Shared Flashcard Set

Details

Heme Pharm
Cancer Drugs and Non-cancer drugs
149
Medical
Graduate
12/07/2008

Additional Medical Flashcards

 


 

Cards

Term
What Safety Measures Have Been Employed to Safe Guard Against Medications Errors with Cancer Drugs?
Definition
1) All chemotherapy orders must be signed by an attending oncologist; 2) No verbal orders are allowed with chemotherapy; 3) No trade names or abbreviations can be used on chemotherapy orders
Term
DNA Alkylating Agents
Definition
Cyclophosphamide (Cytoxan)
Term
Major Side Effects of DNA Alkylating Agents
Definition
Myelosuppression and hemorrhagic cystitis
Term
Examples of Platinum Compounds/ Agents
Definition
Cisplatin (Platinol), Carboplatin, Oxaliplatin
Term
Major Side Effect of Cisplatin
Definition
Nephrotoxicity
Term
Major Side Effect of Carboplatin
Definition
Myelosuppression
Term
Major Side Effect of Oxaliplatin
Definition
Greater risk of neuropathy than any of the 3 Platium Agents (the other two being Cisplatin and Carboplatin)
Term
Examples of Anthracyclines (Antitumor Antibiotics)
Definition
Doxorubicin (Adriamycin)
Term
Major Side Effects of Anthracyclines
Definition
Cardiac - cardiomyopathy, congestive heart failure; Myelosuppression
Term
Examples of Antimetabolites
Definition
Capecitabine, Fluorouracil (5FU), Gemcitabine
Term
Major Side Effects of Antimetabolites
Definition
Mucositis, diarrhea, hand-foot syndrome, and flu-like symptoms
Term
Example of Topoisomerase Inhibitors
Definition
Irinotecan
Term
Major Side Effects of Topoisomerase Inhibitors
Definition
Acute and chronic diarrhea
Term
Examples of Taxanes
Definition
Docetaxel, Paclitaxel (Taxol)
Term
Major Side Effects of Taxanes
Definition
Allergic hypersensitivity reactons, neurotoxicity and fluid retention
Term
Hormonal Therapy for Cancer
Definition
Tamoxifen; LHRH Agonists; Leuprolide (Lupron) and Goserelin - used in metastatic prostate cancer, suppresses FSH and LH secretion by the pituitary resulting in "chemical castration"
Term
Examples of "Targeted Therapy" Drugs
Definition
Trastuzumab (Herceptin), Cetuximab, Rituximab, Imatinib (Gleevec), Bevacizumab
Term
What are the limitations or problems with cancer chemotherapy "cell kill" kinetics?
Definition
100% cell Kill is not achievable with an individual drug, so the approach is to use combination chemo; You see disappearance of symptoms before all the cancer cells have been eradicated (it usually takes a lot of cancer cells to cause s/s). The kinetics of drug induced killing are first-order kinetics.
Term
What are the Consequences of "Drug Resistance" to Cancer Drugs?
Definition
If there is development of drug resistance, then that drug stops working and when the tumor reaches a certain size so that it can be redetected, disease progression is noted.
Term
What are some of the reasons why resistance to cancer drugs may occur?
Definition
Drug resistance occurs when there is increased expression of MDR Gene which codes for P170, a cell surface glycoprotein involved in drug efflux. There is also downregulation of activating enzymes and upregulation of catabolic enzymes. There can also be mutations of target receptors and enzymes as well as constitutive inhibition of apoptosis.
Term
What are the MAJOR toxicities of conventional chemotherapy?
Definition
a) Bone marrow suppression (because the cells here are rapidly dividing, and chemo targets rapidly dividing cells) - Neutropenia, Thrombocytopenia, Anemia; b) Digestive tract injury (again because the cells there are rapidly dividing); Nausea/ vomiting; c) Alopecia (because the hair follicles are active); d) Reproductive toxicity (especially a problem with the alkylators); e) Hyperuricemia; f) Local tissue injury via vesicants (if the chemo gets outside of the veins); g) Carcinogenesis; h) Unique toxicities; Dose-limiting toxicities
Term
What is the MOA of Cyclophosphamide (Cytoxan)?
Definition
It is an alkylating agent. Alkylating agents cause DNA damage – they cause covalent bonds to form between purines on opposite strands, which prevents replication because the bonds are so strong. The p53 gene senses DNA damage and initiates apoptosis in response, with the outcome being disruption of DNA synthesis and cell division.
Term
What are the SE of Cyclophosphamide (Cytoxan)?
Definition
Myelosuppression, hemorrhagic cystitis (because the metabolites are excreted in the urine), n/v, leukemogenesis, ovarian/ testicular failure, immune suppression, and drug-interactions (esp. warfarin).
Term
What is the MOA of Cisplatin (Platinol).
Definition
It is a platinum compound. Covalently binds to DNA, resulting in cross-linked strands that inhibit synthesis and transcription; Linking occurs within the same strand (instead of strand-to-strand like with the alkylating agents).
Term
What are the SE of Cisplatin (Platinol)?
