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97 Cards in this Set

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Direct thrombin inhibitors
the -rudin's
A 65 amino acid peptide obtained from leeches and is a thrombin inhibitor
Recombinant yeast-derived form of hirudin

**Leper who also has a yeast infection
1st agent approved for anticoagulation in patients with Heparin-induced Thrombocytopenia (HIT)
2 new recombinant hirudin analogs that may be used instead of heparins in the future

2nd agent approved for HIT and unlike Lepirudin, it is cleared by the liver and can be used in patients with end-stage renal disease

*an "Argentine Trojan" who has HIT and End-stage Renal Disease
The only oral anticoagulant given in the US
- __1__ derivative
-hemorrhagic substance found in __2__ and used as __3__
1. Coumarin
2. spoiled sweet clover
3. rodenticides
What accounts for the low volume of distribution of Warfarin?
>99% binds to plasma proteins
What is the half-life of Warfarin?
36 hours!!!

**due to extensive plasma protein binding
What is the active form of Warfarin?
S isomer
Warfarin is metabolized to inactive metabolites by _____ in the liver

*site of numerous drug interactions
What clotting factors does Warfarin inhibit the synthesis of?
2, 7, 9, 10, and 12
Explain the mechanism of Warfarin
-Factors 2, 7, 9, 10, and 12 are zymogens which become activated via Vitamin K-dependent Carboxylation
-Warfarin inhibits Vitamin K Epoxide Reductase, which normally frees up just-used Vitamin K's = stops the process of Carboxylation
1. Target
2. Resistance
3. Speed of onset
4. Antidote (2 options)
1. Vitamin K Epoxide Reductase
2. mutations in Vitamin K epoxide reductase
3. Slow
4. Vitamin K (Phytonadione) and fresh, frozen plasma or Factor 9 concentrates containing Prothrombin Complex
What is the pharmacokinetic and the pharmacodynamic as to why the onset of Warfarin action is slow?
Kinetic -> takes ~ 1 week to reach steady state

Dynamic -> time to replace the normal clotting factors with incompletely gamma-carboxylated factors
Takes __1__ (time) for the initial anticoagulant effect and several days to reach maximum __2__
1. 8-12 hours
2. Hypoprothrombinemia
What drug inhibits Oral Warfarin absorption?

What other thing does it affect?

Vitamin K absorption
What 6 things induce hepatic microsomal enzymes and diminish the response to Warfarin? (hint)
1. Barbiturates
2. Carbamazepine
3. Phenytoin
4. Primidone
5. Rifampin
6. St. John's Wort

**1-4 are anticonvulsants
There is low WARfare when BARB eats CARBS and is not a PRIMADONNA. When she doesn't, it causes a RIF with her husband St. John so he hits her in the PHANNY-toin
What stimulates Clotting Factor synthesis in the liver and diminishes Warfarins effects?

**this is why Oral Contraceptives increase risk of thromboembolism
Explain how eating more green vegetables can diminish the effects of Warfarin
Veggies contain Vitamin K
- Vitamin K is involved in activating Clotting Factors
What drug displaces Warfarin from plasma albumin and enhances its effects?
What 8 drugs inhibit Warfarin metabolism and enhance its effects?
1. Amiodarone
2. Allopurinol
3. Cimetidine
4. Ciprofloxacin
5. Erythromycin
6. Co-trimoxazole
7. Metronidazole**
8. Fluconazole**

**selective for S-warfarin
CoME CACA F = increased plasma Warfarin
What would reduce the availability of Vitamin K and therefore enhance the effects of Warfarin?
Broad-spectrum antibiotics
-gut bacteria produce Vitamin K
Treatment for Arterial and Venous thrombi:
__1__ is used for the first 7-10 days with a 3-5 day overlap with __2__, which may be continued for up to 6 months
1. Heparin

2. Warfarin
Aside from treating Arterial and Venous Thrombi, Warfarin is also used to prevent __1__ in patients with __2__
1. blood clots
2. chronic atrial fibrillation
The therapeutic goal of Warfarin is to prolong ______ above normal
Prothrombin time (PT)
Low-intensity anticoagulation is used for __1__
Moderate-intensity anticoagulation is used __2__
High-intensity anticoagulation is used for __3__
1. Long term
2. initially
3. mechanical prosthetic heart valves
The therapeutic goal of Warfarin is achieved after how long?
1 week (4-5 doses with a 1.5 day half-life) = SLOW ONSET
Adverse effect of Warfarin: Serious and possibly fatal bleeding can occur in these 4 places
1. Brain
2. Pericardium
3. Stomach
4. Intestines
Under what 3 conditions is Warfarin Contraindicated?
1. Pregnancy
2. patients with bleeding disorders
3. Liver disease (impaired drug metabolism)***

