spironolactone
104
antihypertensives to avoid in pregnancy and child bearing age
ACE inhibitors and ARBs or d/c as soon as pregnancy dx
105
diuretic for significant kidney dysfunction
loop diuretic instead of thiazide
106
4 classes of antihypertensives (ABCD) and two categories
ACE/ARB, beta blockers, CCB, diuretics
category 1 (AB)= block RAAS
category 2 (CD)= other pathways
combo between two categories more potent than combo from within one category
107
normal, elevated, stage 1, stage 2 hypetension
normal < 120 AND < 80
elevated 120-129 AND < 80
stage 1= 130-139 OR 80-89
stage 2= >= 140 OR >= 90
108
tx elevated BP (120-129/<80)
nonpharm therapy
reassess 3-6 months
109
tx stage 1 HTN (130-139/80-89) if ASCVD risk < 10% or greater than 10%
less than 10% nonpharm therapy reassess 3-6 months
>= 10% risk nonpharm. AND antihypertensive med, reassess in 1 month, if goal not met assess adherence then consider intensification
110
resistant HTN
failure to achieve BP goals despite adherence to optimal doses of THREE meds of diff. classes (one usually diuretic) OR need 4+ meds
screen for secondary causes
111
non pharm tx HTN
rarely sufficient to reach goal BP
lower dietary Na (2.4g) increase K intake
low fat diet (esp. saturated), high fruits/veggies
weight reduction
physical activity
mod ETOH consumption
smoking cessation
112
who gets greater benefit from Na restriction
low PRA (salt sensitive), DM, metabolic syndrome, CKD, older, black
113
first line diuretics baseline initial therapy for HTN
thiazide esp. chlorthalidone (more potent that HCTZ)
114
metabolic SE thiazides
hyperlipidemia, hyperglycemia, low K, low Mg, hyperuricemia, hypercalcemia
if CrCl < 30 loop diuretic indicated
115
loop diuretic admin for HTN
BID except torsemide which is QD d/t long half life
116
SE loop diuretics
excessive diuresis > ***low Na and hypotension***
low K, low Mg, low Ca
117
ex K sparing diuretics and SE
triamteren and amiloride
SE: high K especially w/ renal impairment, NSAIDs, K supplements, or ACE/ARBs which spare K
118
aldosterone antagonists for HTN- properties, ex, SE
spironolactone, eplerenone
K sparing effects; helpful in resistant HTN
SE: hyperkalemia esp in renal impairment or ACE/ARB, NSAIDs, salt substitutes (contain K)
gynecomastia
119
beta blockers for HTN indication, contraindication
NOT first line tx for HTN; lack positive outcomes in elderly. CYP2D6 metabolism
good for comorbidities: CAD, HFrEF, recent MI
contraindicated= asthma or COPD and PVD if non selective
usually avoid in DM, block ssx hypoglycemia
avoid w/ diuretics usually
120
non selective, selective, vasodilatory beta blockers
non selective= propranolol, timolol, nadolol
selective= metoprolol, atenolol, bisoprolol
vasodilatory= labetolol, carvedilol
121
CCB for HTN
indication, first line (dihydropyridine vs nondihydropyridine), ex, SE
effective esp. in elderly & blacks
coronary vasodilatory properties so also good for angina
first line= dihydropyridine CCB nifedipine and amlodipine BUT associated w/ edema; okay to give if dx HF but not routinely recommended
nondihydropyridine= verapamil, diltiazem negative inotropic effects block cardiac conduction good for a-fib + HTN. AVOID in LVEF
122
anihypertensive for HTN + angina or dysrhythmia like a fib
CCB
123
first line for HTN w/ DM, HF, MI, CKD, stroke
ACEi
124
ACEi indication for HTN, SE,
inhibition of angiotensin II synthesis = reduces artery tone and changes intraglomerular pressure (lowers GFR; d/c or reduce if GFR > 30% lower)
more effective for HTN when given diuretic
don't combine with ARB for HTN
first line for HTN w/ DM, HF, MI, CKD, stroke
SE: high K, persistent dry cough, less common= kidney injury, angioedema esp in black/caribbean origin
125
Angiotensin receptor blockers (ARBs) for HTN
more effective for HTN when given diuretic
don't combine with ACEi for HTN
SE angioedema
126
renin inhibitor for HTN
aliskiren
127
alpha 1 blocker for HTN
doxazosin, terazosin, prazosin
NOT used as monotherapy!
