study d6 Flashcards
antiplatlet how they work and result
Antiplatelet Drugs
* Antiplatelet drugs act by suppressing platelet aggregation and adhesion
result =
reduction of platelet aggregation
prolonged bleeding time
ADP receptor antagonist
clopidogrel*, prasugrel#, ticagrelor
- decreased platelet aggregation results from inhibition of ADP released from activated thrombocytes
- some of these drugs* must be activated by hepatic enzymes CYP 2C19
- consequence: slow metabolizers are at risk of not activating enough drug
- used to prevent thrombus formation (e.g. following angioplasty)
Adverse effects:
bleeding
agranulocytosis*
mechanism of coagulation
how are levels of coag factors reduced
- Coagulation is triggered by an injury in a blood vessel wall that exposes tissue factor (TF) or thromboplastin
- tissue factor, with Factor VII, stimulates the activation of Factor X
- The activated Factor X stimulates the formation of thrombin (also known as activated Factor II)
- Thrombin cleaves fibrinogen into fibrin that forms a mesh that will stabilize the clot
- vitamin K is required to make functional Factors II, VII, IX and X
antithrombin III (AT III), helps to control and limit the scope of coagulation - AT III is responsible for the inactivation of Factor Xa and Factor IIa (thrombin) as well as Factors IXa, XIa and XIIa
How levels of coagulation factors are reduced
1. by inhibiting their formation
2. by increasing their destruction
3. genetic causes like hemophilia: factor VIII or IX deficiency
result = prolonged coagulation time (bleeding)
anticoagulants
what and two common ones
Anticoagulants
anticoagulants reduce the ability of blood to form clots
anticoagulants do not dissolve formed clots
these two anticoagulants are:
heparin (and low molecular weight heparin)
warfarin
heparin
what route is used
Heparin
* mixture of molecules of varying length or molecular weights
* exerts its anticoagulant effect by binding to and activating antithrombin (ATIII)
* activating ATIII, heparin increases inactivation of Factor Xa and thrombin (IIa) equally (no preference for one or the other)
also inactivates Factors XIIa, XIa, IXa
result = reduced coagulation
must be administered parenterally, Intravenous (immediate effect) or sub-cutaneous (effect: 1-2 hrs)
requires close monitoring using a aPTT test
dose of heparin is adjusted to obtain a coagulation time of 1.5 to 2.5 times the normal value
heperain
clinical uses and adverse effects
clinical uses include:
prevention or treatment of venous and arterial clots
deep vein thrombosis / pulmonary embolism /acute coronary syndrome
during extracorporeal circulation (bypass, hemodialysis)
toxicity can be treated with protamine
adverse effects:
bleeding –> everywhere imaginable lol
hypotension, increased heart rate, loss of consciousness
headache / confusion / change in vision (cerebral bleed)
abdominal or pelvic pain (ovary)
heparin-induced thrombocytopenia
osteoporosis (long-term, high dose)
low moleular weight heparin
drug examples and advantages
Low molecular weight heparin
dalteparin (Fragmin), enoxaparin (Lovenox)
selective enrichment of heparin molecules having smaller molecular weight vs unfractionated heparin
2-4 X higher selectivity for Factor Xa vs thrombin
Advantages:
more predictable anticoagulant response
fewer haemorrhagic complications
factor xa inhibitors
indirect vs direct
adverse effects: risk of excessive bleeding
indirect:
fondaparinux (s.c.) : activates antithrombin III (ATIII) specifically such that it only increases destruction of Factor Xa
direct:
apixaban (p.o): inhibits Factor Xa specifically by binding directly to Factor Xa
rivaroxaban (p.o): is another direct Factor Xa inhibitor
warfarin
what is it and test used to monitor therapy
- used an oral anticoagulant
- prevents activation of vitamin K –> decreases the synthesis of Factors II, VII, IX and X
treatment requires at least 3-4 days before it has reached full efficacy as only newly synthesized factors will be affected
prothrombin time (PT) is the test used to monitor levels of warfarin therapy
normal = 1.0 (range 0.8-1.2)
therapy aims for INR = 2.0-3.5
used for long-term prophylaxis of thrombosis
(e.g. atrial fibrillation, mechanical heart valves)
adverse effects of warfarin + treatment of overdose
- bleeding, bruising
- can cross placenta; known teratogen,
- warfarin is affected by numerous significant drug-drug interactions
Treatment of overdose =
1. vitamin K (po, iv);
2. prothrombin complex concentrate (II, VII, IX, X)
3. fresh-frozen plasma
dabigatran
overdose treatment ?
is a direct thrombin inhibitor that is used as an oral anticoagulant
benefit vs warfarin:
not sensitive to vitamin K intake, does not have as many drug-drug interactions
effects more predictable, therefore less frequent monitoring is required
Adverse effects:
bleeding/bruising, dyspepsia
treatment of overdose: idarucizumab
thrombolytics
what, types, clinical uses, adverse effects
- used to dissolve formed clots (‘clot buster’)
- increases conversion of plasminogen to plasmin
- plasmin destroys fibrin within blood clots
types
tissue plasminogen activator (tPA)
synthetically modified tPAs (tenecteplase)
streptokinase (bacterial origin)
Clinical Uses:
myocardial infarction
pulmonary embolism
occlusion in cerebral vasculature
(ischemic stroke)
Adverse effects:
plasmin can destroy pre-existing clots (see figure) and can thereby promote recurrence of bleeding at sites of recently healed injury
especially problematic if this leads to intracranial hemmorhage
antifibrinolytics
clinical uses, example, adverse effects
drugs used to reduce fibrinolysis by inhibiting binding of plasminogen to fibrin
e.g. tranexamic acid
clinical uses:
reduce bleeding
menorrhagia
hemophilia
adverse effects:
thromboembolic events
allergic skin reactions
