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Immunopharmacology

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thompk31's version from 2017-05-01 11:12

Molecular Target

Question Answer
Cyclosporinebinds cyclophilin and inhibits calcineurin - blocks NFAT activity and expression of NFAT-regulated cytokines blocks TH cell activation and IL-2 production
Tacrolimusbinds immunophilin FKBP-12 and inhibits calcineurin
Sirolimusbinds FKBP-12, complex inhibits mTOR - blocks IL-2 activity and T cell proliferation -
Everolimusbinds FKBP-12, complex inhibits mTOR - blocks IL-2 activity and T cell proliferation
HydroxychloroquineDecreases antigen processing and loading by increasing pH of sub cellular compartments - reduced T cell activation
SulfasalazineInhibits COX and lipoxygenase, reduces inflammatory cytokines, inhibits NK cells, scavenges ROS
Olsalazine2 molecules of 5-ASA bound by an azo
Balsalazide5-ASA bound to a different carrier
Mesalamineaka 5-ASA - the active drug - Inhibits COX and lipoxygenase, reduces inflammatory cytokines, inhibits NK cells, scavenges ROS
Cyclophosphamideblocks proliferation of active lymphocytes (more effective on B cells) - crosslinks DNA to prevent cell replication
Azathioprineblocks cell proliferation - anabolic pathways generate thioguanin metabolites - metabolites interfere witu purine & DNA replication
Mycophenolate mofetilinhibits de novo guanine nucleotide synthesis - non-competitive inhibitor of inosine monophosphate dehydrogenase (IMPDH) - Decreases T and B cell proliferation
LeflunomideInhibit de novo pyrimidine synthesis - inhibits dihydroorotate dehydrogenase (DHODH) - Causes reduced lymphocyte activation
TeriflunomideInhibit de novo pyrimidine synthesis - inhibits dihydroorotate dehydrogenase (DHODH) - Causes reduced lymphocyte activation
Methotrexatecauses intracellular accumulation of AMP, which is released and converted to adenosine (anti-inflammatory) - reduces neutrophil chemotaxis - inhibits proliferation of inflammatory cells and releases pro inflammatory cytokines - Inhibits DHF reductase (not principal mechanism)
Dimethyl fumarateDMF -> MMF -> Nrf-2 transcriptional program - decreased oxidative stress - protects neurons from inflammation
Glatiramer acetateDecreases immune response to myelin antigens by activating suppressor T (T-REG cells) cells that migrate to CNS
Fingolimod HClBinds S1PR and decreases circulating lymphocytes (peripheral and CNS)
TofacitinibJanus kinase inhibitor (JAK) - interrupts JAK-STAT signaling pathway (JAK3)
ApremilastPhosphodiesterase 4 (PDE4) inhibitor
EtanerceptAnti-TNFalpha recombinant fusion protein - TNF receptor linked to human IgG Fc domain - binds to and inhibits activity of soluble TNFalpha
Certolizumab pegolHumanized anti-TNFalpha antibody fragment conjugated to PEG
InfliximabChimeric anti-TNFalpha antibody - binds soluble and possibly membrane bound TNF alpha
Adalimumabfully human anti-TNFalpha antibody
Golimumabfully human anti-TNFalpha antibody
TocilizumabHumanized anti-IL6 receptor antibody - binds to soluble and membrane bound IL-6 receptors - inhibits IL-6 mediated signaling on B lymphocytes - decreases B lymphocyte activation
UstekinumabAnti-IL 12, 23 antibody - reduces activation of NK and CD4+ T cells and inhibits cytokines
SecukinumabAnti-IL 17 antibody
IxekizumabAnti-IL 17 antibody for psoriasis
BasilizimabAnti-IL 2 receptor antibody - prevents T cell activation
DaclizumabAnti-IL 2 receptor antibody - prevents T cell and NK cell activation
NatalizumabAnti-alpha 4 integrin antibody (expressed by most leukocytes) - Inhibits leukocyte adhesion which reduces chemotaxis
VedolizumabAnti-alpha-4-beta-7 integrin antibody (specific to GI tract) - Inhibits migration of T cells into inflamed GI tissue
AlemtuzumabAnti-CD52 antibody - CD52 is a cell surface protein found on B and T lymphocytes, NK cells, monocytes, macrophages - Depletes these cells by direct antibody-dependent lysis (ADCC)
RituximabAnti-CD20 antibody - CD20 is a cell surface protein found on B cells - depletes B cells by complement activation and ADCC
BelimumabAnti-BLyS antibody - BLyS is a soluble B cell stimulator protein - prevents survival of B cells
AbataceptBinds CD80 / 86 and prevents T cell activation
BelataceptBinds CD80 / 86 and prevents T cell activation
AldesleukinRecombinant IL-2 - stimulates biologic effect of endogenous IL-2
DenosumabAnti-RANKL antibody - binds RANKL and prevents its interaction with RANK - Inhibits osteoclast differentiation/function
MepolizumabAnti-IL-5 receptor antibody - IL-5 responsible for recruitment of eosinophils - reduces eosinophil production and survival
ReslizumabAnti-IL-5 receptor antibody - IL-5 responsible for recruitment of eosinophils - reduces eosinophil production and survival
OmalizumabAnti-IgE antibody - prevents binding of IgE to mast cells and basophils
IvacaftorCFTR potentiator increases channel opening and Cl transport of G551D-CFTR
Lumacaftor + IvacaftorCFTR conformation stabilizer - stabilizes conformation of F508del-CFTREtanercept - Enbrel ®, Erelzi ®Anti-TNFalpha
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Pharmacologic Classes

