FIBRINOLYTICS OR THROMBOLYTICS & ANTIPLATELETS Flashcards
Drugs that cause lysis of clot (thrombus).
THROMBOLYTIC OR FIBRINOLYTIC DRUGS
THROMBOLYTIC OR FIBRINOLYTIC DRUGS
Given————– (rapid, inexpensive,
does not have the risk of—————— ).
intravenously (IV)-catheterization
THROMBOLYTIC OR FIBRINOLYTIC DRUGS
They can affect both ———– and—————-
thrombi; hemostatic thrombi and target
thromboemboli are broken down. They can not
differentiate between ————- of an unwanted
thrombus and that of a beneficial hemostatic
plug
normal- pathogenic-fibrin
Mechanism of action of THROMBOLYTIC OR FIBRINOLYTIC DRUGS:
• These drugs catalyses the conversion of
————— to—————– which causes
degradation of ——————.
• -Plasmin digests not only fibrin but also
—————– and —————& ———————so bleeding may
occur.
plasminogen- plasmin-fibrin-fibrinogen-factors V -VIII
THROMBOLYTIC OR FIBRINOLYTIC DRUGS
They must be administered as———- as
possible after onset of thrombosis or embolism
(since they become more—————–to lysis as
they age).
—————– local thrombi may occur as the clot
dissolves and causes ————- aggregation and
thrombosis.
resistant - early-Increased-increased
Anti dose that affect (decrease) plasminogen action ?
1-Tanexamic acid
2-aminocaproic acid
—————-and——- affect (increase) directly on plasminogen ?
T-PA - Urokinase
——————(indirect) work by activate the proactivator
to become activator to activate plasminogen ?
الميكانزم الثانية هي الاساسيه لا تخربطي
خذي فكرة عن هذه
Streptokinase
Classification of fibrinolytics:
• Fibrin non selective (1st generation):
——————and———————
Streptokinase (SK) and urokinase (UK):
Classification of fibrinolytics:
• Fibrin non selective (1st generation):
• ————–acts indirectly forming a complex with
—————— which then activates free ——————-.
Also affects ———–and factors —————–and———-.
• - ————- expensive and most widely used. Antigenic(from β hemolyticus—————–).
• Has longer half life than ——————–
• Infused for ———-hour in the first 4 hours after infarction
• UK : ———— antigenic.
• - ————– activates plasminogen .
• -Both activate ————- as well as clot bound
plasminogen → —————-.
SK-plasminogen-plasminogen- fibrinogen-V and VII-Least-streptococci-alteplase-one -non-Directly-circulating- bleeding
Fibrin – selective ( 2nd generation ):(Expensive)
• Tissue plasminogen activator (tPA; —————-).
• Activate plasminogen that ———– to fibrin in a thrombus
only with————- affinity to free plasminogen, in contrast with SK which act on ——— plasminogen and produces a generalized ———— state.
• Superior to——— generation in dissolving old clots &
decreased bleeding tendency (clot ———).
• Of —————— efficacy to streptokinase.
• Has very short half life(———- min),given as ———– bolus then by ———- over one hour.
- ———–: similar and used as an
alternative to alteplase
————————-: A complex of streptokinase and
plasminogen. Considered as a———. Streptokinase is released and plasminogen is converted into plasmin
alteplase-bound- low-free-fibrinolytic- 1st-selective-equal
-5-IV-infusion-Reteplase- Anistreplase(anisoylated plasminogen streptokinase
activator complex)-prodrug
Fibrinolytics
Therapeutic uses:
• Acute myocardial infarction; most effective when
administered within 1st ————– hours
Benefits: ———— mortality, reduces area
of ———— , Early and sustained restoration of ————patency and myocardial blood ———-and preserves ————function.
• Massive ———— embolism.
• Acute peripheral —————.
• D—————-.
• Obstructed ————– and occlusion of
———— catheter.
• ————– has been associated with increased
bleeding risk in acute ————- when given
at a dose of ———— million units, and its use is not
recommended in this setting
6-Reduces-myocardial infarction-coronary -flow-ventricular-pulmonary-arterial occlusion-VT-arteriovenous shunt-intravascular
-Streptokinase-ischemic stroke-1.5
Fibrinolytics
Adverse effects
• 1- Bleeding (more with fibrin ————).
