Pharmacology week 1 Flashcards
(127 cards)
1
Q
What is the general mechanism of action of calcineurin inhibitors
A
Binds to an immunophilin → interaction with calcineurin → blocks its phosphatase activity
Dephosphorylation required for movement of NFAT into nucleus → required to induce IL-2
2
Q
Macrolides antibiotic produced by Streptomyces tsukubaensis
A
Tacrolimus
3
Q
Mechanism of action of tacrolimus
A
Binds to FKBP-12
4
Q
Tacrolimus is plasma protein bound to
A
Albumin and a1-acid glycoprotein
5
Q
Therapeutic uses of tacrolimus
A
Prophylaxis for solid-organ allograft rejection
6
Q
Adverse effects of tacrolimus
A
Nephrotoxicity and neurotoxicity
Diabetes mellitus
↑ risk tumors and opportunistic infections
7
Q
Drug interactions of tacrolimus
A
Synergistic nephrotoxicity with cyclosporine
Do not use with sirolimus
8
Q
Cyclic polypeptide produced by fungus Beauveria nivea
A
Cyclosporine
9
Q
Mechanism of action of cyclosporine
A
Binds to cyclophilin
10
Q
Why is cyclosporine administered with castor oil
A
Because it is very lipophilic and hydrophobic
11
Q
Therapeutic uses of cyclosporine
A
Transplants
Rheumatoid arthritis
Psoriasis
12
Q
Adverse effects of cyclosporine
A
Type 4 renal tubular acidosis and hypertension
Hypertrichosis and hirsutism
13
Q
What is the effect of grapefruit use in cyclosporine
A
↑↑ cyclosporine levels
14
Q
Macrocyclic lactone produced by Streptomyces hygroscopicus
A
Sirolimus
15
Q
Mechanism of action of sirolimus
A
Formation of complex with FKBP-12 → inhibition mTOR → blocks cell cycle progression at G1 to S phase transition
16
Q
Metabolization and transportation of sirulimus
A
Metabolized by CYP3A4 and transported by P-glycoprotein
17
Q
Therapeutic uses of sirolimus
A
Prophylaxis of organ transplant rejection
Incorporated into stents to inhibit local cell proliferation
18
Q
Adverse effects of sirolimus
A
Increase in cholesterol and triglycerides
Delayed wound healing and buccal ulcers
DO NOT use with cyclosporine or tacrolimus
19
Q
Same as other calcineurin inhibitors but with lower t1/2
A
Everolimus
20
Q
Therapeutic uses of everolimus
A
Astrocytoma and breast cancer, pancreatic neuroendocrine tumor, renal angiomyolipoma and renal cancer
21
Q
Imidazolyl derivative of 6-mercaptopurine
A
Azathioprine
22
Q
Mechanism of action of azathioprine (AZT)
A
Exposure of gluthatione → AZT cleaved to 6-mercaptopurine → metabolites inhibit de novo purine synthesis
6-thio-IMP → 6-thio-GMP → 6-thio-GTP → inhibition cell proliferation
23
Q
Therapeutic uses of azathioprine
A
Adjunct for prevention of organ transplant rejection
Severe rheumatoid arthritis
24
Q
Adverse effects of azathioprine
A
Bone marrow suppression
Increased susceptibility to infections → varicella and HSV
25
Drug interactions with azathioprine
Allopurinol → blocks xanthine oxidase (needed for catabolism of AZT metabolites)
26
Mechanism of action of mycophenolate acid
Prodrug hydrolyzed to active drug → inhibitor of inosine monophosphate dehydrogenase (enzyme in de novo pathway of guanine synthesis)
27
Metabolization of mycophenolate acid
Metabolized to inactive MPA glucuronide (MPAG)
28
Therapeutic uses of mycophenolate acid
Prophylaxis for transplant rejection
Off-label for systemic lupus
29
Adverse effects of mycophenolate acid
GI and hematological
Increased incidence infection: CMV
30
Drug interactions of mycophenolate acid
Tacrolimus delays elimination
Coadministration with antacids decreases absorption
Acyclovir and ganciclovir compete for tubular secretion
31
Mechanism of action of methotrexate
Inhibits dihydrofolate reductase → blocks DNA synthesis and causes cell death
32
Therapeutic uses of methotrexate
Oncologic → ALL, AML; osteosarcoma, breast carcinoma, lymphoma, choriocarcinoma
Autoimmune → psoriasis, rheumatoid arthritis, Crohn, SLE, dermatomyositis
33
Important consideration when administering methotrexate
Can cause folate deficiency → administer 1 mg/day folate
34
Long term effect of methotrexate use
Mucositis or mucosal ulcers
35
Mechanism of action of glucocorticoids
Broad anti inflammatory effects
Activation of Nf-Kb, suppress formation of proinflammatory cytokines (IL1 and IL6), inhibit activation cytotoxic T lymphocytes
36
Therapeutic uses of corticosteroids
Combined with other immunosuppressive agents to prevent and tx transplant rejection
Routine use in immune disorders
Limit allergic reactions that occur with other immunosuppressive agents
37
Adverse effects of glucocorticoids
Growth retardation in children
**Avascular necrosis of bone**
Increased risk of infection
Cushing sx
38
Long acting glucocorticoid
Dexamethasone
39
Active form of prednisone
Prednisolone
40
Chimeric monoclonal antibody anti-CD20
