Lecture 20: Hemostasis Gout

what is gout

metabolic disorder characterized by high levels of uric acid in blood

• hyperuricemia can lead to urate crystals in tissue esp in joints and kidneys

• immune cells are recruited to phagocytose urate crystals and cause inflammation

what is the cause of hyperuricemia in gout

imbalance between overproduction of uric acid

inability of kidney to excrete uric acid

asymptomatic gout

prior to first attack

uric acid in blood causes urate to form crystals

acute intermittent gout

attacks begin, lasting 3-10 days

causes pain, swelling, stiffness, redness, fatigue, and fever

chronic tophaceous gout

advanced stage

urate crystals form hardened lumps, eroding bone and cartilage

MOA for NSAID usage in gout

inhibits COX enzymes that lead to prostaglandin synthesis

calms inflammation

colchicine MOA for gout

binds tubulin

disrupts immune cell migration and division

MOA for allopurinol febuxostat in tx of gout

xanthine oxidase inhibitor

MOA of probenecid in tx of gout

inhibits urate transporters in proximal tubule hence keeping uric acid in urine

adverse effects of colchicine

nausea, GI, diarrhea, alopecia, aplastic anemia, neutropenia

contraindications to colchicine

pregnancy, hepatic, renal, and cardiovascular disease

MOA for allopurinol

xanthine oxidase inhibitor (purine analog) which reduces uric acid production

adverse effects of allopurinol

hypersensitivity and skin reactions

contraindications of allopurinol

reduces metabolism of theophylline (use lower dose)

action of platelet aggregation inhibitors

• prevent formation of platelet plugs

• treat or prevent cardiovascular events like heart attacks or strokes

action anticoagulant pharmocological agents

• reduce clot formation by targeting the coagulation cascade factors like thrombin or fact Xa

• prevent venous thromboembolism, pulmonary embolism, and stroke in condition like atrial fibrillation

thrombolytic pharmocological agents

• dissolve existing clots by promoting the conversion of the plasminogen to plasmin

• emergency settings such as acute myocardial infarction, ischemic stroke, or pulmonary embolism

thrombus definition

a clot that adheres to the vessel wall

embolus definition

an intravascular clot that floats in the blood

arterial thrombosis definition

are typically platelet rich clot (atherosclerosis)

venous thrombosis

often triggered by blood stasis or inappropriate activation of the coagulation cascade, most dangerous in deep veins

four thrombotic disorders

1. acute myocardial infarction

2. acute ischemic stroke

3. deep vein thrombosis

4. pulmonary embolism

what is the factor V leiden mutation

inherited genetic mutation that makes blood more prone to abnormal clotting by making the coagulation factor V protein resistant to breakdown

von willebrand factor

• platelet adhesion: bridges platelets to exposed collagen and damaged vessel walls during primary hemostasis

• factor VIII stabilization: binds to and protects factor VIII in the bloodstream to prevent its rapid degradation

MOA for aspirin

irreversibly acetylates COX-1 enzyme to reduce tromboxane A2 to inhibit platelet aggregation

therapeutic action of aspirin

reduce platelet aggregation at low doses to reduce risk of cardiovascular event

pharmacokinetics of aspirin

hydrolyzed to salicylic acid in the liver, which has a long half-life

adverse effects of aspirin

bleeding

MOA of ADP receptor blockers

bind to ADP receptors on platelets to prevent the activation of GP receptors needed for platelet aggregation

therapeutic action of ADP receptor blockers

reduce platelet aggregation

pharmokinetics of ADP receptor blockers

eliminated in urine/feces

clopidogrel is metabolized