Drugs with Important actions in Blood, Inflammation and Gout Flashcards
23 year old woman is referred by her OB for evaluation of anemia. If this woman has macrocytic anemia, an icnreased serum concentration of transferrin and a normal serum concentration of Vitamin B12, the most likely cause of her anemia is deficiency of_________
Folic acid
The laboratory data of your pregannt patient indicate that she does not have macrocytic anemia but rather microcytic anemia. Optimal treatment of normocytic or mild micocytic anemia associated with preganncy uses _____
ferrous sulfate tablets
Accidental posioning of ferrous tablet causes ______
Necrotizing gastroenteritis, shock, and metabolic acidosis
Immediate treatment for iron tablet toxicity
Parenteral deferoxamine
- Oral defarasirox is effective for chronic iron toxicity
A 45 year old male stomach cancer patient underwent tumor removal surgery. After surgery he developed megaloblastic anemia. His anemia is caused by a deficiency of _____ and can be treated with _______
Intrinsic factor
Vitamin B12
Which of the following is most likely to be required by a 5 year old boy with chronic renal insufficiency?
Erythropoeitin
In a patient who requires filgastrim (G-CSF) after being treated with anticancer drugs, the therapeutic objective is to prevent
Systemic infection
- Stimulates the production and function of neutrophils, important cellular mediators of the innate immune system that serce as the first line of defense against infection
The megaloblastic anemia that results from vitamin B12 deficiency is due to inadequate supplies ________
dTMP
- Homocysteine and N-methyltetrahydroloate accumulate
Treatment for chemotherapy induced thrombocytopenia
Oprelvekin (IL-11)
- Stimulates platelt production and decreases the number of platelt transfusions
Twenty months after finishing chemotherapy. The woman had a relapse of breast cancer and was now unresponsive to standard doses of chemotherapy. The decion was to use high-dose chemotherapy followed by autologous stemm cell transplantation. Which of the following drugs is most likely to be used to mobilize the peripheral blood stem cells needed for the patient’s autologous stem cell transplantation?
Filgrastim (G-CSF)
Ferrous sulfate
Required for biosynthesis of heme and heme containing proteins, including hemoglobin and myoglobin
Used in IDA
Complicated endogenous system for absorbing, storing and transporting iron. No mechanism for iron excretion other than cell and blood loss
Acute overdose results in necrotizing gastroenteritis, abdominal pain, bloody diarrhea, shock, lethargy, and dyspnea. Chronic iron overload results in hemochromatosis with damae to the heart, liver and pancreas
Parenteral preparations of iron
Iron dextran, iron sucrose complex, sodium ferric gluconate, and ferumoxytol.
- Can cause pain, hypersensitivity reactions
- ferumoxytol may interefere with MRI studies
Deferoxamine
Chelates excess iron
Used in Acute iron poisoning. inherited or acquired hemochromatosis
Preferred routes of administration: intramuscular or subcutaneous
Rapid IV administration may cause hypotension. Neurotoxicity and increased susceptibility to certain infections has occured with long term use
Vitamin B12
(Cyanocobalamin, hydroxocobalamin)
Cofactor required for essential enzymatic reactions that form tetrahydrofolate, convert homocysteine to methionine and metabolize L-methylmalonyl-CoA
Used in Vitamin B12 deficiency, which manifests as megaloblastic anemia and is the basis of pernicious anemia
Parenteral vitamin B12 is required for pernicious anemia and other malabsorption syndromes
No toxicity associtaed with excess B12
Folic Acid
(Folacin/pteroylglutamic acid)
Precursor of an essential donor of methyl groups used for synthesis of amino acids, purines and deoxynucleotides