Definition
Nephrotoxicity (because the drugs are metabolized and excreted by the kidney), neurotoxicity, very severe nausea/vomiting.
Term
What is the MOA of Doxorubicin (Adriamycin)?
Definition
It is an anthracyclin, anti-tumor antibiotic. It Intercalates into the DNA, inhibiting DNA synthesis. Inhibits topoisomerase II causing DNA strand breaks. Alters the cell membrane, affecting fluidity and ion transport. Results in free-radical formation (semiquinone and oxygen free-radicals).
Term
What are the SE of Doxorubicin (Adriamycin)?
Definition
Myelosuppression, dose-dependent CHF, Alopecia, Vesicant (if it gets outside the veins, it can cause tissue damage).
Term
What is the MOA of Fluorouracil (5FU)?
Definition
It is an antimetabolite. These cpds mimic the structure of folic acid, pyrimidines, or purines, interrupting DNA/ RNA synthesis and function. 5FU specifically inhibits thimidylate synthase via the metabolite FdUMP – the 5FU metabolite is incorporated into DNA/RNA.
Term
What are the SE of Fluorouracil (5FU)?
Definition
GI ulceration with continuous infusion, myelosuppression with a bolus, hand-foot syndrome (more with Capecitabine).
Term
What is the MOA of Paclitaxel (Taxol)?
Definition
It is a taxane. Acts on the mitotic spindle, inhibiting it. It binds to tubulin and prevents its depolymerization such that there is continued polymerization, resulting in highly stable, but dysfunctional microtubules. This upsets the dynamic equilibrium of the cell, leading to cell death.
Term
What are the SE of Paclitaxel (Taxol)?
Definition
Myelosuppression, Alopecia, Neurotoxicity, Hypersensitivity reaction, Fluid retention (more so with Docetaxel).
Term
What is the MOA of Irinotecan?
Definition
It is a topoisomerase inhibitor. Irinotecan is a prodrug, requiring activation to SN38; Topoisomerase I inhibition prevents religation of DNA after topoisomerase I cleavage, resulting in double-strand DNA breaks. Normally topo I nicks the DNA backbone to release the torsional strain of advancing replication fork and religates the nick. Irinotecan binds to the topoisomerase I-nicked DNA complex and prevents religation of the nicked strand and release of the enzyme.
Term
What are the SE of Irinotecan?
Definition
Diarrhea – can be severe/ life-threatening, Myelosuppression, Alopecia, Flulike symptoms, Rare renal and Cardiac effects, Somnolence, Confusion.
Term
What is the MOA of Tamoxifen?
Definition
It is a competitive inhibitor of the estrogen receptor, leading to defective signal transduction and transcription; stimulates secretion of TGF-beta. It stimulates the estrogen receptors in bone (good – decreases osteoporosis), breast (good – decreases breast cancer) and uterus (could be bad – causing uterine cancer).
Term
What are the IND/ Uses for Tamoxifen?
Definition
Breast cancer prevention, treatment of all stages of invasive breast cancer, treatment of in-situ breast cancer.
Term
What is the MOA of Goserelin and Leuprolide (Lupron)?
Definition
They are LHRH agonists. Suppression of FSH and LH secretion by the pituitary, resulting in “chemical castration.”
Term
What are the IND/ Uses for Goserelin and Leuprolide (Lupron)?
Definition
Metastatic prostate cancer, ovarian suppression in pre-menopausal women with high-risk breast cancer.
Term
What are the SE of Goserelin and Leuprolide (Lupron)?
Definition
Hot flashes (both sexes), decreased libido, impotence in men.
Term
What is the main Growth Signaling Pathway Inhibitor Discussed by Dr. Horner?
Definition
Imatinib (Gleevec)
Term
What is the MOA of Imatinib (Gleevec)?
Definition
It is a tyrosine-kinase inhibitor. Imatinib inhibits multiple intracellular tyrosine kinases: BCR/ABL, c-kit, and PDGFR.
Term
What are the IND/ Uses for Imatinib?
Definition
All phases of CML, and c-kit positive GI stromal tumor (GIST).
Term
What are the SE of Imatinib?
Definition
Fluid retention, mild myelosuppression, diarrhea.
Term
What is the major monoclonal antibody discussed by Dr. Horner?
Definition
Trastuzimab (Herceptin).
Term
What is the MOA of Trastizumab?
Definition
Trastuzimab is a humanized monoclonal antibody against extracellular domain of HER-2/neu growth factor receptor, with consequent interference with signal transduction and induction of apoptosis.
Term
What are the IND/ Uses for Trastizumab?
Definition
Advanced and early stage breast cancer; should be used with chemo in breast cancer (the two together are better than chemo or tastuzimab alone) – if the tumors are HER-2/neu positive.
Term
What are the SE of Trastizumab?
Definition
Cardiac toxicity (especially after antrhacycline therapy, left ventricular function – ejection fraction – should be evaluated); Infusion-related symptoms (fever, chills, etc. – because it’s a monoclonal antibody, the body sees it as a foreign substance and reacts accordingly).
Term
What is the Major Angiogenesis Inhibitor Discussed by Dr. Horner?
