Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MBBS II HIS > L 16 - Immunosuppressive and immunomodulatory drugs > Flashcards

L 16 - Immunosuppressive and immunomodulatory drugs Flashcards

1
Q

Ig, antigen, effector mechanism of Type I hypersensitivity reaction?

A

IgE
Soluble antigen (e.g. allergen)
Mast cells and basophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

List allergens that cause type I hypersensitivity rxn?

A

 Skin contact: poison plants, animal scratches, pollen, latex

 Injection: bee sting

 Ingestion: medication, nuts, shellfish

 Inhalation: pollen, dust, mold, mildew (霉菌), animal dander

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Define the 2 phases of Type I Hypersensitivity rxn?

A

Early phase: Within minutes of exposure to allergen (quick): Last 30-90 minutes

Late phase: 4-8 hours later: Last Several days: Often leads to chronic inflammatory disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Reaction that forms histamine? Storage form of histamine?

A

histidine decarboxylase decarboxylates histidine

> > histamine + CO2

Stored in intracellular granules Complexed with acidic protein, heparin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which locations in body has high amounts of mast cells?

A

Practically all tissues, but unevenly distributed

High in lung, skin, and the gastrointestinal tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the release of histamine from mast cell after stimulation?

A
  1. Binding of IgE primes the mast cell to respond to allergen.
  2. Allergen induces cross-linking of IgE and clustering of Fc receptors.
  3. Signal transduction to stimulate degranulaion.
  4. histamine released from granules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Type of receptors that get stimulated by histamine?

A

H1 / H2 / H3 / H4 seven transmembrane G-protein coupled receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Response of H1 receptor stimulation on BV and smooth muscles

A

1) Stimulates blood vessel dilation: decrease peripheral resistance
2. Increases capillary permeability: increase exudation and swelling
3. Contracts smooth muscle (other than blood vessel) (e.g. bronchioles)
4. Itch and pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

List some mild forms of Type I Hyersensitivity rxn?

A

skin: urticaria
eyes: conjunctivitis
nasopharynx: rhinitis
gastroenteritis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

List some severe forms of Type I Hyersensitivity rxn?

A

asthma anaphylactic shock

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Histamine can be stored in granules for pronlonged time. T or F?

A

False

if not stored = rapidly inactivated by amine oxidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

List 3 H1 antagonists.

A

Diphenhydramine
Hydroxyzine
Promethazine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

List advantages and disadv. of H1- antogonists first gen.

A

Cheap, effective

  • Short duration of action
  • Penetrate blood-brain barrier = sedation, CNS impairment
  • Low specificity = more ADR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

List ADRs of gen 1 H1-antagonist?

A

Not very specific: binds to other receptors

  • sedation, CNS impairment (**Gen 1 esp.)
  • Anticholinergic: dry mouth, urinary retention, blurred vision
  • Antiadrenergic: dizziness, hypotension, reflex tachycardia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which allergic symptoms are relieved by Diphenhydramine ?

A

allergic rhinitis: sneezing, runny nose, itching, watery eyes

itching, allergic skin reaction

Controls coughs due to cold / allergy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Advantages of gen 2 H1-antagonist over gen 1?

A

1) Poor penetration into CNS system = less CNS toxicity, sedation
2) More specific/selective for peripheral H1 receptors = no/little anticholinergic / antiadrenergic side effects
3) Rapid onset
4) Longer duration of action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

List 3 gen 2 H1 blocker?

A

Cetirizine
Fexofenadine
Loratadine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Explain why fexofenadine has less ADR than Gen 1 H1 blocker?

A

1) Bulky groups eliminate anticholinergic, antiadrenergic effects = increase specificity
2) Cannot cross blood-brain barrier (note the polar COOH, OH) = hydrophilicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

List the 3 therapeutic uses for antihistamines?

A
  1. Allergic, inflammatory conditions: allergic rhinitis, urticaria, cold or allergy
  2. Motion sickness, nausea (prophylaxis)
  3. Somnifacients (inducing sleep): insomnia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does H1 blocker reduce motion sickness?

A

Block central H1 and muscarinic receptors at cerebellum&raquo_space; block activation of vomiting centre in Area Postrema of Medulla oblongata

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

D/D interactions of H1 blocker?

