Angina

•Chronic Stable

• –Increase
• in activity, emotions, large meal, cold

• –Stops
• with rest

•Variant Angina-Prinzmetal’s

• –Coronary
• vasospasm

•Unstable Angina (ACS)

–Medical emergency

• –Occurs at rest, new onset or
• intensification of existing stable angina

•Underlying cause-CAD

• –Fatty
• plague deposits in arteriole walls

•Treatment Goal: reduce O2 demand

• –reduce
• frequency and intensity of attacks

• –decrease
• risk of infarct and extending

•Nitrates

• –Dilate
• veins and decrease preload

•Beta blockers

• –Decrease
• rate and force of contraction

• •Ca+
• channel blockers

• –Dilate
• arteriole-decrease afterload

• –Verapamil
• and diltiazem
• afterload, rate and contractility

• •Unknown mechanism causes coronary
• vasospasm

• •Treatment Goal: reduce frequency and
• intensity of attacks (increasing O2 supply)

• •Nitrates & Ca+
• channel blockers

–Relaxing coronary artery spasm

•Treatment is symptomatic only

•CAD

•vasospasm

•platelet aggregation

•transient coronary thrombi or emboli

•Acts directly on vascular smooth muscle

• –Primarily on veins, modest dilation of
• arteriole

• –Decreases preload and (slightly)
• afterload

–Rapid Inactivation by liver

•Half life-5-7 mins

–Adverse effects:

–

–Drug interactions

• •Sildenafil/Viagra-life threatening
• hypotension

–Tolerance with high dose therapy

•Sublingual-direct from oral mucosa

–.4 mg SL 5 minute intervals-X3-only

•Sustained release oral-prophylaxis only

• –Isosorbide/Imdur
• (no first pass)

• •Transdermal- off
• at night to avoid tolerance

–Ointment:1 inch/15mgs patch: .1-.8mg/hr

•IV infusion-short term only

• –5 ug/min
• up 50 ug/min

•Not used for acute events

• •Ca+
• Channel Blockers

• –Verapamil/Calan,
• diltiazem/cardizem,
• (nifedipine)

• –Arteriole
• dilation

• –Relax
• coronary vasospasm

•Beta Blockers

• –Slow
• HR, increase coronary arterial flow time

• –Mild
• reduction in arterial pressure (mech
• unknown)

• •Reduces accumulation of Na+ and Ca+
• in myocardial cells

• •Helps myocardium use energy more
• efficiently?

•

•

•

•Adverse effects-dysrhythmias, HTN, GI

•Reserved for refractory cases

•Coagulation

–Platelet activation

•Platelets exposed to damaged vessel

• formation of plug

–Fibrin reinforces the platelet plug

• –Plasmin breaks down the clot after
• healing of injury occurs

• •Prevent clots & prevent increasing
• the size of a clot

•Heparin

–inactivates thrombin and factor Xa

• –fibrin production reduced, clotting
• suppressed

–bovine lungs and porcine intestines

–Short half life 1.5 hours

–

–Used for PE, Embolic stroke, MI, DIC

- Highly polar

•Heparin

• –Monitor aPTT
• (22-34 sec) 1.5 – 2X

• –Risk for bleeding. Antidote: Protamine
• Sulfate

–HIT-heparin induced thrombocytopenia

•1-3% with 4 days heparin therapy

• •Antibodies activate platelets and damage
• endothelium

•Decreased platelets and new thromboses

•Heparin

–IV intermittent therapy

• •Not done often because of fluctuating
• drug levels

•

–IV continuous therapy

•Given by weight and managed by protocol

•Q6h after dose given or change made

•

–Low Dose Therapy

• •To prevent DVT
• •Low Molecular Weight Heparins

•Fractionated-use part of the long chains

•Don’t affect aPTT

• –only factor Xa
• (not thrombin)

•Can be done at home

•Less HIT

•Administered SC

• •Enoxaparin/lovenox,
• dalteparin/fragmin

•Oral: Warfarin/Coumadin

•Vitamin K antagonist

• –Affects
• production of VII, IX, X, & prothrombin

• •require
• K

• –Monitor
• prothrombin
• time (PT)

• •Q
• week and once a month when stable

–INR

• •2-3
• is therapeutic (3-4.5 for heart valves)

• –Risk
• for bleeding

• –Many
• drug  & food interactions

•International Normalized Ratio

–Lab tests compare PT to a control

• –Controls are different so labs report
• different values for same specimen.

• –INR is determined by multiplying PT value
• by a correction/calibrating factor specific to the preparations employed for
• the test

• –INR of 2-3 is appropriate for most
• conditions

•Used IV during PCI

–Bivalirudin/angiomax

•Used PO and Sub Q

• –Dabigatren/pradaxa-approved
• for stroke 2010

• –Non-valvular
• at-fib-clot prevention

• •Major bleed occurred less with lower
• doses of pradaxa

• –Thromboemolism
• tx

•Same effects

• •GI side effects caused pradaxa
• discontinuation

•Prevention of aggregation

• •Prevention of thromboses
• in arteries

Inhibits COX2…produces TXA2(irreversible)–TXA2 causes platelet aggregation andarterial constriction•Primary prevention of MI and stroke•Adverse effect-GI bleeding

–Irreversibleblockage of plt ADP

–Hematologiceffects: TTP and Neutropenia

• –Lessside effects
• •Prevention of ischemic stroke and MI

–Lessthromboses,more major bleeding

–Reversible blocking of GPIIb/IIIareceptor to prevent aggregation–In combination with ASA and heparin•Given IV short term for ACS and PCI only–Very expensive •Abciximab/ReoPro,Eptifibatide/Integrillin,–Tirofiban/Aggrastat

–Used only for prevention of thromboemolism following heart valve replacement combined with coumadin

•Reduced incidence of stroke

–Platelet inhibitor and vasodilator forintermittent claudication=Grapefruit juice!

•Remove thrombi that have formed

•Convert plasminogen to plasmin

–Plasmin degrades the fibrin cap

•Indications: Acute MI, DVT, Massive PE,

–Ischemic stroke

•Risk of bleeding

• •Protocols and guidelines for
• administration

•Active Bleeding

•Aortic Dissection

•Intracranial Bleeding

•Cerebral Vascular Disease

•Cerebral Neoplasm

•Acute Pericarditis

•Streptokinase

• –Allergic reactions (from streptococci
• cultures)

•Alteplase (tPA)

–Short half-life

•Tenecteplase

•Retaplase

•Urokinase