Definition
Bevacizumab (Avastin).
Term
What is the MOA of Bevacizumab?
Definition
recombinant monoclonal antibody against vascular endothelial growth factor (VEGF), inhibiting formation of new tumor blood supply. The exact mechanism of action is incompletely understood. Tumors secrete a protein called VEGF that docks with receptors on nearby blood vessels, stimulating the growth of new blood vessels. Bevacizumab binds with VEGF and prevents that protein from attaching to receptors. New blood vessels don’t form, and the tumor starves.
Term
What are the IND/ Uses of Bevacizumab?
Definition
Colon and breast cancer.
Term
What are the SE of Bevacizumab?
Definition
HTN, proteinuria, GI perforation at tumor sites, Hemorrhage of lung cancers, Wound healing complications, Infusion Symptoms.
Term
What is the Therapy of Choice to Prevent/ Minimize Post-Chemotherapy Nausea and Vomiting?
Definition
Ondansetron (Zofran) and Dexamethasone (Decadron).
Term
What is the MOA of Ondansetron?
Definition
Ondansetron (Zofran) works via competitive, selective antagonism of 5-HT3 receptors in the brain and vagal tissue.
Term
What is the IND/ Use of Ondansetron?
Definition
Prevention of radiation and chemotherapy induced n/v; used with dexamethasone (Decadron).
Term
What are the SE of Ondansetron?
Definition
Headache, occ bowel symptoms.
Term
What is the Special Role of Arepitant?
Definition
It is a new anti-emetic therapy.It’s MOA involves Substance P/ Neurokinin 1 Receptor Antagonist. It’s uses include enhancing the effectiveness of anti-serotonin anti-emetics and to treat delayed n/v associated with chemo and radiation. SE – fatigue, hiccups
Term
What is the MOA of Filgrastim?
Definition
Filgrastim stimulates proliferation/ differentiation of granulocyte precursors and enhances neutrophil function.
Term
What is the IND/ Use of Filgastrim?
Definition
Accelerates recovery of WBCs after chemotherapy (this allows a decrease in the recovery time between chemo infusions so that patients can get them more often/ stay on schedule). It is also used to mobilize stem cells in preparation for a bone marrow transplant.
Term
What is the SE of Filgrastim?
Definition
Bone Pain.
Term
Treatment for Iron Deficiency
Definition
Ferrous Sulfate
Term
Absorption of Iron (Ferrous Sulfate)
Definition
Maximal absorption in the fasting state (1hr before or 2 hours after a meal), If iron causes GI side effects pts can take it with or after meals, absorption will decrease by 40-50%, but side effects will decrease (helps improve compliance); Absorption is enhanced by the presence of orange juice, but relatively inhibited by tea and milk.
Term
Duration of Iron Therapy
Definition
Continue oral iron for 3-6 months after correcting anemia to ensure that total body stores are repleated and to avoid relapse
Term
Normal Response to Iron Therapy
Definition
Reticulocytosis - attain maximal level in 5-10 days; Hemoglobin normalizes over 4-8 weeks
Term
SE of Oral Iron (Ferrous Sulfate)
Definition
GI sxs: heartburn, nausesa, cramps, diarrhea, GI sxs occur in 12% of patients; Usually dose-related, Dose adjustments help; Warn the patients that their stools may (will) turn black
Term
Acute Iron Toxicity
Definition
Seen almost exclusively in kids (can be caused by as few as 10 pills); May cause necrotizing gastroentereitis, vomiting, abdominal pain and bloody diarrhea followed by shock, lethargy and dyspnea. May progress to metabolic acidosis, coma and death.
Term
Oral Folic Acid
Definition
Well absorbed (80%), even in those with malabsorption syndromes; 1mg/day in adults; Treat until underlying process resolves, may be indefinite Rx depending upon setting (ex: alcoholics); Preventive therapy in high risk patients (pregnant women, alcoholics, ongoing hemolytic anemias), a 0.4mg dose may be used; IV formulations are rarely used unless the patient is NPO
Term
Response to Oral Folic Acid Treatment
Definition
Rapid - see a rise in hemoglobin in 1 week; Anemia resolves by 1 month
Term
Side Effects of Oral Folate
Definition
Nothing significant, except in very rare allergic reactions
Term
Special Issue in Rx of Megaloblastic Anemia
Definition
Do NOT want to Rx a true vitamin B12 deficiency with folate alone. May see partial hematological response, but neurologically the patient will worsen if they're truly B12 deficient
Term
By What Route is Vitamin B12 (Cobalamin) Replacement Usually Given?
Definition
Parenterally (usu IM) since malabsorption is a common cause of B12 deficiency; The 2 IM preps available are: cyanocobalamin and hydroxycobalamin
Term
What is the Dosage Protocol for Replacing B12 Stores?
Definition
IM cyanocobalamin 100ug daily for 1 week, then every other day for 2 weeks or more (want to replace stores with 2000ug over first 4-6 weeks); Most of the dose is excreted in the urine; Can't give 1 large dose to replace stores; Low doses of 1ug/day will restore heme parameters; Continue frequent doses if CNS abnormalities are present.