add-on (4th/5th line)
**Usually combine with thiazide to min. edema from fluid/Na retention
indicated for elderly men w/ prostatism
SE: dizzy, palps, syncope r/t orthostatic hypotension, priapism, vivid dreams, depression, asthenia
doxazosin= increased cardiovascular and cerebrovascular events
128
central alpha 2 agonists indication, mech. of action, SE
clonidine, methyldopa, guanfacine, guanabenz
limited use d/t SE but good for pregnancy or add-on in resistance
mech. of action: reduce sympathetic outflow increase parasympathetic
SE: orthostasis, sedation, dry mouth, vision disturbances, rebound HTN w/ abrupt d/c of clonidine
129
direct vasodilators for HTN
hydralazine and minoxidil
resistant HTN; relax smooth muscle
***admin w/ betta blockers and diuretics d/t tachycardia and fluid retention
SE: pericardial effusion, T wave change, hypertrichosis
130
HTN and angina tx
beta blockers or long acting CCB
131
HTN post MI tx
esp. with reduced LVEF
beta blockers and ACEi/ARB
aldosterone antagonists if reduced LVEF and DM or HF sx
132
HTN tx with HF
BP target < 130/80
beta blockers, ACEi/ARBs, aldosterone antagonists aka mineralocorticoid receptor antagonists
diuretics only if evidence of fluid volume overload for sx relief
*****Blacks= combo isosorbide dinitrate and hydralazine
133
HTN tx with DM but no CKD
depends if black or not
black= thiazide or CCB or both; consider ACEi/ARB if albuminuria cr
non-black= ACEi/ARB, thiazide, CCB
134
HTN tx if CKD
ACEi/ARB to slow progression of renal disease
ACEi w/ thiazide if ho stroke/TIA
135
HTN tx with a fib
ARB or nondihydropyridine CCB= verapamil, diltiazem negative inotropic effects block cardiac conduction good for a-fib + HTN
136
HTN tx considerations if age > 65
lower starting doses d/t SE esp. postural hypotension
avoid rapid volume depletion and titration
137
population with diminished response to ACEi/ARB
blacks (better w/ diuretics and CCB)
Asians should use RAASi and CCB with/without diuretic
138
antihypertensive med for pregnancy
preferred= methyldopa, nifedipine, labetalol
fetal risk can't be r/o
139
right side vs left side HF sx
right= systemic congestion
left= pulmonary sx
140
what controls HR
ANS > sympathetic stimulation of beta adrenergic receptors= increased HR so increased CO
141
preload
measure of ventricular filling pressure at end of diastole r/t volume of blood in LV before systole
determined by venous return, ventricular relaxation, atrial contraction
142
heart contractility
inotropic state of heart; intrinsic property of cardiac muscle incorporating fiber shortening and tension development
influenced by adrenergic nerve activity & circulating catecholamines epi/norepi
143
compensatory mechanisms that worsen HF
1. preload & frank-starling mechanism
- decreased CO > RAAS > increase fluid/Na to increase CO but heart can't contract fully and increased preload worsens CO
2. tachycardia and increased afterload
- low CO > increased HR from SNS norepi on beta adrenergic receptors > increased CO acutely then increased cardiac O2 demand> ischemia, proarrythmia, further impair
3. cardiac remodeling and ventricular hypertrophy
- regulated by angiotensin II and aldosterone; change in size/shape of heart to maintain CO
- hypertrophy = growth of myocytes. Reduce cardiac stress acutely but then leads to myocyte death d/t increased O2 demand. Contributes to diastolic dysfunction
144
RAAS and SNS in HF
vasoconstriction to redistribute blood but increases afterload (resistance to ventricular ejection) so maladaptive = further decrease in CO, cont. stim of compensatory response, cycle of neurohormonal activation
145
neurohormonal activation to compensate for decreased CO in HF
RAAS, SNS, endothelin, vasopressin, natriuretic peptides, nitric oxide
146
angiotensin II
vasoconstriction to increase vascular resistance and BP
147
aldosterone
released from adrenal glands;
sodium and water retention, electrolyte abnormalities (low K & Mg)= increased arrhythmias
causes SNS stimulation
148
norepinephrine
SNS activation; adaptive role in HF by increasing HR and contractility and mediate vasoconstriction
cardiotoxic & risk for arrythmia & ischemia
contribute to hypertrophy/remodeling
elevated in proportion of HF severity
149
endothelin
vasocontrictor
meds failed to improve outcomes in HFrEF
150
