MOD 3 & 4-Exam 2- UTMB Pharmacology
UPDATED Exam Questions and CORRECT
Answers
Warfarin (Coumadin) - CORRECT ANSWER - Inhibits the synthesis of vitamin K-
dependent clotting factors X, IX, VII, and II (prothrombin)
Warfarin typically does not produce any therapeutic effects until 5-7 days after the first dose, due
to the biologic half-lives of the factors that it inhibits (II, VII, IX, and X). Factor II has the
longest half-life (50-80 hours) of these clotting factors; therefore, parenteral therapeutic
anticoagulation is required to bridge the patient to the use of the oral formulation alone.
half-life is ~40 hrs/ 3-4 days
Peak is 3-5 days
Duration is 2-5 days
Pregnancy category X
Use cautiously in patients with fall risk, dementia, or uncontrolled hypertension.
Avoid in hypermetabolic state.
The antidote is vitamin K.
Clinical use and dosing:
Drug of choice for deep vein thrombosis (DVT) and pulmonary embolism (PE)
Start at 5 mg per day (7.5 mg/d if weight greater than 80 kg).
Consider a lower dose if:
-Older than 75 years
-Multiple comorbid conditions
-Elevated liver enzymes
-Changing thyroid status
,Dose to maintain an international normalized ratio (INR) between 2 and 3.
Monitoring :
INR daily until in therapeutic range for 2 consecutive days
Then two or three times weekly for 1 to 2 weeks
Then less frequently but at least every 6 weeks
Warfarin (Coumadin) therapeutic effect - CORRECT ANSWER - Thus, the ultimate
anticoagulant effect of vitamin K antagonists (VKA) is delayed until the previously synthesized,
functional clotting factors are cleared from the circulation. Depletion of both factor X and factor
II (prothrombin) is important for clinical efficacy, and factor II has the longest half-life of the
vitamin K-dependent factors (approximately three days-72hrs) [3,4]. Thus, the desired
anticoagulant effect of a VKA does not occur for at least 3-4 days after drug initiation despite
prolongation of the prothrombin time (PT) at earlier time points. The initial prolongation of the
PT is due primarily to depletion of factor VII, which has a short half-life (four to six hours)
Metabolized by CYP 1A2 and 2C9.
High bound to Plasma protein.
Well absorbed when taken orally.
What is plasmin? - CORRECT ANSWER - Plasminogen, the precursor molecule to
plasmin, binds fibrin and tissue plasminogen activator (tPA). This ternary complex leads to
conversion of the proenzyme plasminogen to active, proteolytic plasmin.
an enzyme that dissolves the fibrin of blood clots
Fibrinolysis
What does plasmin do? - CORRECT ANSWER - Plasmin — Plasminogen, the precursor
molecule to plasmin, binds fibrin and tissue plasminogen activator (tPA). This ternary complex
leads to conversion of the proenzyme plasminogen to active, proteolytic plasmin.
, Plasmin has broad substrate specificity and, in addition to fibrin, cleaves fibrinogen and a variety
of plasma proteins and clotting factors. Plasmin cleaves the polymerized fibrin strand at multiple
sites and releases fibrin degradation products (FDPs). One of the major FDPs is D-dimer, which
consists of two D domains from adjacent fibrin monomers that have been crosslinked by
activated factor XIII. Plasmin also cleaves factor XIIIa, but not factor XIII, leading to reduced
fibrin crosslinking.
The plasminogen/plasminogen-activator system is complex, paralleling the coagulation cascade.
Plasmin activity is regulated by vascular endothelial cells that secrete both serine protease
plasminogen activators (tissue-type plasminogen activator and urokinase-type plasminogen
activator) and plasminogen activator inhibitors (PAI-1 and PAI-2).
degrades fibrin
Antihemorrhagic agents - CORRECT ANSWER - As most of these products are derived
from human sources, patients should be monitored closely during their administration for
infusion-related reactions, some of which may be severe (e.g., hypotension, bradycardia).
These medications are administered in conjunction with blood products such as PRBCs,
platelets, FFP, and/or cryoprecipitate.
