Pharmacology of Immunosuppressants

Management of acute inflammatory conditions, prevention of organ transplant rejection, treatment of autoimmune disorders

Widespread transcriptional alterations, increased risk of opportunistic infections

Prevention of hemolytic disease of the newborn

<p>Corticosteroid receptor (CR) binding: NF-κB complex stabilization → no nuclear translocation: inhibits transcription of inflammatory cytokines; CR nuclear translocation: promotes transcription of anti-inflammatory cytokines; Reduces expression of adhesion molecules: decreased inflammatory cell recruitment; Inhibits PLA2: inhibits prostaglandin synthesis</p> Signup and view all the answers

<p>Binds Rho(D) antigens on fetal RBCs, facilitating their clearance from maternal circulation; prevents anti-Rho(D) antibody formation in the mother</p> Signup and view all the answers

<p>Prevention of organ transplant rejection</p> Signup and view all the answers

<p>Increased risk of opportunistic infections</p> Signup and view all the answers

<p>Binds CD3 on T cells, leading to initial activation followed by complex internalization and deactivation</p> Signup and view all the answers

<p>Cytokine release syndrome, immunogenic reactions</p> Signup and view all the answers

<p>Prevention of organ transplant rejection</p> Signup and view all the answers

<p>Blocks IL-2 receptor (α subunit) preventing IL-2 binding and T cell maturation; reduces antibody production due to decreasing CD4+ T cells</p> Signup and view all the answers

<p>Bind soluble/free TNFα reducing cytokine signalling through TNFα receptors and suppressing inflammatory cytokine production</p> Signup and view all the answers

<p>Management of TNFα-mediated inflammatory conditions</p> Signup and view all the answers

<p>Increased risk of opportunistic infections</p> Signup and view all the answers

<p>Treatment of pre-cancerous tissues/lesions (topical)</p> Signup and view all the answers

<p>TLR7 agonism; stimulating leukocyte activation and secretion of inflammatory cytokines</p> Signup and view all the answers

<p>Localized inflammation, skin irritation</p> Signup and view all the answers

<p>Binds CD20 on B cells, inducing ADCC</p> Signup and view all the answers

<p>Treatment of HER2+ breast cancer</p> Signup and view all the answers

<p>Cancer immunotherapy</p> Signup and view all the answers

<p>Bind PD-1 preventing its interaction with PD-L1; reverses T cell exhaustion and restores anti-tumor immune responses</p> Signup and view all the answers

<p>Cancer immunotherapy</p> Signup and view all the answers

<p>Binds PD-L1 preventing its interaction with PD-1; enhances T cell-mediated anti-tumor immunity</p> Signup and view all the answers

<p>Binds CTL4, blocking its inhibitory signalling; enables T cell activation through CD28/CD80 promoting anti-tumor immunity</p> Signup and view all the answers

<p>Treatment of Hodgkin's Lymphoma</p> Signup and view all the answers

<p>Binds overexpressed HER2, delivering DM1 aka Mertansine (microtubule inhibitor) which kills cells</p> Signup and view all the answers

<p>Binds CD30, delivering MMAE (microtubule inhibitor) which kills cells</p> Signup and view all the answers

<p>Binds CD22, delivering calicheamicin (DNA-damaging agent) which kills cells</p> Signup and view all the answers

<p>Treatment of relapsed/refractory B cell acute lymphoblastic leukemia</p> Signup and view all the answers

<p>Treatment of relapsed/refractory AML</p> Signup and view all the answers

<p>Binds CD22, delivering calicheamicin (DNA-damaging agent), which kills cells</p> Signup and view all the answers

<p>Treatment of cancer</p> Signup and view all the answers

<p>Bispecific antibody; binds CD3 (on T cells) and CD20 (on tumours) forcing an interaction for T-cell mediated killing; can also initiate ADCC</p> Signup and view all the answers

<p>Treatment of cancer</p> Signup and view all the answers

<p>Bispecific antibody (only antigen-recognition domains); binds CD3 (on T cells) and CD19 (on tumours) forcing an interaction for T-cell mediated killing</p> Signup and view all the answers

<p>Management of rheumatoid arthritis</p> Signup and view all the answers

<p>Recombinant CTLA-4</p> Signup and view all the answers

<p>Competes with CD28 for CD80/86 binding, reducing T cell costimulation and activation</p> Signup and view all the answers

<p>Treatment of CD19+ B cell lymphomas and leukemias</p> Signup and view all the answers

<p>Engineered T cells recognize overexpressed CD19, inducing direct killing of target cells (doesn't require costimulation)</p> Signup and view all the answers

<p>Cytokine release syndrome, severe inflammation, B cell depletion</p> Signup and view all the answers

<p>Acts as a reducing agent at the peroxidase site of COX, reducing prostaglandin synthesis; conjugates with arachidonic acid to form AM404, an endocannabinoid reuptake inhibitor</p> Signup and view all the answers