arginine vasopressin
vasoconstriction & trophic effects on heart, free water retention
hyponatremia
meds failed to improve HFrEF prognosis
151
Natriuretic peptides ANP & BNP
regulate Na/water balance
released when cardiac chamber wall stretched
BNP biomarker for HF
152
bradykinin
linked to RAAS through ACE
vasodilatory peptide, elevated in HF
153
nitric oxide
vasodilatory hormone from endothelium, high in HF
154
antihypertensives that can precipitate or exacerbate HF
antiarrythmics (disopyramide, dronedarone, etc)
beta blockers
CCB
155
HF classifications per NYHA and ACC/AHA
functional class (numbers) can reverse, staging (letters) does not reverse
N/a // A = risk w/o structural heart disease or sx
I // B,C = structural heart disease w/o limitation of activity or sx HF. Ordinary physical activity doesn't cause sx
II // C = structural heart disease, slight limitation in activity or sx HF. Ordinary activity= fatigue, palps, dyspnea, angina
III // C = structural heart disease w/ marked limitation in activity. Comfortable at rest, less than ordinary activity = sx
IV // C,D = structural heart disease that results in inability to carry on activity w/o discomfort, sx at rest. D is end-stage HF
156
goals of tx of HF overall & per stage
no cure; prevent/reduce sx, hospitalizations, slow progression, improve QOL, prolong survival
157
goals of tx of HF overall & per stage
no cure; prevent/reduce sx, hospitalizations, slow progression, improve QOL, prolong survival
A= risk factor control to reduce onset
B= pharm. to reduce further damage/slow progression
C= additional therapies for sx and decrease morbidity/mortality
D= shifts toward palliative care and QOL issues
158
most common etiology of HF
ischemic heart disease
159
pharm. therapy by HF stage
A= reduce risk, antihypertensives, lipid lowering, ACEi/ARB
B= ACEi/ARB, beta blockers
C= diuretics and ACEi/ARB, ARNI (Sacubitril/valsartan ), beta blockers, aldosterone receptor antagonist. Blacks may not respond to ACEi/ARB, use hydralazine & isosorbide dinitrate. Can add digoxin & ivabradine for sx
D= mechanical support, transplant, continuous IV vasoactive therapies
160
diuretics in HF
used for relief of acute sx of congestion and maintenance of euvolemia. Morbidity not mortality. Lowest effective dose. Dose based on sx/fluid
all pt with sx volume overload
can be PRN if mild congestion but scheduled if persistent
thiazide and loop
thiazides weaker so NOT monotherapy usually for mild congestion; not used with impaired renal function
**Loop mostly used in HF; retain function in impaired renal function. Each is equally effective. Torsemide if don't respond to furosemide
161
maximal response to diuretics in HF
reduced; ceiling dose where there's limited added benefit
d/t diuretic resistance bc of compensatory increase in Na absorption
aside from increasing dose, increase frequency to 2-3x/day or combine loop with thiazide (metolazone most often)
162
Diuretic SE/concerns w/ HF
hypokalemia > arrhythmia & death
hypomagnesemia
renal insufficiency d/t overdiuresis
reduction in renal flow amplified if take ACEi/ARB too
163
neurohormonal agents for HF
ACEi, ARBs, beta blockers, aldosterone receptor antagonists
164
what should all patients at risk for HF regardless of sx receive
ACEi
165
ACEi for HF (mech. of action, contraindications, SE)
no one better than another
slows progression
RAAS, slow breakdown bradykinin= vasodilation
absolute contraindications: h/o angioedema, bilateral renal artery stenosis, preganancy
relative: unilateral renal artery stenosis, renal insufficiency, hypotension, hyperkalemia, cough
can either help or worsen renal function depending; if increases Cr/BUN, hold or decrease diuretic
risk of hypotension esp w/ initiation and dose increase; hold diuretic
166
thiazide or loop diuretic for HF
Loop
rarely will increasing the dose of a thiazide diuretic be sufficient to treat
symptoms of volume overload in HF.
No edema= no diuretic
167
how are meds dosed for HF
target doses (those that were proven to minimize mortality in clinical trials)
if cannot tolerate, then highest tolerated dose
*targeting high ACEi dose should not prevent starting beta blocker or aldosterone receptor antagonist on the grounds of limited BP
*ACEi have target dose, but benefit even at lower doses for ALL heart failure pts.