Rituximab
41
Type of administration of antineoplasic monoclonal antibodies
IV
42
Mechanism of action of rituximab
Bind to antigen CD20 of B cells → generated lysis of B cells
43
Therapeutic uses of rituximab
Rheumatoid arthritis
Immune and thrombotic thrombocytopenic purpura
Multiple sclerosis and autoimmune hemolytic anemia
B-cell non Hodgkin lymphoma and chronic lymphoid leukemia
Microscopic polyangiitis
44
Therapeutic use of belimumab
SLE
45
Adverse effects of rituximab
Reactive to JC virus
Depletion of IgG
Flu-like symptoms
46
Anti IL-2 receptors (anti-CD25)
Daclizumab and basiliximab
47
Administration doses of daclizumab and basiliximab
Daclizumab: IV 5 doses with t 1/2 of 20 days
Basiliximab: IV 1 dose with t 1/2 of 7 days
48
Mechanism of action of anti IL-2 receptors
Binds to alpha subunit of IL-2 receptor and works as antagonist → inhibits T lymphocyte activations and proliferations
49
True or false: daclizumab and basiliximab induce apoptosis
False: Does not induce apoptosis only does not allow cell proliferation
50
Therapeutic uses of daclizumab and basiliximab
Solid transplant organ rejection prophylaxis
51
Adverse effects of daclizumab and basiliximab
Hepatotoxicity
Immune mediated disorders: encephalitis, colitis, thyroiditis
Infections and lymphadenopathy
Depression or mood changes
52
Second generation CTLA-4 Ig
Belatecept
53
Mechanism of action of belatecept
Binds to CD28 in T cells → blocks so they cannot bind to CD80/86 in APCs → inhibition T cell activation → anergy and apoptosis
54
Therapeutic uses of belatecept
Alternative to calcineurin inhibitors
55
Contraindications for Betalecept use
Px with EBV seronegative status → can cause post transplant lymphoproliferative disorder
56
Mechanism of action of glatiramer acetate
Binds to MHC II DR molecules
Induces cross reactive CD4 T cells that secrete Th2 cytokines
Mimics myelin basic protein (MBP) to promote Th2 response
57
Administration route of glatiramer acetate
Subcutaneous administration
58
Therapeutic uses of glatiramer acetate
Patients with relapsing-remitting multiple sclerosis
59
Administration route of elapegadamase and pegademase
Intramuscular administration
60
Mechanism of action of elapegadamase
Adenosine deaminase replacement
Converts adenosine and deoxyadenosine to inosine → prevents accumulation of toxic metabolites
61
Therapeutic use of elapegadamase
Severe ADA deficiency
62
Mechanism of action of pegademase
Prevents accumulation of toxic metabolites of nucleotides
63
Therapeutic uses of pegademase
Severe ADA deficiency in infant or children and they have another immunodeficiency
64
CXCR4 antagonist
Perixaflor
65
Mechanism of action of perixaflor
Inhibits binding factor 1a (stromal cells) to CXCR4 → disurpts rentetion signals in bone marrow → mobilization stem cells into bloodstream
66
Therapeutic uses of perixaflor
Mobilize hematopoietic stem cells into peripheral blood
Non Hodgkin lymphoma or multiple myeloma
67
Main adverse effect of perixaflor
Splenomegaly
68
Cytokine dependent kinase 4 and 6
Triciclib
69
Mechanism of action of triciclib
CDK4/6 inhibitor → transiet Gi cell cycle arrest of hematopoetic cells → protects cells from chemotherapy
70
Therapeutic uses of triciclib
Prechemotherapy for small cell lung cancer → preserves hematopoietic cells and lymphocytes
71
Active metabolite of allopurinol
Oxypurinol
72
Mechanism of action of allopurinol
Inhibits xanthine oxidase and prevents synthesis of urate from hypoxanthine and xanthine
73
Urine purines that predominate with allopurinol
Hypoxanthine, xanthine and uric acid
74
Main administration route of allopurinol
Oral administration
75
Excretion of allopurinol
20% excreted in feces: unabsorbed drug
10-30% excreted in urine
Remainder: metabolism to oxypurinol
76
Therapeutic uses of allopurinol
Primary and secondary gout
Hyperuricemia secondary to malignancies
Calcium oxalate calculi
77
Most common adverse effects of allopurinol
Hypersensitivity reactions that manifests after months to years
78
Botanical source of colchicine
Autumn crocus Colchium autumnale
79
Mechanism of action of colchicine
Binds to tubulin → inhibiting microtubule polymerization → disrupts cytoskeletal function in neutrophils
80
Why does colchicine have a large volume distribution
Formation of colchicine-tubulin complexes in many tissues
81
Therapeutic uses of colchicine
Acute gout → prevention and exacerbations
82
Most used NSAID in Europe
Diclofenac
83
Metabolization of diclofenac
Metabolized in liver by member of CYP2C → 4-hydroxydiclofenac
84
Therapeutic uses of diclofenac
Long-term symptomatic tx of:
Rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, pain, primary dysmenorrhea and acute migraine