A

 All CNS depressants (potentiated effects)

 Monoamine oxidase (MAO) inhibitors (increased side effects)

 Cholinesterase inhibitors (decreased effectiveness in treating Alzheimer’s disease)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

OD effects of H1 blocker?

A

CNS: hallucinations, excitement, ataxia, convulsions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

List some indications for immunosuppressants? (think ERS, Neruo, MSS, HIS all have some autoimmune diseases)

A

1) Allograft rejection*****

2) Autoimmune diseases
•DM type 1
•MS
•Rheumatoid arthritis 
•Autoimmune hemolytic anemias 
•Idiopathic thrombocytopenia purpurea(ITP) 
•Acute glomerulonephritis 
•SLE
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Describe the 3 signals between APC and T cells during induction phase?

A
  1. Signal 1 – MHC + TCR (CD3 receptor complex)
  2. Signal 2 – CD80/86 or B7 on APC + CD28 on T-cells
  3. Signal 3 – CD40/CD40L and ICAM-1/LFA-1 interactions enhance activation

Cytokines (e.g. IL-2 + CD25) stimulate T-cell proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Describe the 3 responses in effector phase of APC- T cell response?

A

Cytokine production
Induce Cytotoxic effects
Induce Antibody production

26
Q

Describe the intracellular activation of T-cells via IL-2 ***

A

1) Activated T cell > increase intracellular Ca2+

2) Activate calcineurin > dephophorylate and activate
NFATc (Nuclear Factor of Activated T cells)

3) NFATc moves into nucleus > increase transcription of IL-2
4) IL-2 released > binds to CD25 (autocrine) > activate mTOR
5) mTOR cause clonal expansion

27
Q

List 2 classes of microbial product** immunosuppresants and give 2 examples each

A
  1. Calcineurin inhibitors ◦Cyclosporine ◦Tacrolimus

2. mTOR inhibitors ◦Sirolimus ◦Everolimus

28
Q

Preparation and indication of CsA?

A

IV or oral (poor)
+/- corticosteroids and antimetabolites

first-line therapy in the prophylaxis treatment of transplant rejection

Treat unresponsive severe autoimmune diseases

29
Q

MoA of CsA?

A
  1. binds to a cytoplasmic receptor protein called cyclophilin (CpN)
  2. inhibits calcineurin (CaN) phosphatase
  3. prevents activation of nuclear factor (NFATc)
  4. inhibits synthesis of IL2,
30
Q

Metabolism of CsA?

A

metabolized by the CYP3A system

Affect CYP450 = D/D rxn

31
Q

ADR of CsA?

A

Nephrotoxicity **
Opportunistic infections
Lymphoma **

(others: hypertension, hyperkalemia, tremor, hirsutism …etc)

32
Q

Preparation and indication of Tacrolimus?

A

prevention of rejection of solid organ

+/- corticosteroids and/or an antimetabolite

33
Q

MoA of Tacrolimus?

A
  1. binds to FKBP
  2. inhibits calcineurin phosphatase
  3. prevents activation of nuclear factors
  4. inhibits synthesis of IL-2 in T-cells
34
Q

ADR of Tacrolimus?

A

nephrotoxicity and neurotoxicity (tremor, seizure, hallucination)***

Post-transplant, Insulin-dependent DM

35
Q

Tacrolimus and CsA can be given together. T or F?

A

False
share a mechanism of action and metabolic route

> > never given together (additive nephrotoxicity)

36
Q

Preparation and indication of Sirolimus/ Rapamycin

A

Triple:
Sirolimus + Tacrolimus(/CsA) + Corticosteroids

kidney / heart transplantation

37
Q

MoA of Sirolimus?

A

Binds to cytoplasmic FKBP

> > interferes with mTOR signal (= serine-threonine kinase controlling T cell proliferation)

> > inhibits translation of mRNAs that promote transition from G1 to S phase of cell cycle

> > T cells arrest in G1 phase (unresponsive to IL-2 stimulus)

38
Q

Metabolism and ADR of Sirolimus?

A

Oral, Liver metabolism

hyperlipidemia***, hypertension,

leukopenia, thrombocytopenia

infection

39
Q

D/D rxn of Sirolimus?

A

aggravates cyclosporine-induced renal dysfunction

cyclosporine increases sirolimus-induced hyperlipidemia

40
Q

List 4 Antimetabolites and Cytotoxic agents?