168
how are meds for HF titrated
up over several weeks based on tolerability
169
ARBs for HF
second-line despite equivalent benefit to ACEi d/t ACEi having more clinical trial experience
no cough bc doesn't induce bradykinin like ACEi
can be considered if angioedema w/ ACEi but carefully d/t potential cross-sensitivity
monitor renal function, BP, K
170
what tx if HF patient intolerant or contraindicated to ARBs or ACEi
hydralazine and isosorbide dinitrate
171
sacubitril/valsartan in HF
angiotensin receptor/neprilysin inhibitor (ARNI)
sacubitril needs to be combined with ARB so there's not elevated angiotensin II
***warranted in pt with symptomatic HFrEF who are tolerating ACEi or ARB. That should be replaced with sacubitril/valsartan
more risk of hypotension; contraindicated for use with ACEi d/t angioedema risk. *36 hr washout period needed when switching
172
hydralazine and isosorbide dinitrate in HF
isosorbide dinitrate is a nitrate
cause vasodilation to reduce preload
hydralazine reduces afterload through smooth muscle relaxation
nitric oxide beneficial in HF; blacks respond well likely d/t imbalance nitric oxide production
consider as add on for black patient already on ACEi or ARB
low doses, titrate to target based on tolerability
SE: HA, hypotension, tachycardia, dose-dependent risk for lupus with hydralazine
173
beta adrenergic antagonists for HF
aka beta blockers
block SNS effect at beta adrenergic receptors which outweighs acute neg. inotropic effects if used judiciously
***initiate in all HF patients class I-IV or stage B-D if stable
mortality reduction for metoprolol succ. (selective) and carvedilol (non selective)
*Low dose, Slow titration over weeks to months when stable and euvolemic
volume overload at time of beta blocker initiation increases risk of worse sx
may cause short term worsening HF sx
carvedilol lowers BP more and greater risk of dizziness/hypotension
174
what if patient started on beta blocker gets mild congestion
increase diuretic
if severe, reduction of dose considered
175
ACEi and beta blocker for HF dosing
low doses of both= greater benefit that high dose of only one drug class
176
mineralcorticoid receptor antagonists (MRAs) for HF
spironolactone and eplerenone
inhibit aldosterone that produce weak diuretic effects while sparing K
eplerenone doesn't have endocrine adverse effects
use bc suppress aldosterone not for diuretic;
*recommended in symptomatic pt LVEF <= 35% or post MI w/ LVEF <= 40% w/ sx or DM
SE= hyperkalemia, gynecomastia, menstrual irregularities
177
digoxin for HF
positive inotropic effects; increase intracellular Na thus increased Ca during systole
reduces hospitalization but not survival
numerous adverse effects and toxicity is concern
concentration should be below 1
*indicated to decrease hospitalizations in pt remain sx despite tx
may help to slow rate with a fib and HF but beta blocker more effective
serum drug monitoring with changes in renal function, suspected toxicity, addition/subtraction interacting drug
178
digoxin toxicity
nonspecific- fatigue weakness
CNS: delirium, confusion, psychosis
GI: n/v anorexia
visual disturbances
arrhythmias
electrolyte disturbances: hypokalemia, hypomagnesemia, hypercalcemia
179
Ivabradine for HF
HFrEF with elevated resting HR > 70, LVEF <= 35%, class II and III, NSR, max tolerated doses or contraindication to beta blocker
lowers HR w/o effecting BP or contractility
180
CCB for HF
nondihydropyridine (diltiazem & verapamil) worsen HF
dihydropyridine (amlodipine and felodipine) are ok for HFrEF but not routinely recommended
use for angina or uncontrolled HTN
181
anticoagulants for HF
aspirin can increase hospitalization d/t interaction with RAAS inhibitors; only use with ischemic etiology
warfarin preferred and non vitamin K anticoag. if compelling indication like a fib
based on individual factors
182
pathological cause ischemic heart disease (IHD) & sx
stenosis in coronary arteries = ischemia/decreased O2 blood to heart muscle
vasospasms worsen (Prinzmetal angina= spasms w/o significant plaque; uncommon)
sx: angina, non ST elevation MI, ST elevation MI
since r/t increased O2 demand not acute change in supply, typically angina d/t stress or exercise
183
risk factors IHD
modifiable: HTN, DM, dyslipidemia, cigarettes, EOTH, obesity BMI > 30, low fruit/veggies
nonmod: men >= 45, women >= 55, men & postmenopausal women, family hx
184
HF + IHD + HTN tx
Patients with conditions such as IHD often have multiple comorbidities. Evaluation and treatment of these patients require comprehensive management. BBs have demonstrated benefits and should be part of all patients' therapy with stable HF. The caveat was that only metoprolol succinate, carvedilol, and bisoprolol are approved for use in HF. Therapy of IHD recommends BB as first line therapy (barring contraindications). Contemporary clinical outcomes have demonstrated superiority with carvedilol, but in general the only BB that should not be used are those with ISA. Considering both conditions then, it would be prudent to choose
a BB beneficial for both conditions (metoprolol succinate, carvedilol and bisoprolol).
beta blocker can't be initiated if acute HF, needs to be stabilized first; low dose, slow titration d/t risk of initial worsening HF sx
185
what to do for IHD if patient on beta blocker, still sx, resting HR 55-60
Beta blockers are considered first line therapy and should be dosed to a
resting HR of 55-60 BPM. If the patient is still symptomatic at that HR, then doses
cannot be increased, but rather an additional agent (usually a DHP CCB) is added.
