Drugs Acting on the Blood Flashcards
(88 cards)
1
Q
What are the 4 different categories of drugs acting on the blood?
A
- Antianemic drugs
- Colony stimulating factors
- Drugs affecting hemostasis
- Treatment of thromboembolism in cats
2
Q
Drugs affecting hemostasis can be broken up into drugs that affect __________ or __________.
A
Bleeding/hemorrhage or thrombosis/anti-thrombotic drugs.
3
Q
What are the 2 major categories of anemia?
A
Hypoproliferative and Hyperproliferative.
4
Q
What are the major type(s) of hypoproliferative anemia?
A
- Microcytic
- Normocytic
- Macrocytic
5
Q
What are the major type(s) of hyperproliferative anemia?
A
Hemolytic
6
Q
What are some causes of microcytic anemia?
A
- Iron or Copper deficiency
- Anemia of a chronic disease
- Sideroblastic anemia
7
Q
What are some causes of normocytic anemia?
A
- Anemia of chronic disease
- Endocrine anemia
- Bone marrow failure
8
Q
What are some causes of macrocytic anemia?
A
- Vitamin B12 deficiency
- Folic acid deficiency
- Myelodysplastic syndrome
9
Q
What are some causes of hemolytic anemia?
A
- Hemoglobinopathies
- Autoimmune
- Membrane disorder
- Drug-induced
- Metabolic abnormalities
- Glucose-6-phosphate
- Dehydrogenase deficiency
- Infections
10
Q
What is another name for microcytic anemia?
A
Hypochromic anemia
11
Q
If you have microcytic anemia that is being caused by an iron deficiency, what would you use to treat it with?
A
Iron preparations: either parenteral or oral.
12
Q
Why does iron deficiency cause anemia?
A
Because iron is a compoenent of the pigment called heme that is a component of hemoglobin which is a component of RBC’s.
13
Q
If a pet has microcytic anemia due to copper deficency what can be done to treat it?
A
Copper preparations: parenteral or oral.
14
Q
Why does copper deficiency cause anemia?
A
Copper is important for absorption and metabolism of iron. If Iron is not being absorbed, then as stated earlier you will have anemia because it is part of heme and heme is part of hemoglobin and hemoglobin is part of RBC’s. Also, copper is a part of cytochrome C oxidase.
15
Q
What 2 species are normally affected by microcytic anemia?
A
Dogs (usually due to dietary copper or iron deficiency)
and
Pigs (they are born iron deficient and normally will acquire by ingesting soil.)
16
Q
Parenteral iron preparations are normally mixed with what?
What is the significance of this?
A
Carbohydrate complexes: these are large molecules that are antigenic and cause histamine release and hypersensitivity; this is one of the major adverse effects.
ex: Iron Dextran
17
Q
What is the best parenteral route to give iron?
A
Not IV due to hypersensitivity!!!
IM or SQ are preferred although it can cause pain on injection and a yellowish brown discoloration at the site of injection.
18
Q
Heavy metals like Iron can be _______ or _______.
A
Organic (carbon and hydrogen) or Inorganic (where the valency is important: *oxidative state.*)
19
Q
Heavy metals are astringents meaning what?
A
They can precipitate proteins which can cause constipation.
20
Q
Some major side effecs of both the parenteral and oral iron preparations are what?
A
Vomiting, diarrhea, corosion of the GI tract, ulcers, bloody stools.
21
Q
Specific antidotes for iron toxicity are what?
A
Chelating agents: these are drugs that when absorbed systemically, bind to the metal to form a complex or “chelate” which is a less toxic or non-toxic form and is water soluble and readily secreted in urine.
22
Q
T/F: When giving an oral iron preparation is better to use an inorganic form.
A
False, it is better to use organic.
23
Q
In a microcytic anemia emergency due to iron deficiency you would give what?
A
Parenteral iron preparation: quicker acting.
24
Q
In a microcytic anemia stable patient with iron deficiency, you would use what?
A
Oral iron preparation.
25
Because most animals don't have a way of eliminating iron from the body, care must be taken why?
Can easily cause adverse effects or overdose.
26
What is needed for iron to be transported throughout the body?
Carrier protein
27
What is another name for *macrocytic anemia*?