85
Adverse effect of diclofenac metabolites
4-hydroxydiclofenac (metabolite) can form reactive benzoquinone imines that deplete GSH
86
Primary catalyst in formation of another highly reactive metabolite: diclofenac acyl glucuronide
UGT2B7
87
Mechanism of action of sundilac
Prodrug w/anti inflammatory activity in its sulfide metabolite → inhibitor of COX
88
Therapeutic uses of sundilac
Rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, painful shoulder, gouty arthritis
89
Mechanism of action of ketorolac
Non selective inhibitor of COX1 and COX2 → inhibits prostaglandins, prostacyclin and thromboxane synthesis
90
Therapeutic uses of ketorolac
Short-term management of moderate/severe acute pain → after surgery or injury
Renal colic or musculoskeletal pain
Seasonal allergic conjunctivitis and postoperative ocular inflammation
91
Maximum recommended dose of acetaminophen
4 g/day
92
Mechanism of action of acetaminophen
Nonselective COX inhibitor → acts at peroxide site of enzyme and thus distinct among NSAIDS
93
Metabolization and excretion of acetaminophen
90-100% drug recovered in urine in first day of therapeutic dosing after hepatic conjugation with:
Glucuronic acid → 60%
Sulfuric acid → 35%
Cysteine → 3%
94
Toxic metabolite of acetaminophen
NAPQI
95
Therapeutic uses of acetaminophen
Analgesic and antipyretic uses
96
Most serious acute adverse effect of acetaminophen overdosage
Fatal hepatic necrosis
97
Antidote of acetaminophen
N-acetylcysteine (NAC)
98
When is activated charcoal indicated for acetaminophen intoxication
For those who exceed 7-5 g
99
Mechanism of action of ibuprofen and naproxen
Non selective inhibitor of COX1 and COX2 → inhibits prostaglandins, prostacyclin, and thromboxane synthesis
100
Why are ibuprofen and naproxen contraindicated with aspirin
Ibuprofen and naproxen interfere with antiplatelet effects of aspirin
101
Specific therapeutic use of ibuprofen
Close patent ductus arteriosus in premature infants
102
Therapeutic uses of naproxen
Juvenile and rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, pain, primary dysmenorrhea, tendonitis, bursitis, acute gout
103
Propionic acid derivative with lowers t 1/2
Ketoprofen
104
Adverse effect of ketoprofen
Photosensitivity
105
Nonselective COX inhibitor with longest t 1/2
Piroxicam
106
Mechanism of action of piroxicam
Inhibit activation and aggregation of neutrophils
107
Therapeutic uses of piroxicam
Rheumatoid arthritis and osteoarthritis
Acute gout
108
CYPs in metabolism of celecoxib
CYP2C9 and inhibits CYP2D6
109
Therapeutic uses of celecoxib
Management of acute pain for tx of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, primary dysmenorrhea
110
Adverse effects of celecoxib
Risk of myocardial infarction and stroke
Decrease bone mineral density
111
Mechanism of action of methocarbamol
Depresses CNS with sedative and relaxing skeletal muscle effect → mechanism of action unknown
112
Therapeutic uses of methocarbamol
Rest adjustment, analgesic, physical therapy
113
Adverse effects of methocarbamol
Drowsiness, dizziness, lightheadedness
114
Main use of leukotriene receptor antagonists
Asthma
115
FDA black box warning of montelukast
Serious neuropsychiatric event specially in children (suicidal thoughts)
116
Metabolism of Montelukast
Metabolism CYP3A4 and CYP2C8
117
Mechanism of action of Montelukast
Prevents binding of leukotrienes to their G-protein coupled receptor CysLT1 → receptor does not get activated to create inflammatory properties → lower bronchoconstriction and inflammation
118
First leukotriene receptor antagonist approved for asthma tx
Zafirlukast
119
Mechanism of action of Zileuton
5-lipoxygenase inhibitor (needed for conversion of arachidonic acid to leukotrienes) → inhibits its production → lower bronchodilation and inflammation
120
Contraindication of Zileuton
NO alcohol use
121
Mechanism of action of second generation antihistamines
Selective antagonists (inverse agonists) of histamine H1 receptor
122
2nd generation piperazines
Cetirizine
123
Adverse effects of cetirizine
>12 years of age → somnolence, fatigue, dry mouth
2-11 years of age → headache, pharyngitis, abdominal pain
<2 years of age → irritability, fussiness, insomnia, fatigue, malaise
124
Contraindications of cetirizine
End stage renal disease
<6 months old
125
2nd generation piperidines
Loratadine
126
Adverse effects of loratadine
Children 2-5 years old → diarrhea, epistaxis, pharyngitis, flu-like sx, fatigue, stomatitis, tooth disorders, earache, rash
Children 6-12 years old → nervousness, wheezing, fatigue, hyperkinesia, conjunctivitis, dysphoria
127
Contraindications of loratadine
Severe hepatic impairment
Children <2 years old