186
goals of tx of IHD
prevent ACS & death
alleviate angina sx
prevent recurrent angina
prevent progression of disease
reduce complications
avoid/min tx SE
187
first-line tx for primary/secondary prevention in IHD
lifestyle mod
statins (regardless of lipids) or HMG-CoA reductase inhibitors
ACEi or ARB
antiplatelet therapy (aspirin)
beta blocker especially in HFrEF or h/o MI
188
why ACEi for IHD
vasculoprotective effects (anti-inflammatory, anitplatelet, improved endothelial function, arterial compliance/tone)
189
when to initiate aspirin and P2Y12 (clopidogrel; dual antiplatelet therapy) in IHD
recent ACS, stent placement
190
tx for prinzmetal or variant angina
if high BP= CCB
if low BP= long acting nitrate
191
alternative to beta blocker in IHD
if high BP= CCB
if low BP or low HR= long acting nitrate
192
dosing of meds in IHD
start low, care uptitration PRN to control sx or cardiovascular risk factors
193
who gets high vs mod intensity statin therapy & add on for IHD
high intensity= pretty much everyone; esp. very high risk ADCVD d/t h/o ASCVD event or multiple high risk conditions
mod to high in pt. >= 75 y/o
ezetimibe if ASCVD on max statin LDL > 70
194
who with IHD should receive antihypertensive therapy & first line
BP >= 130/80
ACEi, ARBs, beta blockers w/o ISA
195
If IHD & BP still high despite first line tx & has angina, what do you add
dihydropyridine CCB (nifedipine and amlodipine)
196
dihydropyridine CCB
nifedipine and amlodipine)
197
nondihydropyridine CCB
diltiazem and verapamil
198
If IHD & BP still high despite first line tx & DOES NOT have angina, what do you add
dihydropyridine CCB, thiazide, and/or mineralcorticoid receptor antagonists (MRA)
*think about steps to HTN tx
199
meds recommended for DM with IHD
**#1 (regardless of A1C) GLP-1 receptor agonists liraglutide, semaglutide, dulaglutide
or
SGLT2i empagliflozin, canagliflozin
200
aspirin in IHD
all pt with IHD esp. if h/o MI w/o contraindications
75mg-162mg
if contraindicated/not tolerated, use alternative like clopidogrel
201
what can alter effectiveness of P2Y12 clopidogrel
pt on meds that lower CYP2C19 activity like PPI
202
what ACEi for IHD
ramipril or perindopril
203
first line tx of acute sx angina
short acting nitrates
but not initial monotherapy
204
nitrates for angina in IHD
mech of action, onset/duration/administration, contraindication, SE
venodilation to reduce preload which reduces O2 demand and relief of sx
higher doses reduce afterload and BP
relieve vasospasms
can be given 2-5 min before activity to prevent angina
onset 1-3 min. Repeat Q5 min x3 or until sx resolve. Last x30 min. Isosorbide dinitrate lasts 2 hrs.
SE: standing= lightheaded, dizzy, hypotension
**contraindication= use of phosphodiesterase type 5 inhibitor (sildenafil, vardenafil, tadalafil) bc risk of significant hypotension and reduced cardiac perfusion. Don't take within 24-48 hours!!
205
nitrate pt education on admin
seated position
911 if sx don't improve/worsen x5 min after first dose
keep in original glass container, tighten
repeated use not harmful
206
what drugs prevent ischemic sx in IHD
beta blockers, CCB, nitrates, ranolazine
*no evidence that these improve survival
207
what med for initial therapy to prevent angina in IHD
beta blockers in absence of contraindications esp. h/o MI or HFrEF
208
beta blockers for IHD dosing considerations & contraindications
low initial dose, titration based off sx/response
dose to resting HR 55-60
max HR w/ exercise 100 or less or 20 beats above resting
contraindications: HR < 50, AV conduction defects, caution w/ meds that suppress AV conduction (digoxin, verapamil, diltiazem)
relative contraindications: asthma, COPD, severe depression
**Caution w/ DM, may mask tachycardia/tremor w/ hypoglycemia. Also alter glucose metabolism if insulin dependent
209
CCB in IHD
recommended in IHD when beta blockers contraindicated or not tolerated. Can be used in combo if beta blockers alone unsuccessful
*more effective in unpredictable angina r/t spasms!
inhibits Ca into smooth muscle > less contraction > vasodilation and reduced afterload (reduce cardiac O2 demand)
***nondihydropyridines verapamil & diltiazem have neg chronotropic effects so better for angina!!! reminder dihydropyridines better for HF
better to avoid short acting!
