Stiefel Review - Dermatopharmacology

Front 1

Vitamin A can exist in diifferent forms, give the names for the:
Vitamin A alcohol
Vitamin A aldehyde
Vitamin A acid

Back 1

Vit A alcohol = retinol
Vit A aldehyde = retinal
Vit A acid = retinoic acid

Front 2

What are the precursors of Vitamin A from plants?

Back 2

Carotenoids

Front 3

What transports retinol in the serum?

Back 3

Retinol Binding Proteins
Transthyretin

Front 4

What transports retinol in the cell for translocation to the nucleus?

Back 4

cytosolic retinol binding protein

Front 5

What are the 1st generation synthetic retinoids?

Back 5

Tretinoin (all-trans RA) = Retin-A
Isotretinoin (13-cis-RA) = Accutane = water soluble

Front 6

What are the 2nd generation synthetic retinoinds?

Back 6

Etretinate = Tigason = removed from market and replaced by acitretin
Acitretin = Soriatane = metabolite of etretinate = water soluble

Front 7

What are the 3rd generation synthetic retinoids?

Back 7

aka polyaromatic retinoids:
tazarotene = tazorac
adapalene = differin
baxarotene = Targretin = used to treat MF = water soluble

Front 8

Which retinoids are water soluble?

Back 8

Isotretinoin
Acitretin
bexarotene
Levels are gone after 1 month of stopping therapy

Front 9

Which retinoids are more lipophilic?

Back 9

Etretinate & Acitretin

Front 10

Which proliferative keratins are downregulated by retinoids?

Back 10

K6 & K16

Front 11

Retinoids enhance keratinocyte differentiation -- in which ways?

Back 11

1. increased filaggrin production
2. increased keratohyalin granules
3. increased keratin filaments
4. increased odland body secretion of lipids

Front 12

What does Accutane do to sebaceous glands?

Back 12

reduces the size and decreases differentiation to mature sebocytes
(also inhibits ornithine decarboxylase which lessens inflammatory hyperplasia)

Front 13

What are some common Sfx of systemic retinoids?

Back 13

reduced night vision, diffuse interstitial skeletal hyperostosis (DISH), premature epiphyseal closure, elevated serum lipids and transaminases, pseudotumor cerebri (with TCNs), depression & myopathy

Front 14

What endocrine abnormality has been seen with bexarotene?

Back 14

reversible hypothyroidism

Front 15

What are some birth defects from retinoids?

Back 15

microtia, hearing loss, michrophthalmia, optic nerve atrophy, acral and axial skeletal abnormalities, cardiovascular defects, hydrocephalus, microcephaly, meningomyelocele, thymic aplasia, and anal&vaginal atresia

Front 16

Which retinoids target RXR receptors?

Back 16

Alitretinoin (9-cis-RA)
Bexarotene
Both hit RXR alpha, beta, & gamma

Front 17

Which Abx inhibits bacterial cell wall synthesis by blocking the transpeptidation step?

Back 17

Penicillins

Front 18

This abx blocks bacterial cell wall synthesis through inhibition of penicillin-binding proteins that catalyze transpeptidation

Back 18

Cephalosporins

Front 19

Which cephalosporin has been associated with increased incidence of serum sickness in children?

Back 19

Cefaclor

Front 20

This abx inhibits protein synthesis by binding the 30S ribosomal subunit

Back 20

Tetracyclines

Front 21

This Abx inhibits the 50S ribosomal subunit

Back 21

Macrolides
& Clindamycin

Front 22

This Abx inhibits DNA gyrase

Back 22

Fluoroquinolones

Front 23

This Abx inhibits RNA synthesis by inhibiting DNA-dependent RNA polymerase

Back 23

Rifampin (a rifamycin)

Front 24

What drug is most common cause of fixed drug eruption?

Back 24

Tetracycline

Front 25

What is drug has been assoc with cholestatic hepatitis?

Back 25

Erythromycin

Front 26

Where is the teeth discoloration in minocycline vs. tetracycline?

Back 26

TCN = Tots (in childhood) = in Top third of teeth (top gingival third)
Minocycline = Mid-portion of teeth

Front 27

Imiqumod induces which cytokines?

Back 27

TNF-alpha
IFN-gamma
IFN-alpha
IL-12
(leads to cell mediated immune response)

Front 28

Podophyllin works how?