Folic acid deficiency, which manifests as megaloblastic anemia. Prevention of NTD
Oral is well absorbed; need for parenteral administration is rare
Not toxic in overdose, but large amounts can mask vitamin B12 deficiency
Epoetin alfa
Agonist of erythropoietin receptors expressed by red cell progenitors
Used in anemia, especially associated with CKDm HIV infection, cancer, and prematurity. Prevention of need for transfusion in patients undergoing certain types of elective surgery
Intravenous or subcutaneous adminsitration 1-3 x per week
SE: Hypertension, thrombotic complications and very rarely, pure red cell aplasia. To reduce risk of serious CVD, hemoglobin should be maintained <12 g/dL
Long acting glycosylated erythropoiesis-stimulating agents (ESAs)
Darbepoetin alfa
- Methoxy polyethylene glycol-epoetin beta: adminsitered 1-2x per month
G-CSF
(filgrastim)
Stimualtes G-CSF receptors expressed on mature neutrophils and their progenitors
Used in neutropenia associated with congenital neutorpenia, cyclic neutropenia, myelodysplasiam and aplastic anemia. Secondary prevention of neutropenia in aptients undergoing cytotoxic chemotherapy. Mobilization of peripheral blood cells in preparation for autologous and allogenic stem cell transplantation
Daily subcutaneous adminsitration
SE: bone pain. rarely, splenic rupture
long acting form of filgastrim that is covalently linked to a type of polyethylene glycol
Pegfilgrastim
Myeloid growth factor that acts through a distinct GM-CSF receptor to stimulate proliferation and differentiation of early and late granulocytic progenitor cells, and erythroid and magakaryocyte progenitors.
GM-CSF (sargramostim)
More likely to cuase fever, arthralgia, myalgia, and capillary leak syndrome
Antagonist of CXCR4 receptor used in combiantioon with G-CSF for mobilixation of peripheral blood cells prior to autologous transplantation in patients with multiple myeloma and non-Hodgkin’s lymphoma who responded suboptimally to G-CSF alone
Plerixafor
Oprelvekin (IL-11)
Recombinant form of an endogenous cytokine. activates IL-II receptors
USed in secondary prevention of thrombocyrtopenia in patients undergoing cytotoxic chemotherapy for nonmyeloid cancers
Daily SQ adminsitration
SE: Fatigue, headache, dizziness, anemia, fluid accumulation in the lungs, and transient atrial arrythmias
genetically engineered protein in which the Fc components of ahuman antibody are fused to multiple copied of a peptide that stimualtes the thrpombopoetin receptors
Romiplostim
Approved for treatment of ITP
Orally active agonist of thrombopoetin receptor; restricted use because of risk of hepatotoxicity and hemorrhage
Eltrombopag
Which drug accelarates the conversion of plasminogen to plasmin
Reteplase
If a fibrinolytic drug is used for treatment of acute MI, which of the following adverse drug effects is most likely to occur
Hemorrhagic stroke
Mechanism of action of clopidogrel?
Thea ctive metaboliye of clopidogrel binds to an inhibits the platelet ADP receptors
Dabigatran is a ______________
Direct inhibitor of thrombin
Sudden discontinuance of apixaban can lead to?
stroke
Which test would provide accurate information about the coagulation status of patient taking apixaban?
Factor X test
Relative to unfractionated heparin, enoxaparin ______
can be used without monitoring the patient’s aPTT
TO prevent severe hemorrhage caused by excessive warfarin, what can be given?
Vitamin K
A patient develops severe thrombocytopenia in response to treatment with unfractionated hepatin and still requires parenteral anticoagulation. The patient is most likely to be treated with ________
Bivalirudin
- Direct thrombin inhibitors such as bivalirudin and argatroban provide parenteral anticoagulation similar to that achieved with heaprin.
