Immunomodulatory treatment Flashcards
(49 cards)
1
Q
List tx options
A
- 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
Q
Aim - tx
A
- halting ongoing damage
- satisfy nutrional and nursing requirements
- non-specific immunosuppression is key
3
Q
What are possible adjunctive therapies to corticosteroids?
A
- diet
- topical therapy and GIT barrier protection
- splenectomy?
- blood products and darbepoietin (synthetic erythropoeitin)
- danazol? plasmapherisis?
4
Q
What is danazol?
A
drug which suppresses gonadotrophin production and has some weak androgenic effects
5
Q
Indications - splenectomy
A
- IMTP
- intractable haemolysis
6
Q
Indications - topical therapy and GIT barrier protection
A
- 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
Q
What is plasmapheresis?
A
- filtering plasma using external filter
- for temporary/emergency control of intractable haemolysis
8
Q
What are the important aspects of nursing care?
A
- 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
Q
Action - corticosteroids
A
- 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
Q
What are GREs associated with?
A
= Growth Response Element
- associated with pro- and anti-inflammatory genes
11
Q
What does fluorination of prednisone do?
A
increases GC and MC activity
12
Q
What does addition of CH3 to prednisone to make it dexamethasone do?
A
abolishes MC activity so only left with GC activity
13
Q
Is dexamethasone or prednisone most potent?
A
dexamethasone is 7-8 times more potent vs prednisone thus lower dose can last > 48 hours
14
Q
Potential averse effects of corticosteroids
A
- CNS
- MSK
- GIT
- fluid, electrolyte balance
- metabolic
- endocrine
- immune system
15
Q
What stage of the cell cycle do vinca alkaloids target?
A
M phase
16
Q
Which drugs target G1 of cell cycle?
A
- calcineurin inhibitors
- leflunomide
17
Q
Which drug targets cells b/w G1 and S phases?
A
rapamycin (but typically not used clinically)
18
Q
Which drugs target the āSā phase of the cell cycle?
A
- corticosteroids
- antimetabolites
- Mycophenolate mofetil
19
Q
Action - alkylating agents
A
- 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
Q
Examples - alkylating agents
A
- cyclophosphamide, ifosfamide, chlorambucil
- melphalan, mechlorethamine, nitrosoureas
- procarbazine, dacarbazine
21
Q
Is cyclophosphamide or chlorambucil more frequently used as an alkylating agent in I-M dz?
A
- CHLORAMBUCIL most commonly
- (cyclophosphaide not used for I-M dz but for shock chemo tx of lymphoma)
22
Q
Action - chlorambucil
A
- 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
Q
Name 2 antimetabolites
A
- AZATHIOPRINE
- (methotrexate)
24
Q
Action - azathioprine
A
- 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
Action and use - ciclosporin
- IV and oral forms
- large volume of distribution
- primary hepatic metabolism
- therapeutic drug monitoring
- acute and chronic
- ketoxonazole may be used to reduce costs
- GIT, renal, hepatic toxicity, also hirsutism, gingival hyperplasia, papillomatosis, +/- diabetogenic (thus CI if DM).
31
Which drugs target the 'S' phase of the cell cycle?
- corticosteroids
- antimetabolites
- Mycophenolate mofetil
32
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
33
Examples - alkylating agents
- cyclophosphamide, ifosfamide, chlorambucil
- melphalan, mechlorethamine, nitrosoureas
- procarbazine, dacarbazine
34
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)
35
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
36
Name 2 antimetabolites
- AZATHIOPRINE
| - (methotrexate)
37
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
38
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)
39
What is vinorelbine?
- semi-synthetic derivative of vinblastine
| - can cause neutropaenia
40
Name 2 calcineurin inhibitors
- ciclosporin
| - tacrolimus
41
What is ciclosporin isolated from?
2 different fungal organisms
42
Action and use - ciclosporin
- IV and oral forms
- large volume of distribution
- primary hepatic metabolism
- therapeutic drug monitoring
- acute and chronic
- ketoxonazole may be used to reduce costs
- GIT, renal, hepatic toxicity, also hirsutism, gingival hyperplasia, papillomatosis, +/- diabetogenic (thus CI if DM).
43
What is human IVIG?
- polyspecific IgG derived from healthy donor plasma
- primary use in human medicine is in tx of immunodeficiency
- blockade of Fc R on mononuclear phagocytic cells accounts for rapid response
- inhibits phagocytosis of Ab-coated RBCs
- possible role in acute rx IMHA, immune-mediated non-regen anaemia, pure red cell aplasia, ITP, EM, TEN and SARDS
- SIDE EFFECTS: thromboembolism, hypersensitivity possible
- high cost, limited availability
44
What is Mycophenolate mofetil?
- increasingly common immunosuppressive drug
| - antagonises the enzyme needed for BC and TC growth
45
List guidelines for immunosuppressive tx
- start with prednisone or prednisolone
- cats tolerate better
- max dose in dogs >30kg is 60-80mg/dog
- caution if used in parallel with doxycyline for ricekettsial or protozoal infection.
- caution if IMHA or aggressive I-M dz, consider adjunctive tx from outset: azathioprine in dogs or chlorambucil in cats
- caution as rx of acquired MG represents special case
- always consider co-morbidities
46
What is response to immunosuppressive therapy is porr?
- add adjunctive immuno-suppressants if not already being administered
- caution if combination rx used from outset and still no response, consider additional measures (vincristine, hIVIG)
- beware of occult infsn, neoplasia, iatrogenic cause
- always consider supportive measures (FWB, PLT-rick plasma)
47
How often should the CBC and UA be monitored?
- q7-14 days
- also examine urine sediment
(+/- monitor synovial fluid with sterile technique)
48
How should corticosteroid dose be tapered?
- over 3-4mo following initial remission
- 20-25% decrease in dose every 4-6 wks so long as clinical remission maintained
- don't alter adjunctive rx at same time unless essential (e.g. fulminant infxn)
- if signs recur, return to previous dose: attempt reinduction of remission, taper more slowly next time
- corticosteroid rx may be stopped completely if clinical remission persists
- cautious tapering of additional agents over following 2-3 months
- caution if several immunosuppressant used, taper one at a time and slowly
- all rx may be stopped if long-term remission
- TLC essential
49
T/F: phenobarbital has a known I-M reaction sometimes
True
