Anticoagulants + the like (under CVS) Flashcards
1
Q
- Warfarin
- a. Blocks the gamma-carboxylation of glutamate residues in Protein C
- b. Has poor oral bioavailability.
- c. Does not cross the placenta.
- d. Anticoagulant activity is reduced by amiodarone.
- e. Inactivates activated factors II, VII, IX, X.
A
a. Blocks the gamma-carboxylation of glutamate residues in Protein C, protein S, and factors II, VII, IX, X
Warfarin inhibits vitamin K dependent synthesis of active forms of II, VII, IX, X as well as Protein C, S, and Z. Does this by inhibiting gamma carboxylation of glutamic acid residues. Mechanism is warfarin inhibits epoxide reductase, and hence stops vitamin k being converted back into its active form.
- b. Has 100% oral bioavailability.
- c. Crosses the placenta, and can cause fetal haemorrhage or birth defects
- d. Anticoagulant activity is increased by amiodarone.
- e. Prevents activated factors II, VII, IX, X. but does not inactivate them once they have been formed
2
Q
- Which is correct regarding warfarin?
- a. Broken down in GIT
- b. Added to transfused blood
- c. Decreases thromboplastins
A
Trick question: none are correct
- a. Broken down in GIT. - wrong: 100% bioavailability
- b. Added to transfused blood - wrong
- c. Decreases thromboplastins (Synonyms for III, IX, XI) - decreases II, VII, IX, X (vitamin K dependent factors)
3
Q
- Which drug does not interact with warfarin?
- a. Phenobarbitone
- b. Loop diuretics
- c. Benzodiazepines
- d. Cephalosporins
A
- a. Phenobarbitone - reduces INR through enzyme induction
- b. Loop diuretics - reduce INR through increased clotting factor concentration
- c. Benzodiazepines
- d. Cephalosporins - increases INR through pharmacodynamic means
4
Q
- Regarding fibrinolytics
- a. Urokinase is cheap but less selective.
- b. Streptokinase comes from human cells.
- c. HIMA says GIT haemorrhage is most common haemorrhagic complication.
- d. GIT haemorrhage within 12 months is a contraindication.
- e. Aminocaproic acid is a potent fibrinolytic inhibitor
A
e. Aminocaproic acid is a potent fibrinolytic inhibitor
An old form of tranexamic acid, they block plasminogen activation
- a. Urokinase is cheap but less selective -> directly cleaves plasminogen to plasmin unlike streptokinase which seems to act more indrectly. Less selective than tPA in that it does not act preferentially on plasminogen bound to fibrin
- b. Streptokinase comes from Streptococci
- c. HIMA says Minor bleeding like puncture sites is most common haemorrhagic complication.
- d. GIT haemorrhage within 1 month is a contraindication.
5
Q
- Ticlodipine
- a. Decreases platelet aggregation by inhibiting ADP pathway of platelets
- b. Has no GIT side effects
- c. Inhibits prostaglandin metabolism
A
Ticlodipine is similar to clopidogrel
a. Decreases platelet aggregation by inhibiting ADP pathway of platelets
Dipyridimole inhibits adenosine uptake
Aspirin blocks COX 1 and 2 -> less TXA2 (and prostaglandin)
6
Q
- Heparin
- a. Inhibits antithrombin III.
- b. Causes alopecia
- c. Decreases rate of conversion of prothrombin to thrombin
- d. Decreases rate of conversion of fibrinogen to fibrin.
- e. Decreases rate of conversion of VII to VIIa
A
- a. activates antithrombin III
- b. Causes alopecia
- c. Decreases rate of conversion of prothrombin to thrombin - wrong, it Inhibits thrombin
- d. Decreases rate of conversion of fibrinogen to fibrin.
- e. Decreases rate of conversion of VII to VIIa
- Heparin binds to Antithrombin III causing a confromational change exposing an active site
- Enchances inactivation of IXa, Xa, thrombin 1000x
7
Q
- Warfarin
- a. Is an orally administered anticoagulant with low bioavailability.
- b. Blocks the alpha carboxylation of glutamate residues in protein C.
- c. Has an anticoagulant action which is immediate.
- d. Does not cross the placenta-blood barrier.
- e. Causes decreased prothrombin time when given with diuretics
A
- a. Is an orally administered anticoagulant with 100% bioavailability.
- b. Blocks the gamma carboxylation of glutamate residues in protein C.
- c. Has an anticoagulant action which takes several days to reach affect due to inhibiting formation of factors (and is a _pro_coagulant early in administration).
- d. Does cross the placenta-blood barrier, and can cause fetal haemorrhage or birth defects
-
e. Causes decreased prothrombin time when given with diuretics
- increased factor concentration
8
Q
- Heparin
- a. Consists of a heterogenous group of glycoproteins.
- b. Acts by decreasing activity of blood coagulant factor VII.
- c. Is associated with osteomalacia.
- d. Increases the reaction rate of antithrombin III on clotting factors
- e. Is consumed in anticoagulation activity.
