Cardio: antiPlat., antiCoag., Thrombolytic Drugs

Question 1

• Permanently Acylates COX enzymes (irreversibly inhibit COX-1 and COX-2), prevents the conversion of Arachidonic acid to Prostaglandins and TXA₂
• AA → COX-1 → PGH₂ → TXA₂ (potent agonist that induces platelet aggregation - in the platelet membrane
• ↓ Risk of CHD
• Used to treat Unstable Angina
• Side Effects: GI bleeding, Ulcers, Peptic Ulcer Disease, occasionaly triggers Allergies as Asthma, Reye syndrome in children, Tinnitus at very high doses

Answer 1

Aspirin

Question 2

• Class Thienopyridines which are irreversible antagonists of the ADP (P2Y₁ and P2Y₁₂) on the platelet surface
• Activated by Hepatic P450 of the receptors: ↑ IP3, ↓cAMP
  → promotes expression of GPIIb/IIa (figrinogen recptor)
• Used w/ Asprin for additional activity after Acute Coronary Syndrome (ACS), MI or after a Stent
• Best choice when pt. allergic to Aspirin
• Pts. w/ CYP2C19 and CYP3A4 are poor activators
• SEx: Upset Stomach, Neurotropenia, Thrombocytopenia

Answer 2

Chopidogrel (Plavix)

Prasurgel (Effient)

Ticlopidine

Question 3

• A reversible ADP-receptor antagonist
• Circumvents CYP450 activation
• Pts. should NOT skip doses
• Better efficacy than Clopidogrel

Answer 3

Ticagrelor

Question 4

• Inhibits Adenosine uptake by the platelet
• increases cGMP and cAMP phoshodiesterases (PDEs)
• Vasodilator which may lead to Headaches
• Post operative prophylaxis of Thromboemboli w/ heart valves when given w/ alone.
• Slow release w/ Asprin is phrophylactic for Stroke
• SEx: Hypersensitivity, Hypotension

Answer 4

Dipyridamole

Question 5

• Binds to glycoprotein - GPIIB/IIIA on platelets and prevents interaction between fibrinogen and IIb/IIIa
• Fab fragment of monoclonal Ab directed toward GPIIB/IIIA protein → blocks interaction of platelets w/ vasculature and w/ each other → prevents thrombis for up to one week after administration
• SEx: Excessive bleeding, Major Hemorrhage
• A synthetic reversible, non-peptide inhibitor is also available.

Answer 5

Abciximab

Tirofiban

Eptifibatide

Question 6

• Secreted by Mast cells
• Bind antithrombin proteins present in normal blood and dramatically enhance their activity
• Catalyzes the activation of Antithrombin III - decrease activity of Factor IIa and Factor Xa
• Immediate onset when given IV
• Not cleared by the Kidneys
• Negatively charged, sulfated mucopolysaccharides (glycosaminoglycans)
• Tx: DVT, PE, MI,
• SEx: HIT (antidote - Protamine sulfate)

Answer 6

Heparin

Question 7

• All drugs of this class end in -parin
• Does not inhibit Thrombin, mainly inhibits Factor Xa which means that aPPT is not monitored
• Synthetic selective inhibitor of activated Factor Xa
• Cleared by the Kidneys
• Never given INTRAMUSCULARLY

Answer 7

Low MW Heparin

Fondaparinux (synthetic)

Question 8

• **Synthetic derivative of hirudin **(leeches salivary gland)
• Reversible, direct Thrombin inhibitor
• Inhibit Fibrin-bound as well as Circulating Thrombin
• Alternative if pt. has HIT
• Affects both aPTT and INR
• Cleared by Kidneys

Answer 8

Lepirudin

Bivalirudin

Question 9

• Most frequently used Anticoagulant
• Inhibits γ carboxylation of Vit. K-dependent clotting factors (Coag. Factors X, IX, VII, and II and Protein C and S), back to its active Hydroquinone form, **inhibiting the carboxylation, **depleting the co-factor of the rxn
• Levorotary S-form is 4x more potent
• No effect on already synthesized and carboxylated coag. factors
• Tx: MI, reduced LVf, AF, Prosthetic heart valves, V Thromb
• NO PREGNANCY: birth defect and abortion,
• Extreme caution in pts. w/ Hepatic or Renal disease

Answer 9

Warfarin (Coumadin)

Answer 10

Dabigatran

Rivaroxaban

Apixiban

Question 11

• Thrombolytic drug that **activates Plasminogen
• -> Plasmin**
• A protein produced by streptococci
• Forms a stable complex w/ Plasminogen facilitating its conversion into plasmin not bound to fibrin clots
• Tx: Acute MI, Stroke, PE
• SEx: Surgery, Recent/Current bleeding, History of cranial bleeds, Allergic response in ~5% of patients.

Answer 11

Streptokinase (bacteria)

Question 12

• Fibrin-specific
• Only activates Plasminogen molecules that are bound to fibrin clots
• It does not induce systemic activation of plasmin, only on the Thrombus
• Tx: Coronary Thrombolysis, Multiple PEs, DVTs, Acute MI, Stroke
• SEx: Bleeding, Hemorrhage
• Contra: Surgery, GI tract bleeding, Aneurysm, Hypertension, Active bleeding, etc.

Answer 12

Tissue Plasminogen Activator (tPA)

Question 13

• Inhibits PDE₃, which ↑ cAMP levels and ↑ PKA activation
• Vasodilation inhibits platelet aggregation
• Indicated for intermittent claudication due to Peripheral Arterial Disease
• Caution when used with drugs that inhibit CYP3A4 and CYP2C19

Answer 13

Cilostazol

Question 14

• Cleared by Hepatic **CYP450s **from the Liver
• Use with caution in pts. w/ compromised Liver funtion
• May lead to elevate INR values
• Indicated for use in pts. in HIT-induced thrombosis and during Angioplasty

Answer 14

Argatroban

Question 15

• An enzyme produced by human kidney
• Purified from cultured Kidney cells
• Directly converts Plasminogen into Plasmin

Answer 15

Urokinase