Back 28

[extract of the May apple plant]
Is antimitotic, arresting cells in metaphase by binding protein tubulin

Front 29

What is a serious side effect of Protease Inhibitors? and, which one is most commonly associated with this sfx?

Back 29

Lipodystrophy - manifests as abnormal fatty deposits aka 'buffalo hump' and 'protease pouch'
Most notably = indinavir (also causes gynecomastia)

Front 30

Which HIV medications have been reported to cause periungual/paronychial eruptions (PG-like lesions)?

Back 30

Indinavir
Zidovudine
Lamivudine

Front 31

What sfx is uniquely seen in Foscarnet?

Back 31

Penile erosions are known to occur

Front 32

What drug has been assoc with reversible obstructive nephropathy?

Back 32

Acyclovir (rapid IV infusion)

Front 33

What fatal/severe sfx is seen with valacyclovir when used in AIDS or transplant patients in high doses?

Back 33

TTP/HUS syndrome

Front 34

Mechanism of Terbinafine

Back 34

blocks the biosynthesis of ergosterol, a sterol essential to the integrity of the fungal cell membrane; inhibits squalene epoxidase (fungal inhibited 4X more than mammalian)

Front 35

What is the advantage of using Terbinafine (vs. the azoles)

Back 35

No cytochrome p450 inhibition!! however, transformed in the liver, therefore slow elimination by 30% in liver pts

Front 36

This drug blocks synthesis of ergosterol

Back 36

Terbinafine

Front 37

An allylamine

Back 37

Terbinafine

Front 38

A Triazole

Back 38

Itraconazole

Front 39

Pregnancy Category:
Acitretin

Back 39

X

Front 40

Pregnancy Category:
Etretinate

Back 40

X

Front 41

Pregnancy Category:
Estrogens

Back 41

X

Front 42

Pregnancy Category:
Finasteride

Back 42

X

Front 43

Pregnancy Category:
5-FU

Back 43

X

Front 44

Pregnancy Category:
Flutamide

Back 44

X

Front 45

Pregnancy Category:
MTX

Back 45

X

Front 46

Pregnancy Category:
Stanozolol

Back 46

X

Front 47

Pregnancy Category:
Tazarotene

Back 47

X

Front 48

Pregnancy Category:
Aspirin

Back 48

D

Front 49

Pregnancy Category:
Azathioprine

Back 49

D

Front 50

Pregnancy Category:
Bleomycin

Back 50

D

Front 51

Pregnancy Category:
Colchicine

Back 51

D

Front 52

Pregnancy Category: Cyclophosphamide

Back 52

D

Front 53

Pregnancy Category:
Hydroxyurea

Back 53

D

Front 54

Pregnancy Category:
Mechlorethamine

Back 54

D

Front 55

Pregnancy Category:
Penicillamine

Back 55

D

Front 56

Pregnancy Category:
Potassium iodide

Back 56

D

Front 57

Pregnancy Category:
Tetracycline

Back 57

D

Front 58

Pregnancy Category:
Griseofulvin

Back 58

unrated, but probably D

Front 59

Pregnancy Category:
Spironolactone

Back 59

unrated, but probably D

Front 60

Pregnancy Category:
Quinolones/ciprofloxacin

Back 60

C

Front 61

Pregnancy Category:
TMP/SMX

Back 61

C

Front 62

Pregnancy Category:
Cyclosporine

Back 62

C (but believed to be safe in pregnancy)

Front 63

Pregnancy Category:
Acyclovir

Back 63

C

Front 64

Pregnancy Category:
fluconazole, ketoconazole, itraconazole

Back 64

C

Front 65

Pregnancy Category:
Benzoyl peroxide

Back 65

C

Front 66

Pregnancy Category:
topical retin-A

Back 66

C

Front 67

Pregnancy Category:
topical and oral steroids

Back 67

C

Front 68

Pregnancy Category:
Efalizumab

Back 68

C

Front 69

Pregnancy Category:
Penicillin

Back 69

B

Front 70

Pregnancy Category:
Emycin

Back 70

B (not estolate form due to hepatotoxicity in mother)

Front 71

Pregnancy Category:
Dimenhydrinate

Back 71

B

Front 72

Pregnancy Category: Cyproheptadine

Back 72

B

Front 73

Pregnancy Category: azeleic acid

Back 73

B

Front 74

Pregnancy Category: Permethrin

Back 74

B

Front 75

Pregnancy Category: cephalosporins

Back 75

B

Front 76

Pregnancy Category: Lidocaine

Back 76

B

Front 77

Pregnancy Category:
etanercept, alefacept, infliximab

Back 77

B

Front 78

Pregnancy Category:
Folic Acid

Back 78

A

Front 79

Pregnancy Category:
Levothyroxine

Back 79

A

Front 80

What drugs have been assoc with IUD failure?

