Session 6 - Autoimmunity Flashcards Preview

Semester 5 - Farmocology > Session 6 - Autoimmunity > Flashcards

Flashcards in Session 6 - Autoimmunity Deck (53)
1

What is autoimmunity?

the state that is present when an individual has made an immune response to self-antigens.

2

What can aid in the diagnosis of autoimmunity?

the presence of autoantibodies in serum provides evidence for autoimmunity, and these may be helpful in diagnosing and monitoring autoimmune diseases.

3

What does autoimmune disease mean?

the term applied to a disease in which autoimmunity is thought to play a significant pathogenic role.

4

What are two overall categories of autoimmune disease?

Organ specific (target antigen in one specific tissue) vs Non-organ specific (if target antigen in many different tissues)

5

Give some organ specific autoimmune diseases

Hashimoto’s
Thyrotoxicosis
Primary myxoedema
Chronic atrophic gastritis
Pernicious anaemia
Addison’s Disease
Myasthenia gravis
Diabetes mellitus (type 1)
Premature ovarian failure
Male infertility

6

Give some mixed autoimmune diseases

Goodpasture’s syndrome
Primary biliary cirrhosis
Autoimmune haemolytic disease
Ulcerative colitis

7

Give some non-organ specific immunse diseases

Systemic Lupus Erythematosus
Rheumatoid arthritis
Sjogren’s syndrome
Progressive systemic sclerosis

8

Name some immunosupressant categories of drugs

Glucocorticoids
Azathiporine
Cytotoxic alkylating agents
Calcineurin inhibitors
Mycophenolate mofetil

9

What is the mechanism of action of glucocorticoids

 Diffuse into cytoplasm and bind receptor. Complex moves to nucleus and binds Hormone Response Element (HRE). Inducers/Inhibits transcription.

10

Give three examples of glucocorticoids

 Prednisolone (Oral)
 Beclometasone (Topical/Inhaled)
 Hydrocortisone (Cortisol) (Oral for replacement, IV for status asthmaticus and anaphylactic shock)

11

What are the indications for glucocorticoids?

 Immunosuppression
 Anti-inflammatory therapy
 Replacement of endogenous corticosteroids

12

What are the contraindications for glucocorticoids?

Systemic infection

13

Give five adverse drug reactions of glucocorticoids

 Cushingoid effects
 Suppression of HPA axis
 Osteoporosis
 Suppression of growth in children
 Mineralocorticoid effects if the glucocorticoid also has those actions

14

Why should long term therapy with glucocorticoids be withdrawn slowly?

 Long term therapy must be withdrawn slowly, due to HPA suppression

15

What is the mechanism of action of azathioprine?

 Azathioprine is a pro-drug, which is converted into 6-Mercaptopurine in the liver
 6-Mercaptopurine is a fraudulent purine nucleotide that impairs DNA synthesis and has a cytotoxic action on dividing cells

16

What are four indications for azathioprine?

 Rheumatoid Arthritis, Inflammatory Bowel Disease
 Prevention of graft and transplant rejection
 Autoimmune conditions where corticosteroid therapy alone inadequate
 Leukaemia

17

What is the route of administration for azathioprine?

 Oral / IV

18

What are three adverse drug reactions for azathioprine?

 Myelosuppression  Leukopenia, thrombocytopenia, anaemia
 Increased infection susceptibility
 GI disturbances (nausea, vomiting, diarrhoea)

19

Give a drug interaction with azathioprine

 Interacts with Allopurinol (treats gout), necessitates lowering of dose

20

Give a therapeutic note for the use of azathioprine

 6-Mercaptopurine is eliminated by the enzyme TPMT, which is subject to a high rate of genetic polymorphism. High levels of TPMT expression will lead to under-treatment, low levels of TPMT expression gives toxicity.

21

What is the mechanism of action of cytotoxic alkylating agents

 Pro-drug, that is activated by CYP450s.
 Alkylating agent, which creates cross-links in DNA so that it cannot replicate. Therefore it selectively acts on cells with a higher mitotic rate.

