Hematology Drugs

Drug

Mechanism and Therapeutic effects

Indications

Side effecs and contraindications

Antiplatelet Drugs

Rational: 1)lower patelet fxn (activation and aggregation), 2)Inhibt Thromboxane A2 (TXA2) synth., 3)Prevent release of other platelet products that promote atherogensis.

Aspirin

81-325mmg/day

·         For inhibition of Platelet aggregation

·         Cox inhibitor.  Inhibition of thromboxane synthesis.  There are no thromboxane receptor antagonists

·         Note: Endogenous Prostacycline [PGI2] and NO inhibit platelet aggregation by an increase in c[AMP]

·         Effect is greatest when chewed followed by dissolved in sol, and finally In tablet form.

·         Halfprin marketing strategy for 162mg asprin for MI and stroke.  No therapeutic diff. than 81 mg

·         Lowered incidence of MI and death by 30-50% in people with unstable angina

·         Benefit to MI survivors less clear.

·         Increases bleading time nd average of 11 min

·         Dose related risk to gastro-intestinal ulceration with long term tx

·         Antithrombotic effect persists for 7-10 days after cessation of tx.

·         Test platelet fxn using bleeding time.  Normal is 5 min

·         Also causes a reversible decrease in prostacycline (this does not occur with Ticlid or Plavix)

·         Higher doses are several times more gastro toxic but don’t appear to be more efficacious

·         Do not take Ibuprofen.  It blocks the effects of asprin

Dipyridamole

·         Increases c[AMP]

·         Usually used in combination with low dose aspirin (aggrenox)

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Ticlopodine

Ticlid

·         Blocks ADP induced aggregation at low-affinity purinergic receptor (type II)

·         Irreversible effect on platelet

·         Not a salicylate

·         Nearly identical therapeutic effect as ASA

·         For pts intolerant to aspirin

·         Management of pt at risk of thrombotic stroke

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·         Risk of Aggranulocytosis necessitates regular lab tests, and thrombotcic thrombocytopenia purpura 2.4%

Clopidogrel

Plavix

·         risk of aggranulocytosis is lower than toclopodine

Tirofiban

Aggrastat

·         Non-peptide antagonist of GPIIb/IIIa platelet receptor involved in binding of fibrinogen causing aggregation of platelets

·         Reversible platelet aggregation inhibition

·         Indicated in unstable angina and acute coronary syndromes

·         I.V. only

·          

Fibrinolytic Drugs

t-PA (tissue plasmin activator), Urokinase, and streptokinase

·         Cleave plasminogen into plasmin, which in turn attacks fibrin, fibrinogen and factors V and VI.

·         Therapeutic effect is due to dissolution of Fibrin clots

·         Use for treatment of acute thrombolytic and embolytic events.

·         Must be administered parenterally

·         Risk of hemorrhage

·         Streptokinase is highly immunogenic and cannot be used repeatedly

Anticoagulants

Heparin

·         Obtained from hog intestines or beef lung

·         Acts by activating plasma antithrombin III in turn leading to increased rate of inhibition of factor Xa and thrombin production

·         Not plasma bound

·         Immediate onset ( for acute tx)

·         Must be given I.V. or S.C.

·         Anticoagulant of chice in pregnant women

·         For tx and prevention of venous thromobosis and pulmonary embolism

·         risk of Thrombocytopenia, hypersensitivity, and transient hypercoagulability upon discontinuation

·         Bleeding risk increases as the dose increases.

·         Antidote: protamine sulfate

Coumarin

(Warfarin)

·         Acts by interfering with synthesis of several factors (including 10a) necessary for the conversion of prothrombin to thrombin.

·         Blocks Vitamin K

·         Vitamin K is required for the production of factors VII, IX,  prothrombin, and anticoagulant proteins c and s.

·         97% plasma bound, and metabolized by the liver

·         ineffective in vitro

·         For tx and prevention of venous thromobosis and pulmonary embolism

·         Use one stage PT test to evaluate therapeutic effect (given via INR)

·         Only effects the production of new clotting factors so there is a 2-3 day delay in therapeutic effect.

·         First 30 days have an increased risk of bleeding complications

·         Effect may be increased by any drug that inhibits P450 system (Erythromycin)

·         Risk of drug interactions.  Be sure to look at the the handout

·         Antidote is Vit. K, or phenytonadione

Dicoumaral

·         ?

·         ?

·         ?

Theraputic goals

·         determined by INR score

·         INR goal is 2.0-3.0(2.5 ideal) for everything except mechanical prosthetic valves, post-acute MI prophylaxis, where the range is 2.5-3.5(ideal 3.0)

·         INR5.0-5.9 give .05 mg vit. K

·         INR 6.0-9.9 give 2.5 mg vit K

·         INR >10 give 5.0 mg vit K

·         Warning signs: epitaxis, GI bleeding, hematuria, hemoptysis, hemorrhoids… anything with bleeding

Coagulation Promotors

Amacar (aminocaprionic acid)

·         for tx of  bleeding due to excessive fibrinolysis

·         emergency use, ussualy after transfusion

·         also during major surgery to control hemostasis.

·          

Tranexamin acid

·         Mouth rinse PO for 2-8 days post surgery

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