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Therapeutics Exam 3 Maynard
Therapeutics Exam 3 Maynard
39
Pharmacology
Graduate
09/06/2010

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Term
adhesion -> activation -> aggregation
1) within seconds of injury, platelets adhere to collagen fibrils through GP 1a/2a receptors. Von willebrand factor allows platelets to stay attached to the vessel wall
2) following adhesion, platelets are activated to secrete a variety of agonists including thrombin, serotonin, ADP, TXA2. These further augment platelet activation, bind to specific receptor sites on platelets to activate GP IIb/IIIa receptor complex - final common pathway to platelet aggregation
3) Once activation, GP IIb/IIIa receptor undergoes a conformational change that enables it to bind to fibrinogen
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Definition
platelet cascade in thrombus formation
Term
smoking
family history
adverse lipid profile
DM
hypertension
Definition
major risk factors for CAD/AMI
Term
chest pain: pressure, tightness, or heaviness. Crushing sternal pain. Radiating to shoulder, down 1 or both arms, to the jaw, neck, or back
lasts > 20 minutes
non specific: N/V, SOB, lightheadedness/dizziness, sweating
patients who do not have typical chest pains: women (fatigue, sleep disturbances, anxiety, atypical CP), elderly (usually more generalized symptoms), diabetics (silent MI)
Definition
symptoms of a heart attack
Term

looking for signs of myocardial necrosis

creatine kinase: from any muscle (cardiac, skeletal, brain)

creatin kinase myocardial band: from cardiac muscle

cardiac troponins: 3 subunits - troponin I, troponin T, troponin C. more cardiac specific. High sensitivity to MI. the higher the troponin, the greater the cardiac damage, and thus the higher mortality.