<p>Pain relief, fever reduction</p> Signup and view all the answers

<p>Hepatotoxicity at high doses</p> Signup and view all the answers

<p>Pain, fever, inflammation management</p> Signup and view all the answers

<p>Irreversibly inhibits COX-1 and COX-2 by acetylating Ser529 and blocking arachidonic acid entry, preventing prostaglandin synthesis</p> Signup and view all the answers

<p>Pain, fever, inflammation management</p> Signup and view all the answers

<p>Inhibits COX-1 and COX-2 through non-covalent interaction (ion pair with Arg120), blocking arachidonic acid entry, preventing prostaglandin synthesis</p> Signup and view all the answers

<p>GI irritation, risk of ulcers, kidney damage with chronic use</p> Signup and view all the answers

<p>Withdrawn from market (NSAID)</p> Signup and view all the answers

<p>Increased cardiovascular event risk</p> Signup and view all the answers

<p>Selective COX-2 inhibitor, reduces prostaglandin synthesis</p> Signup and view all the answers

<p>Mimics endogenous PGE2; stimulating uterine contractions and cervical softening</p> Signup and view all the answers

<p>Labor induction, pregnancy, abortion</p> Signup and view all the answers

<p>Labor induction, pregnancy, abortion</p> Signup and view all the answers

<p>Mimics endogenous PGF2α; stimulating uterine contractions</p> Signup and view all the answers

<p>Postpartum hemorrhage, abortion</p> Signup and view all the answers

<p>Stimulates uterine contractions and promotes hemostasis, reducing bleeding in the uterus</p> Signup and view all the answers

<p>Treatment of HER2+ metastatic or resistant breast cancer</p> Signup and view all the answers

<p>True (A)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>True (A)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>True (A)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>True (A)</p> Signup and view all the answers

<p>True (A)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

Management of acute inflammatory conditions, prevention of organ transplant rejection, treatment of autoimmune disorders

Corticosteroid receptor (CR) binding: NF-κB complex stabilization → no nuclear translocation: inhibits transcription of inflammatory cytokines; CR nuclear translocation: promotes transcription of anti-inflammatory cytokines; Reduces expression of adhesion molecules: decreased inflammatory cell recruitment; Inhibits PLA2: inhibits prostaglandin synthesis

Prevention of hemolytic disease of the newborn

Binds Rho(D) antigens on fetal RBCs, facilitating their clearance from maternal circulation; prevents anti-Rho(D) antibody formation in the mother

Prevention of organ transplant rejection

Binds CD3 on T cells, leading to initial activation followed by complex internalization and deactivation

Prevention of organ transplant rejection

Blocks IL-2 receptor (α subunit) preventing IL-2 binding and T cell maturation; reduces antibody production due to decreasing CD4+ T cells

Management of TNFα-mediated inflammatory conditions

Bind soluble/free TNFα reducing cytokine signalling through TNFα receptors and suppressing inflammatory cytokine production

Treatment of pre-cancerous tissues/lesions (topical)

TLR7 agonism; stimulating leukocyte activation and secretion of inflammatory cytokines

Treatment of B cell lymphomas and autoimmune conditions

Binds CD20 on B cells, inducing ADCC

Cancer immunotherapy

Bind PD-1 preventing its interaction with PD-L1; reverses T cell exhaustion and restores anti-tumor immune responses

Cancer immunotherapy

Binds PD-L1 preventing its interaction with PD-1; enhances T cell-mediated anti-tumor immunity

Cancer immunotherapy

Binds CTL4, blocking its inhibitory signalling; enables T cell activation through CD28/CD80 promoting anti-tumor immunity

Treatment of Hodgkin's Lymphoma

Binds CD30, delivering MMAE (microtubule inhibitor) which kills cells

Treatment of relapsed/refractory B cell acute lymphoblastic leukemia

Binds CD22, delivering calicheamicin (DNA-damaging agent) which kills cells

Treatment of relapsed/refractory AML

Binds CD22, delivering calicheamicin (DNA-damaging agent), which kills cells

Treatment of cancer

Bispecific antibody; binds CD3 (on T cells) and CD20 (on tumours) forcing an interaction for T-cell mediated killing; can also initiate ADCC

Treatment of cancer

Bispecific antibody (only antigen-recognition domains); binds CD3 (on T cells) and CD19 (on tumours) forcing an interaction for T-cell mediated killing

Recombinant CTLA-4

Management of rheumatoid arthritis

Competes with CD28 for CD80/86 binding, reducing T cell costimulation and activation

Treatment of rheumatoid arthritis and autoimmune conditions

Fusion protein; neutralizes soluble/free TNFα, reducing inflammatory cytokine signalling

Treatment of CD19+ B cell lymphomas and leukemias

Engineered T cells recognize overexpressed CD19, inducing direct killing of target cells (doesn't require costimulation)

Cytokine release syndrome, severe inflammation, B cell depletion