22

Give a cytotoxic alkylating agent

 Cyclophosphamide

23

Give an indication for cytotoxic alkylating agents

 Immunosuppression
 Cancer chemotherapy

24

Give a contraindication for cytotoxic alkylating agents

 Pregnancy

25

Give an adverse drug reaction for cytotoxic alkylating agents

 Induction of bladder cancer (urine concentration of acrolein metabolite)
 Lymphoma and Leukaemia
 Infertility & Teratogenesis

26

Give a drug-drug intteraction for cytotoxic alkylating agents

 Pro-drug is activated by CYP450s (inducers/inhibitors)

27

What is the mechanism of action of Calcineurin Inhibitors

 Reduction in IL-2 synthesis and release, via Calcineurin inhibition suppressing both cell-mediated and antibody-specific adaptive immune responses. Active against T helper cells.
 Ciclosporin binds to Cyclophilin and Tacrolimus binds to Tacrolimus-Binding-Protein
 Drug/Protein complexes bind to and inhibit Calcineurin, which normally has a phosphatase activity on the Txn factor for IL-2. Therefore, inhibition of Calcineurin reduces IL-2

28

What is the indication for Calcineurin Inhibitors

 Prevention of graft and transplant rejection
 Prevention of graft vs. host disease
 Atopic dermatitis, psoriasis

29

Give two calcineurin inhibitors

 Cyclosporin (Binds Cyclophilin)
 Tacrolimus (Binds Tacrolimus-Binding-Protein)

30

Give three adverse drug reactions of calcineurin inhibitor

 Nephrotoxic (proximal tubule), renal damage almost always occurs
 Hypertension in 50% of people
 GI disturbances

31

What is a drug-drug interaction of calcineurin inhibitor ?

 Metabolism is by CYP450, so is affected by inducers/inhibitors

32

Give a therapeutic note for calcineurin inhibitoprs

 Unlike most immunosuppression agents, Cyclosporin does not cause myelosuppression

33

What is an indication for Mycophenolate Mofetil

 Transplant immunosuppression (agent of choice)

34

What is a mechanism of action for Mycophenolate Mofetil

 Inhibits the enzyme Inosine Monophosphate Dehydrogenase, which is required for Guanosine synthesis
 Impaired B-cell and T-cell proliferation

35

What is an adverse drug reaction for Mycophenolate Mofetil

 Myelosuppression  Leukopenia, neutropenia
 Increased risk of infection (especially viral)

36

What is a therapeutic notes for mycophenolate mofetil

 Highly selective. Spares other rapidly dividing cells, due to the presence of guanosine salvage pathways

37

Name a couple disease modifying anti-rheumatic drugs (DMARDS)

Methotrexate
Aminosalicylates
Anti-TNF agents

38

Give an indication for methotrexate use

 Immunosuppression and Cancer chemotherapy

39

Give a contraindication for methotrexate

 Pregnancy

40

Give four routes by which methotrexate can be administered

 Orally, intravenously, intramuscularly, intrathecally

41

What is the mechanism of action for methotrexate?

 Antifolate
 Competitively antagonises Dihydrofolate Reductase (DHFR), preventing the regeneration of intermediates (tetrahydrofolate) essential for the synthesis of purines and thymidine, thus inhibiting DNA synthesis.

42

What is an adverse drug reaction to methotrexate? (5)

 Mucositis
 Myelosuppression
 Hepatitis, cirrhosis
 Increased infection risk
 Teratogenesis

43

Give a drug-drug interaction for methotrexate

 Adverse DDIs with drugs affecting renal blood flow and renal elimination, e.g. NSAIDs

44

What clinical monitoring should be carried out while on methotrexate?

 Baseline chest X-ray, FBC, LFT, U+E + Creatinine
 Monthly FBC, LFT, U+E + Creatinine

45

What should you be worried about if giving methotrexate with NSAIDs?

 Plasma protein binding ~50% - NSAIDs displace, raising plasma concentration

46

How often is methotrexate given?

Weekly

47

What do aminosalicylates treat,and how?

 Rheumatoid arthritis
 Inflammatory bowel conditions

 Sulfasalazine is broken down in the gut to the active component 5-aminosalicylate (5-ASA) and sulfapyridine, which acts as a vehicle to transport the drug to the colon.
 Inhibition of T-cell proliferation and IL-2 production. Reduced Neutrophil chemotaxis and degranulation.

48

What are some contraindications for aminosalicylates?

 Renal impairment
 Hypersensitivity

49

Give four adverse drug reactions of aminosalicylates

 Myelosuppression
 Hepatitis
 Rash
 GI disturbances (Nausea, vomiting, abdominal pain)

50

Name two anti-tnf agents

 Infliximab (Monoclonal Antibody)
 Etanercept (Fusion protein)

51

Give a mechanism of action of tnf-a

 Blocks the effects of TNF-α
 Decreased inflammation, decreased Angiogenesis, decreased joint destruction

52

Give an adverse drug reaction of anti-tnf (4)

 Increased infections
 Tiredness, dizziness
 Itching
 GI disturbances

53

Appreciate the pharmacological rationale for using Immunosuppressants in treating certain cancers

o Some immunosuppressants work by inhibiting the division of cells
 E.g. Azathioprine, Methotrexate, Cyclophosphamide, Cyclosporin
o Some cancers are the uncontrolled division of immune cells
 Therefore immunosuppressants will work to suppress the cancer