Term
What is the Protocol for B12 Maintenance?
Definition
100ug/mL per month. Duration is often for life - eg in pernicious anemia
Term
Side Effects of Vitamin B12 (Cobalamin) Therapy
Definition
Rare; Hypersensitivity reactions
Term
When might Oral B12 Therapy Be Used?
Definition
Bleeding disorders, patient refuses IM prep; Use High dose (300-1000ug/day) since in pernicious anemia only 1% is absorbed; Need careful follow up if oral therapy is used
Term
Response to B12 Therapy
Definition
Reticulocytosis after 2-3 days with maximum response at days 5-8; Blood count normalizes in about 1 month or more; WBC hypersegmentation resolves in 14 days; Neurologic improvement varies (some improvement in most, if S/S less than 3 months it's more reversible, may need to wait 6 months for maximal response)
Term
IND for the Clinical Use of Erythropoietin
Definition
Used primarily in the anemia of: Chronic renal failure, Cancer/ cancer chemo, HIV infections; Also, for reduction of blood transfusions for certain types of elective surgery in anemia patients; Longterm ICU patients are being studied
Term
Epoetin Alpha
Definition
AKA Procrit; A recombinant form of erythropoietin; Given SC or IV, usually 2-3x/week; Starting dose 50-100u/kg TIW, but lower doses may work and clinicians titrate its use; Because of time for erythropoiesis, you'll see a clinical response in 2 to 6-8 weeks; EXPENSIVE (ex: in a chronic renal failure patient it can cost about $300/month)
Term
Side Effects of Epoetin Alpha
Definition
Rare allergic reactions; Hypertension (hard to Rx); Headache, edema, local skin reactions; Uncommon seizures, thrombotic events
Term
Why Do you Need to Exclude Fe Deficiency Before Giving a Patient Epoetin Alpha?
Definition
Because you can give them all the Epo you want, but if they're Fe-deficient, they won't be able to make RBCs no matter how much Epo you give
Term
Darbepoetin
Definition
AKA Aranesp; A long-acting erythropoietin; Approved in late 2001; Half-life is 2-3 times longer than epoetin alpha, so you only need to give it once weekly; It is as effective as epoetin in renal failure patients
Term
IND for Use of Hydroxyurea
Definition
Sickle Cell Anemia
Term
MOA of Hydroxyurea
Definition
Increases Fetal Hemoglobin
Term
Main Toxicity of Hydroxyurea
Definition
Neutropenia
Term
How are RBC Transfusions Typically Administered?
Definition
As packed RBCs
Term
What is the Ideal Hematocrit at Which to Give a Patient a RBC Transfusion?
Definition
It's changing/ evolving: it used to be 30%, but it has been decreasing over the years in an attempt to minimize transfusions so as to reduce: cost, transmission of rare blood-borne disease (HIV, HCV, etc.), reduce the risk of transfusion-related reactions, and conserve the blood supply
Term
What is The "Optimal" Hematocrit level in Someone with an Acute MI?
Definition
Classically has been taught to be >30%, recent paper suggests at least this, and a HCT > 33% may actually lower mortality rates, but overall the "optimal" Hct level in ischemic heart disease is still debated
Term
Risks of RBC Transfusions
Definition
Fatal Hemolytic Reaction (1/500,000); HIV (1/500,000); HCV (1/100,000); HBV (1/63,000); Volume Overload; Bacterial Contamination; Wrong Unit Given; Nonspecific immunosuppresion
Term
MOA of Action of Unfractionated (Standard) Heparin
Definition
Heparin binds to a plasma protease inhibitor antithrombin-III (AT-III) which serves as a major inhibitor of serine protease clotting enzymes; The Heparin-AT-III complex changes the conformation of AT-III so that the affinity for factors Xa, Thrombin and IXa increase by 1000-fold
Term
Route of Administration of Unfractionated (Standard) Heparin
Definition
Not absorbed after oral administration. Must be given by injection, usually IV for therapy; Subcutaneous especially in prophylaxis. With IV use, intermittent doses can cause more bleeding, so continuous infusions are preferred
Term
Onset of Action of Unfractionated Heparin
Definition
IV - immediate and preferred when you want rapid therapy (eg pulmonary emboli); Subcutaneous - onset in 1-2 hours
Term
How and Why is Unfractionated Heparin Dosing Individualized?