A

Azathioprine Mycophenolate mofetil Cyclophosphamide Methotrexate

41
Q

MoA of Azathioprine?

A

Prodrug: converted to 6-mercaptopurine&raquo_space; 6-thioinosinic acid

blocks the de novo purine synthesis for lymphocyte proliferation

42
Q

Preparation and indication of Azathioprine?

A

Triple:
Azathioprine + CsA/ Tacrolimus + Corticosteroids

Haemolytic anemia, kidney transplantation and autoimmune disorders: Crohn’s, GN

43
Q

ADR and D/D interactions of Azothioprine?

A

MAJOR ADR = MYELOSUPPRESSION*** especially for subjects with defective TPMT

Other: increased risk of cancer, and GI irritation

D/D: Allopurinol, Xanthine oxidase cause accumulation

44
Q

Preparation and indication of Mycophenolate mofetil?

A

Triple:
Mycopehnolate mofetil + CsA/ Tacrolimus + Corticosteroids

sole agent for heart, kidney, and liver transplants

45
Q

MoA of Mycophenolate mofetil?

A

GI: hydrolyze to mycophenolic acid (MPA)&raquo_space; inhibit inosine monophosphate dehydrogenase (IMP Dehydrogenase )

> > blocking de novo formation of guanosine phosphate, lymphocytes cannot divide

46
Q

ADR of Mycophenolate mofetil?

A

diarrhea, nausea, vomiting, abdominal pain,

leukopenia, and anemia

47
Q

List 4 Polyclonal & Monoclonal antibodies

A

Antilymphocyte globulins
Intravenous immunoglobulins (IVIG)
IL2 receptor antagonists, daclizumab/basiliximab
Alemtuzumab, Rituximab etc

48
Q

Indication and preparation of Antilymphocyte globulins?

A

prevent early allograft rejection, or severe rejection episodes

Used with other immunosuppressive agents

49
Q

Metabolism and MoA, admin. of Antilymphocyte globulins?

A

IV

ADCC - Antibody-bound cells are depleted in liver and spleen

50
Q

ADR of Antilymphocyte globulins

A

Chills and fever,and skin rashes

leukopenia, thrombocytopenia,
infections,

51
Q

Difference in source between Antilymphocyte globulins and Intravenous immunoglobulins (IVIG)

A

Antilymphocyte globulins = prepared by immunization of rabbits / horses with human lymphoid cells

IVIG = prepared from human plasma pooled from many donors

52
Q

Indication of IVIG? MoA?

A

autoimmune diseases, pretransplant desensitization, and treatment of antibody-mediated rejection (AMR)

Unclear MoA: B-cell apoptosis and modulate B-cell signalling

53
Q

ADR of IVIG?

A

Flu-like symptoms: headache, fever, chills, myalgias

hypotension/hypertension,

aseptic meningitis**

acute renal failure and thrombotic events**

54
Q

MoA of IL-2 receptor antagonist? Give 2 examples?

A

basiliximab, daclizumab

anti-CD25 antibodies&raquo_space; bind to the α chain of IL-2 receptor on activated T cells

> > inhibit IL-2 mediated T-cell activation and proliferation

55
Q

Indication of IL-2 receptor antagonist?

A

induction therapy in transplantation

decreasing the incidence of acute rejection: Prophylaxis of kidney transplantation in combination with steroids or CsA

56
Q

Administration and ADR of IL-2 Receptor antagonist?

A

intravenously;

very well tolerated, virtually no side effects

57
Q

Difference in composition between Basiliximab and Daclizumab?

A

Basiliximab = a chimeric antibody: 25% murine & 75% human sequences

Daclizumab = humanized antibody: 90% human sequences

58
Q

MoA of cortical steroids in treating organ transplant rejection?

A

Inhibit cytokine production by T cells and macrophages

> > inhibition of nuclear factor kappa B activation

> > Bind glucocorticoid response elements in the promoter regions of cytokine genes

> > disrupting T cell activation and macrophage mediated tissue injury.

59
Q

Name 2 corticosteroids and indication in organ transplant?

A

prednisone or methylprednisolone

acute rejection + chronic graft-versus-host disease + autoimmune disease

60
Q

ADR of corticosteroids?

A

Diabetogenic, hypercholesterolemia, cataracts, osteoporosis, and hypertension, Glucose intolerance, Cushing syndrome …etc

MBBS II HIS (30 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions