Pharm Section 3 Flashcards
more than ____% of americans have 1 or more types of CVD (cardiovascular disease)
20% of males and females (more than 60 million)
heart disease, tx, and prevention accounts for ____% of healthcare expenditures in the US
17%
_______ from heart disease has gone down, but the number of ________ has remained virtually the same
death; coronary events
stent
sleeve inserted into an obstructed artery that has been ballooned open by angioplasty (PCTA).
rapamycin
an imunosuppresant that prevents rejection (coats stents)
traditional risk factors for CVD
increasing age (45+ male, 55+ female)
fam hx of premature cardiac heart disease
smoking, second-hand smoke
HDL <40mg/dL
hypertension (double risk for every 20/10mmHg increase)
lack of physical activity, being overweight
diabetes/insulin resistance
newer markers for CVD
Lipoprotein a (Lp(a)) Apolipoproetin B (APOB) homocysteine hematological factors troponin Myeloperoxidase (MPO) Brain natriuretic peptide (BNP) high sensitivity C-reactive protein (hs-CRP)
BNP is used to rule out….
heart failure
C-reactive protein levels are indicative of…
inflammation. hs-CRP levels >3mg/L = high risk; 1-3 mg/L normal, <1mg/L = low risk
c-reactive protein can be lowered by
diet, exercise, statins, aspirin, alcohol
CAD spectrum of acute coronary syndromes & ST elevation
stable angina > unstable angina > NSTEMI > STEMI. ST elevation @ STEMI only.
ACS (acute coronary syndrome) treatments strategies
reperfusion or revscularization therapy including thrombolysis, PCI +/- stunting, CABG, and medical therapy. antithrombic cotherapy (ASA, UFH, LMWH, Penta., DTI, GP IIb, IIIa), ADP agonist) and acute and long-term medical therapy (Nitrates, beta blockers, ACEIs, ARBs, CCBs, Statins, APT)
antithrombic drugs include what types of drugs?
anticoagulants, antiplatelets, and thrombolytic agents
drug of choice for prevention and tx of arterial thrombosis?
anti platelet drugs. Used primarily for ACS (acute coronary syndrome) and STEMI (ST-elevation myocardial infarction)
ACS is an all-encompassing term that refers to…
Unstable angina (UA), Non-Q wave myocardial infarction, and Q-wave myocardial infarction
drug of choice for prevention and treatment of venous thromboembolism (VTE), DVT, PE in patients undergoing PCI or PTCA or for prevention of cardioembolic events in pts with a fib
anticoagulants
arterial thrombi are composed of…
mainly of platelet aggregates held together by small amounts of fibrin. Anti platelet drugs are #1 for pv/tx of arterial thrombosis, but anticoagulants also effective/can add to effect of antiplatelets
venous thrombi are composed of…
mainly of fibrin and trapped RBCs (relatively few platelets). anticoagulants are #1 for pv/tx
what are fibrinolytic agents used for?
rapid dissolution of thromboemboli, usually during MIs
clotting cascade
intrinsic and extrinsic pathways, common pathway.
vitamin K antagonists
aka warfarin. disrupt extrinsic pathway of clotting cascade during transition from Factor VII to VIIa. also disrupt @ intrinsic pathway during transition from Factor IX to IXa, @ common pathway between Factor X and Xa and prothrombin to thrombin.
oral Xa inhibitors
inhibit Factor Xa directly in common pathway
direct thrombin inhibitors
act to directly inhibit thrombin in common pathway
parenteral anticoagulant agents include
Unfractionated heparni (UFH), low-molecular-weight heparins (LMWHs), Pentasaccharide (selective Factor Xa inhibitors), Thrombin-Specific anticoagulants or direct thrombin inhibitors (DTIs), oral anticoagulants, newer oral anticoagulants (NOACs), new antithrombis for A fib, anti platelet drugs, glycoprotein IIb/IIIa inhibitors
heparin is only administered via what route?
parenteral with small gauge needle to avoid hematoma formation at injection site
heparin is derived from…?
hog mucosa or bovine lung
heparin MOA (mechanism of action)
decreases thrombin by binding to antithrombin II. forms complex, inactivates factor Xa, prevents conversion of prothrombin to thrombin (inhibits fibrinogen to fibrin).
heparin does NOT have ________ activity
fibrinolytic
effects of heparin
anticoagulation, inhibits platelet function, increases vascular permeability (all contribute to hemorrhagic effects of heparin)
antidote for bleeding related to heparin overdose
protamine sulfate
how do you test for heparin?
activated partial thromboplastin time (aPTT) or anti-Xa heparin assay (HA)
aPTT levels should remain between 1.5 and 2.5 times the normal control level
herpain-induced thrombocytopenia (HIT)
prothrombic adverse drug effect. platelet activating antibodies react against complexes of platelet factor IV and heparin. Rare, but significant mortality. Less common with LMWH. Associated with thrombosis, not bleeding.
is suspect HIT, what do you do?
immediately stop heparin tx. initiate alternative anticoagulant (i.e. argatroban, bivalirudin, fondaparinux)
heparin is available in two strengths…?
10 units/mL and 10,000 units/mL
LMWH derivatives are formed by…
cleaving standard heparin into shorter chains
benefits of LMWHs
- more effect on factor Xa
- more bioavailable with with dose-dependent plasma levels
- produce more predictable plasma heparin concentrations (can use fixed doses w.o monitoring)
- have longer half life (need fewer doses)
- decreased risk of bleeding/HIT (less effect on platelet function)
- less bone loss
protamine and LMWHs
doesn’t neutralize b/c absorbed faster than UFH, but reverses 60% of its effects
LMWH does is dependent on…?
actual body weight
1st line prevention and treatment for venous thromboembolism (VTE)?
LMWHs
LMWH agents
enoxaparin (Lovenox–inpt and outpt approved), dalteparin (Fragmin), Ardeparin (Normiflo), and Tinzaparin (Innohep)
Fondaparinux (Arixta)
antithrombotic action. inhibits single, targeted step in coagulation cascade (factor Xa). does NOT directly inhibit thrombin. Evidence suggests works as well as LMWH Lovenox and may cause fewer bleeds.
protamine and fondaparinux
protamine will not reverse its effects. must monitor factor Xa levels.
fondaparinux black box warning
warning for risk of bleeding with spinal or epidural hematoma, which could lead to long term or permanent paralysis.
fondaparinux contraindications
don’t give to patients with severe renal impairment (levels can accumulate).
thrombin specific anticoagulant/ direct thrombin inhibitors (DTIs)
cause the inhibition of thrombin independent of antithrombin. greater specificity. reduced tendency for bleeding b/c don’t directly affect platelet function.
injectable DTIs
Bivalirudin (Angiomax)
Desirudin (Iprivask)–recombinant of leech anticoagulant protein. Expensive.
Argatroban (no brand name)
oral anticoagulants (antithrombotics)
warfarin (Coumadin), newer oral anticoagulants (NOACs)
warfarin MOA
used orally. primary MOA is to interfere with the production of vitamin-K dependent clotting factors II, VII, IX, and X.
vitamin K
fat soluble vitamin. “K” derived from german word “koagulation”
clotting factor activity reduced by _____% when therapeutic doses of warfarin are given
30-50%
warfarin action @ liver
interferes with hepatic recycling of vitamin K by inhibiting reductase enzyme system that converts Vit K epoxide to Vit K. Accumulation of Vitamin K epoxide reduces effective concentration of Vit K and reduces the synthesis of coagulation factors.
vitmin K supplementation in pts taking warfarin?
usually pts educated to avoid vitamin K, but recent research shows supplementation with low dose k vitamins might reduce serious bleeding complications associated with warfarin therapy.
antidote for warfarin
vitamin K (injection or oral) can also administer: fresh frozen plasma, recombinant factor VIIa, prothrombin complex concentrates,
current vitamin K recommendations
take orally. use less.
warfarin INR (international normalized ratio)
2-3. anything =+4 shows no added benefit and increases risk of bleeding.
complications of long term anticoagulant therapy
major bleeding events like intracranial hemorrhaging. black box warning for potential fatal bleeding
warfarin original use
rat poison
warfarin and pregnancy
contraindicated for use in pregnancy
why is warfarin involved in so many drug interactions?
metabolized at the liver by P450 system. highly plasma protein bound ,but easily displaced so easy to interact with other drugs (tylenol, celebrex)
genetic testing and warfarin
CYP2C9 and VKORC1 genetic carriers face higher risk of bleeding on warfarin
NOACs
new oral anticoagulants. all have boxed warning for discontinuation and increased risk of stroke. shorter acting w. 12 hour half lives (40 hours for warfarin). includes dabigatran (Pradaxa), rivaroxaban (Zarelto), apixaban (Eliquis), and Edoxaban (Savaysa)
Dabigatran (Pradaxa)
NOAC. has an antidote: idarucizumab (Praxbind). IV injection. Expensive.
the only once-daily factor Xa inhibitor?
endoxaban (Savaysa)
black box warning for endoxaban (Savaysa)
don’t use in A fib patients with creatinine clearance < 95 mL/min. avoid using in patients with STRONG renal function.
NOACs vs warfarin
NOACs at least as effective as warfarin
NOACs have faster onset, fewer interactions, cause less bleeding
Afib pts 4x more likely to die from ______ than ______.
stroke than GI bleed.
NOACs and adherence
strict adherence is critical with NOACs because most don’t have antidotes and missing just a couple of doses increases risk for stroke (NOACs have much shorter durations than warfarin).
In what patient populations would warfarin be recommended over NOACs?
end-stage kidney disease pts, hemodialysis pts, and pts with mechanical heart valves.
Compared to warfarin, NOACs were associated with a _____% reduction in stroke or systemic embolic events and ____% inc. in GI bleeding.
19% reduction in stroke and 25% inc. in GI bleed.
NOACs and MIs/ ischemia strokes?
meta-analyses show a small, statistically insignificant reduction in stroke and MIs with NOACs
anticoagulation in afib patients after a GI bleed?
15% of pts on anticoagulant will have GI bleed, 25% of those won’t restart. Much more likely to die of stroke than GI bleed, so it’s recommended they do start back if @ high risk for stroke. Take warfarin or Eliquis over others, less chance of GI bleed. NOT PRADAXA–riskiest. Also recommended PPI in pts with upper GI bleed (benefits outweigh risks).