Definition
Why - heparin can bind to a variety of plasma proteins, proteins secreted by platelets and endothelial cells so it can cause marked variability in its anticoagulant response among patients (one dose does not fit all adult patients); How - most commonly by weight-based heparin dosing
Term
Monitoring of Treatment with Unfractionated Heparin
Definition
Serial activated partial thromboplastin times (aPTT); Do a baseline aPTT every 4-6 hours until in range, then once a day
Term
Metabolism of Unfractionated Heparin
Definition
Heparin is bound by surface receptors on endothelial cells and macrophages, internalized, and depolymerized into low-molecular weight moieties
Term
Side Effects of IV Unfractionated Heparin
Definition
Bleeding in 6.8% of patients - a prior GI bleed is a relative contraindication and must be carefully assessed, If bleeding from heparin is serious you may need to reverse it with PROTAMINE SULFATE (a strong basic protein that binds and neutralizes heparin); Heparin-Induced Thrombocytopenia (HIT)
Term
Heparin-Induced Thrombocytopenia (HIT)
Definition
Two types - non-idiosyncratic (benign and transient), and Immune-Related (IgG, Serious, occurs in 1-2% of patients, platelet counts drop to 50-60,000 or less within 3-5 days of Rx, can be associated with paradoxical thrombi including arterial, STOP heparin); Experts recommend serial platelet counts for patients on heparin, stop if counts decrease <30% or more, seek consultation; Lepirudin (Refludan), a direct inhibitor of thrombin, has been used instead of heparin in these cases (IV)
Term
MOA of Low-Molecular Weight Heparin (LMWH)
Definition
Inhibits factor Xa more than thrombin
Term
Low-Molecular Weight Heparin (LMWH) vs. Unfractionated Heparin
Definition
LMWH is less protein bound, has less binding to epithelium, and less platelet interaction than Unfractionated Heparin (it can still cause Heparin-Induced Thrombocytopenia though); The result is that it has excellent bioavailability, a more predictable response than unfractionated heparin, fixed dosing once a day or twice a day, no monitoring, and so far less thrombocytopenia; LMWH is much more expensive than heparin (8-10x more) - however, it is often more cost effective than IV heparin since with LMWH there is no laboratory monitoring needed and there are fewer hospitalizations
Term
Situations in Which you Should Avoid Using Low-Molecular Weight Heparin (LMWH)
Definition
Renal Failure (creatinine clearance <30ml/min); Massively obese patients
Term
Fondaparinux
Definition
AKA Arixtra; A type of Low-Molecular Weight Heparin (LMWH); Does NOT seem to cause HIT; Does NOT cross the placenta, so it's safe for use in pregnancy
Term
MOA of Oral Warfarin (Coumadin)
Definition
Inhibits vitamin K epoxide reductase which is the enzyme that is responsible for carboxylating factors 2,7,9 and 10 (with warfarin, these clotting factors don't get carboxylated, so they're not active and can't participate in the clotting cascade)
Term
Pharmacokinetics of Warfarin
Definition
100% Oral bioavailability; Crosses the placenta and can cause hemorrhagic disorder in the fetus, therefore, DO NOT USE IN PREGNANCY; Metabolized into inactive compounds which are excreted in urine and stool; Potential for many drug interactions; Pharmacokinetci mechanisms include enzyme induction or inhibition and reduced absorption (TMP-SMZ will increase PT by inhibiting warfarin metabbolism, Cholestyramine reduces absorption of warfarin); NOTE - Whenever you add or take away medication in someone on coumadin, reassess affect on PT
Term
Dosing Warfarin
Definition
No set dosage; "Trial and Error" titration - start often with 5mg qd dose, often will need less but it's not predictable, often takes 3-5 days before you see the full effect; Monitor PT frequently - daily initially for about 1 week and then twice weekly, then once weekly, for chronic therapy: once a month; Maintenance doses vary in individuals, it is often between 2 and 7.5mg qd; Therapeutic range is defined in terms of an INR to provide uniformity in laboratory measurements - the usual goal is an INR between 2 and 3, for artificial heart valve patients you want the INR between 2.5 and 3.5; Dosing of warfarin (coumadin) requires intermittent and long-term patient/ caregiver and health care system interactions (chart results, careful monitoring, various methods) - this all fits into the 'patient communication' AOA competency
Term
Complications/ Side Effects of Warfarin
Definition
1) Bleeding - the most important complication, if GI or GU bleeding occurs and INR is in the therapeutic range you need to R/O underlying pathology, Options are to stop coumadin, give vitamin K or give the patient fresh frozen plasma; 2) Skin necrosis - rare, 1/3 may be protein C deficient; 3) Fetal effects - so avoid use in pregnancy
Term
Contraindications to Anticoagulants
Definition
Active bleeding (eg GI), Patient noncompliance (coumadin), Recent CNS or eye surgery, Significant liver disease, Melanoma in the CNS
Term
MOA of Aspirin (ASA)
Definition
Blocks thromboxane A2 synthesis from arachidonic acid in platelets by irreversible acetylation and inhibition of a key enzyme, cyclooxygenase; Effects last the life of the platelet (7-10 days)
Term
Dipyridamole
Definition