***seem to forget this one
Why is Warfarin contraindicated with Pregnancy?
1st trimester = Teratogen

1-3 trimester = fetal hemorrhage
Thrombolytic drugs:
-therapy is directed towards the conversion of __1__ to __2__, which degrades fibrin and lyses thrombi
-Circulating __3__ preclude the possibility of using plasmin itself for thrombolytic therapy
-Plasma does not contain inhibitors of __4__ or the comblex formed betwen plasminogen and __5__
1. Plasminogen
2. Plasmin
3. Antiplasmins
4. Urokinase
5. Streptokinase
Why are Urokinase and Streptokinase not inhibited by circulating Antiplasmins?
B/C they convert Plasminogen -> Plasmin INSIDE the Thrombus, where plasmin is protected from the inhibitory effects of circulating antiplasms
List 6 indications for Anticoagulant Therapy
1. MI
2. Rheumatic heart disease
3. Cerebrovascular disease
4. Venous thrombosis
5. Pulmonary embolism
6. DIC
What is the definition of Thrombolytic drugs?
lyse thrombi by catalyzing the formation of the serine protease Plasmin from its precursor Plasminogen
Describe the selectivity of tissue plasminogen activator (t-PA)
preferentially converts fibrin-bound plasminogen over free plasminogen = more likely to select for plasminogen in a clot
t-PA is more efficacious than streptokinase or anistreplase for thrombolytic therapy in __1__, but carries a higher risk of __2__
1. MI

2. Hemorrhage stroke
What are the 2 disadvantages of t-PA compared to Streptokinase or Urokinase?
1. more expensive
2. higher risk of hemorrhagic stroke
-__1__ protein produced by __2__
-facilitates thrombolysis through the formation of __3__
1. Nonenzymatic
2. group C beta-hemolytic streptococci
3. activator complex with plasminogen
What 4 things does Plasmin degrade?
Factor 5
Factor 8
What 2 drug combo may be as effective as t-PA?

What adverse effect of Streptokinase may occur?

**protein from Group C Strep
What is Antistreplase?
Acylated form of Plasminogen-Streptokinase-Activated Complex (APSAC)

*increases the duration of action relative to Streptokinase alone
-Parenteral thrombolytic agent derived from human cultured KIDNEY CELLS
-Hypersensitivity reactions OCCUR LESS FREQUENTLY than with Streptokinase
What uses is Urokinase indicated for?
Lysis of Pulmonary emboli

Lysis of coronary artery thrombi associated with evolving transmural MI
List the 3 recombinant Thrombolytic agents
1. Alteplase
2. Reteplase
3. Tenecteplase
List 2 properties of Alteplase
1. considerably more expensive than streptokinase
2. not associated with Hypersensitivity reactions
List a property of Reteplase
Longer half-life than Alteplase

**Re-Re-Re = keep re-doing things takes longer = longer half-life
Compared to Alteplase:
-prolonged half-life
-increased specificity for fibrin
-resistance to plasminogen activator inhibitor-1
Thrombolytic therapy should be followed with anticoagulant therapy with __1__ and then __2__
1. Heparin

2. Warfarin
For Myocardial Infarction, this may be used as an adjuvant therapy in combination with Thrombolytic agents
Aspirin due to its anti-platelet effect
List 7 Contraindications for Thrombolytic Therapy
1. Surgery within 10 days
2. Serious GI bleeding within 3 months
3. History of HTN (diastolic pressure > 110 mm Hg)
4. Active bleeding or hemorrhagic disorder
5. previous Cerebrovascular accident or active intracranial process
6. Aortic dissection
7. Acute pericarditis
Vitamin K:
-Is a __1__ soluble vitamin found in __2__
-also produced by bacteria colonizing the human intestine; need __3__ for absorption
1. fat
2. leafy green vegetables
3. bile salts
What process is Vitamin K required for?
gamma-carboxylation of glutamate residues in Prothrombin and Factors 7, 9, and 10
List 4 drugs used to treat Bleeding Disorders
1. Vitamin K
2. Plasma Fractions/Clotting Factors
3. Antihemophilic Factor
4. Aminocaproic acid
What discourages the use of plasma fractions in the treatment of patients with Hemophilia?
AIDS and Viral Hepatitis
What is Aminocaproic Acid's mechanism of action?
It binds to Plasminogen and inhibits its binding to Fibrin, preventing conversion to Plasmin
Antihemophilic Factor is commercially prepared using genetically altered mammalian cells to secrete _______
Factor 8
Aminocaproic Acid is used to treat these 3 things
1. Systemic or urinary hyperfibrinolysis (aplastic anemia, abruptio placentae, hepatic cirrhosis)
2. Bleeding associated with neoplastic diseases (carcinoma of the prostate, lung, stomach, or cervix)
3. Bleeding following cardiac surgery
In what 2 ways can anemia arise?
1. from failure to make sufficient RBC's
2. failure to synthesize adequate quantities of Hemoglobin
What are 5 symptoms of Anemia?
1. Paleness
2. Fatigue
3. Shortness of breath
4. exercise intolerance
5. increased heart rate
Anemia due to a decrease in the amount of Hemoglobin per RBC
Microcytic, hypochromic anemia
Anemia due to a decrease in the number of circulating RBC's
Megaloblastic, Hyperchromic anemia
Anemia due to a decrease in hemopoietic growth factors, especially Erythropoietin
Normocytic anemia or mixed
Microcytic Hypochromic Anemia:
__1__ deficiency -> impaired __2__ synthesis -> __3__ red cells with insufficient __4__ -> Microcytic Hypochromic Anemia
1. Iron
2. Hemoblobin
3. small
4. hemoglobin
What is Megaloblastic Anemia due to a deficiency of?