Back 80

Azathioprine, NSAIDs

Front 81

What drugs have been assoc with OCP failure?

Back 81

griseofulvin, rifampin
~ by incr estrogen metabolism by hepatic enzyme induction

Front 82

Nitrogen mustard derivative that is cell-cycle non-specific

Back 82

Cyclophosphamide

Front 83

What is the toxicity assoc with cyclophosphamide -- which metabolite causes it? And, what is used to reduce the effect?

Back 83

Hemorrhagic cystitis (in 40%) of pts, can lead to transitional cell carcinoma.
Bladder toxicity is due to the acrolein metabolite
Mesna (aka sodium 2-mercaptoethanesulfonate) has been used to reduce this toxic effect

Front 84

Which pt's are at higher risk for pancytopenia when using MTX?

Back 84

renal patients
NSAIDS
Bactrim

Front 85

What is used to rescue pts from MTX induced myelosuppression?

Back 85

Leukovorin (folinic acid) -- can bypass dihydrofolate reductase in the cell division pathway

Front 86

What is a unique side effect of MTX?

Back 86

radiation recall (aka sunburn recall)

Front 87

Purine analog that acts only during the S-phase of the cell cycle in the formation of adenine and guanine nucleotides

Back 87

Azathioprine

Front 88

There are three enzyme pathways for Azathioprine -- name them

Back 88

1. Hypoxanthine guanine phosphoribosyl transferase (HGPRT)
2. Xanthine oxidase
3. Thiopurine methyltransferase (TPMT) activity

If pathway #1 becomes the primary pathway, toxic purine analogs can accumulate --> BM suppression!
This can happen in the setting of concurrent use of allopurinol (inhibits xanthine oxidase) or low TPMT allele activity

Front 89

Rituximab is what type of drug?

Back 89

Anti-CD20 antibody

Front 90

Methotrexate blocks what?

Back 90

Folic Acid Analog, inhibits dihydrofolate reductase

Front 91

Mycophenolate Mofetil

Back 91

Inhibits Inosine Monophosphate in de novo purine synthesis

Front 92

Azathioprine

Back 92

6-mercaptopurine analog that inhibits purine synthesis; check thiopurine methyl transferase levels prior to giving

Front 93

Interferon Gamma

Back 93

Inhibits TH2 cells

Front 94

Cyclosporine

Back 94

calcineurin inhibitor, blocks T-lymphocytes; reduces transcription of cytokines (IL-2); monitor BP, CBC, LFTs, Mg and Uric Acid

Front 95

Efalizumab mechanism?

Back 95

Recombinant monoclonal antibody that binds to CD11a, subunit of Leukocyte function antigen-1 to block ICAM-1;

Front 96

Sfx of Raptiva?

Back 96

Efalizumab
Thrombocytopenia, anemia, 5% of pts have anti-raptiva antibodies
Loading dose 0.7 mg/kg x 1 week, then 1mg/kg sc weekly.

Front 97

Rituximab is approved for what use?

Back 97

1997 FDA approved for B-cell lymphomas and treatment resistant RA

"off-label" use for pemphigus vulgaris, paraneoplastic pemphigus, all pemphigus
- Atopic dermatitis
- EBA
- ANCA-mediated vasculitis
- cryoglobulinemia
- dermatomysositis (unknown mechanism)
- Chronic GvHD
- Lupus

Front 98

Target of Rituximab

Back 98

CD20 receptor (B-cell specific antigen)

CD20 not found on plasma or stem cells (so they are spared!)

B-cells recover in appx 6 months

Front 99

What type of antibody is rituximab?

Back 99

Monoclonal IgG1 (chimeric murine-human antibody):

Fc fragment is human -- recruits immune cells to lyse CD20 cells

Fab fragment is mouse -- binds CD20 Ag

Front 100

Side Effects of Rituximab?

Back 100

IV infusion reactions are most common
RARE: PML