Hematology Pharm

Enhances antithrombin III activity

2) Decreases thrombin and Xa.

So inhibits thrombin from converting fibrinogen to fibrin.

Immediate anticoagulation for PE, stroke, angian, MI, DVT.

Heparin because it does not cross the placenta!

PTT time.

Bleeding, thrombocytopenia.

Protamine sulfate (positively charged molecule that acts by binding negatively charged heparin) --> rapidly reverses heparinization.

Enoxaparin

Acts more on blocking Xa

Xa converts prothrombin to thrombin!

1) Enoxaparin --> better bioavailability, 2-4x longer half life, can be administered SubQ and without lab monitoring.

Disadvantage: enoxaparin overdose cannot be easily reversed with protamine sulfate!

Inhibits vitamin K epoxide reductase. You therefore cannot convert Vit K to its active form.

Active vit K --> needed for gamma carboxylation of glutamate residues of factors, 2, 7, 9, and 10, and protein C and S.

PT time. Affects Extrinsic pathway.

Long half life.

cimetidine, disulfuram, and chlroamphenicol.

Barbituates
Rifampin
Alcohol.

Chronic anticoagulation. Not used in pregnant women (because warfarin unlike heparin, can cross the placenta).

**DRUG HAS A NARROW THERAPUETIC INDEX SO ESSENTIAL TO MONITOR PATIENTS ON THIS DRUG.

Large anionic polymer, acidic (so cant cross the placenta)

Small lipid-soluble molecule (so can cross the placenta).

Blood

Liver

Acute (hours)

Chronic (weeks or months).

HEPARIN!!

wafarin.

IV vitamin K and for acute bleeding --> fresh frozen plasma.

Streptokinase, urokinase, tPA (alteplase), APSAC (anistreplase)

Aids in the conversion of plasminogen to plasmin.

Plasmin can then cleave thormbin and fibrin clots!

Early ischemic stroke

Early MI.

Bleeding. Contraindicated in patients with active bleeding, history of intracranial bleed, recent surgery, or severe hypertesion.

Aminocaproic acid, an inhibitor of fibrinolysis.

Converts plasminogen BOUND TO FIBRIN within a clot to plasmin which cleaves fibrin and lyses the thrombus. But TPA only binds plasminogen already bound to fibrin.

Converts plasminogen to plasmin. Streptokinase can lead to hypersensitivity, since it is a foreign protein (unlike urokinase which is not foreign).

Plasmin can degrade fibrinogen into its products

2) Plasmin can also break down fibrin into its split products.

Inhibits conversion of plasminogen to plasmin.

Aceylates and irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) to prevent conversion of arachidonic acid to prostaglandins.

Increases bleeding time.

Normal PT and PTT.

Antipyretic

Analgesic

Anti-inflammatory

Anti-platelet.

Gastric ulceration, bleeding, hyperventilation, Reye's syndrome, tinnitus.

Causes mixed acid-base disorder: first respiratory alkalosis then metabolic acidosis.

1) Blocks ADP receptors --> inhibit platelet aggregation

2) Prevents glycoprotein IIb/IIIa expression --> inhibits fibrinogen binding.

acute coronary syndrome; coronary stenting.

Neutropenia, agranulocytosis, so use clopidogrel instead.

Monoclonal antibody that binds to glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation. Prevents fibrinogen binding!

Inhibits adenosine deaminase and phosphodiesterase.

1) Accumulation of adenosine/cAMP

Adenosine and cAMP inhibit platelet aggregation.

Decrease thymidine synthesis

Decreases purine synthesis

DNA intercalation

strand breakage and DNA intercalation

Actually inhibits ATIII --> this leads to a conformation change of ATIII that actually allows it to rapidly combine with and inhibit thrombin. This prevents conversion of fibrinogen to fibrin.

1) Easier to administer: SubQ
2) Longer half life

COX-1 expressed constitutively in platelets and the GI tract.

Expressed preferentially at sites of inflammation.

Dont impair platelet function b/c platelets predominantly express COX-1.

Heparin induced thrombocytopenia. Leads to paradoxical thrombus! Autoimmune reaction with antibodies formed against platelet factor 4 (PF4), neutrophil-activating peptide 2 (NAP-2) and interleukin 8 (IL8) which form complexes with heparin,

Direct thrombin inhibitors!!

Hirudin, leipirudine, argatroban: inhibit thrombin.

(Thrombin normally converts fibrinogen to fibrin)

Directly inhibit thrombin. Drug of choice for HIT!! They bind to thrombin active site.

1) increase level of clotting factors
2) Decrease protein S
3) Pressure of uterus on IVC allows for stasis
4) Presents as unilateral leg pain, swelling, and warmth.

Keeps the patent ductus arteriosus open.

Indomethacin or aspirin because they inhibit COX preventing formation of prostaglandin E.

Non-selective irreversible inhibition of COX, causing decreased prostaglandin and thromboxane production. If block prostaglandins at thermoregulatory centers in hypothalamus, asprin, and other NSAIDs act as antipyretics.

Prostaglandins sensitive pain receptors to chemical and mechanical stimuli, and also acts on thermoregulatory center to cause fever.

Reversible, non selective inhibitor of COX....

Remember aspirin in IRREVERSIBLE NONSELECTIVE INHIBITOR OF COX.

Selective Cox II inhibitors.

Fewere side effects on GI and on bleeding.

It has 100% hypersensitivity cross-reactivity with aspirin. The hypersensitivity consists of rashes, urtricaria, and acute asthmatic attacks!

constitutively expressed in platelets.

2) COX1 products are responsible for mucous secretion of gut.

It is inactivated in peripheral tissues.

Used in acute attacks of gout. Acute!!

1) Blocks mitotic spindles
2) Blocks tubulin which decreases mobility of granulocytes to affected areas

Agranulocytosis, aplastic anemia.

Used to prevent attacks of gout.

Inhibits uric acid reabsorption

It also blocks tubular secretion of penicillin, so used to increase the antibiotic.

Inhibits xanthine oxidase, and used for chronic suppression of gouty attacks.

If given during gouty attack, allopurinol has the potential to actually exacerbate the condition.