ImmunoPharm #2 Flashcards
Immunosuppressants
▪ Immunosuppressatory drugs act by a _____ of mechanisms
▪ These drugs interfere with combinations of critical pathways in the ___________ cascade
▪ “Cytotoxic” drugs: cause cell _______, _________, or impaired ________.
▪ “Lymphocyte” drugs: ______ immune system by inhibiting function or proliferation of _______, production of ______ etc
▪ Glucocorticoids: have many effects upon _____ and ______ immunity
variety, inflammatory, necrosis, apoptosis, proliferation, suppress, lymphocytes, cytokines, innate, adaptive
Immunosuppressants: Classification
- Antimetabolites
- Inhibitors of Matrix Metalloproteinase (MMPs)
- Other immunomodulators
- Inhibitors of Cytokines
Antimetabolites
➢ _______ synthesis inhibitors
✓ Azathioprine (ImuranR), ✓Mycophenolic acid
OR
➢ _______ synthesis inhibitor
B: ✓ Leflunomide
Purine, Pyrimidine
An Inhibitors of Matrix Metalloproteinase (MMPs) is the drug?
Tetracycline
Other Immunomodulators
➢ _____ Therapy (chrysotherapy)
✓ Auranofin
✓ Gold sodium thiomalate
OR
➢__________
Gold, Niacinamide
❑ Inhibitors of Cytokines
➢ IL-__ inhibitors
✓ Cyclosporine
✓ Tacrolimus
OR
➢ _______ ________ ________ ____ (____) inhibitor
✓ Pentoxyfylline
2, Tumor-necrosis factor-α (TNFα)
Azathioprine (________): a ________ Synthesis Inhibitor
ImuranR, Purine
Antimetabolic drugs inhibit cellular synthesis of _______ _____ that are required for RNA and DNA synthesis resulting in cellular ______ and ______ arrest
nucleic acids, proliferation, function
Azathioprine MOA: ______ DNA synthesis of __- and __-lymphocytes
Blocks ____ signaling on ___-cells resulting in impaired _____ synthesis
inhibits, B, T, CD28, T, RNA
Azathioprine Uses
In conjunction with _______ to treat ______-mediated diseases such as?
steroids, immune
▪ Immune-mediated hemolytic anemia = dogs
▪ Immune-mediated thrombocytopenia
▪ Colitis and skin disease
▪ Myasthenia gravis
▪ Inflammatory bowel disease
▪ Immune-mediated inflammatory conditions and perianal fistulas in dogs
▪ Autoimmune skin disease in horses
Azathioprine PK
▪ Azathioprine is a _______, well absorbed by the gut
▪ Several metabolic steps to become ___
▪ Detoxification is important, cats and ____% dogs are ____ in enzymes
▪ Do not give to _____
prodrug, active, 10, low, cats
Azathioprine Adverse Effects
▪ _________ _______ suppression
▪ Fatal ______ and ________
▪ Increase risk for _____
▪ ____________ and ___ pancreatitis
▪ _________ (changes in genetic material), __________ (reversible structural malfunctions in fetus) and __________ (cancerous tumors) effects
Bone marrow, leukopenia, thrombocytopenia, infection, Hepatotoxicity, acute, Mutagenic, teratogenic, carcinogenic
Leflunomide: a ________ Synthesis Inhibitor
MOA?
Inhibits _________ enzyme necessary for ____ ________ ______ synthesis
Affects particularly ___- and ____-lymphocytes DNA synthesis
Pyrimidine, mitochondrial, de novo pyrimidine, B-, T-
Leflunomide Uses
▪ Immune-mediated hemolytic anemia
▪ Immune-mediated thrombocytopenia
▪ Immune-mediated polymyositis
▪ Multifocal nonsuppurative encephalitis/meningomyelitis
▪ Evan’s syndrome
Leflunomide PK
▪ OP: good _________ of ____ metabolite
▪ High ______ bound
▪ _____ metabolism
▪ Conversion of Leflunomide to a toxic metabolite is ______ in cats then dogs
bioavailability, active, protein, Liver, slower
Leflunomide Adverse Effects
▪ Uncommon in ____
▪ May include ___ disturbances
▪ ______
dogs, GI, Anemia
Polymyositis is a relatively common ________ disease in ____ that causes muscle ________ and ______.
There are 3 main causes of polymyositis in dogs:
▪ Infectious agents (?)
▪ Immune-mediated ( ______diseases)
▪ ______________ causes (tumors affecting muscles, ex. Lymphoma)
inflammatory, dogs, weakness, fatigue
bacteria, viruses, protozoa or parasites, autoimmune, Paraneoplastic
What are the signs and symptoms of polymyositis in dogs?
▪ __________ weakness that worsens with ______
▪ Muscle _____ and ___
▪ _______ (lack of _____)
▪ Exercise _________
▪ Muscle ___________
Generalized, exercise, swelling, pain, Anorexia, appetite, intolerance, wasting
Treatment for polymyositis:
Azathioprine
Leflunomide
Cyclosporine
Prednisone
Polymyositis In Dogs: Causes, Symptoms And Treatment
Cyclosporine: an IL-__ Inhibitor MOA
Cyclophillin is a mitochondrial protein expressed in ___ cells, important for protein ______. It bins to receptor in mitchondria of t cells.
Calcineurin is a protein phosphatase that activates _________ by then phosphorylating and translocating to the nucleus. It is important for dephosphorylation of NFAT__ –> NFAT__ which enters nucleus and activates IL-__.