Unfractionated heparin
Complexes with ATIII. irreversibly inactivated the coagulation factors thrombin and factor Xa
Used in venous thrombosis, PE, MI, unstable angina, adjuvant to PCI and thrombolytics
Parenteral administration
SE: bleeding (monitor with aPTT, protamine is reversal agent). Thrombocytopenia, osteoporosis with chronic use
Rivaroxiban
Binds to the active site of factor Xa and inhibits its enzymatic action
Used in venous thrombosis, pulmonary embolism, prevention of stroke in patients with nonvalvular atrial fibrillation
Oral administration. Fixed dose, no routine monitoring (factor Xa test)
SE: bleeding. no specific reversal agent
Direct thrombin inhibitors
(Bivalirudin, argatoban, dabigatran)
Bind to thrombin’s active site and inhibit its enzymatic action
Anticoagulation in patients with Heparin induced thrombocytopenia
Bivaluridin and argatroban: IV adminsitration, Dabigatran: oral administration
SE: Both: bleeding(monitor with aPTT). Idarucizumab (Fab fragment binds and reverses effect of dabigatran)
Warfarin
Inhibits Vitamin K epoxide reducatase and therby interferes with production of functional vitamin K-dependent clotting and anticlotting factors
Used in venous thrombosis, PE, prevention of thromboembolic complications of aFIb or cardiac valve replacement
Oral adminsitration. delayed onset and offset of anticoagulant activity. many drug interactions
SE: bleeding (monitor with PT, vitamin K is a reversal agent). Thrombosis early in therapy due to protein C deficiency. Teratogen
Alteplase, recombinant human tissue plasminogen activator
Converts plasminogen to plasmin, which degrades the fibrin in thrombi
Used in coronary artery thrombosis, ischemic stroke, PE
Parenteral administration
SE: bleeding, especially cerebral hemorrhage
Bacterial protein that forms a complex with plasminogen that rapidly converts plasminogen to plasmin. Subject to inactivating antibodies and allergic reactions
Streptokinase
Aspirin
Nonselective, irreversible COX inhibitor. reduces platelet production of thromboxane A2, a potent stimulator of platelet aggregation
Used in prevention and treatment of arterial thrombosis
Dose required for antithrombotic effect is lower than anti-inflammatory dose. Duration of activity is longer than pharmokinetic half-life due to irreversible action
SE: GI toxicity, nephrotoxicity, hypersensitivity reaction due to increased leukotrienes; tinnitus, hyperventilation metabolic acidosis, hyperthermia, coma in overdoe
Abciximab
GP IIB/IIIa inhibitor
Inhibits platelet aggregation by interfering with GP IIb/IIIa binding to fibrinogen and other ligands
Used during PCI to prevent restonsis. ACS
Parenteral adminsitration
SE: Bleeding, thrombocytopenia with prolonged use
Eptifibate, tirofiban
reversible GP IIb/IIIa inhibitors of smaller size than abciximab
Clopidogrel
Prodrug: active metbolite by CYP2C9 and CYP2C19 irreversible inhibits platelet ADP receptor
ACS, prevention of restenosis after PCI, prevention and treatment of arterial thrombosis
Oral administration
SE: Bleeding, GI disturbances, hematologic abnormalities
older ADP receptor antagonist with more toxicity, particularly leukopenia and TTP
Ticlodipine
Newer drug, similar to clopidogrel with less variable kinetics, activation primarily by CYP3A4
Prasugrel
Reversible ADP receptor antagonist that does not require activation
Ticagrelor
Dipyridamole
Inhibits adenosisne uptake and inhibits PDE enzymes that degrade cAMP, cGMP
used in prevention of thromboembolic complciations of cardiac valce repalcement. Combined with aspirin for for secondary prevention of ischemic stroke
Oral administration
SE: headache, palpitations, contraindicated in congestive heart failure
Vitamin K
(ohytonadione)
Increase supply of reduced vit. K, which is required for synthesis of functional vitamin K dependent clotting and anticlotting factors
Used in Vit. K deficiencym reversal of excessiv warfarin anticlotting activity
Oral or parenteral administration
SE: severe infusion reaction when given IV or IM
vasopressin V2 receptor agonist increases concentrations of vWF and factor VIII
Desmopressin
Aminocaproic acid
Competitively inhibits plasminogen activation
Used in exxcessive fibrinolysis
Oral and parenteral administration
SE: thrombosis, hypotension, myopathy, diarrhea
Tranexamic acid : analog of aminocaproic acid
Pj is a year old boy. AT his checkup. noted cutaneous xanthoma. Serum cholesterol of >936. Further testing confirms diagnosis of homozygous familial hypercholesterolemia.