Some afib patients will need warfarin plus…?
an anti-platelet drug. CAUTION against triple anti-thrombotic therapy b/c inc. bleeding risk.
who is at high risk for stroke?
those with prior stroke or TIA, 75 years or older, diabetes, hypertension, etc.
what anti-thrombotic for VTE tx?
direct oral anticoagulants (DOACs) like Eliquis (apixaban) or Xarelto (rivaroxaban)
Why are Eliquix (apixaban) and Xarelto (rivaroxaban) preferred for tx of VTEs?
they don’t require pretreatment with LMWHs like dabigatran (Pradaxa) and edoxaban (Savaysa), work as well as warfarin, and have lower risk of bleeding.
what anticoagulant is recommended for pts with severe renal impairment, esp those over 75 or who are underweight?
warfarin
what anticoagulant is recommended when adherence is problematic?
warfarin. longer duration so more forgiving when doses are missed.
what anticoagulant is recommended for pts with mechanical heart valves? what kind are not recommended?
warfarin is recommended, DOACs are not (less effective with mechanical valves)
When might you see anticoagulants and LMWHs?
special cases like pregnancy, severe liver diseases, or in pts that develop clots while on oral anticoagulants
What is recommended tx for pts with clots above the knee or clots that result in PE?
tx with anticoagulant for at least three months
BOTTOM LINE for anticoagulants for afib pts?
Pts well controlled on warfarin should remain on warfarin; for all others, one of the DOACs might be a better choice.
DOACs are _______ as effective as warfarin in preventing stroke or systemic embolism in fib pts, and they appear to be _______.
at least as effective and appear to be safer.
PAIs…?
platelet aggregation inhibitors aka anti-platelet drugs.
mechanisms of action for PAIs?
COX inhibition ADP or P2Y12 inhibition GP IIb-IIIa inhibition PDE inhibition PAR-1 inhibition
COX inhibitors include…?
aspirin and NSAIDs
antiinflammatory agents inhibit what?
COX-1 (prostaglandins and thromboxane > GI protection and platelet function) and COX-2 (prostaglandins > mediate inflammation, pain, fever. All starts with arachidonic acid (beginning of pathway).
drug used for secondary prevention (second heart attack)?
aspirin (since 1974!)
how does aspirin work to inhibit platelet activation/aggregation?
acetylates COX-1, blocking thromboxane synthesis and inhibiting platelet activation/aggregation IRREVERSIBLY for the life of the platelet (usually 5-7 days, up to 10 days.
Platelets have daily turnover of about _____%?
10-15%
Durlaza
RX extended release aspirin, most feel it’s no more effective than OTC aspirin.
aspirin effect on thromboxane synthesis?
one dose of oral aspirin almost completely suppresses the biosynthesis of thromboxane within one hour (non-aspirin, non-acetylated salicylates do not have this effect)
Aspirin vs traditional NSAIDS?
both alter aggregation of platelets, but NSAIDs have limited effects that disappear after 1-3 days. (similar effect, but NSAIDs not as much and reversible)
ibuprofen and aspirin together?
ibuprofen impairs the effect of aspirin by blocking its access to the TXA2 receptor. Reduces aspirins cardioprotective effect and may worsen cardiovascular risk if taken together.
COX-2 inhibitors and platelets?
COX-2 inhibitors (like Celebrex) don’t affect platelets.
reasons why people take aspirin?
mostly to prevent heart attack and stroke, but 20% also list cancer prevention as reason
____% of surveyed adults report using aspirin regularly?
50%
Low dose aspiring as secondary prevention reduces all-cause mortality by ____% and subsequent MIs by ____% in people with CVD.
18% and 30%
aspirin as primary prevention for MIs?
controversial.
effective dose of aspirin
10-325mg daily. Usually 1mg/kg/day, so ~81mg (“low dose” aspirin) closest dose.
twice daily dosing and aspirin?
no advantage to twice daily dosing
risks associated with increased doses of aspirin?
GI bleed
taking aspirin @ what time of day might reduce acute cardiac events?
bedtime
why should you use caution when giving aspirin to babies, children, adolescents?
it’s been linked to Reye’s syndrome (swelling @ liver, brain)
what’s recommended for secondary prevention of stroke?
mono therapy of aspirin (50-325mg/daily)
combination therapy of aspirin (25mg) and XR dipyridamole/Aggrenox (200mg 2x/daily
mono therapy of clopidrogrel/Plavix (75mg/daily)
when deciding whether or not to use aspirin for primary prevention of heart attack or stroke, what parameter should you use?
age.
generally low dose aspirin for men 45-79 and women 55-79. Only for those 80 if have no risk for GI bleed.
what should you give in combination with aspirin to a pt with GI risks who requires aspirin therapy?
PPI
recommendations for avoiding local effects during aspirin administration?
give regular aspirin with food or use enteric coated to avoid/reduce stomach irritation
aspirin and cancer?
aspirin can help prevent colorectal cancer
what happens when you rapidly stop taking aspirin?
cessation of aspirin can cause platelet rebound phenomenon and pro-thrombotic state leading to major adverse cardiovascular events
aspirin before surgery
traditionally has been discontinued 7-10 days before surgery, but meta-analysis suggests this increases thrombo-embolitic risks and the practice should be discontinued
NSAIDs and platelet function
all NSAIDs work in varying degrees to inhibit platelet function and prolong bleeding time. All (except aspirin) reversible when drug cleared (1-3 days).
ibuprofen an aspirin together?
ibuprofen interferes with the cardio-protective and anti-platelet effects of aspirin. if take together, take aspirin 2 hours before ibuprofen. Acetaminophen, diclofenac, COX-2 inhibitors better than ibuprofen with aspirin.
P2Y12 receptor
receptor for ADP
Theinopyridine anti-platelet drugs are used for?
prevention of coronary stent thrombosis in pts undergoing percutaneous coronary intervention with stent placement
P2Y12 inhibitors include…(drugs)?