contraindication to verapamil & diltiazem= bradycardia and conduction disease; also not good in HF
210
combo beta blocker and CCB in IHD
long acting dihydropyridine CCB recommended d/t risk bradycardia and AV block
211
what population to avoid CCB
HFrEF; can exacerbate d/t neg inotropic effects
amlodipine and felodipine exceptions
212
long acting nitrates for IHD
limited d/t tolerance with continuous use; loss of antianginal effects within 24 hr
best way to avoid= 8-12 hr intervals w/o nitrate use (when sleeping)
SE: hypotension, dizzy, flushing, HA
tx with APAP, resolves with cont. use
213
why is monotherapy with nitrates for prevention of ischemia in IHD avoided and what is needed?
when can it be used as monotherapy?
increase sympathetic response/HR > increase O2 demand secondary to nitrate venodilation
****add to baseline therapy with beta blocker or CCB or combo of both
can be used if baseline low BP or sx hypotension with low dose BB/CCB
214
ranolazine for IHD
anti-ischemic agent, unknown action
reduced angina, increases exercise capacity but doesn't reduce incidence of Major adverse cardiovascular events (MACE)
*min. effect on BP/HR so option if low at baseline
*expensive!!! so reserved for those who don't respond to first line
SE: prolonged QT, dizziness, constipation, HA, nausea
contraindications: hepatic disease, digoxin, cyclosporin, should lower statin/metformin, CYP3A4 meds: ketoconazole, clarithromycin, phenytoin, carbamazepine
215
pharm with no benefit or cause harm in IHD
hormone replacement, folic acid, antioxidants, st. johns wort
COX-2i & NSAIDs increase risk MI and stroke
216
4 statin benefit groups for dyslipidemia? Who falls into groups and recommendation for each?
1. established ASCVD risk (secondary prevention)
-high intensity statin, no PCE risk estimator needed
2. primary prevention w/ high LDL 190+
-high intensity statin, no PCE risk estimator needed
3. primary prevention w/ DM, age 40-75 regardless of LDL
-moderate intensity statin
4. primary prevention w/o DM, age 40-75, 10 year ASCVD risk 7.5% +, LDL 70-189
- check CAC score; usually high intensity
217
desirable cholesterol, LDL, HDL, triglycerides
Cholesterol < 200
non HDL < 130
LDL < 100 (aim for < 70 in high risk)
HDL > 60 (low would be < 40 in men < 50 women)
TG < 150
218
nonpharmacologic tx dyslipidemia
plant stanols/sterols & fiber
weight loss
exercise >= 150 min/week mod intensity, 75 min vigorous
dietary cholesterol < 200
reduced trams and saturated fats
219
PCE risk groups for ASCVD
low risk < 5%
borderline 5-7.4%
intermediate 7.5-19.9%
high > 20%
220
high, moderate, low intensity statin doses and expected decrease in LDL
high (>= 50%)
atorvastatin 40mg target 80mg
rosuvastatin 20mg target 40 mg
moderate (30-49%)
atorvastatin 10mg target 20mg
rosuvastatin 5mg target 10mg
simvastatin 20-40mg
pravastatin 40mg target 80mg
lovastatin 40mg target 80mg
fluvastatin 80mg
pitavastatin 1-4mg
low (< 30%)
simvastatin 10mg
pravastatin 10-20mg
lovastatin 20mg
fluvastatin 20-40mg
221
When to add ezetimibe or PCSK9i to statin
50% reduction goal in ASCVD not met or LDL remains > 70
222
risk of having and tx high triglycerides
TG >500 risk of pancreatitis esp. if > 1000. Tg primary target for intervention
reduce fats/carbs, no ETOH, weight, exercise
goal reduce < 150
>1000 niacin, fibrates, OM3FA
500-999 triglyceride lowering agent or statin
AVOID bile sequestrants if TG 300+
200-499 *statins first line
223
statins (HMG-CoA reductase inhibitors) for dyslipidemia
preferred med
reduce ASCVD risk and mortality
usually taken in PM when produce most cholesterol (atorvastatin, rosuvastatin anytime)
well-tolerated
CYP450 metabolism (except pravastatin and pitavastatin)
takes 4-6 weeks for max effect
224
adverse effects statins & who's at higher risk
elevated LFT, statin-associated muscle sx (SAMS): rhabdo., myopathy, myalgia
obtain baseline LFTs and CK
higher risk for SAMS: small body, DM, CKD, periop., multi meds like fibrates, cyclosporine, azoles, macrolifes, verapamil, amiodarone, grapefruit juice, ETOH abuse
r/o secondary causes: vit D deficiency, hypothyroidism, muscle disorders
other SE: high A1c, may cause DM, memory loss, confusion. Cardiac benefit usually outweighs risk