A
a. Consists of a heterogenous group of Mucopolysaccharides
b. Acts by decreasing activity of blood coagulant factor Xa and IIa
c. Is associated with Osteoporosis
d. Increases the reaction rate of antithrombin III on clotting factors - 1000x (factors IXa, Xa. IIa)
e. Is not consumed in anticoagulation activity.
9
Q
- Low molecular weight heparins
- a. Have a higher affinity for antithrombin than high molecular weight heparin
- b. Are less effective in preventing the development of deep venous thrombosis.
- c. Have a higher bioavailability from the subcutaneous site of injection than normal heparin
- d. Require more frequent dosing than normal heparin.
- e. Level monitoring may be required in liver failure
A
- a. Have a equal affinity for antithrombin than high molecular weight heparin.
- b. Are equally effective in preventing the development of deep venous thrombosis
- c. Have a higher bioavailability from the subcutaneous site of injection than normal heparin
- d. Require less frequent dosing than normal heparin (heparin usually an infusion)
- e. do not require level monitoring like heparin, but can be measured with anti-Xa
10
Q
- Heparin induced mild thrombocytopenia is caused by
- a. Release of lipoprotein lipase
- b. Aggregation
- c. Thrombosis
- d. Antiplatelet antibodies.
- e. none of the above are true
A
b. Aggregation
- Mild thrombocytopenia is due to platelet aggregation*
- More severe HIT is due to Auto-Ig directed against platelet factor 4 in combination with heparin. Platelets then removed by RES or thrombosis*
Heparin-Induced Thrombocytopenia is notable for being marked by VTE formation (DVT etc) as its complication rather than bleeding, as occurs in other forms of thrombocytopenia
11
Q
- Which is NOT true of warfarin?
- a. It has a half life of 6 hours
- b. It is reversed by FFP
- c. It is 99% protein bound
- d. It affects vitamin K synthesis
- e. It is 100% bioavailable
A
- a. It has a half life of 40 hours
- b. It is reversed by FFP - contains all missing factors that warfarin inhibits formation of
- c. It is 99% protein bound to albumin, and thus has a low Vd
- d. It affects vitamin K synthesis - technically affects synthesis of active vitamin K (warfarin binds to the reduced form, preventing it from being oxidised. The oxidised form donates oxygen to allow carboxylation of glutamate residues in II, VII, IX, X)
- e. It is 100% bioavailable
12
Q
- Which drugs increase the INR?
- a. Benzodiazepines
- b. Barbiturates
- c. Rifampin
- d. Cholestyramine
- e. Amiodarone
A
- a. Benzodiazepines - No effect
- b. Barbiturates - Decrease INR via enzyme induction
- c. Rifampin - Decrease INR via enzyme induction
- d. Cholestyramine - Decrease INR by reducing absorption
- e. Amiodarone
13
Q
- Regarding fibrinolytics
- a. All thrombolytics act to convert free plasminogen to plasmin.
- b. Urokinase is a human product
- c. tPA and APSAC lack the streptococcal antigen
- d. Reactions to tPA and anistreplase are preparation related.
- e. tPA does not occur naturally
A
a) All fibrinolytics convert free plasminogen to plasmin - not all: Streptokinase combines with a pro-activator, which in turn converts plasminogen -> plasmin
b) Urokinase is a human product - collected from urine (takes 1500L to produce 1 dose)
c. tPA and APSAC lack the streptococcal antigen: APSAC has strep, t-PA doesn’t. APSAC (aka anistreplase) is a combination of streptokinase and plasminogen
d) Reactions to anistreplase (and streptokinase) are anti-strep Ig mediated
e) tPA is a naturally occuring compound in the human body
14
Q
- Regarding heparin
- a. Dose reduction is necessary in the elderly.
- b. LMW fractions have more effect on thrombin than HMW.
- c. It may cause alopecia
- d. It inhibits antithrombin III
- e. Protamine is a competitive antagonist of heparin
A
- a. Dose reduction is necessary in the Renally impaired
- b. LMW fractions have less effect on thrombin (IIa) than HMW.
- equal effect on Xa, equal efficacy clinically
- c. It may cause alopecia
- d. It activates antithrombin III.
- e. Protamine binds irreversibly to heparin to form an inactive complex
15
Q
- regarding streptokinase
- a. the GUSTO trial showed a higher risk of haemorrhagic stroke compared to t-PA
- b. it is administered intravenously as a single rapid bolus dose
- c. it converts plasmin to plasminogen
- d. there are no in vivo inhibitors for the streptokinase-proactivation complex
- e. urokinase is made by bacteria.
A
- a. the GUSTO trial showed a higher risk of haemorrhagic stroke compared to t-PA-??
- b. it is administered intravenously as a 1hr infusion
- c. it converts plasminogen to plasmin
- d. there are no in vivo inhibitors for the streptokinase-proactivation complex
- e. urokinase is made by the Human kidney (and collected in urine, streptokinase is made by streptococci)