Ticlopidine (Ticlid), clopidrogel (Plavix), prasurgrel (Effient), and ticagrelor (Brilinta), cangrelor (Kengreal)
dual anti-platelet therapy to decrease cardiac events in ACS pts undergoing percutaneous coronary interventions consists of..?
combination of aspirin and ADP/P2Y12 inhibitors
should be continued minimum of 12 months in those with drug-eluting stents and up to 12 months in those with bare metal stents
PPIs recommended in addition for those with hx or risk of GI bleeding
Ticlopidine (Ticlid)
largely replaced by clopidogrel (Plavix) bc of its toxicities and hematological adverse reactions
Clopidogrel (Plavix)
pro drug converted to CYP2C19
onset of action delayed
more effective than aspirin @ reducing atherosclerotic events
similar tolerability to aspirin, but lower risk of bleeding
more expensive than aspirin
clopidogrel (plavix) dosing
300 mg tablets for loading dose
75 mg tablets for chronic use
clopidogrel and timing
early initiation is important. if wait to fill RX after drug-eluting stent is placed, inc risk of poor outcomes
clopidogrel (plavix) and PPIs?
reports of loss of efficacy of clopidogrel when taken concurrently with PPIs b/c PPIs inhibit the enzyme that converts clopidogrel to its active form CYP2C19
clopidogrel boxed warning
for people who carry a variant of the CYP2C19 gene, may be poor metabolizers (lack of drug effect). 2-14% of patients. genetic test can be used to tell ($500).
if poor metabolizer, what can pts do?
take double dose of plavix or use Effient, which is not affected by the CYP2C19 gene
which specific PPI is not recommended for use in pts taking clopidogrel? Which one is recommended if PPI is required?
omeprazole (Prilosec) is not recommended; if must take one, take prantoprazole (Protonix)
prasugrel (Effient) compared to clopidogrel (Plavix)
prasugrel (Effient) is ten times more potent and has quicker onset of action (not a prodrug so doesn’t require bio-activation)
also less prone to drug-drug interactions and pt nonresponsiveness
prasugrel (Effient) boxed warning
potential for significant, sometimes fatal bleeding.
DONT USE in pts with bleeding, hx of stroke, or urgent need for surgery
Ticagrelor (Brilinta)
binds to same P2Y12 receptors as thienopyridines
recommended to give with aspirin, but only @ doses < 100 mg/day
Ticagrelor (Brilinta) boxed warning
warns against giving with aspirin doses < 100 mg/day b/c of inc risk for bleeding
ticagrelor (Brilinta) compared to clopidogrel (Plavix) Plavix and prasugrel (Effient)?
- -faster onset than other two (not a prodrug) but binds REVERSIBLY instead of permanently
- -more effective than clopidogrel (Plavix)
- -must be taken twice a day (possible disadvantage)
cangrelor (Kengreal)
I.V. P2Y12 inhibitor
used in pts undergoing percutaneous coronary intervention (PCI), but have not been treated with P2Y12 platelet inhibitor or GP IIb/IIIa inhibitor
cangrelor (Kengreal) compared to clopidogrel (Plavix)
cangrelor has rapid, reversible anti-pletelet effect
conflicting results on which is better, but overall cangrelor appears more effective.
PAR-1 antagonist/inhibitor does what?
blocks PAR-1 (major thrombin receptor on platelets), inhibiting thrombin-induced platelet aggregation
vorapaxar (Zontivity)
- -PAR-1 antagonist/inhibitor
- -used to reduce risk of MI, stroke, cardiovascular death, need for re-vascularization procedures
- -approved for use with aspirin or clopidogrel
- -high risk of bleeding
- -long 1/2 life (8 days) and no antidote to reverse effects
- -unsure if it’s better than standard therapy (aspirin + clopidogrel)
PDE inhibitors do what?
block phosphodiesterase, resulting in an inc in cAMP levels, inhibition of platelets, and vasodilation
dypyridamole (Persantine)
PDE inhibitor
alternative to aspirin
available in combination with low-dose aspirin as Aggrenox
pentoxyfylline (Trental)
- -PDE inhibitor, rarely used
- -increases erythrocyte flexibility, decreases fibrinogen concentration, prevents aggregation of RBCs and platelets
- -decreases viscosity of blood, improves flow
cilostazole (Pletal)
- -PDE inhibitor
- -contraindicated with any CHF
- -most effective drug available for tx of PVD, PAD, intermittent claudication
- -improves maximal walking distance, absolute claudication distance, and pain-free walking distance
PVD/IC
- -result from poor blood flow to muscles
- -exertional aching pain, cramping, fatigue
- -@muscle groups, not joints
- -consistent/reproducible from 1 day to next
- -resolves completely in 2-3 min
GPIs
- -glycoprotein IIb/IIIa inhibitors
- -most potent platelet aggregation inhibitors available
- -directly block GPIIb/IIIa receptor preventing platelet aggregation induced by ALL agonsits
- -indicated for PCI adjunct and tx of ACS (including unstable angina, nonQwave MI)
populations where GPIs indicated?
use in addition to aspirin and heparin in pts with continuing ischemia, elevated CK-MB, elevated myoglobin, elevated cardiac troponin, and in pts with planned PCI
Interesting chemical similarity of GPI drugs?
they are chemically similar to proteins derived from snake venom
most common side effect of GPIs?
bleeding
essential monitoring with GPIs?
