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IHO Wk 5 > Immunosuppressive Agents--Regel > Flashcards

Immunosuppressive Agents--Regel Flashcards

1
Q

Diphenhydramine

Chlorpheniramine

A

MOA: H1, mAChR, α-adrenergic, 5-HT antagonist

Distribution: CNS penetrant, PO, P-glycoprotein resistant

Metabolism: inactivated in liver, excreted in urine

Adverse: sedation, secretion drying (anti-mAChR), acute like atropine tox, allergic dermatitis

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2
Q

Diphenhydramine

vs

Chlorpheniramine

for motion sickness

A

dephenhydramine

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3
Q

Diphenhydramine

vs

Chlorpheniramine

for daytime use

A

chlorpheniramine

less sedating

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4
Q

Ceterizine

Fexofenadine

Loratidine

A

MOA: H1 antagonist (no anti-cholinergic)

Distribution: less CNS penetration (less sedating), P-glycoprotein sensitive

Met/Elim: met in liver, renal excretion

Adverse: not cardiotoxic

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5
Q

NSAIDs

A

MOA: COX1/2 inihbitors

TU:

  • analgesia (PG lower pain threshold)
  • antipyrentic (decreases PGE2 synthesis)
  • anti-inflammatory

Adverse: gastic ulceration, gestation prolongation, nephrotoxicity, hepatotoxicity, increased bleeding time–prolonged PTT

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6
Q

Acetylsalicylate

A

MOA: irreversibly binds/inhibits COX

Adverse: aspirin hypersensitivity (not antibody-mediated), Reye’s syndrome–esp. children with chickenpox

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7
Q

Indomethicin

A

MOA: COX inhibitor

*most potent*

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8
Q

Peroxicam

A

MOA: COX inhibitor

PK: PO once daily

Adverse: dose-related serious GI bleed

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9
Q

Celecoxib

A

MOA: COX2 inhibitor

Adverse: no effect on thromboxane, thrombus

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10
Q

Acetaminophen

A

MOA: COX inhibitor mostly in brain

TU: analgesic, antipyretic, not anti-inflammatory

Toxicity: hepatotoxicity at high doses

*650 mg just as effective as 1000 mg*

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11
Q

What is the TU for leukotriene inhibitors?

A

asthma prophylaxis

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12
Q

Zileuton

A

MOA: 5-lipoxygenase antagonist, prevents LTB4 and peptide leukotrienes

PK: liver cytochrome P450s, drug-drug

Adverse: hepatotoxic

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13
Q

Zafirlukast

A

MOA: leukotriene receptor antagonist (P450 isoenzyme), LTD4 receptor (Cys LTR1)

Adverse: drug-drug

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14
Q

Montelukast

A

MOA: leukotriene receptor antagonist (LTR4, Cys LTR1)

PK: once daily

*first choice leukotriene inhibitor*

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15
Q

Steroids

MOA

(cortisone, hydrocortisone, betamethasone, dexamethasone, methylprednisalone, prednisone)

A

MOA:

glucocorticoid receptor, glucocorticoid response element (GRE)

interacts with NF-kB and AP1

  • reduce COX2 expression-
  • inhibit arachadonic acid release –> decreased prostaglandins and leukotrienes-
  • inhibit degranulation of basophils/mast cells-
  • inhibit release of TNF, IL-1, IL-2, IFN
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16
Q

Steroids and WBC

A

Neutrophils: steroids promote demarginalization of neutrophils, promote release from BM, and increase neutrophilic t1/2 in blood –> neutrophilia

Lymphocytes: profound transient lymphopenia, cells migrate out of the blood into lymphoid tissue

17
Q

Anti-inflammatory | Sodium Retention | Duration

Cortisone

Hydrocortisone

A

Anti-inflammatory: +

Sodium retention: +

Duration: short

18
Q

Anti-inflammatory | Sodium Retention | Duration

Betamethasone

Dexamethasone

A

Anti-inflammatory: ++

Sodium retention: –

Duration: long

19
Q

Anti-inflammatory | Sodium Retention | Duration

Methylprednisalone

Prednisone

A

Anti-inflammatory: +

Sodium retention: ±

Duration: intermediate

20
Q

Glucocorticoid distribution

A

PO, IV, topical, or inhaled (complete first pass metabolism)

21
Q

Glucocorticoid metabolism

A

hepatic metabolism

renal excretion

22
Q

Calcineurin inhibitors

A

cyclosprorin

tacrolimus

23
Q

Cyclosporin

A

MOA: cyclophilin receptor antagonist in cytosol–> decreased calcineurin activity –> inhibits cytokine gene expression and T-cell activation

PK: hepatic metabolism, drug-drug

Toxicity: nephrotoxicity (75% of patients), must delineate from rejection

24
Q

Tacrolimus

A

MOA: binds FK506 binding protein –> inhibits calcineurin activity –> decreases T-cell activaiton

Tox: nephrotoxicity

25
Q

Sirolimus

A

MOA: binds FK-binding protein

–> inhibits mTOR –> blocks G1 -> progression

PK: CYP3A4 substrate –> drug/drug

Adverse: nephrotoxic w/ cyclosporin, increased infection and lymphoma risk, increased triglycerides

26
Q

Mycophenolate Mofetil

A

MOA: inhibits inosine monophosphate dehydrogenase (IMPDH)

–> inhibits de novo guanisine synthesis

–>B- and T-cells depend on this pathway, so becomes antiproliferative

Toxicity: leukopenia, diarrhea, vomitting

27
Q

Anti-Thymocyte Globulin

A

MOA: binds thymocytes (hematopoietic progenitor cells)

TU: prevents solid organ rejection by decreasing ciruculating lymphocytes

Adverse: serum sickness, nephritis, anaphylaxis

28
Q

Muromonab-CD3

A

MOA: anti-CD3, cell internalizes TCR complex

TU: prevents rejection of solid organ transplants

Adverse: cytokine release syndrome, HAMA reactions

29
Q

Daclizumab

A

MOA: anti-CD25 (IL2R) –> block IL-2 mediated T-cell proliferation and activation

TU: solid organ rejection prophylaxis

Adverse: no cytokine release syndrome, lower risk of lymphoproliferative disorders, anaphylaxis

30
Q

Basiliximab

A

MOA: anti-CD25 (IL2R) –> block IL-2 mediated T-cell proliferation and activation

TU: solid organ rejection prophylaxis

Adverse: no cytokine release syndrome, lower risk of lymphoproliferative disorders, anaphylaxis

IHO Wk 5 (8 decks)

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