**Megaloblastic** anemia
28
Macrocytic anemia is generally associated with what?
Normally seen in ruminants (cattle) with cobalt deficiency. Cobalt deficiency leads to Vitamin B12 deficiency.
Signs of cobalt deficiency include weight loss, muscle wasting, depraved appetite, anemia and eventually death.
29
Anemia due to CRF (chronic renal failure) causes what?
A decreased output of erythropoieten and therefore a decrease in the # of RBCs produced.
30
What can cause bone marrow suppression?
Chemotherapy (not limited to anti-cancer drugs) can also include, anti-bacterials, anti-virals, anti-fungals etc. etc....
The bone marrow is normally where erythropoeisis takes place.
31
How would you treat anemia where there is a decreased prodution of erythropoieten?
What is a major side effect of the drug used to treat this type of anemia?
EPO/Epogen: this is synthetic erythropoieten given parenterally.
Side effects: vasoconstriction and hypertension.
32
With IMHA (Immune Mediate Hemolytic Anemia) which is a type of hyperproliferative anemia, what would the treatment be for that?
1. Supportive treatment: Fluid therapy, Acid-base balance, and organ perfusion.
2. Blood transfusion (in emergency situation)
33
What are some examples of immunosuppressents that are used to treat a hyperactive immune system causing hemolytic anemia?
1. Glucocorticoids (Prednisone, Prednisolone)
2. Cytotoxic drugs (Azathioprine~injectable, Cyclophosphamide)
3. Danazol
4. Cyclosporin A (capsules)
5. IV γ globulin
34
What are colony stimulating factors?
Aka **growth factors.**
## Footnote
*Used to treat and prevent neutropenia due to anti-cancer drugs.*
35
What are the 2 types of colony stimulating factors?
**G-CSF** (*Granulocyte colony stimulating factor*)
and
**GM-CSF** (*Granulocyte-macrophage colony stimulating factor*)
36
What is an example of Granulocyte Colony Stimulating Factor?
**Filgrastim**
*Lineage specific*
37
What is an example of Granulocyte-Macrophage Colony Stimulating Factor drug?
**Sargramostim aka Leukine**
*Non-lineage specific*
38
What is the mechanism of action of colony stimulating factor drugs?
*At therapeutic doses **Filgrastim*** *stimulates the progenitor of neutrophils only causing maturation, differentation, and proliferation.*
***Sargramostim*** *stimulates the growth and development of neutrophils, eosinophils, basophils, erythrocytes and macrophages.*
39
What are some adverse effects of colony stimulating factors?
1. Bone pain
2. Sargramostim can cause fever and cardiopulmonary toxicity.
40
What are the 2 categories of drugs that affect hemostasis?
1. Hemostatics (promotes hemostasis/stops bleeding.)
2. Antithrombotic drugs (reduces the formation of blood clots/thrombi.)
41
What are the stages of hemostasis starting with vascular injury?
1. Contraction of the injured vessel (vasoconstriction).
2. Primary hemostasis (formation of a platelet plug).
3. Secondary hemostasis (protein plug) due to the _coagulation cascade_.
4. Lastly you have fibrinolysis (Prevents blood clots that occur naturally from growing and causing problems. Normal breakdown of clots.)
42
Within a thrombus, platelets are bound together by what?
Fibrin
43
What can be found on the surface of platelets?
Fibrinogen receptors (GP IIb/IIIa)
## Footnote
*When fibrinogen binds to these receptors, aggregation begins to take place.*
44
What is secondary hemostasis?
**The coagulation cascade.**
* You have the _extrinsic and intrisic pathways_ occuring indepedently of one another.*
* A _prothrombinase complex_ converts _Prothrombin II_ (**Factor II**) into _Thrombin IIa._*
* Thrombin then gets converted to _soluble fibrin_ (a soft clot) via _fibrinogen._*
*_XIII_ gets converted to _XIIIa_ via Thrombin.*
*XIIIa then converts soluble fibrin (a soft clot) into a _cross-linked fibrin_ (hard clot).*
45
What is fibrinolysis?