Question Answer
EtanerceptAnti-TNFalpha
InfliximabAnti-TNFalpha
AdalimumabAnti-TNFalpha
CertolizumabAnti-TNFalpha
GolimumabAnti-TNFalpha
NatalizumabAnti-Integrin
VedolizumabAnti-Integrin
TocilizumabAnti-IL
UstekinumabAnti-IL
SecukinumabAnti-IL
IxekizumabAnti-IL
BasiliximabAnti-IL
DaclizumabAnti-IL
AlemtuzumabMisc.
RituximabMisc.
BelimumabMisc.
CyclosporineImmuniphilin Ligands
TacrolimusImmuniphilin Ligands
SirolimusImmuniphilin Ligands
EverolimusImmuniphilin Ligands
HydroxychloroquineImmuniphilin Ligands
PimecrolimusImmuniphilin Ligands
SulfasalazineAminosalicylates
OlsalazineAminosalicylates
BalsalazideAminosalicylates
MesalamineAminosalicylates
CyclophosphamideCytotoxic Agents
MercaptopurineCytotoxic Agents
AzathioprineCytotoxic Agents
Mycophenolate mofetilCytotoxic Agents
LeflunomideCytotoxic Agents
TeriflunomideCytotoxic Agents
MethotrexateCytotoxic Agents
Dimethyl FumarateMisc. Small Molecules
Glatriamer AcetateMisc. Small Molecules
FingolimodMisc. Small Molecules
TofacitinibMisc. Small Molecules
ApremilastMisc. Small Molecules
AbataceptTolerogens
BelataceptTolerogens
AldesleukinRecombinant IL-2
DenosumabOsteoporosis Biologics
MepolizumabAsthma Biologics
OmalizumabAsthma Biologics
IvacaftorCF Agents
Lumacaftor + IvacaftorCF Agents
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Indications

Question Answer
Liothyronineused when rapid onset & cessation of action is required, e.g. in heart disease. IV form - drug of choice for emergency treatment of myxoedema coma.
LevothyroxineDrug of choice for HRT in hypothyroidism & suppression therapy
Radioactive Iodinetreatment of thyrotoxicosis
PropranololReduces some of the thyrotoxic manifestations of hyperthyroidism
Beclomethasone inhalerprevention of asthma attacks and allergy relief
BetamethasoneDermatologic disorders
PrednisoloneOcular inflammation
DexamethasoneBacterial infection of the eye and diagnosis of cushings syndrome
FludrocortisoneAdison's disease and chronic postural hypotension
RaloxifeneOsteoporosis
ClomipheneInfertility (ovulation)
FluvestrantEfficacious in women who become resistant to tamoxifen (breast cancer)
AnastrozolePostmenopausal breast cancer
MifepristoneTerminates early pregnancies
TamoxifeneTreatment of metastatic breast cancer; adjuvant therapy following mastectomy or radiation
OxymetholoneOsteoporosis in post-menopausal women, aplastic anaemias, chronic biliary obstruction
StanozololOsteoporosis in post-menopausal women, aplastic anaemias, chronic biliary obstruction
KetoconazoleCRPC
EnzalutamideCRPC
FlutamideCRPC
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MOA

