Regal- Thursday Drugs and stuff Flashcards
Generally speaking: Phase 1 of hemostasis
Phase 1: Vascular constriction limits the flow of blood to the area of injury
Generally speaking: Phase 2 of hemostasis
Phase 2: Platelets become activated and aggregate at the site of injury, forming a temporary, loose platelet plug (Primary Hemostasis)
Generally speaking: Phase 3 of hemostasis
Phase 3: A fibrin mesh (also called the clot) forms and entraps the plug (Secondary Hemostasis)
Generally speaking: Phase 4 of hemostasis
Phase 4: The clot is dissolved in order for normal blood flow to resume following tissue repair.
Aspirin
Acetylsalicylate Irreversible inhibitor of COX decreasing the expression of gpIIb/IIIa Platelets do not have COX2 Antipyretic, analgesic and anti-inflammatory
Adverse effects: Bleeding, GI disturbances, Tinnitus Low dose (platelet effect) vs high dose (anti-inflammatory)
Clopidogrel
Irreversible ADP receptor antagonist that prevents activation of ADP receptor
Oral
lasts days
Used during stenting
recommended for patients that don’t tolerate aspirin
Adverse effects include:
BLEEDING, nausea, diarrhea, rash (10-50% of patients)
severe leukopenia (1% of patients)
thrombotic thrombocytopenic purpura (TTP) – very rare (usually with ticlopidine)
requires activation via CYP2C19 so drugs that impair this isoform (e.g. omeprazole) should be used with caution
Prasugrel
Irreversible ADP receptor antagonist that prevents activation of ADP receptor
Oral
lasts days
Used during stenting
recommended for patients that don’t tolerate aspirin
Adverse effects include:
BLEEDING, nausea, diarrhea, rash (10-50% of patients)
severe leukopenia (1% of patients)
thrombotic thrombocytopenic purpura (TTP) – very rare (usually with ticlopidine)
have fewer side effects than Ticlopidine
Prasugrel has fewer side effects than Ticlopidine
Ticlopidine
Irreversible ADP receptor antagonist that prevents activation of ADP receptor
Oral
lasts days
Used during stenting
recommended for patients that don’t tolerate aspirin
Adverse effects include:
BLEEDING, nausea, diarrhea, rash (10-50% of patients)
severe leukopenia (1% of patients)
thrombotic thrombocytopenic purpura (TTP) – very rare (but more likely to happen with ticlopidine)
ADP Receptor Antagonists Class: names
Clopidogrel, Prasugrel, Ticlopidine
GPIIb/IIIa Receptor Inhibitors Class: names
Tirofiban, Abciximab, Eptifibatide
Abciximab
humanized MAB against GPIIb/IIIa
GPIIb/IIIa Receptor Inhibitor
Prevent binding of adhesive glycoproteins such as fibrinogen and vWF to activated platelets
Inhibits the final common pathway for platelet aggregation
Given IV: with aspirin and heparin during angioplasty for acute coronary syndromes
Adverse effects include: Bleeding, Thrombocytopenia (chronic use)
Eptifibatide
fibrinogen analogue
GPIIb/IIIa Receptor Inhibitor
Prevent binding of adhesive glycoproteins such as fibrinogen and vWF to activated platelets
Inhibits the final common pathway for platelet aggregation
Given IV: with aspirin and heparin during angioplasty for acute coronary syndromes
Adverse effects include: Bleeding, Thrombocytopenia (chronic use)
Tirofiban
GPIIb/IIIa Receptor Inhibitor
non-peptide competitive inhibitor
Prevent binding of adhesive glycoproteins such as fibrinogen and vWF to activated platelets
Inhibits the final common pathway for platelet aggregation
Given IV: with aspirin and heparin during angioplasty for acute coronary syndromes
Adverse effects include: Bleeding, Thrombocytopenia (chronic use)
Dipyridamole
Increases cAMP and inhibits platelet activation
Phosphodiesterase 3 inhibitor (increases cAMP by preventing it’s breakdown to 5’AMP by phosphodiesterase)
Inhibits platelet uptake of adenosine and thus increases adenosine interaction with Adenosine A2 receptor-> increased cAMP.
Also a vasodilator –> adverse effect is headache
Little or no beneficial effect by itself
Used in combination with aspirin or warfarin
Indirect thrombin inhibitors: names
Unfractionated heparin
Low molecular weight heparin
Fondaparinux
direct thrombin inhibitors: names
Bivalirudin
Argatroban
Dabigatran etexylate
Unfractionated heparin (UFH) is the same thing as
high molecular weight (HMW) heparin, often just called heparin
Indirect thrombin inhibitors: mechanism
Bind to antithrombin to have their effect
Antithrombin inactivates both thrombin and Factor Xa
Heparin’s activity against thrombin is size dependent
Heparin is mainly obtained from porcine intestine
Also binds to plasma proteins, platelet (platelet factor 4), macrophages, and endothelial cells limiting its bioavailability and and gives highly variable anticoagulant response
Inactivates several coagulation enzymes, including Factors IIa (thrombin), Xa, IXa, XIa, and XIIa, by binding to the cofactor AT
Heparin’s activity against thrombin is size dependent
can cause thrombocytopenia
Patients on Unfractionated heparin (UFH) or High molecular weight heparin (HMW heparin) require what
Requires close monitoring of activated partial thromboplastin time (aPTT or PTT)
Less predictable pharmacokinetics (large ranges of molecular weights in this treatment)
Do patients on Low molecular weight heparin = LMW heparin require monitoring?
No monitoring required in most patients
More predictable pharmacokinetics
Fewer non-hemorrhagic side effects
Clotting time: aPTT test
aPTT tests intrinsic pathway
If you add negatively charged PL and particulates, Factor XII is activated and it clots faster –> activated partial thromboplastin time
If the aPTT is prolonged (and PT normal), then the person is considered to have a defect in the intrinsic pathway
Normal PTT times require the presence of the following coagulation factors: I, II, V, VIII, IX, X, XI, & XII
Clotting times: PT and derived INR test
PT and derived INR tests extrinsic pathway
Recalcified plasma clots in 12-14 sec if you add thromboplastin (TF + phospholipids)
If PT is prolonged (and aPTT normal), then the person has a defect in the extrinsic pathway
PT measures factors I (fibrinogen), II (prothrombin), V, VII, and X
Heparin-induced thrombocytopenia
Thrombotic complications may precede the drop in platelets
Twice as likely in women than men
Probably due to development of IgG antibodies against complexes of heparin with platelet factor 4
Protamine
Highly basic positively charged peptide that combines with negatively charged heparin to form a stable complex that lacks anticoagulant activity
Only binds long heparin molecules
HMW heparin has a short half life.
Incompletely reverses activity of LMWH
Will not reverse the activity of fondaparinux.