monitor for bleeds and thrombocytopenia (too few platelets in blood)
–baseline platelet count before admin and 6 hours after infusion; thrombocytopenia usually seen 1-24 hours after infusion
contraindications for GPIs?
thrombocytopenia
<100K/mm3
use with caution in folks with platelet count <150K/mm3
abcixamab (ReoPro)
- -very effective GPI
- -fast tracked by FDA because showed 70% reduction in MIs in 30 days, not fair to continue control group
- -longer acting than other GPIs
eptifibatide (Integrilin)
GPI
Tirofiban (Aggrastat)
GPI
standard of care for pts undergoing PCI for acute MI?
dual-agent anti platelet therapy with aspirin and a P2Y12 inhibitor
standard of care for pts undergoing PCI for acute MI that also have fib or prosthetic valves?
dual therapy with oral anticoagulants replacing anti platelet agents (plus P2Y12 inhibitor)
MI patients treated with triple therapy show…?
significant bleeding risks after PCI
dual therapy vs triple therapy?
dual = anti-platelet + P2Y12 inhibitor triple = oral anticoagulant + P2Y12 inhibitor, + aspirin
epidurals and anti coagulated patients?
epidurals, spinal anesthesia, spinal punctures (esp indwelling epidural catheters) in patients taking anticoagulants run increased risk of resulting in epidural or spinal hematoma, which can result in long-term or permanent paralysis
largest malpractice case in TN history
- -22.2 million
- -auto accident
- -nurse put in epidural catheter for pain control
- -should have considered inc risk for bleeding @ spinal cord when cath removed
- -no consent form on record
thrombolytic therapy
“clot busters”
- -commonplace in 1990s for acute MI
- -now use angioplasty, so use of thrombolytics unnecessary for MIs
- -now, used mostly for tx of ischemic stroke
gold standard for tx of ischemic stroke or “brain attack”
tx with thrombolytic agents within 3-4.5 hours of acute ischemic strokes (in certain eligible patients) significantly improves outcomes
heparin often give in conjunction to reduce risk of another clot formation
streptokinase [SK] (Kabikinase, Streptase)
thrombolytic drug, protein produced by group C streptococci
binds with plasminogen to form activator complex, converts plasminogen (in circulation and bound to fibrin) to plasmin
adverse effects of SK?
- -antigenicity (induce formation of antibodies–subsequent doses may be ineffective from 6mo-life)
- -hypotension
- -bleeding complications
alteplase [tPA] (Activase)
tPA is a naturally occurring enzyme
produced by recombinant DNA technology
not antigenic or allergic
adverse effects of tPA?
bleeding
rapid drop in BP
anistreplase (Eminase)
anisolayted plasminogen-sk activator complext (APSAC)
active portion is SK
longer lasting than SK, more bleeding risk
Reteplase (Retavase)
tPA derivative
Tenecteplase (TNKase)
modification of alteplase (tPA)
longer 1/2 life, so 1st thrombolytic than can be administered over 5 sec in single dose
Fastest admin of any thrombolytic agent
hemostatic agents for surgical bleeding include
Absorbable gelatin songes (USP) and thrombin for oozing
thrombin drugs include (Thrombin JMI, Thrombogen, and Evithrom)
antifibrinolytics (hemorrhage-sparing medications)
aminocaproic acid (Amicar) and Tranexamic acid (Cyklokapron, Lysteda)
Tranexamic acid;;anti hemophilic agent for SAH, also used for heavy menstrual bleeding (Lysteda)
anticoagulants/antiplatelets and dental surgery?
almost never since risk of thrombosis if stopped higher than risk of bleeding if stay on it
can usually manage dental bleeding with gelatin sponges, sutures, compression, aminocaproic mouth rinse
aspirin and surgery?
can be continued before and after surgery if high risk for thrombosis or for procedures with low bleed risk
if held, stop 7-10 days out to minimize anti platelet effects
clopidogrel (Plavix) and surgery?
stop 7-10 days out unless a stent patient (prevent clots)
Pradaxa or Xarelto and surgery?
stop one day before if low bleed risk and at least 2 days before if higher bleed risk. restart 24 hours after.
NSAIDs and surgery?
stop 5 1/5 lives before surgery. 1 day for ibuprofen, 10 days for nabumetone (Relafen)
warfarin and surgery?
- -continued for minor dental/derm procedures
- -stop 5 days before invasive procedures
- -restart 12-24 hours after surgery
- -can bridge therapy with heparin to use during gap (start 2 days after warfarin, hold —-for surgery, resume 24-72 h after surgery until warfarin resumed)
Vitamin E, A, & beta carotene as tx for CVD/CAD?
meta-analysis shows mortality actually increases as follows:
E: 4%
A: 16%
beta-carotene: 7%
vitamin C as tx for CVD/CAD?
no long-term studies published; small/short trials show no benefit on mortality
Vit B6, B12, and folic acid for CVD/CAD
gen used to lower plasma homocysteine levels
–may lower levels, but no evidence of corresponding benefit on incidence of major vascular events, cancer, or all-cause mortality
multivitamins and CVD/CAD
no cardiovascular effect
most in developed countries eating normal diet get necessary nutrients
may be “waste of money”
not harmful @ correct doses, not sure if helpful
alcohol and CVD/CAD
thought to reduce platelet aggregation and thrombotic markers, plus have anti-inflammatory effects
scientific world divided on its cardio-protective effects; studies problematic b/c of confounders
“goldilocks amount” - 1 or 2 drinks daily, but this also may be associated with inc risk for hypertension
reservatrol and CVD/CAD?
polyphenol compound found in red wine, dark chocolate
studies show it doesn’t inc longevity or reduce CVD risks; has anti-inflammatory, antioxidant effects in vitro and in animals
omega 3 fatty acids (fish oil, flaxseed, krill oil) and CVD/CAD?
refers to DHA and EPA (acids), not plant-based alpha-linolenic acid
older studies show it lowers triglycerides, increases HDL
more recently, no benefit shown, esp in those already well treated
three FDA approved “fish oil” drugs: Lovaza, Viscera, and Epanova
side effect of omega3s?