AKA (Persantine); MOA - some controversy; Better at preventing platelet binding to artificial surfaces (eg valves) than biological surfaces; Absorption can be variable; BID regimens
Term
Ticlopidine
Definition
AKA Ticlid; MOA - inhibits ADP pathway, involved in the binding of platelets to fibrinogen and each other; BID Dosing; Oral; SE - neutropenia (monitor WBC count, especially for the first 2 months), may also cause agranulocytosis and thrombotic thrombocytopenia purpura (TTP), which is why it now has a PDR Warning (this will appropriately discourage many caregivers from prescribing it and patients will be unwilling to take it); Expensive; Was used in patients allergic to ASA or with GI intolerance to ASA
Term
Clopidogrel (Plavix)
Definition
Approved in mid-1998 for secondary prevention of MI, stroke and other vascular events; Dose - oral, 75 mg qd; Rapidly absorbed and metabolized; MOA - similar to that of ticlopidine; At least as effective as ASA in trials; Expensive ($87/month); SE - comparable to medium-doses of ASA (Rash, GI upset, GI bleed); Medical Letter concluded that Plavix is "safer than ticlopidine" and should replace ticlopidine as an alternative to aspirin
Term
Eptifibatide (Integrilin); Abciximab (ReoPro)
Definition
Newer IV Antiplatelet Drugs; MOA - platelet glycoprotein IIb/ IIIa receptor antagonists, Prevent platelet aggregation by blocking the binding of fibrinogen and vWF to the IIb/IIIa receptor on the surface of the platelet (Eptifabatide). Abciximab also acts as an antagonist at other receptors; USES - acute coronary syndromes, After/ with angioplasty (to decrease post-procedure clots or stent problems); Administered as an IV bolus or IV infusion; Expensive ($1200/ patient); SE - increased risk of bleeding especially at arterial access site, unclear if one agent causes fewer problems than the other, major bleeds can occur; Eptifibatide is a smaller molecule and is more rapidly cleared from the plasma than Abciximab (persisting antiplatelet effect 4 v. 24-48 hours after cessation)
Term
Recombinant forms Tissue Plasminogen Activator (t-PA, a thrombolytic)
Definition
Reteplase, Aletplase
Term
MOA of Reteplase/ Alteplase
Definition
Fibrinolytic drugs are enzymes or large proteins that convert plasminogen to plasmin; Plasmin degrades fibrin and fibrinogen and thereby causes clot dissolution; Reteplase and Alteplase do this directly (older forms of t-PA must first combine with plasminogen to form an activator complex)
Term
IND for Reteplase/ Alteplase
Definition
1) Acute coronary occlusion (for ST elevation MIs); 2) Rx in selected cases of acute ischemic stroke (eg IV t-PA given within 3 hours of onset of acute stroke); 3) Massive PE with severe hypoxemia and hypotension (uncommon, heparin used for most PEs, but this may be changing - heparin is used for most PEs because most PEs aren't "massive" i.e. immediately life-threatening)
Term
SE of Reteplase/ Alteplase
Definition
Worry that thrombolytic agents may cause excessive bleeding (fibrinolytic agents create a general lytic state that may lyse both normal and pathologic thrombi, especially intracerebral bleed (stroke), agents are contraindicated in some settings, especially those in which bleeding tendencies increase and stroke risk is incresed); Reperfusion arrhythmias; Recombinant forms of t-PA such as Reteplase and Alteplase may selectively activate plasminogen that is bound to fibrin with less risk of hemorrhage vs the older t-PAs (such as streptokinase); t-PAs are expensive
Term
Bacterial v. Viral Meningitis
Definition
Bacterial - sicker patients, often faster pace of the disease, CSF with poly predominance and decreased glucose, Increased peripheral WBC and left shift, CSF culture will show pathogen if the patient is not on antibiotics;

Viral - Patients usually not as ill, CSF with lymphocytic predominance and normal glucose ("aseptic"), PCR helps identify enteroviruses; NOTE - early on in bacterial meningitis patients may only be mildly ill, and the CSF of a partially treated patient with bacterial meningitis may look viral due to the antibiotics
Term
When Do You Do a L.P.?
Definition
Acute presentation with fever, new headache, toxic, etc.; Subacute (3-5 days) headache and fever - must individualize the decision; Contraindications to doing a careful LP - Suspect mass lesion or increased intracranial pressure (focal/ asymmetric neuro findings, papilledema, ophthalmoparesis, "cushing response" - bradycardia and increased BP), Coagulopathy (anticoagulation with heparin, coumadin, etc., thrombocytopenia, PT prolonged by >2 sec), Severe scoliosis or infected/ contaminated lumbar area
Term
Commonly Used Empiric Antibiotic Regimen for Meningitis in Adults and Children
Definition
IV ceftriaxone and IV vancomycin; Ceftriaxone covers pneumococci, N.meningitidis and H.influenza, and it gets into the CSF and is well tolerated; Vancomycin is used in case of pneumococcal resistance to ceftriaxone
Term
Commonly Used Empiric Antibiotic Regimen for Meningitis in Neonates
Definition
IV ampicillin and IV cefotaxime with or without gentamicin; Ampicillin covers GBS; You would use gentamicin if the patient was in the hospital; You use cefotaxime instead of ceftriaxone because ceftriaxone can cause hyperbilirubinemia in a neonate
Term
When would you consider giving antibiotics to cover for Listeria as a cause of Meningitis?
Definition
Extremes of age; Immunocompromised patients; ? Pregnant women
Term
Role of Dexamethasone (Decadron) in Meningitis
Definition
This steroid decreases cerebral edema, intracranial pressure, vasculitis, cytokine release, etc.; In selected patients, its use is associated with less hearing loss and better patient outcomes; In kids, recommended for HIB meningitis; In adults, the experts recommend dexamethasone in pneumococcal meningitis; NOTE - give dex 10-20 minutes prior to, or at least concomitant with the FIRST antimicrobial dose, it's no good to give it after antibiotics have been started; Downside - it may decrease CSF penetration of vancomycin
Term
Keys when Treating Meningitis
Definition
The abx used MUST penetrate the CSF; Don't use new abx unless they've been proven to work in meningitis; Use adequate doses of abx; Meningitis is a medical emergency, so don't delay; Many experts use 2x the "normal" dose of vancomycin in meningitis patients because it has only modest CSF penetration; If dexamethasome is used, add rifampin since CSF penetration of vancomycin may decrease as the inflammation decreases
Term
Treatment of Meningitis "Close Contacts"
Definition
HIB - tx close contacts, especially those <2 years old, Rifampin in non-pregnant patients (ceftriaxone for pregnant patients), Rx the initial patient with Rifampin too to eradicate colonization; N. Meningitidis - Rx close contacts, Rifampin x2days, Ceftriaxone IM once as an alternative, Ciprofloxacin if not contraindicated; S.pneumoniae - Rx of close contacts is not indicated
Term
Clinical Presentation of Herpes Simplex Encephalitis (HSE)
Definition
Altered mentation and decreased levels of consciousness with focal neuro findings; 60% have focal or generalized seizures
Term
Dx of Herpes Simplex Encephalitis (HSE)
Definition
PCR to detect HSV DNA in a CSF sample is the optimal way to Dx HSE; CSF formula looks like "aseptic meningitis" with modest increased WBC count with a lymphocytic predominance (initial CSF exam may be normal in 5-10% of patients, RBCs may be seen in the CSF); Best imaging test is an MRI with enhancement (lesions are seen in the orbital-frontal and temporal lobes)
Term
Rx of Herpes Simplex Encephalitis (HSE)
Definition
IV Acyclovir is the DOC; Need high doses of IV in order to penetrate the CSF; Dose = 10mg/kg q8h if renal function is normal, Protracted course: 14-21 days
Term
Clinical Manifestations of Brain Abscesses
Definition
S/S occur secondary to the presence of a space-occupying mass (rather than signs of an infection); Headache, nausea/vomiting, seizures, papilledema; Focal neuro changes in 50% of cases (sxs depend upon the location of the abscess); Fever only in 50% of cases
Term
Dx of Brain Abscess
Definition
MRI is now the preferred imaging technique; Early changes seen on MRI = cerebral edema, cerebritis; CT guided bx and aspiration to guide abx therapy, and are needed to R/O fungal infections (Bacteria involved - streptococci, anaerobes, and gram negs; Fungi - candida, aspergillus, mucormycosis)
Term
Rx of Bacterial Abscesses
Definition
Neurosurgical help (depending upon the location surgical excision may be optimal); Empiric abx for polymicrobial bacteria - High dose IV penicillin to cover for strep or a 3rd generation cephalosporin, IV metronidazole for anaerobes including B.fragilis, 3rd generation cephalosporine (eg ceftriaxone) for gram negs, Nafcillin at max doses in patients with S.aureus bacteremias (if MRSA is involved, IV vancomycin); ID consult is suggested; Duration of abx Rx: 6-8 weeks of high dose IV, then oral abx if appropriate agents are available
Term
Clinical Presentation of Septic Joints
Definition
Fever, joint effusion, erythema of joint and decreased range of motion
Term
Dx of Septic Joints
Definition
Do "joint fluid analysis" for cell count, cultures/ specificities, gram stains and crystal exam. In Lyme ds do PCR
Term
Rx of Septic Joints (nongonococcal)
Definition
Worrisome pathogens: s.aureus and gram neg bacilli until c/s; Empiric Rx: ceftriaxone in most patients, in very debilitated complex patients - nafcillin + gentamicin perhaps until c/s are back
Term
Presentation of Early Gonococcal Joint Infections
Definition
Polyarthritis, Tenosynovitis, Fever, Pustular or Hemorrhagic skin lesions of the distal extremities (s/p bacteremia); Some patients can present with a single joint involved with an effusion, a septic joint, these patients usually have no rash
Term
Rx of Gonococcal Joint Infections
Definition
If you suspect this Dx, you must use an abx which penetrates joint fluid and is active against GC - initially IV ceftriaxone once daily until sxs are controlled for 24-48 hours; Complete Rx with oral Rx (cefixime 400mg bid)
Term
Antibiotics in Osteomyelitis
Definition
Need abx which will penetrate bone, may need high doses; Evidence-based medicine mandates prolonged Rx (at least 4 weeks, often 6 weeks)
Term
Nontreponemal tests
Definition
Used for screening of Syphilis and exploit the fact that patients with syphilis develop IgG antibodies; Many Tests - VDRL, RPR, ART, TRUST; Screening test only - if positive, you must confirm it with the more specific treponemal test; Positive titers can be "quantified" and proper Rx should be reflected in a 4-fold drop in titer
Term
Treponemal Tests
Definition
Confirmatory tests for syphilis using T.pallidum or fraction thereof as antigen. These are more specific and sensitive tests; Tests include - FTA-ABS, MHA-Ab and newer tests Serodia TP-PA and PK-TP as well as treponemal ELISA tests, Dr. Reese suggests checking with each hospital's lab as to which test is available there
Term
Rx of Neurosyphilis
Definition
Penicillin is the DOC; Must give high doses to cause adequate CSF concentrations (eg if renal function is normal, in adults, give 18-24 million units/day for 10-14 days); In penicillin allergic patients, consider skin testing and/or desensitization because there's not really a good alternative for a -cillin allergic patient; Prior recommendations that benzathine penicillin G (Bicillin) could be used IM are probably NOT effective, the levels of penicillin achieved are not high enough
Term
How Do You Treat a Febrile Leukopenic Patient?