Treated by ———– infusion, fresh blood and
————– in sever cases(due to
increased level of circulating plasminogen which
may precipitate bleeding by dissolving hemostatic
plugs) .
• 2————– with streptokinase : rash,
fever, rarely anaphylaxis may occur.
• Fibrinolytic action may be neutralized by
—————- ———- that may be present in some
people who have had streptococcal infection,
thus start therapy with a————– to overcome AB and produce fibrinolytic effect
non specific stopping aminocaproic acid Hypersensitivity antistreptococcal AB loading dose
Fibrinolytics Contraindications: • ------------surgery(healing wounds), ------------------ bleeding and --------------- ulcer. • - ------------, metastatic cancer. • - ------------, -------------, old age. • History of cerebrovascular accidents
Recent -gastrointestinal-peptic-Hypertension
metastatic-Pregnancy-childern
ANTIPLATELET DRUGS (ANTITHROMBOTIC)
• Platelet aggregation:
• Platelets ————— to healthy endothelium, but if
a vessel wall is injured; the exposed collagen in
sub endothelium will result in platelet ————–,
followed by release reaction resulting in platelet
———————-.
• The released factors (—–,——–,——,——–,——–) bind to their receptors on
platelets resulting in exposure of a glycoprotein
complex (————–) on the platelet membrane,
which act as a receptor for ——————, regulate
platelet-platelet interaction and thrombus
formation.
•——— simultaneously binds to GP IIb/IIIa
receptors on two separate platelets resulting in
their cross linking and —————.
do not stick-adhesion-aggregation-ADP, TXA2, and serotonin(5HT),thrombin and PAF-(GP IIb/IIIa)-fibrinogen
- Fibrinogen-aggregation
—————-Atiplatelet inhibit platelet aggregation
Prostaglandin A2
ANTIPLATELET DRUGS (ANTITHROMBOTIC) Therapeutic uses: • -------------(coronary bypass, angioplasty, prosthetic heart valves). • - Prevention and treatment of------------ • - Prevention of ------ & transient -------- ischemic attacks. • Antiplatelets are either administered alone or as adjuncts to ------------ therapy, along with heparin.
Cardiac surgery myocardial infarction. DVT cerebral thrombolytic
ANTIPLATELET DRUGS (ANTITHROMBOTIC)
ASPIRIN
• Selectively inhibit———– synthesis from arachidonic acid in platelets by ——– (low dose aspirin; 81-325 mg)
inhibit ———( COX-I), thus shifts the balance of chemical mediators towards —————– (since the
endothelium can synthesiz more enzyme but platelets
cannot. They can only form enzyme when new platelets are synthesized)→ inhibit platelet ——————.
• Inhibition by aspirin lasts for the life span of platelets(7-10
days).
• Bleeding time is ————–.
• Used for prophylactic treatment for —————,
decrease incidence and mortality from —————-
These drugs not taken with aspirin
• ———— antagonize the action of aspirin if taken with or prior to aspirin by ——– hours.
• ———– (selective COX2 inhibitor)shift chemical balance in favor to TXA2
TXA2 irreversibly cyclooxygenase prostacyclin aggregation prolonged ischemic attacks myocardial infarction. Ibuprofen 2 Celecoxib
acetylsalicylic acid is other name for ——————
Aspirin
Aspirin with Pepsi will cause :( ?
ulcer
ASPIRIN and her sisters take ———–eating ?
after
ANTIPLATELET DRUGS (ANTITHROMBOTIC) Ticlopidine and clopidogrel Used during-------- interventions, during -----------, stroke or established--------------
coronary-myocardial
infarction- peripheral arterial
disease.
ANTIPLATELET DRUGS (ANTITHROMBOTIC) Ticlopidine and clopidogrel Both are extensively bound to -------------, eliminated by -------- and -------- routes.(food affects absorption of ----------------- no-------------) .
pp renal fecal ticlopidine clopidogrel
ANTIPLATELET DRUGS (ANTITHROMBOTIC)
Ticlopidine and clopidogrel
Adverse effects:
• Serious adverse effects may occur with ticlopidine that’s why it is reserverd for ——– cases to other drugs.