order 3 sets of cardiac enzymes every 8 hours

myoglobin: non specific marker of muscle damage

CBC (complete blood count): WBC, Hgb, Hct, platelets

chem8: electrolytes

BNP: a marker of left ventricular heart stress, normal <100 mcg/ml

C-reactive protein (CRP): a marker of inflammation

FLP: within 24h of presentation

Definition
enzymes to check for a heart attack
Term
look for ST-segment elevation
ischemia (lack of blood flow without infarction): can be evidenced by T-wave inversion, ST-segment depression
which coronary artery has been affected
Definition
what to look for in an EKG to see if a heart attack occured
Term
unstable angina
Definition
acute angina at rest, typically prolonged >20 minutes, ST segment depression, T-wave inversion, or no EKG changes at all, but no biomarkers for cardiac necrosis present
non-occlusive thrombus developed on a disrupted atherosclerotic plaque but did not result in evidence of necrosis
Term
NSTEMI
Definition
acute angina at rest, typically prolonged >20 minutes, ST segment depression, T-wave inversion, or no EKG changes may occur, positive cardiac enzymes of necrosis
prolonged partial occlusion of coronary arteries where necrosis has occurred
white clots are typical (more platelets than fibrin - use antiplatelet therapy)
Term
STEMI
Definition
acute angina at rest, typically prolonged > 20 minutes, positive cardiac enzymes, and ST-elevation of > 1mm on EKG in 2 contiguous leads
typically a red clot (more fibrin than platelets - use a fibrinolytic)
thrombus leads to complete occlusion of the coronary artery resulting in necrosis of the affected region
Term
dynamic obstruction
Definition
an intense spasm of the coronary artery resulting in an incomplete obstruction of blood flow
the presumed mechanism of cocaine-induced UA/NSTEMI
Term
secondary UA
Definition
primary cause is outside the coronary arteries
precipitated by conditions that increase myocardial O2 requirements, reduce coronary blood flow, or reduce myocardial oxygen delivery
ex) anemia, excessive blood loss, hypotension
Term
age > 65
at least 2 anginal attacks in last 24 hours
use of aspirin in the last 7 days
elevated cardiac enzymes
ST-segment deviation on EKG (either depression or transient elevation)
prior coronary artery stenosis of >50%
at least 3 risk factors for CAD (smoking, DM, HTN, family history of coronary heart disease, hypercholesterolemia)
Definition
What risk factors constitute a TIMI risk score for UA/NSTEMI patients?
Term
GRACE (determines all cause mortality in-hospital and at 6 months)
Definition
found to be superior to TIMI (assesses the risk of mortality, new or recurrent MI, or severe ischemia within 14 days) and PURSUIT (prediction of 30 day mortality or rate of death and MI) in predicting risk of mortality in UA/NSTEMI patients
more complicated to use
Term
bare metal stent (BMS) - if there is going to be an adverse event, it will be early. early stent thrombosis (in 30 days)
drug eluding stent (DES) - higher rate of late stent thrombosis (9-12 months)
ex) sirolimus, paclitaxel, erolimus, zotarolimus
2009 study - DES are as safe and superior to BMS
Definition
What types of stents are available and what is the difference between them?
Term
Percutaneous Coronary Intervention (PCI)
Definition
treatment of choice for reestablishing coronary blood flow in STEMI
a guidewire is inserted in the femoral artery. the guidewire is threaded to the affected coronary artery where a balloon is inflated in order to push the thrombus back against the vessel wall. A stent, or wire mesh, is also inflated at the site of thrombus to keep the artery open.
In the event of STEMI, should be performed within 90 minutes of arrival
Term
the left main coronary artery is affected
multiple vessels are affected
diffuse disease is unlikely to be remedied by PCI
Definition
When is a CABG typically indicated in atherosclerotic coronary vessles?
Term
MONA-B
morphine, oxygen, NTG, ASA, B-blocker
Definition
What initial treatment should all patients receive unless contraindicated?
Term
if oxygen saturation is < 90% or in respiratory distress
no evidence to support its use in any other ACS patients although often provided as a means of comfort
Definition
when should oxygen be used in patients.
Term
Morphine
Definition
MOA: acts as an analgesic, anxiolytic
place in therapy: for patients whose symptoms are unrelieved by nitroglycerin or whose symptoms recur despite optimal treatment
adverse effects: hypotension, N/V, respiratory depression
monitoring: respiratory rate, mental status changes, pain relief
cautions/contraindications: hypotension, intolerance
Term
nitroglycerin
Definition
MOA: increases intracellular cGMP in smooth muscle cells. dilates coronary arteries and vascular smooth muscle in veins and arteries.
adverse effects: headache, hypotension
monitoring: pain relief, BP, signs of tolerance
contraindications: recent use of PDE inhibitors (sildenafil and vardenafil within 24 hours, tadalafil within 48 hours), SBP < 90
Term
You should feel a tingling sensation under your tongue when taking SL NTG. (may or may not feel a tingling sensation)
Once opened, the NTG tablets are only good for 6 months. (good until the date on the bottle)
Definition
What are the myths/misconceptions of SL NTG use?
Term
beta blockers
Definition
MOA: due to B1 receptor inhibition: decrease cardiac work, decrease HR, decrease contractility, decrease BP, decrease myocardial oxygen demand, increase duration of distole and improve ventricular filling and forward coronary flow
indication: for all patients with ACS (unless contraindicated), start early (within 24 hours), po preferred, may use IV for those not at risk for cardiogenic shock or in the first 24 hours of STEMI
adverse effects: hypotension, bronchoconstriction, bradycardia, AV block, Raynaud's phenomena, depression, masks symptoms of hypoglycemia in diabetics
monitoring: BP, EKG, HR, signs/symptoms of HF
cautions/contraindications: 2nd/3rd degree AV block, severe reactive airway disease, severe LV dysfunction or signs of heart failure, at high risk of cardiogenic shock (age > 70, SBP < 120, HR > 110 or < 60), HR < 50, SBP < 90.
Term
Ca channel blockers
Definition
MOA: blocks Ca influx -> inhibit vascular and myocardial muscle contraction, slows AV node conduction, decrease afterload -> decrease cardiac O2 demand, improve myocardial blood flow
indication: reserved for patients with true contraindication to BB that do not have significant LV dysfunction, non-dihydropyridines are preferred, short acting DHP CCB (nifedipine) can actually worsen ischemia by causing reflex tachycardia
adverse effects: fluid retention, bradycardia, hypotension, constipation, AV block
monitoring: HR, BP, EKG
cautions/contraindications: HF, evidence of LV dysfunction, hypotension, bradycardia, heart block
Term
ACE inhibitors
Definition
MOA: inhibits ACE which converts angiotensin I to angiotensin II, thus inhibiting vasoconstriction
benefits: mortality reduction, inhibits ventricular remodeling
indications: use early and after initiation of BBs, initiate within the first 24 hours for patients with pulmonary congestion or EF < 40%
adverse effects: hypotension (some patients may not tolerate addition of ACEi to BB), cough, hyperkalemia, acute renal failure, angioedema (can occur any time)
monitoring: BMP (BUN/SrCr, K), BP, facial swelling
cautions/contraindications: pregnancy, angioedema, bilateral renal artery stenosis, hyperkalemia (K > 5)
Term
aspirin
Definition
MOA: inhibition of COX1 within platelets, which prevents formation of TXA2, thereby limiting platelet aggregation. Relatively weak anti-platelet agent.
benefits: 25% reduction in recurrent vascular events found in doses as low as 75mg
indications: recommended for all patients, non-enteric coated preferred for more rapid absorption, ***avoid 81 mg non-enteric coated aspirin with 200 mg IBU (causes aspirin to be ineffective). Take IBU 30 minutes after aspirin or 8 hours before.***
adverse effects: bleeding
monitoring: bleeding
cautions/contraindications: active bleeding, hypersensitivity, severe asthma
Term
thienopyridines:
clopidogrel
ticlopidine
prasugrel
Definition
MOA: prevent ADP from binding to its receptor on platelets, stopping activation of GP IIb/IIIa complex and thus inhibiting platelet activation. Platelet effects are irreversible and take several days to reach maximal effect is no loading dose given
indication: for those allergic to aspirin, for those undergoing PCI (clopidogrel is often not initiated until after angiography. In the event the patient will require CABG, CABG may need to be delayed if clopidogrel has already been administered)
adverse effects: N/V/D, thrombotic throbmocytopenic purpura (TTP), bleeding, rash
monitoring: CBC/platelets, signs/symptoms of bleeding
cautions/contraindications: active bleeding, planned surgery - should hold clopidogrel at least 5 days before CABG (ideally hold for 7 days)
drug interaction: proton pump inhibitors
Term
more evidence to support its use
more rapidly inhibits platelets
more favorable side effects profile
Definition
why is clopidogrel preferred over ticlopidine?
Term
dipyridamole
Definition
MOA: directly stimulates prostacylin synthesis, potentiates the platelet inhibitory actions of prostacyclins, and inhibits PDE to raise cAMP levels
these effects to not occur at therapeutic levels to have a noted effect on MI
Term
GP IIb/IIIa inhibitors:
abciximab, tirofiban, eptifibatide
Definition
MOA: following platelet activation, the IIb/IIIa receptors undergo a conformational change to allow fibrinogen to bind. the binding of fibrinogen to receptors on adjacent platelets results in platelet aggregation. inhibiting this receptor inhibits platelet aggregation.
indications: NSTEMI - tirofiban and eptifibatide in high risk patients, recommended for all patients under going PCI, recommended for non-high risk patients not undergoing PCI. STEMI - recommended for primary PCI
adverse effects: bleeding, thrombocytopenia
monitoring: bleeding
cautions/contraindications: active internal bleeding or bleeding disorder in the last 30 days, history or ICH, neoplasm, arteriovenous malformation, aneurysm, or stroke in the last 30 days, major surgical procedure or trauma within 1 month, aortic dissection, pericarditis, or severe hypertension, hypersensitivity, platelet < 150,000
Term
unfractionated heparin
Definition
MOA: binds to antithrombin to inhibit the activity of clotting factors IIa (thrombin) and Xa
indication: NSTEMI - recommended for use in combination with aspirin. STEMI - recommended for patients undergoing PCI and those receiving fibrinolytics
adverse effects: bleeding, thrombocytopenia
monitoring: aPTT, ACT (activated clotting time), CBC (H/H, platelets)
cautions/contraindications: active bleeding, allergy/history of heparin induced thrombocytopenia, recent stroke, severe bleeding risk
Term
LMWH:
enoxaparin, dalteparin
Definition
MOA: inhibits thrombin indirectly through complex with antithrombin III, selective inhibition of Xa
indication: recommended for NSTEMI and STEMI, for PCI recommended as an alternative to UFH
adverse effects: bleeding, thrombocytopenia
monitoring: bleeding, platelets
***anti-Xa levels are recommended to be checked in the following patients: pregnancy, renal dysfunction, morbid obesity***
cautions/contraindications: use caution in renal failure, history of heparin induced thrombocytopenia, CABG planned immediately, high bleeding risk, active bleeding
Term
factor Xa inhibitor: fondaparinux
Definition
MOA: pentasaccharide that selectively binds to antithrombin III thereby neutralizing factor Xa
indication: should not be used as sole anticoagulant
adverse effects: bleeding
monitoring: bleeding
cautions/contraindications: active bleeding, patient < 50kg, CrCl < 30 ml/min, thrombocytopenia
Term
direct thrombin inhibitor: bivalirudin
Definition
MOA: directly inhibits thrombin by binding to thrombin. can inactivate both soluble and clot-bound thrombin
indications: used during angioplasty procedures, requires adjustments for renal dysfunction
adverse effects: bleeding
monitoring: signs/symptoms of bleeding, ACT (activated clotting time) 5 minutes after bolus dose
cautions/contraindications: active major bleeding
has not been shown to be superior to UFG or GP IIb/IIIa inhibitors, but less risk of major bleeding
Term
statins
Definition
MOA: inhibits conversion of HMG-CoA to mevalonate, rate limiting step of cholesterol biosynthesis, reduces inflammation at the site of the atherosclerotic plaque and can inhibit platelet aggregation. usually used in MI patients for plaque stabilization
benefits: LDL reduction - reducing morbidity/mortality, plaque stabilization, reduce levels of inflammatory markers
should be initiated prior to discharge: studies have found that starting post-MI patients on statin therapy during their hospitalization increases the chance that at one year the patient will still be on therapy
Term
aldosterone receptor antagonists: spironolactone/eplerenone
Definition
MOA: inhibits the effects of aldosterone in the distal tubule. increases the secretion of water and Na, while decreases secretion of K
indication: Class I recommended for patients with EF < 40% and either DM or CHF symptoms who are already on an ACEi
adverse effects: hypotension, hyperkalemia, gynecomastia
monitoring: BMP(SrCr, K)
cautions/contraindications: hyperkalemaia (K > 5), SrCr > 2.5 mg/dL
Term
restore blood flow to the infarct-related artery
minimize infarct size
prevent complications (arrhythmias/death)
Definition
goals of treatment for STEMI
Term
fibrinolytics
streptokinase has antigenicity
(antibodies are formed against it, patient can only have streptokinase once in 2 years)
greater risk of systemic bleeding with streptokinase
Definition
MOA: plasminogen is a proenzyme and is converted to the active enzyme plasmin by plasminogen activators (endogenous or exogenous tPA derivatives); plasmin digests fibrin to soluble degredation products
indications: for STEMI only (***increased mortality seen when used in patients with NSTEMI***), administer within 12 hours of symptom onset (preferably within 6 hours) - less mortality benefits as time goes on, used if PCI not possible or may be delayed - more often used in rural areas which may not have a cath lab, use in patients over 75 is controversial - increased risk of intracranial hemorrhage and death, administer with UFH
adverse effects: systemic bleeding, intracranial hemorrhage (ICH)
monitoring: bleeding (hemoglobin/hematocrit)
Term
previous hemorrhagic stroke at any time; other strokes or cerebrovascular events within 1 year
known intracranial neoplasm
active internal bleeding
suspected aortic dissection
significant closed head or facial trauma within 3 months
Definition
absolute contraindications to fibrinolytics
Term
severe, uncontrolled hypertension upon presentation (BP > 180/110)
history of prior cerebrovascular accident or known intracerebral pathology not covered in absolute contraindications
current use of anticoagulants in therapeutic doses (INR > 3)
known bleeding tendency
recent trauma (within 2-4 weeks), including head trauma or traumatic or prolonged (>10 minutes) CPR or major surgery (<3weeks)
noncompressible vascular puncture (recent liver biopsy or carotid artery puncture)
recent (within 2-4 weeks) internal bleeding
pregnancy
active peptic ulcer
history of severe, chronic hypertension
for streptokinase: prior exposure in the last 2 years or prior allergic reaction
age > 75
Definition
relative contraindications to fibrinolytics
Term
antiplatelet medications: aspirin (1st line in all patients unless contraindicated), clopidogrel (1st line in combination with aspirin for bare metal stents x30d, 1st line in combination with aspirin for sirolimus eluting stent x3 months, 1st line in combination with aspirin for picrolimus eluting stent x6 months, may use in place of aspirin if patient has contraindication to aspirin as 2nd line recommendation
blood pressure control: BP < 130/80, BB - mortality prevention, ACEi/ARB - prevent remodeling/mortality reduction
lipid lowering: statins - mortality reduction/plaque stabilization/LDL goal < 100; optimal < 70
aldosterone antagonists: indicated to be given within the 1st 2 weeks following an MI in patients already receiving an ACEi with EF < 40% and either HF symptoms or a diagnosis of diabetes/prevent vascular and myocardial fibrosis, endothelial dysfunction, hypertension, and LV hypertrophy
diabetes management: A1c < 7%
smoking cessation
weight management
exercise
immunizations: annual flu shot
avoid NSAIDs: may increase mortality in the first month after a heart attack
Definition
post MI care
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