Definition
Start empiric abx once you have c/s drawn; If there is no obvious deep line infection, there are many abx options - ceftazidime monotherapy, piperacillin-tazobactam + an aminoglycoside, imipenem monotherapy, cefepine monotherapy; If there may be a deep line infection, add vancomycin (because the above drugs won't cover gram positives and vanc will); In carefully selected "low-risk patients" oral abx may be an option; In most patients, no pathogen is isolated, so you put them on abx until their WBC count increases
Term
When Should you Consider Fungal Infection in a Leukopenic Patient, and How Would You Rx Them?
Definition
Consider fungal infection (eg candidemia) if there is persistent fever (>3-5 days) despite broad spectrum abx; Rx with IV amphotericin B, or PO or IV Fluconizole
Term
Chemoprophylaxis for Travel to Countries with Malaria
Definition
To a Country with Chloroquine-susceptible malaria - DOC = chloroquine; To a Country with Chloroquine-Resistant Malaria - 3 options: Mefloquine (Lariam), Doxycycline, Atovaquone + proguanil (Malarone)
Term
Chloroquine
Definition
Chemoprophylaxis prior to travel to a chloroquine-susceptible area; Oral tablets are well absorbed; Take 1 dose/ week; Crosses the placenta, but chloroquine has not caused harmful effects on the fetus and pregnancy is not a contraindication
Term
SE of Chloroquine
Definition
Minimal when used for prevention of malaria; May cause minor GI upset or dizziness
Term
Typical Regimen for Chloroquine
Definition
Adults - 300mg base (500mg salt) once per week po beginning 1-2 weeks before travel, while traveling, and 4 weeks post trip; Children - can make up lower dose capsules with the proper dose (5mg/kg of base) at hospital pharmacies; Avoid overdoses in kids - store in child-proof containers
Term
Mefloquine
Definition
AKA Lariam; Excellent drug with a long track record, but it has potentially serious side effects; Mefloquine-resistance has been noted in some areas (see CDC maps) recently; Oral; Slow and incompletely absorbed over 24 hours; Metabolism and elimination are slow via bile and feces; Several day half-life, so it may be given once a week, which improves compliance
Term
What is Recommended for Travelers with Prolonged (Months to Years) Travel to areas with Malaria?
Definition
These patients are candidates for presumptive "anti-relapse" Rx or so-called "terminal prophylaxis" with oral Primaquine; You always need to first R/O G6PD deficiency with a blood screen since primaquine can cause life-threatening hemolysis in G6PD-deficient patients; Terminal chemoprophylaxis is eradicating the exo-erythrocytic (hepatic) phase of the P.vivax or P.ovale life-cycle
Term
SE of Mefloquine
Definition
Usually well tolerated in prophylactic regimens (vs Rx regimens)
Term
Contraindications for Mefloquine Use
Definition
Travelers with a hx of seizures, hx of depression or severe psychiatric disorders, patients with cardiac conduction abnormalities (eg A.fib) because Mefloquine can trigger any of these things
Term
Regimen for Mefloquine
Definition
Adults - one 250mg tab per week beginning 1-2 weeks before trip, during travel, and 4 weeks post trip; It is relatively expensive (about $8/ pill)
Term
Atovaquone + Proguanil
Definition
AKA Malarone; New as of 2000; Appealing since it's a safe agent, but relatively expensive; Oral, one/day beginning 1-2 days before trip, while in the risk area, and for 7 days after return since this drug has a short half-life; Taken for a short duration after a trip (only 7 days compared to the 4 weeks of Mefloquine or Doxycycline) because it works on the liver phase of the parasitic infection; Expensive (about $4/day); Very well tolerated, and may be the DOC for a short trip; AVOID in pregnancy; This agent has been used in "Self-treatment" regimens of acute malaria (P.falciparum) when travelers are in very remote areas and not on this as chemoprophylaxis (higher dose regimens are used for Rx)
Term
Doxycycline
Definition
A tetracycline which must be taken daily during travel and for 4 weeks after return and has annoying side effects; Oral; SE - sun-related rashes (so advise sun-screen >15), yeast vaginitis; Most AVOID in children <8yo and in pregnant women
Term
Drugs Used for Treatment of Active Malaria Disease
Definition
Quinine sulfate, Primaquine, Doxycycline; NOTE - Dr. Reese listed these in the heme key drug list, but they were not in any of the lecture material from this year
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