Pharmacology: Anticoagulants, Chemotherapyantibiotics Flashcards
Ancrod is a defibrinogenating agent derived from venom. What is it not recommended for use?
Associated with severe bleeding
Antifungal are targeted to fungal cell wall. Name some. What can these cause?
Amphotericin B, flucytosine, fluconozole, itraconazole, metronidazole, voriconazole; can case nephrotoxicity
Bacterial cell wall inhibitors are used to treat gram negative bugs.
- Vancomycin
- Monolactum
- Cabapenam
- Penicillins, cephalosporins, bacitracin
Can you give Heparin for Type I or Type II?
onCPB for Type 1
For type 2, only if they haven’t received heparin in the last 90 days
Can you give platelets for Type II?
No
DNA inhibitors block DNA gyrase and DNA synthesis. Name some
Quinolones, fluroquinolones, metronidazole
DO NOT USE _______ with a topical irrigation of antibiotics, collagen implants, etc…
Cell saver
The dose of DTI is adjusted by achieving a _______ of ______
- PTT; 60-80 secds or
2. a PTT of 1.5-2.5x the pts baseline aPTT
Fibrinolytics and thrombolytics are used to treat what?
Acute MI or PE
Fibrinolytics and thrombolytics convert ______ to ______, enhancing fibrolyisis
Plasminogen, plasmin
Give some examples of Glycoproteins IIb/IIIa? When should you stop use B4SX?
- Abciximab (Reopro): 72 hours
- Eptifibatide (Integrillin): 24 hours
- Tirofiban (Aggrastat): 24 Hour
Give some examples of gram negative bacteria
S. aureus (skin), S. epidermis (surgery wounds, indwelling catheters), Group A beta hemolytic streptococus (strep throat, rheumatic fever)
Glucagon ______ glucose levels and insulin _____ glucose level. (increase or decrease)
Increases, decreases
Glycoproteins ______ the fibrinogen/ GB IIb/IIIa receptor
antagonizes
Glycoproteins IIb/IIIa inhibitors are used to prevent platelet _____ and ______ formation?
Aggregation, thrombus
These Hirudins have the highest affinity for _____ and work by inhibiting ______ of protein C.
Thrombin, thrombin activation
How common is HIT?
3% of Sx
How does Glucagon help Tx hypoglycemia?
- It promotes glycogenolysis & glyconeogenesis
2. Also can be used in heart failure due to excessive beta blockage
How does Protamine reverse Heparin?
It neutralizes it by combing to heparin to form an inert salt
How does warfarin work?
An anticoagulant; it’s a vitamin K antagonic that causes reduction of synthesis of factors: 2, 7, 9, 10
How fast should you give protamine?
1mg/kg or 20 mg per 60 second period
How is Argatroban eliminated?
hepatic
How many days should a patient stop using Clopidogrel (plavix) before surgery? Tricildopine?
- 7 days
2. 4 days
How much will 1 unit of insulin decrease glucose by?
25-30mg/dL
How soon should you stop Heparin before surgery?
6 hours
How would you reverse DTIs?
Wait for the half life, then ultrafiltrate (45-69% amt removed vai UF)
Give recombinant FVIIa
How would you treat Heparin resistance?
- FFP= 2-4 units in adults
2. ATIII conc = 1000U dose will increase ATIII levels 30 % in adults: this is = to 4-5 units of FFP
How would you treat Warfarin use or Vitamin K deficiency?
Give FFP (15ml/kg) to treat INR>1
Is Amicar (EACA) or Cyclokapron (TXA) a more potent antifibrinolytic?
Cyclokaptron by 10x
Is LMWH used in Cardiac Sx?
No, it is poorly neutralized and has an incomplete reversal with protamine
Is the half life for LMWH longer or shorter than regular heparin?
longer 4-5 hours
Name the 3 most common antifibrinolytics
- Amicar
- Txa
- DDAVP
NPH and regular insulin, which one is short acting?
Regular insulin
On a TEG what does alpha measure?
the speed to reach a solid clot; it is decreased by thrombocytopenia
Platelet activation is caused by what?
Thromboxane A2 and ADP activation of platelets causes PLT activation. becomes “sticky”
Protein synthesis inhibitors bind to ribosomal 30/50 subunit inhibiting normal translation of bacterial proteins. Name some.
- tetracycline, doxycycline
- aminoglycosides, gentamycin, streptomycin
- macrolides- erythromycin, azithromycin
- lincosamides- clindamycin
What 2 drugs can cause cardiac toxicity?
