Immunosuppresants Flashcards
Indications for Secondary Immunosuppressant Use
inadequate initial response, negative prognostic indicators, contraindications to steroids, relapse after steroid administration
4 Selection Criteria for Secondary Immunosuppressants
- Onset of Action
- Specific Indications
- Adverse Reactions
- Cost
Azathioprine MOA
antimetabolite that interferes with DNA synthesis, of which lymphocytes are particularly susceptible because they lack a nucleotide salvage pathway (so they have to make DNA from scratch everytime)
Azathioprine Indications
IBD, anemia, colitis in DOGS in combination with other therapy with EOD dosing goal
Adverse Effects/Disadvantages of Azathioprine
slow onset of action, very hepatotoxic and myelotoxic, and some proof that it could cause pancreatitis
Only advantage of Azathioprine?
CHEAP (like seriously very cheap)
What happens if you give azathioprine to cats?
it is incredibly toxic, causes myelosuppression
Cyclosporine MOA
calcineurin inhibitor, therefore decreasing T-cell activation
Indications for Cyclosporine Use
atopic dermatitis (brand name: Atopica), and immune-mediated systemic dz
Formulations of Cyclosporine
- Oil-based Suspension (Sandimmune)
- Microemulsions
What formulation of cyclosporine has the most reliable bioavailability?
microemulsions
Ketoconazole and Cyclosporine
can sometimes be given in combination to lower the cyclosporine dose (mainly to save the pet owner some money); ketoconazole inhibits cyclosporine metabolism therefore prolonging blood levels
Most Common Adverse Reaction of Cyclosporine
GI upset
Other Adverse Reactions of Cyclosporine
hair loss, gingival hyperplasia, secondary infection, nephro/hepato toxicities and lymhoid neoplasias
Chlorambucil MOA
prevents DNA synthesis via cross-linking (it’s an alkylating agent)
Chlorambucil Indications
primarily for chronic enteropathies like IBD, and sometimes low grade GI lymphoma in cats
Chlorambucil Adverse Effects/Disavantages
slow onset and VERY expensive; can cause GI upset, myelosuppression, and sometimes neurotoxicity or Fanconi syndrome in cats
Fanconi Syndrome
proximal tubular reabsorptive defect; can be acquired; essentially lose solutes in the urine
Mycophenolate MOA
prodrug which inhibits de novo guanosine synthesis (again, affects DNA in lymphocytes d/t lack of salvage pathway), inhibits B and T cells
IMHA
immune-mediated hemolytic anemia
Indications for Mycophenolate
IMHA/ITP/IMPA, immune-mediated skin diseases, meningoencephalitis, immune-complex glomerulonephritis
Adverse Effects of Mycophenolate
dose-dependent GI upset (anorexia/diarrhea), myelotoxicity, and a few get skin lesions
Leflunomide MOA
activated to teriflunomide and inhibits de novo pyrimidine (thymine and cytosine) synthesis, targeting the B and T cells which again lack the salvage pathway
Disadvantages/Adverse Effects of Leflunomide
very expensive, unknown onset of action but probs slow; can cause diarrhea, lethargy, hemorrage, thrombocytopenia, and increased liver enzymes
Indications for Leflunomide Use
mainly for IMPA (most evidence), but also rheumatoid arthritis, IMHA/ITP, systemic histiocytosis, and chronic enteropathies and skin disease
H1 Antagonists
the fancy name for antihistamines; reversible competitive for the H1 receptor
2 Histamine Pools
- Mast Cell Pool
- Non Mast Cell Pool
Mast Cell Pool of Histamines
synthesized SLOWLY in mast cells and basophils, RELEASE is regulated
Non Mast Cell Pool of Histamines
synthesized QUICKLY in ECLs, neurons, and others; production is REGULATED and release is CONTINUOUS
H1 Receptors Location
present in smooth muscle of cardiovascular, respiratory, GI, and urogential systems, also the CNS and PNS and immune cells
H2 Receptor Location
parietal cells of stomach, also some smooth and cardiac muscle
Primary Role of H1 Receptors
anaphylactic/anaphylactoid reactions
Primary Role of H2 Receptors
gastric acid secretion
Cutaneous Effects of Histamine
wheals and flares, angioedema, itch
Systemic Effects of Histamine
blood pressure, increased gastric acid secretion, broncho- effects
Histamine on Blood Pressure in Rodents and Rabbits
increases blood pressure (hypertension)
Histamine on Blood Pressure in Carnivores and Large Animals
decreases blood pressure (hypotension)
Histamine on Respiratory System in Sheep
bronchodilator (in all/most other species it is a bronchoconstrictor)
First Generation H1 Antagonists
antagonize more than just the H1 receptor (dopamine, serotonin, muscarinic Ach, etc); can readily cross blood brain barrier
Second Generation H1 Antagonists
pretty damn specific to H1 receptor; cannot cross the blood brain barrier
Turtle
i drew this
Examples of First Gen Antihistamines
Benadryl, Dramamine
Examples of Second Gen Antihistamines
Zyrtec, Allegra, Claritin
Indications for Antihistamine Use
acute allergic reactions/anaphylaxis, sometimes in chronic skin condition cases, mast cell tumors, nausea (only first gen)
Adverse Effects of First Gen Antihistamines
sedation, but also excitation at higher doses, antimuscarinic effects (but mainly these are in humans)
Xerostomia
dry mouth
Adverse Effects of Second Gen Antihistamines
minimal adverse effects!!!
IL-31
a mediator in itch, secreted from Th2 cells; pathway a target of new anti-pruritic drugs
JAK
Janus kinase involved in cytokine signal transduction; different isoforms are associated with different cytokine receptors
Apoquel (oclacitinib)
targets JAK1 therefore blocking the itch signal from IL-31; also affects other cytokines! (2, 4, 6 and 13)
small molecule inhibitor (-nib)
small drugs which target enzymes involved in signal transduction
CONTRAindications for Apoquel
young animals (puppy/kitten), serious infections, previous neoplasias, breeding/pregnant/lactating animals
Adverse Effects of Apoquel
vomiting/diarrhea, anorexia, otitis/pyoderma, neoplasia (eh), and rarely, reversible bone marrow suppression
Cytopoint (lokivetmab)
caninized mAb against IL-31 (so it binds the cytokine and removes it from circulation)
Adverse Effects of Cytopoint
can cause vomiting/diarrhea, lethargy, or immune-mediated disease