225
how to handle SAMS
screen Q6-12 weeks after start/change med and each visit
CK level if sx (muscle pain, weak, tender, brown urine)
if CK < 3x upper limit of normal, cont. statin & monitor
CK > 3x normal but < 10x cont. if mild sx, repeat CK x1 week
CK increasing, statin d/c, CK reassessed when sx resolve
CK > 10x normal, stop statin, fluids
CK > 40x normal= rhabdo so ER, risk ARF
226
cholesterol absorption inhibitors for dyslipidemia
ezetimibe
reduces LDL by 18%, TG 7-9%, mod increase HDL
usually used as add on to statin when reductions not achieved or intol. of statins
2 weeks for max effect
contraindicated in liver disease or unexplained elevated LFT
227
bile acid sequestrants/resins for dyslipidemia
cholestyramine, colestipol, colesevelam ("coles-")
lower LDL only and may even increase triglycerides
usually adjunct to statins if ezetimibe and PCSK9i not option or can't tolerate statin
they aren't absorbed so GI effects- flatulence, bloating, constipation
*can inhibit absorption of other drugs (digoxin, warfarin, thyroxine, thiazides, beta blockers, fat soluble vitamins, folic acid) take 1 hr before or 4 hr after
228
ATP citrate lyase inhibitors for dyslipidemia
bempedoic acid
reduces LDL 15-25% and up to 38% when with ezetimibe
indicated for use WITH ezetimibe for familial HeFH or need additional LDL lowering agent after max statin
SE: increase uric acid
229
niacin for dyslipidemia
aka B3
limited d/t SE: flushing, hepatotoxicity, pruritus
aspirin or NSAID 30 prior or w/ food, avoid hot liquid & EOTH, slow titration, can reduce flushing & pruritus
suppls. labeled "no flush" pointless/ineffective for lowering LDL
230
fibrates for dyslipidemia
gemfibrozil
decrease triglycerides 20-60%, increase HDL 9-30%. *most effective at lowering TG
primarily used for high TG/low HDL
SE: dyspepsia, abd. pain, diarrhea, flatulence, rash, muscle pain, fatigue, cholecystitis, elevated LFTs. DO NOT increase glucose or uric acid like niacin, risk of bleeding with warfarin
with statin or renal insufficiency SAMS can occur
CK & LFTs before therapy & if sx. Increased INR if take warfarin
contraindicated: avoid if renal dysfunction eGFR < 30, gallbladder disease, liver dysfunction
231
OM3FA for dyslipidemia
lower triglycerides 45%
DHA in it can increase LDL but EPA lowers
232
microsomal triglyceride transport inhibitors for dyslipidemia
lomitapide
when with max lipid med, lowers LDL 40%
SE: GI, elevated LFT
risk of hepatotoxicity so need REMS program
pregnancy category X
233
antisense oligonucleotide inhibitor of Apo B-100 sythesis for dyslipidemia
mipomersen
1x/week SQ injection
when with max lipid med, lowers LDL 25%
risk of hepatotoxicity so need REMS program
pregnancy risk B
234
PCSK9 inhibitors for dyslipidemia
alirocumab and evolocumab
SQ human monoclonal antibodies
reduce LDL 48-71% with statins
**add to max tolerated satin in very high risk ASCVD; add ezetimibe first d/t cost
235
metabolic syndrome
elevated waist circumference (truncal obesity)
elevated TG >150
low HDL < 40 men < 50 women
high BP > 130/85
high fasting glucose >= 100
236
Heparin mech. of action, clotting factor inhibition, how is therapy monitored/adjusted? Labs?
UFH > LMWH in renal pt CrCl < 30
UFH:
rapid anticoag. in acute VTE
augments natural anticoagulant AT (antithrombin)
dose correlated with pt weight
*achieve therapeutic aPTT within 24h; other labs: whole blood clotting time, ACT, antifactor Xa, plasma heparin concentration. h/h, BP, platelets.
close monitoring, periodic adjustment
antidote= protamine sulfate
LMWH (dalteparin & enoxaparin/Lovenox):
improved properties; more predictable anticoag.
mediated through pentasaccharide sequence that binds to AT
not as much monitoring/dose changes
CBC; sometimes antifactor Xa activity measurement needed if underweight, obese, or renal impair.
can admin at home/outpatient uncomplicated VTE
***pregnancy; don't cross placenta; NEED to monitor Xa activity Q4-6 weeks
237
Heparin vs LMWHs and fondaparinux
238
Mech. of action warfarin, clotting factor inhibition, how it initiated/monitored/adjusted? Labs?
use decreased in favor to DOACs
inhibits production of vitamin K-dependent coag. factors (prothrombin & others) and anticoag. proteins.