“fish burp”
fish oil vs flax seed and krill oil
stick to fish oil
DHA, EPA better than plant based acid or kill oil
high blood pressure is mathematically defined as…?
B.P = C.O. * SVR CO = cardiac output SVR = systemic vascular resistance
antihypertensives are the ____ largest selling class of meds worldwide
3rd largest
51.6 billion in 2012
hypertension in the US population
1/3 of pop are hypertensive
- > 1/3 of those are medicated
- > 1/3 of those are actually controlled
so, 1/9th well controlled
risk of death from heart disease and stroke _______ for each 20/10 mmHg inc beginning at 115/75 mmHg
risk of death doubles
____% of middle-aged americans will at some point develop high BP
90%
!!!
why are so few people with HTN adequately controlled
silent disease (“i feel fine”)
med compliance b/c side effects
lack of knowledge about harmful effects
cost of medications
hypertension definition
elevation of systolic BP, diastolic BP, or both
non-pharmacologic tx of HTN
lifestyle measures: smoking cessation, lose weight, restrict sodium, restrict sat fat, stop drugs that inc BP, supplement K+/Ca2+/Mg2+, more exercise
four classes of meds equally recommended as antihypertensive agents for non-black HTN population?
ACEIs (ACE inhibitors)
ARBs (angiotensin receptor blockers)
CCBs (calcium channel blockers)
thiazide-type diuretics
which two classes of antihypertensive agents should not be used together?
ACEIs and ARBs should not be used together
recommended initial therapy for black HTN population?
BBC or thiazide-type diuretic
diuretics (mechanism of action)
aka NaCl inhibitors b/c prevent reabsorption of sodium (water follows sodium, so excrete more water)
thiazides also have direct smooth muscle relaxant effect
loop diuretics work @ loop of Henle to inhibit Na-K-Cl
DCT or thiazide-type diuretics include…?
hydrochlorothiazide (HCTZ), chlorothalidone (Hygroton), inapamide (Lozol), and metolazone (Zaroxolyn)
diuretics are usually taken when?
once daily preferably in the AM
some with shorter 1/2 life are twice daily
initial drug of choice for hypertension?
thiazide diuretics, particularly chlorothalidone 12.5-25 mg
HCTZ vs chlorothalidone
chlorothalidone most evidence of improved outcomes, but causes more K+ loss
HCTZ shorter acting
thiazides and osteoporosis
may reduce the risk of fractures from osteoporosis b/c decrease calcium secretion and bone loss
thiazides and diabetes
may increase blood glucose, but still recommended as 1st line therapy
side effects of thiazides?
hypokalemia (low K+) hyperurecemia (excess uric acid @ blood) hyperglycemia (excess glucose @ blood) hyperlipidemia (excess lipids) hypercholesterolemia (excess cholesterol)
loop diuretics va thiazide type diuretics?
- -loops less effective in pts with normal renal function (no vasodilatory action), but more effective in pts with renal insufficiency
- -loops more effective at diuresis, but less effective at controlling BP
loop diuretics and hypersensitivity?
loops contain sulfonamide moiety and may illicit allergic reaction in those allergic to sulfas
side effects of loop diuretics?
same as thiazides, plus ototoxicity with furosemide (Lasix)
loop diuretic agents include…?
bumetanide (Bumex)
furosemide (Lasix) primary. also ototoxic
torsemide (Demadex)
ethacrynic acid (Edecrin) only sulfa free loop diuretic
replacement of _____ is essential in pts taking diuretics that cannot obtain enough from diet
potassium, b/c hypokalemia is a side effect of diuretics
potassium supplementation with diuretics is especially important in patients taking what other drug? why?
digoxin (Lanoxin) b/c hypokalemia increases risk for digoxin toxicity
potassium supplements are notoriously irritating to what area of the body?
GI tract
potassium supplementation agents include…?
potassium chloride, postassium gluconate
potassium-sparing diuretics or CCT diuretics
used with thiazide and loop diuretics to correct hypokalemia
if used alone can cause hyperkalemia (too much K+) esp in pts with renal probe or taking drugs that reduce aldosterone secretion (NSAIDs, ACEI, ARBs)
K+ sparing or CCT diuretics include..?
spironolactone (Aldactone), triamterene (Dyrenium), amilorider (Midamor), and eplerenone (Inspra)
spironolactone (Aldactone)
aldosterone receptor agonist with anti androgen (estrogen) effects
Used with heart failures, b/c blocks aldosterone which causes water and salt retention
also used in acne for androgen blocking effects
side effects of spironolactone
hyperkalemia, mastodynia (breast pain), gynecomastia (breast swelling), and menstrual abnormalities
patiromer (Veltassa)
oral powder option for reversing hyperkalemia (side effect of heart failure meds, antialdosterone agents, ACEIs, and ARBs)
eplerenone (Inspra)
1st SARA (selective aldosterone receptor antagonist) agent for HTN tx
RAAS
in response to low BV or BP: liver secretes angiotensinogen, which is cleaved to angiotensin I by renin (secreted @ kidney). Angiotensin I is converted to angiotensin II by angiotensin converting enzyme (ACE) @ the lungs. Angiotensin II is a potent vasoconstrictor and stimulates adrenal gland to make/secrete aldosterone. Aldosterone increases Na+ and H2O reabsorption @ kidneys, as well as inc. secretion of K+ and H+ into urine. Retain more sodium, water, which increases blood volume and returns BP to normal.
what effect to beta blockers have on renin?
beta blockers decrease renin production
RAAS agonists include…?