Question Answer
Liothyronine(T3)
Levothyroxineconverted to T3 in vivo (T4)
Methimazoleprevent hormone synthesis by inhibiting TPO-catalyzed reactions and blocking iodine organification - Block coupling of the iodotyrosines.
Radioactive Iodineemission of β particles (t1/2 ∼ 5 days) destroys the thyroid parenchyma within a few weeks
PropranololBeta-adrenoceptor blocking agent
Aminoglutethimideblocks the production of steroids
DexamethasoneLong acting GC; 1st most potent anti-inflam and 1st topical
BetamethasoneLong acting GC; 2nd most potent anti-inflam and 1st topical
Prednisolone4th most potent anti-inflam and 3rd most potent topical
Fludrocortisoneagonist binds to mineralocorticoid receptor and promotes  in Na+ reabsorption. 3rd most potent anti-inflam.
Raloxifeneestrogen agonist in bone - ↓ bone resorption, ↑bone density, & ↓vertebral fractures
Clomiphenepartial estrogen agonist & interferes with negative feedback of estrogens on the hypothalamus - ↑secretion of GnRH & gonadotropins → stimulation of ovulation.
FluvestrantMixed agonist/antagonist. Recruit different co-regulators to the ER upon binding. Activate heterodimers (ERα-ERβ) versus homodimers
Anastrozolereversibly bind to the enzyme active site and inhibit aromatase
Mifepristone“19-norsteroid” that binds strongly to PR. Competes with progesterone for the PR & glucocorticoid receptors (antagonist) producing a PR-modulator effect. Has luteolytic properties.
Tamoxifenecompete with estrogen for binding to the estrogen receptor in breast tissue.
Oxymetholoneandrogenic; stimulate protein synthesis, promote wound & fracture healing
Stanozololandrogenic; stimulate protein synthesis, promote wound & fracture healing
Ketoconazoleinhibit testosterone secretion - inhibit CYPs →block steroid hormones synthesis
Enzalutamidepure antagonists of androgens at target cell
Flutamidepure antagonists of androgens at target cell - metabolite has agonist activity
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ADR's

Question Answer
LiothyronineArrhythmias, tachycardia, anginal pain, cramps, headache, restlessness, sweating, weight loss. avoid in CVD.
LevothyroxineArrhythmias, tachycardia, anginal pain, cramps, headache, restlessness, sweating, weight loss. avoid in CVD and thyrotoxicosis.
MethimazoleOccur in 3% to 12% of treated patients. Nausea, GI distress & commonly maculopapular pruritic rash. Agranulocytosis.
FludrocortisoneCV (HTN) and CNS (HA)
Dexmethasonelatrogenic cushing's syndrome
Raloxifenedeep vein thrombosis, & leg cramps
Clomiphenehot flushes – mild & reversible; headache, constipation, allergic skin rxns. Stimulation of the ovaries, ovarian cysts, multiple births. N, V, ↑nervous tension, depression, fatigue, breast soreness, weight gain, urinary frequency, & heavy menses
Fluvestrantback pain, & pharyngitis
Anastrozoleminor hot flashes, asthenia, arthritis, pain, & skin reactions
MifepristoneV, D & abdominal or pelvic pain. 5% of patients have prolonged vaginal bleeding requiring intervention.
Tamoxifenefluid retention, hypercalcemia, vaginal discharge or dryness, nausea, ↑ bone & tumor pain, risk of thromboembolic dx & endometrial cancer
OxymetholoneAcne, Na retention → edema, virilization in women, amenorrhoea, inhibition of spermatogenesis, liver tumors
StanozololAcne, Na retention → edema, virilization in women, amenorrhoea, inhibition of spermatogenesis, liver tumors
Ketoconazolehave DI with 5-alpha-reductase inhibitors - may induce adrenal insufficiency & are associated with hepatotoxicity
EnzalutamideGeneral pain, back pain, asthenia, hot flashes, constipation, nausea
Flutamide antiandrogen withdrawal syndrome - hepatotoxicity possibly associated with the agonist action of the metabolite hydroxyflutamide
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