What is the least effective drug class for this
HMG-CoA reducatase inhibitors
A 46 year old patient had this lipid profile
- Before treaments
- TG: 1000 TC: 640 LDL: 120 VLDL 500 HDL 20
- 6 months after
- TG: 300 TC: 280 LDL: 90 VLDL 150 HDL 40
What is the most likely drug given to the patient?
Niacin
A patient is a diagnosed case of familial combined hyperlipidemia. He has elevated total cholesterol, LDL cholesterol, and TG. her HDL is somewhat reduced
What drug is most likelyto increase TG and VLDL when used as monotherapy?
Cholestyramine
Cholesterol lowering drug contraindicated in pregnancy
HMG-CoA reductase inhibitors
Major mechanism of action of gemfibrozil
Increased TG hydrolysis by lipoprotein liapse
Major toxicity by gemfibrozil
Cholelithiasis
Consumption of alcohol is associated with what changes in lipid concentration?
Increased TG
Increased VLDL
If aptient has gout, what lipid lowering drug will exacerbate it?
Niacin
The 2 primary adverse effects of HMG-CoA reductase?
Hepatotoxicity adn myopathy
Major recognized effct of ezetimibe
Inhibition of absorption of cholesterol in the intestine
Statins
(Atorvastatin, Simvastatin, rosuvastatin, pitavastatin)
Inhibits HMG-CoA reductsae
Used in atherosclerotic vascular doisease (primary and secondary prevention). Acute coronary syndromes
Oral adminsitration. P450-dependent metabolism (CYP3A4, CYPC9) interacts with P450 inhibitors/competitors
SE: myopathy, hepatic dysfunction, teratogen
FIbrates
(Gemfibrozil, fenofibrate)
PPAR-alpha agonist
Used in hypertriglyceridemia (VLDL), low HDL cholesterol
Oral adminsitration
Myopathy, heaptic dysfunction, cholestasis
Bile acid binding resins
(Colestipol)
Prevents reabsorption of bile acids from the GI tract
Used in elevated LDL cholesterol, pruritus
Oral administration. Interferes with absorption of some drugs and vitamins.
SE: constipation, bloating
Sterol absorption inhibitor
(Ezetimibe)
Reduces intetsinal uptake of cholesterol by inhibiting sterol transporter NPC1L1
Used in elevated LDL cholesterol, phytosterolemia
Oral administration
Rarely, heaptic dysfunction, myositis
Niacin
Decreases catbolism of apo A-1 reduces VLDL secretion from liver. Icnreases HDL cholesterol
USed in low HDL cholesterol, elevated VLDL and LDL
Oral administration
SE: GI irritation, flushing, heaptic toxicity, hyperuricemia, may reduce glucose tolerance
PCSK9 inhibitors
(Evolucumab, alirocumab)
Complexes PCSK9. Inhibits catabolism of LDL receptor
Used in familial or ther resitant hypercholesterolemia not responsive to oral therapy
Parenteral
SE: injection site reactions, nasopharyngitis, flu-like symptoms
Lomipatide
Microsomal triglcyeride transfer protein (MTP) inhibitor
- MTP plays an essential role in accretion of TG to nascent VLDL in liver and to chylomicrons in the intestine.
- Its inhibition decreases VLDL secretion and consequently the accumulation of LDL in plasma
Mipomersen
An antisense oligonucleide that targets apo B-100, mainly in the liver.
Among NSAIDs, aspirin is unique because it
Irreversibly inhibits its target enzyme
Analgesic and antipyretic drug that lacks an anti inflammatory action
Acetaminophen
ASpirin overdose
Hypethermia, metabolic acidosis, dehydration, coma
What drug is most likely to increase serum concentrtions of conventional dose of methotrexate, a weak acid that is primarily cleared in the urine?
Probenecid
- competes with the methotrexate for binding to the proximal tubule transporter and thereby decreases the rate of clearance of methotrexate
The main advantage of ketorolac over aspirin is that ketorolac is _______________
Availbale in a parenteral formulation that can be injected IM or SQ
An 18 month old boy dies from an accidental overdose of acetaminophen. Which of the following is the msot likely cause of this patient’s death?
Liver failure
Many physicians prefer to treat acute gout with a corticosteroid or indomethacin because, high doses of colchicine are likely to cause
Severe diarrhea
In treating chronic gout, What drug could be used to decrease rate of production of uric acid?
Allopurinol
Most compelling reason for avoiding celecoxib in the treatment of arthritis
History of Myocardial infarction
Parenterally administered DMARD whose mechanism of anti inflamatory action is antagonism of TNF alpha
Etenercept
Anti IL1 drugs
anakinra, rilonacept, canakinumab
Anti-IL6 drug
tocilizumab
Inhibits B-lymphocyte stimulator
Belimubab
Janus kinase inhibitor
Tofacitinib
Aspirin
Acetylation of COX-2 and COX-2 results in decreased prostaglandin syntheis
Used in analgesia, antipyretic, antiinflamamtory and antithrombotic (low dose)
Duration of activity is longer than pharmacokinetic halflife of drug due to irreversible COX inhibition.
SE: GI toxicity, nephrotoxicity, and icnreased bleeding time at therapeutic levels. Bronchonstrictor raction due to increased leukotrienes. Tinnitus, hyperventilation, metabolic acidosis, hyperthermia, coma in overdose
Aspirin dosages
- Low range (<300 mg/d)
- reducing platelet aggregation
- Intermediate dose (300-2400 mg/d)
- antipyretic and analgesic effects
- High dosaes (2400-4000 mg/d)
- anti-inflamatory effect
At low dose - first order at high dose - zero order kinetics
Ibuprofen
Reversible inhibition of COX-1 and COX-2 results in decreasd prostaglandin synthesis
Used in analgesia, antipyretic, and anti-inflammatory. CLosure of patent ductus arteriosus
Rapid metabolism and renal elimination
SE: GI toxicity, nephrotoxicity. Reaction due to increased leukotrienes. Interfere with aspirin’s antithrombotic action
Celecoxib
Selective, reversible inbition of COX-2 results in decreased prostaglandin synthesis
Used in analgesia, antipyreticm and anti-inflammatory
Hepatic metabolism
Nephrotoxicity, Reaction die to increased leukotrienes. Less risk of GI toxicity than nonselective NSAIDs. greater risk of thrombosis than nonselective NSAIDs
Acetaminophen
Mechanism unknown, Weak COX inhibitor
Analgesia, antipyretic
Hepatic conjugation
Hepatoxicity in overdose (antidote is acetylcysteine). Hepatotoxicity more likely with chronic alcohol consumption which induces P450 enzymes
Methotrexate
DMARD
conventional syntehtic cytotoxic to rapidly dividing immune cells due to inhibition of dihydrofolate reductase
Anticancer, Rheumatic disorders
Renal elimination
SE: nausea, mucosal ulcers, hematotoxicity, hepatotoxicity, teratogenicity
Infliximab
Biologic (b) anti-TNF alpha
Used in rheumatoid arthritis
SE: opportunistic infections and reactivation of latent TB and HBV. Increased risk of skin cancer
Colchicine
Inhibition of mictorubile assembly decreases macrophage migration and phagocytosis
Used in chronic and acute gout, familial mediterranean fever
Oral drug
SE: diarrhea, severe liver and kidney damage in overdose
Probenecid
Inhibition of renal reabsorption of uric acid.
Chronic gout, prolongation of antimicrobial drug action,
Oral drug
SE: exacerbation of acute gout, hypersensitivity reactions, inhibits renal tubular secretion of weak acids such as MTX
Allopurinol
Active metabolite irreversibly inhibits xanthine oxidase and lowers production of uric acid
Chronic goutm adjunct to cancer chemotherapy
Activated by xanthine oxidase, oral drug
GI upset, hypersensitivity reactions, bone marrow suppression
Pegloticase
Recombinant mammalian uricase converts uric acid to the soluble allantoin
USe din chronic refractory gout
IV
SE: Rapid change in uric acid levels can precipitate gout flare. Prophylaxis with NSAIDs or colchicine
