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605 Pharmacology > Immunosuppresants > Flashcards

Immunosuppresants Flashcards

(55 cards)

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1
Q

Indications for Secondary Immunosuppressant Use

A

inadequate initial response, negative prognostic indicators, contraindications to steroids, relapse after steroid administration

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2
Q

4 Selection Criteria for Secondary Immunosuppressants

A
  1. Onset of Action
  2. Specific Indications
  3. Adverse Reactions
  4. Cost
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3
Q

Azathioprine MOA

A

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)

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4
Q

Azathioprine Indications

A

IBD, anemia, colitis in DOGS in combination with other therapy with EOD dosing goal

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5
Q

Adverse Effects/Disadvantages of Azathioprine

A

slow onset of action, very hepatotoxic and myelotoxic, and some proof that it could cause pancreatitis

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6
Q

Only advantage of Azathioprine?

A

CHEAP (like seriously very cheap)

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7
Q

What happens if you give azathioprine to cats?

A

it is incredibly toxic, causes myelosuppression

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8
Q

Cyclosporine MOA

A

calcineurin inhibitor, therefore decreasing T-cell activation

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9
Q

Indications for Cyclosporine Use

A

atopic dermatitis (brand name: Atopica), and immune-mediated systemic dz

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10
Q

Formulations of Cyclosporine

A
  1. Oil-based Suspension (Sandimmune)
  2. Microemulsions
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11
Q

What formulation of cyclosporine has the most reliable bioavailability?

A

microemulsions

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12
Q

Ketoconazole and Cyclosporine

A

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

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13
Q

Most Common Adverse Reaction of Cyclosporine

A

GI upset

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14
Q

Other Adverse Reactions of Cyclosporine

A

hair loss, gingival hyperplasia, secondary infection, nephro/hepato toxicities and lymhoid neoplasias

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15
Q

Chlorambucil MOA

A

prevents DNA synthesis via cross-linking (it’s an alkylating agent)

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16
Q

Chlorambucil Indications

A

primarily for chronic enteropathies like IBD, and sometimes low grade GI lymphoma in cats

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17
Q

Chlorambucil Adverse Effects/Disavantages

A

slow onset and VERY expensive; can cause GI upset, myelosuppression, and sometimes neurotoxicity or Fanconi syndrome in cats

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18
Q

Fanconi Syndrome

A

proximal tubular reabsorptive defect; can be acquired; essentially lose solutes in the urine

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19
Q

Mycophenolate MOA

A

prodrug which inhibits de novo guanosine synthesis (again, affects DNA in lymphocytes d/t lack of salvage pathway), inhibits B and T cells

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20
Q

IMHA

A

immune-mediated hemolytic anemia

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21
Q

Indications for Mycophenolate

A

IMHA/ITP/IMPA, immune-mediated skin diseases, meningoencephalitis, immune-complex glomerulonephritis

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22
Q

Adverse Effects of Mycophenolate

A

dose-dependent GI upset (anorexia/diarrhea), myelotoxicity, and a few get skin lesions

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23
Q

Leflunomide MOA

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A

activated to teriflunomide and inhibits de novo pyrimidine (thymine and cytosine) synthesis, targeting the B and T cells which again lack the salvage pathway

24
Q

Disadvantages/Adverse Effects of Leflunomide

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A

very expensive, unknown onset of action but probs slow; can cause diarrhea, lethargy, hemorrage, thrombocytopenia, and increased liver enzymes

25
Indications for Leflunomide Use
mainly for IMPA (most evidence), but also rheumatoid arthritis, IMHA/ITP, systemic histiocytosis, and chronic enteropathies and skin disease
26
H1 Antagonists
the fancy name for antihistamines; reversible competitive for the H1 receptor
27
2 Histamine Pools
1. Mast Cell Pool 2. Non Mast Cell Pool
28
Mast Cell Pool of Histamines
synthesized SLOWLY in mast cells and basophils, RELEASE is regulated
29
Non Mast Cell Pool of Histamines
synthesized QUICKLY in ECLs, neurons, and others; production is REGULATED and release is CONTINUOUS
30
H1 Receptors Location
present in smooth muscle of cardiovascular, respiratory, GI, and urogential systems, also the CNS and PNS and immune cells
31
H2 Receptor Location
parietal cells of stomach, also some smooth and cardiac muscle
32
Primary Role of H1 Receptors
anaphylactic/anaphylactoid reactions
33
Primary Role of H2 Receptors
gastric acid secretion
34
Cutaneous Effects of Histamine
wheals and flares, angioedema, itch
35
Systemic Effects of Histamine
blood pressure, increased gastric acid secretion, broncho- effects
36
Histamine on Blood Pressure in Rodents and Rabbits
increases blood pressure (hypertension)
37
Histamine on Blood Pressure in Carnivores and Large Animals
decreases blood pressure (hypotension)
38
Histamine on Respiratory System in Sheep
bronchodilator (in all/most other species it is a bronchoconstrictor)
39
First Generation H1 Antagonists
antagonize more than just the H1 receptor (dopamine, serotonin, muscarinic Ach, etc); can readily cross blood brain barrier
40
Second Generation H1 Antagonists
pretty damn specific to H1 receptor; cannot cross the blood brain barrier
41
Turtle
i drew this
42
Examples of First Gen Antihistamines
Benadryl, Dramamine
43
Examples of Second Gen Antihistamines
Zyrtec, Allegra, Claritin
44
Indications for Antihistamine Use
acute allergic reactions/anaphylaxis, sometimes in chronic skin condition cases, mast cell tumors, nausea (only first gen)
45
Adverse Effects of First Gen Antihistamines
sedation, but also excitation at higher doses, antimuscarinic effects (but mainly these are in humans)
46
Xerostomia
dry mouth
47
Adverse Effects of Second Gen Antihistamines
minimal adverse effects!!!
48
IL-31
a mediator in itch, secreted from Th2 cells; pathway a target of new anti-pruritic drugs
49
JAK
Janus kinase involved in cytokine signal transduction; different isoforms are associated with different cytokine receptors
50
Apoquel (oclacitinib)
targets JAK1 therefore blocking the itch signal from IL-31; also affects other cytokines! (2, 4, 6 and 13)
51
small molecule inhibitor (-nib)
small drugs which target enzymes involved in signal transduction
52
CONTRAindications for Apoquel
young animals (puppy/kitten), serious infections, previous neoplasias, breeding/pregnant/lactating animals
53
Adverse Effects of Apoquel
vomiting/diarrhea, anorexia, otitis/pyoderma, neoplasia (eh), and rarely, reversible bone marrow suppression
54
Cytopoint (lokivetmab)
caninized mAb against IL-31 (so it binds the cytokine and removes it from circulation)
55
Adverse Effects of Cytopoint
can cause vomiting/diarrhea, lethargy, or immune-mediated disease

605 Pharmacology (11 decks)

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