• - ———–(no specific antidote).
• - Thrombocytopenia and ——– anemia (especially
————).Thus frequent blood monitoring is required in
the 1st three months of treatment.
• - Enzyme inhibitors (increase levels of ————-).
• - Neutropenia with ———–, less with ————–.
intolerant-bleeding-aplastic-ticlopidine
warfarin-ticlopedine-clopidogrel
ANTIPLATELET DRUGS (ANTITHROMBOTIC)
Abciximab
• ————- AB.
• -Binds to —————, blocking the binding of fibrinogen and von Willebrand factor( which is binding to other proteins, in particular factor ——–, and it is important in platelet adhesion to
wound sites), inhibiting ————-.
• -Given ——- with aspirin or heparin .
• Action persists for ——to—– hours after cessation of
therapy.
• - Main adverse effect is —————-
Monoclonal- GP IIb/IIIa VIII aggregation IV aspirin heparin 24 – 48 h bleeding
ANTIPLATELET DRUGS (ANTITHROMBOTIC)
Eptifibatide and tirofiban:
• - Block ——— receptors.
• -As ——, it decreases incidence of thrombotic
complications associated with ———–.
• ——– is the major adverse effect of both drugs.
• NB:———— preparations of GPIIb/IIIa blockers are too toxic
GP IIb/IIIa abciximab acute coronary syndromes Bleeding Oral
Dipyridamole
• -Inhibits ——- → increasing
c-AMP → decreasing ————-, may potentiate
effect of ———– to antagonize platelet
stickiness.
• - Not effective alone, usually combined with
———- or ——–.
• When combined with warfarin, is effective for
inhibiting of embolization from ———————
phosphodiesterase TXA2 prostacyclin aspirin or wafarin. embolization from prosthetic heart valves
ANTIPLATELET DRUGS (ANTITHROMBOTIC) Prostaglandine analogue: PGI2 cause ?
abortion
DRUGS USED IN BLEEDING DISORDERS
• May be due to genetic disorder such as ———- or
as the result of ———– states or use of
——————-.
• Vitamin K
• -Needs ———— for its absorption
• -Deficiency of vitamin K leads to spontaneous
—————-.
• -Used in treatment of bleeding due to anticoagulants
(———-).
• -Response is ——– (24 hours), thus whole blood,
fresh frozen plasma, plasma concentrates of the
blood factors are used if immediate hemostasis in
needed
hemophilia-fibrinolytic-anticouglants
bile acids-hemorrhage-oral-slow
Fibrinolytic inhibitors (antiplasmin):
Aminocaproic acid and tranexamic acid:
-Competitive inhibitor of —————-.
- ————-active.
-Adverse effect is potential ————.
plasminogen activators
Orally
intravascular
thrombosis
Protamine sulfate:
• - Used to antagonize ———— – induced
bleeding.
• - the positive charge of the drug neutralizes the
negative charge of ———– forming a complex .
• - Excess protamine should be avoided; it also
has an ————— activity.
heparin
heparin
anticoagulant
Fibrinolytic inhibitors (antiplasmin):
Aprotinin
• -Stops bleeding by blocking———— ; can
inhibit —————.
• -Reduce———— blood loss in
cardiopulmonary bypass surgery.
• May cause ————dysfunction and
—— as anaphylactic reactions.
• Should not be used in patients previously
exposed to the drug in the last 12 months for
fear of————–
plasmin streptokinase perioperative renal hypersensitivity anaphylaxis.
ANTIPLATELET DRUGS (ANTITHROMBOTIC)
Cilostazol
Antithrombotic, antiplatelet and vaso——– action
Inhibits———– , and thereby, increases cAMP levels Used for intermittent ———- and peripheral vascular disease
dilatory
phosphodiesterase type Ill
claudication
Used in treatment of bleeding due to anticoagulants
(oral).—————–
Vitamin K