*no effect on circulating coag. factors & antithrombotic activity delayed 5-7 days!!!
**Need overlap w/ heparin, LMWH, or fondaparinux bc paradoxical hypercoag. state first few days!
metabolism in liver CYP & varies greatly between pts. Genotype info recommended.
dose depends on response through freq. labs; adjustments based on weekly dose
adjusted for INR 2-3; INR Q2-3 days x1 week then weekly then Q2 weeks, Q4-6 weeks
consider pt related influences on dose too
SE: bleeding, necrosis, purple toe syndrome, teratogenic
239
Why is warfarin initiation overlapped with either heparin or LMWHs when initiated?
warfarin doesn't achieve antithrombotic effect for several days
paradoxical hypercoag. state first few days!
overlap x5 days until INR 2+ for 24-48 hrs
240
How to manage elevated INR w/ warfarin
vitamin K
if life-threatening bleeding fresh-frozen plasma
241
Significant interactions w/ warfarin (rx & OTC)
pharmacokinetic
change in hepatic metabolism or binding to plasma protein
pharmacodynamic
enhance/diminish effect of warfarin but don't alter INR
increase effect:
APAP
amiodarone
ETOH
ABX
fluoxetine, sertraline, fluvoxamine
flu vaccine
omeprazole
testosterone
cranberry
garlic
ginger
celery
onion
parsley
tumeric
lower effect:
sucralfate
ETOH
phenytoin, phenobarbital, carbamazepine
st john's wort
green tea
ginseng
coQ10
bleeding risk:
ASA, NSAID
clopidogrel
LMWH, heparin
242
When are antiplatelets like aspirin indicated? Alternative if sensitive to ASA?
IHD
243
oral direct thrombin inhibitors and oral direct Xa inhibitors (DOACs) indication/MOA/monitoring
Xa inhibitors (rivaroxaban, apixaban) for hip/knee replacement, superior to LMWH. No lab monitoring or dosing adjustments, oral admin.
oral direct thrombin inhibitors (DTI) dabigatran for hip replacement only. Can't be used CrCl < 30 or with P-gp
244
oral direct thrombin inhibitors (DTI) and oral direct Xa inhibitors (NOACs) compared to warfarin
245
who should receive VTE prophylaxis
patients with mod-high risk VTE unless contraindicated
246
drug with most protection against VTE in medical pt and major ortho surgery pt
low molecular weight heparins (LMWHs) when compared to unfractionated heparin (UH) and warfarin
247
approved meds to prevent VTE in hospitalized general med/surg pt
UFH 5000 unit SQ Q8-12h
enoxaparin 40mg SQ daily
dalteparin 2500-5000 units SQ daily
fondaparinux 2.5mg SQ daily
also betrixaban
248
prevent of VTE following MAJOR ortho surgery
UFH, ***LMWH, ***fondaparinux, adjusted dose warfarin, asa, direct oral anticoags (apixaban, dabigatran, edoxaban, rivaroxaban)
249
how long VTE prophylaxis for total knee, hip or hip fx repair?
Minimum 10-14 days but extend to 35 d/t VTE risk up to 1 month
250
factor Xa inhibitors for VTE (parenteral & oral aka DOAC)
parenteral: fondaparinux
indirect inhibitor of factor Xa, anticoag activity by accelerating AT
SQ daily; anticoag x2-4 days after d/c
No routine monitoring/dose adjust
few drug interactions; don't affect platelets
Help w/ tx and alternative if pt has HIT bc not affecting by heparin antibodies
oral aka direct oral anticoagulants (DOACs) : apixaban, rivaroxaban, edoxaban, betrixaban
VTE/PE tx
monotherapy, NO NEED for parenteral overlap
warfarin better as preventing death d/t VTE, these lower bleeding risk
no routine monitoring/dose adjust; aPTT, INR, PT have no place in therapy
take w/ food, avoid with renal impairment
251
Direct thrombin inhibitors (DTIs) for VTE (parenteral & oral)
Bind to thrombin and prevent interactions w/ their substrates
parenteral: *drug of choice VTE + HIT
*argatroban, bivalirudin, desirudin, lepirudin
do not require AT unlike heparins; predictable
oral: dabigatron
**need overlap treatment w/ UFH & LMWH 5-10 days first
no monitoring/dose adjust needed
aPTT to monitor but not widely used
252
**preferred tx for acute VTE tx and if CrCl < 30
LMWH or fondaparinux preferred over UFH unless CrCl < 30 then UFH preferred
253
**preferred tx for long term/extended VTE tx phase
DOACs (rivaroxaban, apixaban)
254
preferred tx for acute, long term, extended phase treatment for cancer related thrombosis
LMWH; ex: Enoxaparin (Lovenox)