ACEIs, ARBs
renal effects of RAAS antagonists
may have renal protective effects or cause renal failure, depending on how used and in whom. slows progression of kidney diseases in pts with macroalbuminuria. can cause renal failure in pts taking multiple agents (ACEIs, ARBs, diuretics, NSAIDs)
patients with (micro/macro)albuminuria should take and ACEI or an ARB. (choose)
macroalbuminuria indicates ACEI or ARB use.
RAAS agents and creatinine
RAAS agents might slightly bump creatinine levels up, but okay. protects kidneys in the long run.
as BP imporves, SCr should move back toward baseline. continue using as long as SCr inc less than 30% above baseline
“beta blockers of the kidneys”
ACEIs and ARBs
when using ARB, ACEIs in pts with chronic kidney disease, what are some important points for patient education?
force fluids to avoid dehydration
avoid NSAIDs, especially chronically
both dehydration and NSAIDs compromise kidney fucntion.
RAAS agents in pts with diabetes
recommended for diabetes patients with HTN and/or macroalbuminuria, not micro. for both populations, suggest lowering glucose to lower renal risk and lowering lipids/BP to lower CV risk. IF DIABETES + HTN, recommend ACEI/ARB to improve CV risk.
current diabetes guidelines do/do not recommend starting ACEI or ARB for microalbuminuria? (choose one)
current guidelines do recommend it, but recent research shows diabetes pts don’t benefit from ACEI/ARB to prevent kidney disease
ACEIs
prevent ACE from converting angiotensin I to angiotensin II (powerful vasoconstrictor)
effects of angiotensin II
- -powerful vasoconstrictor
- -increase in glomerular hypertension, inflammation, and fibrosis
ACEIs used for?
- -standard therapy for HTN
- -also for diabetic nephropathy in pts with macroalbuminuria
- -CHF
- -post MI secondary prevention
ACEIs in black patients
less effective, unless combines d with thiazide diuretic or CCB.
associated with higher incidence of angioedema and worse cardiovascular outcomes in black patients
ACEIs and plasma lipids + glucose
no effect on plasma lipids or glucose tolerance
major side effects of ACEIs?
dry, non-productive cough (rule out post nasal drip, GERD/reflux)
hyperkalemia, angioedema
how to ACEIs cause cough?
catalyzes the hydrolysis of bradykinin and substance P and also induce prostaglandins (accumulation of these causes cough). prostaglandin inhibitors (aspirin, NSAIDs) may help prevent/relieve cough.
ARB or ACEI more likely to cause angioedema?
ACEI
most common in black populations
ACEI boxed warning
discontinue use as soon as possible after detecting pregnancy. Don’t use during 2nd or 3rd trimester b/c of fetal injury or death.
drugs ending in -pril belong to what class?
ACEIs
drugs ending in -sartan belong to what class?
ARBs
ARBs are also called…?
A-II blockers because they interfere with the binding of A-II to the AT-1 receptor site.
ARBs and heart failure
not all ARBs are effective for heart failure, just some are
ARB and cough?
No effect on prostaglandins, bradykinin, so no cough side effect. Still can have angioedema, but less likely than with ACEIs
if get angioedema on ACEI, can you give ARB?
2% of patients who have angioedema with ACEI will also have it with ARB
ARBs and pregnancy?
contraindicated (relatively)
ARBs in black and low renin hypertension populations?
less effective than in white populations
direct renin inhibitor (DRI)
aliskiren (Tekturna)
no longer promoted because increases incidence of nonfatal stroke, renal complications, hyperkalemia, and hypotension.
drugs ending in -pine belong to what class?
dihydropyridine calcium channel blockers
CCBs
- -calcium channel blockers
- -divided into two groups (dyhydropyridines and non-dihydropyridines)
- -block voltage-dependent Ca2+ channels on cell membranes (keep Ca2+ from entering cell), resulting in lower systolic calcium, relaxation/vasodilation of vascular smooth muscle, and decrease in cardiac contractility and AV conduction.
dihydropyridine vs nondihydropyridine CCBs
both decrease peripheral resistance
both mostly increase cardiac output
dihydros (mostly) increase HR, nondihydros decrease HR (mostly)
caution with short acting dihydropyridine CCBs!
don’t use with tachyarrythmias or tachycardia, can cause reflex tachycardia due to vasodilation, which in turn may cause MI or arrhythmia.
primary side effect of CCB class of drugs?
peripheral edema
diuretics won’t help & doesn’t change over time.
side effects of verapamil (nondihyrdo)
muscle relaxant
constipation (most common complaint)
GERD
bronchial relaxation worsening of COPD
caution with nondihydro CCBs and beta blockers
nondihydro CCBs can affect AV conduction, use with caution in clients taking beta blockers or with heart failure.