**The normal breakdown of clots.**
* Plasminogen gets converted to plasmin via activators.*
* Cross-linked fibrin (hard clot) gets chopped by plasmin into fibrin degradation products.*
* Fibrinogen factors V and VIII then get cleaved by plasmin.*
46
What are hemostatics and what are the 2 categories of hemostatics?
**Drugs that treat bleeding or hemorrhage.**
1. Local hemostatics (**styptics**)
2. Systemic hemostatics~ this can lead to hemorrhagic shock.
47
What are 4 different types of hemostatics (styptics)?
1. Vasoconstrictors
2. Astringents
3. Surgical
4. Physiological
48
What is a vasoconstrictive local hemostatic?
Epinephrine
49
What is an astringent local hemostatic?
1. Tannic acid
* Tea and coffee are rich in tannic acid and this has a hemostatic effect so it can be used for local hemorrhage.*
2. Ferric chloride
* Ferric is better topically and ferrous is better systemically.*
50
What is a surgical local hemostatic?
1. Oxidized cellulose
2. Gelatin sponge
3. Collagen
51
What is a physiological local hemostatic?
1. Thromboplastin
2. Thrombin
3. Fibrinogen
4. Fibrin foam
***For physiological styptics only use them topically, never give them systemically if you do it can cause a thrombus and this is contraindicated.***
52
This bottle of Clot-It Plus says it contains Styptic Powder and Benzocaine, because you're a Pharmacology II student you immediately know that a styptic powder is what? What is Benzocaine and is it an esther or an amide (what is an easy way to tell the difference?)
Styptic powder= local hemostatic
Benzocaine= local anesthetic, and it's an esther.
* The easy way to tell the difference is that all amides have an "i" in it before the suffix -caine. Examples include L**i**docaine and Bup**i**v**i**caine.*
* Esthers would include Benzocaine, Proparacaine, and Prorocaine.*
53
What are some systemic hemostatic drugs?
1. Clotting factor: blood transfusion-although this can be used to control any sort of bleeding or fresh frozen plasma (FFP).
2. Vitamin K
3. Protamine sulfate
4. Aminocaproic acid
5. Desmopressin (DDAVP)
54
Vitamin K is specifically used to treat _________ poisoning.
**Warfarin**
55
Protamine sulfate is specifically used to treat ________ poisoning.
**Heparin**
56
Aminocaproic acid is specifically used to treat _______ \_\_\_\_\_\_\_\_ poisoning.
**Thrombolytic agents**
57
Desmopressin is specifically used to treat _____ \_\_\_\_\_\_\_ Disease.
**Von Willebrand's**
* It is a synthetic analog of ADH.*
* It is also used in the central treatment of Diabetes insipidus.*
58
What are the 3 types of Vitamin K?
**Vitamin K1** (*phytonadione*)
**Vitamin K2** (*menaquinone*)
**Vitamin K3** (*menadione*)
59
**Vitamin K1** has what origin?
Plant origin
60
**Vitamin K2** is formed how?
Bacteria in the GI tract.
61
How is **Vitamin K3** formed?
Which species would you _not_ want to use this in?
It is synthetic. (this is a very weak Vitamin K)
## Footnote
**Do not use in horses!!!**
62
Vitamin K is highly _____ soluble.
Lipid
63
Vitamin K is available _______ or \_\_\_\_\_\_\_\_.
**Orally** or **parenterally.**
64
What is the mechanism of action of Vitamin K?
* There are precursor proteins in the blood (PIVKA proteins) for II, VII, IX and X.*
* They need to be activated to the active II, VII, IX and X. [coagulation factors].*
* This activation occurs by adding carboxyl groups.*
* The enzyme that does this is called carboxylase.*
* For this enzyme to work there needs to be a co-factor (active or reduced form of Vitamin K1).*
65
What is the potential side effect of giving Vitamin K IV?
You can get hypersensitivity reactions.
It is better to use IM or SC routes.
66
What is the mechanism of action of Warfarin?
After you use active Vitamin K1 as a cofactor to get coagulation factors it becomes inactive Vitain K1. You need an enzyme called reductase for it to go back to active Vitamin K1. **Warfarin blocks reductase. *Therefore no carboxylation can take pace.***
67
T/F: The mechanism of action of Warfarin is very quick.