What does that cause an impaired synthesis of?
Vitamin B12 or Folate

What are the 3 physiological functions of Iron?
1. Required for Hemoglobin synthesis
2. Co-factor in such enzymes as Cytochromes
3. Required for Myoglobin synthesis
Where is Iron absorbed?
Duodenum and Proximal Jejunum
Iron Absorption:
-involves active transport of __1__, which is oxidized to __2__ in the intestinal mucosa
-Ferric iron can be stored as __3__ in the intestinal mucosa, or it can be transported by __4__ to other sites
1. ferrous iron
2. ferric iron
3. ferritin
4. transferrin
What percent of dietary elemental iron is absorbed?
Heme-iron from meat can be absorbed with iron in the _______ state
What increases iron absorption and the rate of erythopoiesis?
Low iron stores = low ferritin in the intestinal mucosa
What 5 things decrease iron absorption?
1. food
2. metal chelators
3. antacids
4. Fluoroquinolones
5. Tetracycline
What 2 things increase the absorption of Iron?
1. Hydrochloric acid

2. large amounts of ascorbic acid (Vitamin C = OJ)
Iron Distribution:
-__1__ is a specific ferric iron transport protein
-Erythroid cells have __2__, thus, iron is actively transported into hemoglobin-synthesizing cells in the bone marrow
-__3__ converts ferrous iron into the ferric state, and this copper-containing, plasma protein appears to be important for cellular uptake of iron
1. Transferrin
2. Transferrin receptors
3. Ceruloplasmin
Iron Distribution:
-10-20% total iron store in __1__
-70% in __2__
-10% in __3__
-1% in __4__
1. ferritin and hemosiderin, which are stored in macrophages in the liver, spleen and bone marrow
2. hemoglobin (RBCs)
3. myoglobin (muscle)
4. cytochromes and transferrin
What is iron balance regulated by?
Intestinal absorption

*there is no specific mechanism for excreting iron
About 1 mg of iron is lost daily by such processes as __1__ of mucosal cells, which contain __2__
1. exfoliation
2. ferritin
What are 4 possible causes of Iron Deficiency?
1. Inadequate intake: rare in US
2. Malabsorption
3. Increased requirements: growth, pregnancy, menstruation
4. Blood loss: bleeding, CA
What are 3 indicators of Iron Deficiency?
1. Serum ferritin decreases (<10 ųg/L)
2. Serum iron decreases (<40 ųg/dL)
3. Total iron-binding capacity of transferrin increases (>400 ųg/dL) = due to decreased saturation
What are the DOC's for Iron deficiency anemia?
Ferrous Salts (ORAL)
-ferrous sulfate
-ferrous gluconate
-ferrous fumarate
Iron deficiency anemia:
-treatment results in a rapid increase in __1__, and a measurable response to iron therapy should be detectable within __2__
-normal hemoglobin levels should be reachedd in __3__
-treatment should last 3-6 months or longer if the dose of iron was decreased due to __4__
1. reticulocytosis
2. 1 week
3. 1-3 months
4. intolerance
Normal hemoglobin levels for:
1. men

2. women
1. 14-18 g/dL

2. 12-16 g/dL
What is the Parenteral form of treatment for Iron deficiency anemia?
Iron Dextran
When should Iron Dextran be used?
1. patients with Gastric or Small Bowel resections

2. patients with Inflammatory Bowel Disease involving the proximal small intestine
What is the antidote for Acute Toxicity from Oral Iron?
Deferoxamine = iron-chelating drug

What are some symptoms of Acute toxicity from Oral Iron?
1. GI irritation
2. GI necrosis
3. nausea
4. cyanosis
5. Hematemesis
6. Green and tarry stools
7. CV collapse
8. Metabolic acidosis

GI = irritation, necrosis, nausea, hematemesis, green stools (5)
Others = Cyanosis, CV collapse, Metabolic acidosis
What are some symptoms of Acute Toxicity from Iron Dextran?
1. Headache
2. Light headedness
3. Fever
4. Arthralgia
5. N/V
6. Back pain
7. Flushing
8. Urticaria
9. Bronchospasm
10. Anaphylaxis -> can cause death (very rare)
What should be done before administering Iron Dextran?
give small doses to check for signs of immediate hypersensitivity
This is an inherited disorder where there is excessive iron absorption
Hemochromatosis = iron overload
What can Hemosiderosis be the result of?
numerous blood transfusions
Iron overload may also occur in the presence of anemia other than that caused by iron deficiency, such as the anemia of __1__ or __2__
1. chronic disease

2. hemolytic anemia
Excess iron is deposited in these organs
1. heart
2. liver
3. pancreas
In the absence of anemia, Iron overload is treat by _______

*one unit of blood removed 250-mg of iron
What would a loss of Hemosiderin granules in Bone Marrow indicate?
Iron deficiency