CCBs and lipids?
they are lipid neutral
drug of choice for isolated systolic hypertension (ISH) in older clients?
long-acting CCBs
nifedipine (Procardia) caution
DONT ADMINISTER SUBLINGUALLY. pseudo-emergency to real emergency if BP precipitously (too quickly) lowered
CCB food interaction
grapefruit
serious adverse reactions
class of drugs ending in -olol
beta blockers
beta blockers are notorious for adverse side effects including…?
mask hypoglycemia
bradycardia
fatigue/mental dullness
prevents bronchodilation, can cause spasms
decrease in HDL cholesterol
cautions: don’t use in asthma/COPD pts, use with caution in diabetics, don’t stop abruptly, don’t use with PVD
beta blockers and uncomplicated HTN
beta blockers are no longer recommended for initial tx of uncomplicated HTN. recommended for pts with CAD b/c improve outcomes in pts with angina, systolic heart failure, and after heart attack.
how to beta blockers affect BP?
reduce BP by lowering adrenergic stimulation to beta receptors and by decreasing renin release from the kidneys.
beta blockers and cardioselectivity?
beta-1- blockers are more cadioselective (less selective as dosage increases, even low doses may cause broncho-spasms in pts with asthma).
benefits of beta blockers with ISA
those with ISA (intrinsic symptathomimetic activity) may have fewer side effects (esp bradycardia)
beta blockers with ISA should NOT be used for what?
angina, cardiac protection during surgery, or after MI
contraindications for beta blockers
asthma, COPD
diabetes
don’t stop therapy abruptly (super sensitive myocardium if you do)
cardiac sympatholytics include..?
central alpha adrenergic agonists
peripheral adrenergic neuron antagonists
alpha adrenergic blockers
central alpha adrenergic agonists do what?
agonists, but result in drop in peripheral drop in BP
agonist effect with antagonist outcomes by blocking an increased effect to decrease BP
act centrally*
central alpha adrenergic agonists include…?
clonidine (most used), methyldopa, and guanfacine
central alpha adrenergic agonists side effects
sedation, dry mouth impotence, depression
clonidine
most used central alpha adrenergic agonist
short half life, must be taken 2-3x/day
often used for HTN emergencies
sometimes used in opioid detox programs to reduce withdrawal
sometime abused for sedative effects or to “boost” effects of opiods
recently approved for ADHA as Kapvay
Kapvay
clonidine form approved for ADHD
peripheral adrenergic neuron antagonists do what?
taken up by adrenergic nerve endings and then decrease the release of catecholamines
peripheral adrenergic neuron antagonists include…?
guanadrel (Hylorel) and rauqolfia alkaloids (primarily reserpine)
side effect of peripheral adrenergic neuron antagonists?
severe depression (reserpine) snake dreams (reserpine & serpent roots) postural/exertional hypotension (guanadrel)
alpha adrenergic blockers do what?
block post synaptic alpha1 adrenoreceptors
cause less tachycardia than direct vasodilators
alpha adrenergic blockers used to treat what?
hypertension
benign prostatic hyperplasia (BPH)
side effects of alpha adrenergic blockers
1st dose syncope! take @ bedtime
postural hypotension
floppy iris syndrome which complicates cataract surgery
drugs that end in -zosin belong to what class?
alpha adrenergic blockers
alpha adrenergic blockers include…?
prazosin (Minipress), terazosin (Hytrin), and doxazosin (Cardura)
direct vasodilators
directly dilate blood vessels via vascular smooth muscle relaxant effect
2nd or 3rd line agents for hypertension b/c side effects
side effect of direct vasodilators
reflex tachycardia
give direct vasodilators with what else?
beta blocker or centrally-acting drug to minimize reflex tachycardia and inc c.o.
also with loop diuretic to avoid Na2+ and H2O retention.
can patients quit taking BP meds?
no
possibly if very mild and make necessary lifestyle changes to control it.
self-BP readings
home blood pressure monitoring good as long as pts are educated to look for patterns, take at same time each day.
may reduce need to antihypertensives.
recommended that all patients receiving HTN tx monitor BP at home.
tx HTN during pregnancy
not usually treated unless SBP>160 or DBP>100 use labetalol (oral or IV)
labetalol
1st line therapy for htn in pregnancy
alpha and beta blocker so doesn’t compromise fetal blood flow or cause growth restriction or still births
another option for HTN tx in pregnancy?
ER nifedipine (Procardia XL) or methyldopa (Aldomet), but methyldopa is weak antihypertensive with more side effects. only use if can't use the other two. hydralazine falling out of favor b/c fetal and maternal side effects
what HTN drugs should you definitely avoid during pregnancy?
ACEIs and ARBs
HTN tx in athletes/active people?
Use ACEIs or ARBs
diuretics and beta blockers (precision) banned in many sports
chronotherapeutics with CV meds
BP dips at night, increases in early AM
Blockers lower BP more @ daytime
ACEIs better at lowering BP @ night
recommend taking BP meds at bedtime
agents used only for hypertensive crisis include…?
nitroprusside (Nipride) *cyanide toxicity
fenoldopam (Corlopam) *reflex tachycardia
Clevidipine (Cleviprex) most used today; is latest-gen IV dihydro CCB
anti-hypotensive agents are used to treat what?
orthostatic hypotension (dec SBP by 20 or DBP by 10)
what drugs are considered antihypotensives?
midodrine (ProAmatine) most often used, also for syncope
Pyridostigmine (Mestinon) * for myasthenia gravis primarily*
Fludrocortisone (Florinef) pressor effect, volume expander
Droxidopa (Northera) prodrug of norepi
