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605 Pharmacology > Immunosuppresants > Flashcards

Immunosuppresants Flashcards

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

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

A

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

25
Q

Indications for Leflunomide Use

A

mainly for IMPA (most evidence), but also rheumatoid arthritis, IMHA/ITP, systemic histiocytosis, and chronic enteropathies and skin disease

26
Q

H1 Antagonists

A

the fancy name for antihistamines; reversible competitive for the H1 receptor

27
Q

2 Histamine Pools

A
  1. Mast Cell Pool
  2. Non Mast Cell Pool
28
Q

Mast Cell Pool of Histamines

A

synthesized SLOWLY in mast cells and basophils, RELEASE is regulated

29
Q

Non Mast Cell Pool of Histamines

A

synthesized QUICKLY in ECLs, neurons, and others; production is REGULATED and release is CONTINUOUS

30
Q

H1 Receptors Location

A

present in smooth muscle of cardiovascular, respiratory, GI, and urogential systems, also the CNS and PNS and immune cells

31
Q

H2 Receptor Location

A

parietal cells of stomach, also some smooth and cardiac muscle

32
Q

Primary Role of H1 Receptors

A

anaphylactic/anaphylactoid reactions

33
Q

Primary Role of H2 Receptors

A

gastric acid secretion

34
Q

Cutaneous Effects of Histamine

A

wheals and flares, angioedema, itch

35
Q

Systemic Effects of Histamine

A

blood pressure, increased gastric acid secretion, broncho- effects

36
Q

Histamine on Blood Pressure in Rodents and Rabbits

A

increases blood pressure (hypertension)

37
Q

Histamine on Blood Pressure in Carnivores and Large Animals

A

decreases blood pressure (hypotension)

38
Q

Histamine on Respiratory System in Sheep

A

bronchodilator (in all/most other species it is a bronchoconstrictor)

39
Q

First Generation H1 Antagonists

A

antagonize more than just the H1 receptor (dopamine, serotonin, muscarinic Ach, etc); can readily cross blood brain barrier

40
Q

Second Generation H1 Antagonists

A

pretty damn specific to H1 receptor; cannot cross the blood brain barrier

41
Q

Turtle

A

i drew this

42
Q

Examples of First Gen Antihistamines

A

Benadryl, Dramamine

43
Q

Examples of Second Gen Antihistamines

A

Zyrtec, Allegra, Claritin

44
Q

Indications for Antihistamine Use

A

acute allergic reactions/anaphylaxis, sometimes in chronic skin condition cases, mast cell tumors, nausea (only first gen)

45
Q

Adverse Effects of First Gen Antihistamines

A

sedation, but also excitation at higher doses, antimuscarinic effects (but mainly these are in humans)

46
Q

Xerostomia

A

dry mouth

47
Q

Adverse Effects of Second Gen Antihistamines

A

minimal adverse effects!!!

48
Q

IL-31

A

a mediator in itch, secreted from Th2 cells; pathway a target of new anti-pruritic drugs

49
Q

JAK

A

Janus kinase involved in cytokine signal transduction; different isoforms are associated with different cytokine receptors

50
Q

Apoquel (oclacitinib)

A

targets JAK1 therefore blocking the itch signal from IL-31; also affects other cytokines! (2, 4, 6 and 13)

51
Q

small molecule inhibitor (-nib)

A

small drugs which target enzymes involved in signal transduction

52
Q

CONTRAindications for Apoquel

A

young animals (puppy/kitten), serious infections, previous neoplasias, breeding/pregnant/lactating animals

53
Q

Adverse Effects of Apoquel

A

vomiting/diarrhea, anorexia, otitis/pyoderma, neoplasia (eh), and rarely, reversible bone marrow suppression

54
Q

Cytopoint (lokivetmab)

A

caninized mAb against IL-31 (so it binds the cytokine and removes it from circulation)

55
Q

Adverse Effects of Cytopoint

A

can cause vomiting/diarrhea, lethargy, or immune-mediated disease

605 Pharmacology (11 decks)

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