Flashcards in Immunomodulatory treatment Deck (49)
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1
List tx options
- corticosteroids (mainstay, various adjunctive tx may be helpful)
- other immunosuppressive drugs (alkylating agents, antimetabolites, mitotic inhibitors - vinca alkaloids, calcineurine inhibitors, others)
* novel agents offer more potent and targeted immunosuppression
2
Aim - tx
- halting ongoing damage
- satisfy nutrional and nursing requirements
- non-specific immunosuppression is key
3
What are possible adjunctive therapies to corticosteroids?
- diet
- topical therapy and GIT barrier protection
- splenectomy?
- blood products and darbepoietin (synthetic erythropoeitin)
- danazol? plasmapherisis?
4
What is danazol?
drug which suppresses gonadotrophin production and has some weak androgenic effects
5
Indications - splenectomy
- IMTP
- intractable haemolysis
6
Indications - topical therapy and GIT barrier protection
- Topical: only if concurrent dz which increases tendency for ulcers to form - look out for GIT bleeding
- GIT protection: usually for IMTP as ramifications bad if bleeding d/t ulcers occur
7
What is plasmapheresis?
- filtering plasma using external filter
- for temporary/emergency control of intractable haemolysis
8
What are the important aspects of nursing care?
- recumbency: urination, defecation, hygiene, gentle exercise
- CS of clinical deterioration?
- analgesia and general comfort
- nutrition (naso-oesophageal, oesophageal, PEG tubes)
- water access and ability to drink
- IV catheter care, IVFT
- procurement of diagnostic samples
- client communication
- TLC
9
Action - corticosteroids
- associate with binding proteins (transcortin and albumin)
- following dissociation from binding proteins, passively diffuse into cell
- bind to a cytoplasmic receptor (>/3)
- conformational change of receptor unmasks DNA binding domain; associates with GREs following nuclear translocation
10
What are GREs associated with?
= Growth Response Element
- associated with pro- and anti-inflammatory genes
11
What does fluorination of prednisone do?
increases GC and MC activity
12
What does addition of CH3 to prednisone to make it dexamethasone do?
abolishes MC activity so only left with GC activity
13
Is dexamethasone or prednisone most potent?
dexamethasone is 7-8 times more potent vs prednisone thus lower dose can last > 48 hours
14
Potential averse effects of corticosteroids
- CNS
- MSK
- GIT
- fluid, electrolyte balance
- metabolic
- endocrine
- immune system
15
What stage of the cell cycle do vinca alkaloids target?
M phase
16
Which drugs target G1 of cell cycle?
- calcineurin inhibitors
- leflunomide
17
Which drug targets cells b/w G1 and S phases?
rapamycin (but typically not used clinically)
18
Which drugs target the 'S' phase of the cell cycle?
- corticosteroids
- antimetabolites
- Mycophenolate mofetil
19
Action - alkylating agents
- alkylate DNA causing breaks in molecule and cross-linking of twin strands
- inhibit protein synthesis in resting cells, prevent mitosis and kill dividing cells
20
Examples - alkylating agents
- cyclophosphamide, ifosfamide, chlorambucil
- melphalan, mechlorethamine, nitrosoureas
- procarbazine, dacarbazine
21
Is cyclophosphamide or chlorambucil more frequently used as an alkylating agent in I-M dz?
- CHLORAMBUCIL most commonly
- (cyclophosphaide not used for I-M dz but for shock chemo tx of lymphoma)
22
Action - chlorambucil
- rapidly metabolised to phenylacetic acid mustand
- site of biotransformation poorly define
- slowest acting, least toxic of all alkylating agents
- myelosuppression (main side effect) generally not observed until administered for > 1mo
- urinary and faecal excretion
- administered without food
23
Name 2 antimetabolites
- AZATHIOPRINE
- (methotrexate)
24
Action - azathioprine
- greater decrease of cellular than humoral immunity
- hepatic metabolism to active 6-mercaptopurine, then to 6-thioinosinic, 6-thioguanylic, thiouric acids
- compete with endogenous adenine and guanine to form non-function nucleic acid strands
- slow immunosuppressive effect? (at least 2 weeks, may be faster with steroids)
- these side effects are relatively uncommon: haematological, GIT, hepatic +/- neuromuscular toxicity
- CI in cats because narrow therapeutic window because cuases irreversible immunosuppression
25
What are vinca alkaloids? Examples?
- originally extracted from common periwinkle plant
- vincristine and (vinblastine) are the most commobly used
- difference is presence of a methyl (vinblastine) or formyl group (vincristine)
26
Action - vinca alkaloids
- bind to tubulin, block polymerisation, also break down pre-formed microtubules - increased release of PLTs from megakaryocytes
- both vincristine and viblastine used in the tx of ITP (usually vincristine)
- can be bolus IV or to pre-load PLTs
- severe extra-vascular vesicants!
- toxicity: haematological, GIT, neurologicall
27
Potential averse effects of corticosteroids
- CNS
- MSK
- GIT
- fluid, electrolyte balance
- metabolic
- endocrine
- immune system
28
Name 2 calcineurin inhibitors
- ciclosporin
- tacrolimus
- ACTION: target calcineurin which is a phosphatase enzyme
29
Which drugs target G1 of cell cycle?
- calcineurin inhibitors
- leflunomide
30
