Corticosteroids Flashcards
What are the genomic actions fo corticosteroids?
Monomer tehering transactivation
Monomer tethering transrepression
^ for both of this they bind to other things directly
Monomer trasncactivation
monomer trasncrepression
^ bind thogouh a co activator
dimer actiaction
dimer repression
^form dimers
Anti-inflammatory Actions of Steroids: genes that decrease
Gene Targets decreased expression by Steroids
CYTOKINES
TNF-α, IL-1β, IL-2-6, 11-13, GM-CSF
CHEMOKINES
RANTES, Eotaxin, MIP-1α, MCP-1
INFLAMMATORY ENZYMES
COX-2
5-Lipoxygenase (5-LOX)
Phospholipase A2 (PLA2)
ADHESION MOLECULES
ICAM-1, VCAM-1, E-Selectin
RECEPTORS
IL-2R, T-Cell Receptor
Anti-inflammatory Actions of Steroids: genes that increase
Gene Targets increased by Steroids
Annexin-A1: A PLA2 inhibitor
β2-Adrenoceptor
IL-1 Receptor Antagonist (Anakinra)
IL-1R2 (Decoy Receptor)
Neutral Endopeptidase (NEP)
Endonucleases
IκB-α (Inhibitor of NF-κB)
MAPK Phosphatase-1 (MKP-1)
Glucocorticoid-induced Leucine Zipper
(GILZ)
Biological outcomes of Steroids
DECREASE Circulating T cells, B cells, monocytes, eosinophils & basophils via increased apoptosis
INCREASE circulating neutrophils via increased production and reduced extravasation
DECREASE The size and lymphoid content of lymph nodes
Have more effects on cellular immunity than humoral immunity
INCREASE Macrophage efferocytosis and promotion of resolution of inflammation
DECREASE Type-IV delayed hypersensitivity reaction (e.g., transplantation rejection)
First-line immunosuppressant in solid organ and hematopoietic stem cell
transplantation
PK/PD of the cortisol
DOA: 8-12H
GC:1
MC:1
Dose:20
DOA: Duration of Action
GC: Glucocorticoid (Anti-inflammatory Potency Effect)
MC: Mineralocorticoid (Water-Retention Side Effect)
PKPD of Prednisone
DOA: 12-36H
GC:4
MC:0.3
Dose:5
DOA: Duration of Action
GC: Glucocorticoid (Anti-inflammatory Potency Effect)
MC: Mineralocorticoid (Water-Retention Side Effect)
PKPD of Prednisone
DOA: 12-36H
GC:5
MC:0.3
Dose:5
DOA: Duration of Action
GC: Glucocorticoid (Anti-inflammatory Potency Effect)
MC: Mineralocorticoid (Water-Retention Side Effect)
PKPD of Methylprednisolone
DOA: 12-36H
GC:5
MC:0
Dose:4
DOA: Duration of Action
GC: Glucocorticoid (Anti-inflammatory Potency Effect)
MC: Mineralocorticoid (Water-Retention Side Effect)
PKPD of Methylprednisolone
DOA: 12-36H
GC:5
MC:0
Dose:4
DOA: Duration of Action
GC: Glucocorticoid (Anti-inflammatory Potency Effect)
MC: Mineralocorticoid (Water-Retention Side Effect)
PKPD of Dexamethasone
DOA: 24-72H
GC:30
MC:0
Dose:0.75
DOA: Duration of Action
GC: Glucocorticoid (Anti-inflammatory Potency Effect)
MC: Mineralocorticoid (Water-Retention Side Effect)
List the clinical use of Steroids
Inflammatory Diseases
anything related to inflammation itself
Allergic
Reactions
Asthma, Atopic Dermatitis, Rhinitis,
Urticaria, Serum Sickness, Anaphylaxis
Collagen-Vascular
Disorders
Lupus erythematosus, Rheumatoid
arthritis,
GI Diseases Ulcerative colitis, Crohn’s disease
Hematologic
Disorders
Leukemia, Lymphoma, Hemolytic
Anemia, Thrombocytopenia
Renal Disorders Nephrotic syndrome
Organ
Transplants
Graft-versus-Host Syndrome, Organ
Rejection
Eye Diseases Uveitis, Conjunctivitis
Side effects of Steroids in Endocrine-Metabolic Effects
Hyperglycemia (increased glucose level)
Moon Face, ‘Buffalo Hump’ & Truncal Obesity (Fat Redistribution) bc of increased glycogenesis and fat redistribution to trucal regions
Muscle Wasting(breakdown)
Growth Retardation (Pediatric Patients)
Acne, Hirsutism & Menstrual Disturbances(humoral side effects)
Delayed Wound Healing(bc protein breakdown)
Skin Thinning, Easy Bruising(collagen down regulation
Increased Appetite, Weight Gain
Na/Fluid Retention, Edema, HTN, CHF
Side effect of Steroids in Musculoskeletal system
Osteoporosis (Trabecular Bone)
Aseptic Necrosis of Femoral Head
Myopathy (Dexamethasone/Triamcinolone)
Side effect of Steroids in Immune system
Opportunistic Infections
Bacterial (TB)
Viral (Herpes & CMV)
Fungal (Candida, Aspergillus & Crytococca)
Parasitic (Toxoplasmosis)
Side effect of Steroids in Eye
Posterior Subcapsular Lens
Cataract
Glaucoma