Protamine sulfate-fish sperm
antihemophilic factor- human or porcine (pig)
thrombin-human or bovine (cow)
When anticoagulant therapy should be withheld... - CORRECT ANSWER - -any bleeding
that does not stop with in 5 mins
-nose bleeds and bleeding gums
-red or pink-tinged urine
-faintness or weakness
-headaches
-stomach pains
UPDATED Exam Questions and CORRECT
Answers
Warfarin (Coumadin) - CORRECT ANSWER - Inhibits the synthesis of vitamin K-
dependent clotting factors X, IX, VII, and II (prothrombin)
Warfarin typically does not produce any therapeutic effects until 5-7 days after the first dose, due
to the biologic half-lives of the factors that it inhibits (II, VII, IX, and X). Factor II has the
longest half-life (50-80 hours) of these clotting factors; therefore, parenteral therapeutic
anticoagulation is required to bridge the patient to the use of the oral formulation alone.
half-life is ~40 hrs/ 3-4 days
Peak is 3-5 days
Duration is 2-5 days
Pregnancy category X
Use cautiously in patients with fall risk, dementia, or uncontrolled hypertension.
Avoid in hypermetabolic state.
The antidote is vitamin K.
Clinical use and dosing:
Drug of choice for deep vein thrombosis (DVT) and pulmonary embolism (PE)
Start at 5 mg per day (7.5 mg/d if weight greater than 80 kg).
Consider a lower dose if:
-Older than 75 years
-Multiple comorbid conditions
-Elevated liver enzymes
-Changing thyroid status
,Dose to maintain an international normalized ratio (INR) between 2 and 3.
Monitoring :
INR daily until in therapeutic range for 2 consecutive days
Then two or three times weekly for 1 to 2 weeks
Then less frequently but at least every 6 weeks
Warfarin (Coumadin) therapeutic effect - CORRECT ANSWER - Thus, the ultimate
anticoagulant effect of vitamin K antagonists (VKA) is delayed until the previously synthesized,
functional clotting factors are cleared from the circulation. Depletion of both factor X and factor
II (prothrombin) is important for clinical efficacy, and factor II has the longest half-life of the
vitamin K-dependent factors (approximately three days-72hrs) [3,4]. Thus, the desired
anticoagulant effect of a VKA does not occur for at least 3-4 days after drug initiation despite
prolongation of the prothrombin time (PT) at earlier time points. The initial prolongation of the
PT is due primarily to depletion of factor VII, which has a short half-life (four to six hours)
Metabolized by CYP 1A2 and 2C9.
High bound to Plasma protein.
Well absorbed when taken orally.
What is plasmin? - CORRECT ANSWER - Plasminogen, the precursor molecule to
plasmin, binds fibrin and tissue plasminogen activator (tPA). This ternary complex leads to
conversion of the proenzyme plasminogen to active, proteolytic plasmin.
an enzyme that dissolves the fibrin of blood clots
Fibrinolysis
What does plasmin do? - CORRECT ANSWER - Plasmin — Plasminogen, the precursor
molecule to plasmin, binds fibrin and tissue plasminogen activator (tPA). This ternary complex
leads to conversion of the proenzyme plasminogen to active, proteolytic plasmin.
, Plasmin has broad substrate specificity and, in addition to fibrin, cleaves fibrinogen and a variety
of plasma proteins and clotting factors. Plasmin cleaves the polymerized fibrin strand at multiple
sites and releases fibrin degradation products (FDPs). One of the major FDPs is D-dimer, which
consists of two D domains from adjacent fibrin monomers that have been crosslinked by
activated factor XIII. Plasmin also cleaves factor XIIIa, but not factor XIII, leading to reduced
fibrin crosslinking.
The plasminogen/plasminogen-activator system is complex, paralleling the coagulation cascade.
Plasmin activity is regulated by vascular endothelial cells that secrete both serine protease
plasminogen activators (tissue-type plasminogen activator and urokinase-type plasminogen
activator) and plasminogen activator inhibitors (PAI-1 and PAI-2).
degrades fibrin
Antihemorrhagic agents - CORRECT ANSWER - As most of these products are derived
from human sources, patients should be monitored closely during their administration for
infusion-related reactions, some of which may be severe (e.g., hypotension, bradycardia).
These medications are administered in conjunction with blood products such as PRBCs,
platelets, FFP, and/or cryoprecipitate.
Protamine sulfate-fish sperm
antihemophilic factor- human or porcine (pig)
thrombin-human or bovine (cow)
When anticoagulant therapy should be withheld... - CORRECT ANSWER - -any bleeding
that does not stop with in 5 mins
-nose bleeds and bleeding gums
-red or pink-tinged urine
-faintness or weakness
-headaches
-stomach pains