___________ competes with ______ to bind to receptors and interfere with IL-2 proliferation.
2, T, folding, nuclear factor NF-ATc, c, n, 2, Cyclosporine, cyclophillin
Cyclosporine: an IL-2 Inhibitor (cont)
Pharmacological effects?
▪ T-lymphocytes:
Decrease production of IL-?
Decrease production of _____
Decrease TNF__
Decrease proliferation of both CD__+ and CD__+ lymphocytes
Increase TGF__ (inhibits IL-__)
▪ Mast cells: Decrease _______ release in canine mast cells
2, IL-3, and IL-4, G-CSF, α, 4, 8, β, 2, histamine
Cyclosporine Uses?
Uses:
▪ ________________ ________: topical application , increased ____ production
▪ _____________ ______: elimination/reduction in ____, OP, __-__ months of treatment
▪ ______: in conjunction with glucocorticoids
Keratoconjunctivitis sicca, tear, Perianal fistulas, size, 2-3, IMHA
Cyclosporine PK?
PK:
▪ ____, not well ______
▪ Distribution: ?
▪ ____ metabolism
▪ ____/____ excretion
OP, absorbed,
liver, fat, red blood cell and lymphocytes
Liver,
bile/urine
Cyclosporine Adverse Effects?
Adverse effects:
▪ ____ disturbances
▪ Gingival ________
▪ ___________ in dogs
▪ Viral infections in ____
GI, hyperplasia, Papillomatosis, cats
Tacrolimus (FK-506): an IL-2 Inhibitor
MOA?
Tacrolimus, also called FK506, prevents the dephosphorylation of NF-AT by binding to FKBP12 –> Prevents IL proliferation
Tacrolimus
Therapeutic uses?
▪ Keratoconjunctivitis sicca
▪ Localized topical treatment of immune-mediated dermatological disease
Tacrolimus PK
Since it applied topically, very little is absorbed systemically
Tacrolimus Adverse effects
Local irritation
Pentoxyfylline (PTX): TNFα inhibitor
MOA: ? __________ the release and production of the _______ _____,
suppresses the production of __________-_______ factor, and
inhibits its action on _______.
downregulates, profibrotic TNF, platelet-activating, neutrophils
Pentoxyfylline (PTX): TNFα inhibitor
Uses: ?
Canine skin diseases:
▪ Vasculitis
▪ Dermatomyositis
▪ Contact allergy
▪ Atopic dermatitis
▪ Vaccine-induced ischemic dermatitis
Equine:
▪ Systemic inflammatory response syndrome
▪ Caudal heal syndrome
Pentoxyfylline PK ?
PK: rapid absorption in ____
Adverse effects?
Adverse effects: ___
▪ __ disturbance
▪ CNS ?
dogs, Rare, GI, excitement/nervousness
Tetracyclines are a broad spectrum antibiotics
Tetracyclines and tetracycline derivatives are able to inhibit ______ activity, _____________ of their anti-microbial action.
MMPs: play a major role in cell ?
MMP, independent
proliferation, diffferentiaon, migration, apoptosis, angiogenesis, and host defense.
Describe the duration of action of the following drugs?
See below
Tetracyclines uses?
▪ Systemic
▪ Topical ophthalmic
Tetracycline adverse effects?
▪ Vomiting, diarrhea
▪ Kidney damage
▪ Liver damage
▪ Loss of appetite
➢ Gold Therapy (chrysotherapy)
✓ __________
✓ _________ ____________ _________
1. MOA:
2. Uses: ?
3. Adverse effects: ?
Auranofin, Gold sodium thiomalate
- Not completely understood [ inhibition of phagocytes (macrophages) and T-cells]
- Idiopathic polyarthritis
Rheumatoid arthritis
Pemphigus foliaceus (PF)
Chronic gingivitis/stomatitis - ▪ Stomatitis
▪ Skin lesions
▪ Hepatic necrosis
▪ Renal toxicity
▪ GI disturbances
➢ Niacinamide is a vitamin _____ (nutritional supplement or with other medications)
MOA: ?
Uses: particularly in dogs?
PK:
▪ OP, well ______
▪ ______ distributed in the body
▪ ____ metabolism
▪ _____ excretion
Adverse effects:
▪ ___ disturbances
▪ _____
▪ Elevation of _____ enzymes
- B3
- poor understood (blocks mast cell degranulation and inhibits protease release from leukocytes)
- ▪ Discoid lupus erythematosus
▪ Pemphigus erythematosus
▪ Pemphigus foliaceus (PF)
▪ Autoimmune diseases
absorbed, Widely, Liver, Urine, GI, Lethargy, hepatic
Do not need to know
Do not need to know
Autoimmune disorders
▪ Immune system attacks the ______ cells in the body by mistake
▪ The body has lost its ability to differentiate between antigens on its ______ cells and antigens on ______ cells
▪ Antibodies attack _____-antigens
▪ ______ is a major mechanism of tissue damage
Cause: ?
healthy, own, foreign, self, Inflammation, Genetic
Environmental
Hemolytic Anemia in Dogs
▪ Autoimmune hemolytic anemia (AIHA) is an immune system disease, in which the body attacks and destroys its own _____ (_______).
▪ Immune-Mediated Hemolytic Anemia (IMHA) causes severe _____ in dogs and is
associated with considerable _____ and _____
▪ IMHA is the most common autoimmune disease in _____
RBCs, hemolysis, anemia, morbidity, mortality, dogs
Management of IMHA:
Controlling the immune response:
Skipped?