Cyclophosphamide & Doxorubicin
What are antifibrinolytics used for?
Enhance postoperative hemostasis by binding to plasmin and plasminogen preventing degradation of fibrin to FSP
What are DTI? What do they do?
- Direct thrombin inhibitors
2. bind to the active site of thrombin for the use of pts with HIT
What are Hirudins?
Hirudin is a compound made by medicinal leeches that interferes with the body’s ability to form blood clots. Such anticoagulation invovles the inhibition of the protein thrombin, which catalyzes blood clot formation
What are some antibiotic protein synthesis inhibitors?
Tetracycline, doxycycline, clindamycine -> things that end in (-cyclin)
What are some antibiotic DNA inhibitors?
Qunolones, fluroquinolones, metronidiazole
What are some fibrinolytics and thrombolytics?
- streptokinase
- urokinase
- tPA
What are the acquired ATIII deficiency?
- decreased synthesis from liver cirrhosis
- drug induced
- increased excretion
- accelereated consumption
- dilutional
What are the drugs to give for antifungal?
Amphotericin B, flucytocin, fluconozole, itraconazole, metronidazole, voriconzole
What are the extrinsic pathway factors?
7, 3
What are the factors in the common pathway?
1, 2, 5, 10
What are the inherited ATIII deficiency?
- 1 in every 2000 to 20000 people, autosomal dominant
2. levels are
What are the intrinsic pathway factors?
12, 11, 9, 8
What are the various factors involves in the clotting cascade?
I- Fibrinogen II. Prothrombin III. Tissue factor (Thromboplastin) IV. Calcium V. proaccelerlin (Labile) VII. Proconvertin (stable) VIII. ANF (antihemophilic) IX. Christmas Factor (plasma thromboplastin component) X. Stuart-Prower XI. Plasma Thromboplastin XII. Hageman Factor XIII. Fibrin Stabilizing Factor
What are the various Hirudins
- Desirudin/Lepirudin
- Bivalrudin (angiomax)
- Argatroban
What are the Vitamin K dependent factors?
2, 5, 7, 9, 10
What can you give to help Tx hypoglycemia?
Glucagon
What can you reverse the effects of ASA with?
You can’t!! Effects stay with through the lift of the platelet
What common pathogens are we concerned with the most? Why?
- Gram negative (S. aureus/skin)
S. epidermis (surg. wounds, indwelling catheters) Group A beta hemolytic stretpcoccus (strep throat, rheumatic fever) - Gram positive: E. Coli (GI), Shigella, Salmonella, Klebsiella, H. influenza, Neisseri, Pseudomonas, Nosocomial infections
What do NSAIDS inhibit? For how long?
- Inhibit tXA2 (THromboxane A2)
2. for 24-48 hours
What does ASA ihibit? For how long? Used to treat what?
- Blocks Cox-1 and Cox-2 enzyme activity which inhibits TXA2 synthesis and ADP release by platelets
- 9-12 days (life of platelet)
- Used to treat stroke, acute MI
What does Clopidogrel (Placix) and Ticlidopine do to platelets?
Cause inhibition of ADP released by platelets
What does DDAVP increase?
The release of factor VIIIC and vWF THUS increasing platelet adhesiveness
What does dexamathasone do?
PRevents SIRS and cerebral edema; preserves lung f(x) during CPB, controls rejection post transplant
What does Dipyridomole (persantine) inhibit? When should patient stop taking drug before surgery?
- Inhibit Adenosine
2. 24 hours
What does Heparin bind to?
ATIII
What does insulin do?
Promotes glucose and K+ entry into cells
What does NPH do?
Protamine helps delay insulin absorption and prolongs its effects
What does solu-cortef do?
Inhibit cytokine production
What does solu-medrol do?
Inhibit leukocyte chemotaxis; increases the stress response in kidneys
What does the MA measure on a TEG?
platelet function; the clot strength, the dynamic properties of fibrin and platelet bonding
What drug blocks platelet activation by ADP?
- Clopidogel (plavix); Ticlidopine
- NSAIDs (ASA, ibuprofen, naproxen)
- ASA
What factors are affected by the PT?
Factor 7 (extrinsic) and common factors (1, 2, 5, 10)
What is an infection w/ mix of gram - and gram + pathogens that’s usually encased in an abscess wall? Give some examples?
- Anaerobe
- Bacteriodes fagalis
- Dificile C. Botulinum C Tetani
What is considered to be physiological heparin concentration that we all aim for?
3-4 units/ mL per blood circulating volume
What is considered to be triple therapy for heart transplant patients?