**False**, *very slow b/c the animal has existing clotting factors that must be depleted before you start seeing hemorrhage. Onset is about 2 days!!!*
68
T/F: The onset of Vitamin K is very slow.
**True,** *slow onset. It can take up to 24 hours to stop the bleeding. It is slow b/c of it's mechanism. It must go and act as a cofactor to carboxylate the precursor.*
69
What are the clinical uses of Vitamin K?
1. Used as an antidote for Warfarin poisoning
2. Treatment of spoiled sweet yellow clover. (*Melilotus* spp.) occurs frequently in cattle.
3. Treatment of Vitamin K deficiency which is rare. (Vitamin K is typically abundant in the diet and is found in most foods. The problem would lie with whether you have a problem with absorption or metabolism of Vitamin K, like ulcerative colitits or liver disease/necrosis. You can try giving Vit. K but it may not work.)
4. You can combine it with local hemostatics for the treatment of epistaxis in dogs and horses. (Can use 1:100,000 Epinephrine in a syringe up the nose and shove a gauze up there and give a Vitamin K injection.)
70
Protamine sulfate is a strongly _____ drug that binds with acidic _______ to form a salt.
Strongly **basic** drug.
Binds with acidic **heparin.**
71
Protamine sulfate is given slowly \_\_\_\_\_.
**IV** (intravenously)
72
Protamine sulfate overdoses should be avoided b/c why?
It has an anticoagulant effect.
## Footnote
*Causes bleeding/hemorrhage.*
73
What is the mechanism of action of **Aminocaproic acid**?
What is it used to treat?
Inhibits conversion of plasminogen to plasmin.
Used to treat hemorrhage due to hyperfirbrinolysis. (overdose of hemolytic agents).
74
**Aminocaproic acid** is used to treat _______ \_\_\_\_\_\_\_\_ in German shepherds (by antiprotease activity).
**Degenerative myelopathy**
75
What is the mechanism of action of Desmopressin (DDAVP)?
Increases VWF levels for about **2 hours** in dogs by causing release from endothelial cells and macrophages.
## Footnote
* Von Willebrand Disease (vWD) is the most common inherited bleeding disorder in dogs.*
* Most common in Doberman Pinschers.*
76
VWF (*Von Willebrand Factor)* is important for what?
Adherence of platelets to an injured vessel, and to platelet aggregation in addition to stabilizing factor VIII.
77
What are the clinical uses of Desmopressin (DDAVP)?
* Control bleeding in dogs with Von Willebrand's disease (vWD).*
* During surgery in dogs with von Willebrand's disease.*
* In blood donor dogs with von Willebrand's disease.*
78
What are the 3 categories of antithrombotic drugs?
1. Anticoagulants
2. Thrombolytic agents
3. Antiplatelet drugs
79
What are 2 anticoagulant drugs?
1. Heparin
2. Warfarin (Coumadin)
80
Heparin is a poorly ______ soluble drug; hence it has poor oral bioavailability and isn't really given any other parenteral route aside from IV.
Poorly **lipid** soluble
81
T/F: Heparin has a short onset of action and a short duration.
**True!!!**
82
What is the MOA (mechanism of action) of Heparin?
* Has an anticoagulant effect.*
* Activates antithrombin III then it activates it which inhibits thrombin (IIa) and _activates coagulation factors IX, X, XI and XII in the liver._*
83
Heparin is rapidly metabolized by the \_\_\_\_\_.
Liver
84
Heparin does not cross the ________ and is not excreted in \_\_\_\_\_\_\_.
Does not cross the **placenta** and is not excreted in **milk.**
## Footnote
*Therefore it is a suitable anticoagulant to use during pregnancy.*
85
What are the clinical uses of Heparin?
* Treatment of acute thromboembolism.*
* The anticoagulant of choice during pregnancy.*
* Also used as an anticoagulant in vitro.*
86
Heparin has a narrow ______ \_\_\_\_\_\_.
Safety margin
87
What is the main toxic side effects of Heparin?
Excessive bleeding.
Also may cause allergy (low molecular weight Heparins "LMWH"s are less antigenic).
88
Heparin toxicity is treated with what?
Protamine sulfate, blood transfusion or fresh frozen plasma.