Cyclosprine, Azathioprine, Corticosteroids
What is heparin resistance?
The inability to achieve ACT >400 sec despite heparin doses >600 u/kg
What is highly absorbable in plastic?
Insulin; this is why we don’t give this on pump
What is HIT Type I?
Mild degree of thrombocytopenia resulting from heparin therapy; onset is 2-5 days
What is HIT Type II?
IgG-mediated antibodies recognize platelet factor 4 heparin complexes on platelets surface; causes activation of platelets, monocytes
Rirsk for DIC
Antibodies level drop w/n 4-8 weeks onset is 5-10
What is hypoglycemia associated with?
Increased morbidity
Why is LY30?
Meausres the % of lysis 30 mins after the MA is reached
What is PT and the normal value for it?
Prothrombin Time; 9-15 secs
What is PTT?
Partial Thromboplastin time; 22-36 secds
What is so different about LMWH?
It is poorly neutralized and has an incomplete reversal with Protamine
What is the Gold Standard for HITT assays?
Heparin Induced serotonin release assay
What is the intermediate acting Corticosteroids?
Solu-medrol
What is the long acting Corticosteroids?
Dexamethasone
What is the major elimination method of Bivalrudin?
80% proteolysis, renal 20%; half life 25 min
What is the NaCHO3 formula?
- (BE x wt (kg))/ 4
2. Give half of the calculated dose
What is the ratio of Heparin to protamine?
1: 1.3 for every 100 u heparin
What is the short acting Corticosteroids?
Solu-cortef
What is Warfarin?
Coumadin (warfarin sodium) is an anticoagulant that acts by inhibiting vitamin K- dependent coagulation factors
What other drug is Dipyridamole administered along with? Persantine is used to treat what? In what kind of patients?
- Warfarin
- PVD
- pts with stents or prosthetic valves
What pathogen stain weakly gram + and are responsible for TB and leprosy? What would you treat it with?
- Mycobacteria
2. Isoniazid rifampin, streptomycin
What pathways are reflected by ACT (activated clotting time)? What drugs affects ACT?
- Intrinsic and common
2. Heparin therapy, DTI
What pathway does Heparin affect?
The instrinsic and common; affects factors 9, 10, 11, 12 and plasmin
What pathways does Warfarin affect?
Extrinsic and common
What tests would indicate Warfarin use or Vitamin K deficiences?
- prolonged PT or INR goal 2-3
- Normal to mildly prolonged PTT
- Bleeding time and platelet count is unaffected
What type of affinity binding quality does Bivalrudin (Angiomax) have for thrombin?
Intermediate
What type of drugs are cell wall inhibitors?
Vancomycin, monolactum, cebapenam, penicillins, cephalosporins, bacitracin
What type of pathogen are sensitive bacterial cell wall inhibitors?
Gram (-) bacteria
What will happen if you give Protamine too fact?
Histamine release causing systemic Hypotension
What would you give to help tx hyperglycemia?
NPH and regular insulin
What yeast-form produces spores/budding? Sites and treatment?
- Fungus (Candida)
- Mouth (thrush) = nystatin
- Brain = fluconazole, flucytosine
- Vaginitis = miconazole, metronidazole
- Systemic = amphotericn B, fluconazole, itraconazole
What is it most beneficial to give antifibrinolytics?
Before CPB and maintained throughout
When might patients be on cyclophosphamide and Doxorubicin drugs?
If they are getting limb perfusion
When should you stop argatroban?
4-6 hours before surgery
When should you stop Bivalrudin (angiomax)?
2-3 hours before Sx
When should you stop LMWH?
12-24 hours before Sx
When should you stop Warfarin?
2-4 days before Sx
When would you stop Hirudins (desirudin/lepirudin)?
8 hours before Surgery
Which Hirudins has the lowest affinity for thrombin? Should you use it on CPB?
Argatroban; NO (not currently approved yet)
Who would have a Heparin allergy?
DM patients that take NPH have fish allergies, have been previously exposed to Heparin or those who have had a vasectomy
Why are topical irrigation beneficial?
- High sustained cone, at site of infections
- Limited potential for systemic absorption & toxicity
- Reduced volumes of antibodies use
- Less potential for development of antibiotic resistance
Why cant you give Hirudins to renal failure patients?
Because it is eliminated by renals
Why is Cyclokaptron more potent?
Because it has a greater affinity to plasminogen than EACA
Why is hyperglycemia bad?
Because it can contribute to neuro dysfunction and impair wound healing
